[Logetronic micro-film in radiological diagnosis with an integrated system of filming and filing(author's transl)]. The results of one year's routine use of primary microfilm in a large diagnostic radiological institute is reviewed. Positive views were treated by electronic contrast enhancement in an integrated system of immediate filming and filing. The resulting changes and improvements in running the department are described. This involves a fundamental reorganisation of the department, as well as equipment which is not yet commercially available. The latter had therefore to be improvised and is described. Similar procedures introduced elsewhere are critically evaluated. The advantages of immediate filming are stressed and a comparison with conventional large film filing demonstrates its financial advantages. Logical application of the method results in saving in personnel and material, but implies that the radiologist must be prepared to change to positive films in routine diagnosis. By using microfilm positives with a resolution of 4.0 pairs of lines per mm., the results equal those from large film negatives.


[Assessment of radiologists workload in Scandinavia(author's transl)]. Experience in Sweden, Norway and Finland (University Clinic, Oulu) indicates that the points system instituted by the Scandinavian Association of Radiologists provides a satisfactory means of measuring radiologists' workload. A similar system for assessing radiographic technicians' workload is desirable.


[Marginal atelectasis of the lower lobes (author's transl)]. During one year ward films showed opacities with sharp upper margins at the borders of the upper and lower lobes in 17 seriously ill patients, aged between 67 and 87 years. These were interpreted as marginal atelectases of the lower lobes; they have not been previously described. Hypoventilation, with incomplete expansion and marginal atelectasis in seriously ill patients in bed first affect the lower lobes, according to the laws of respiratory physiology and pathology. Marginal atelectasis of the lower lobes occurs unilaterally or bilaterally and in the early stages is reversible. Radiologically, it is clearly distinguishable from intralobar effusions into the major fissure. Other differential diagnosis, such as small pneumothoraces or overlying soft tissue shadows, are not a significant problem.


[The radiological diagnosis of calcifying coronary sclerosis (author's transl)]. There has, up to now, not been general acceptance in the German literature of a definite relationship between radiologically visible coronary calcification and coronary heart disease. Anglo-American authors in general agree with our coronographic findings, which show a significantly increased incidence of such coronary changes in stenosing coronary artery disease. In a random sample of patients over 40 years of age, coronary calcification was found radiographically in 25%. Two-thirds of these patients were more than 60 years, but one quarter of the 50 to 60 year age group, and 15% of the 40 to 5-year age group showed these findings. In one group of 150 patients with coronary calcification, 68.9% suffered from coronary heart disease, 7.9% were suspicious and 23.2% had no symptoms. Conversely, in 100 patients with coronary heart disease, coronary calcification was present in 42. Calcification in several vessels was confined almost entirely to patients with advanced coronary disease. Coronary angiography in patients with normal E.C.G.'s, both at rest and after exercise, usually showed some reduction in the lumen corresponding to the area of calcification. In these patients the prognostic significance of the calcification in terms of further development of atherosclerosis must be considered. The localisation of the calcification in these cases is of significance. The clinical features, histology, localisation and investigation of the calcification by radiography is discussed. In our view this has considerable significance in the screening of coronary heart disease.


[The effect of biological factors during functional scintigraphy of the heart (author's transl)]. The parameters relating to functional scintigraphy of the heart (average circulation time, peak time) depend not only on the method (injection technique, radiopharmaceutical), but also on biological factors. Failure to take these into consideration may result in an erroneous interpretation of the findings. Circulation time in normal children aged 6 to 14 years, as determined by isotope methods is significantly shorter than in normal adults. Patients with compensated heart disease, as well trained athletes, show significantly shorter than in normal adults. Patients with compensated heart disease, as well trained athletes, show significant increase in all portions of the circulation time, when compared with normals of similar ages. This indicates that deviation in the haemodynamics of the circulation as shown by functional scintigraphy, can only be interpreted in the light of clinical findings.


[Tracheobronchopathia chondro-osteoplastica (author's transl)]. Tracheobronchopathia chondro-osteoplastica is a relatively rare abnormality, which has hardly been illustrated in the radiological literature. It has, however, been accurately defined pathologically and is of clinical significance by causing obstruction of the airways. The disease must be distinguished from changes in the trachea and bronchi due to ageing, which may be associated with calcification of the tracheal cartilage, but in which there is no thickening of the wall of the trachea.


[Ultrasound examination in obstructive biliary disease (author's transl)]. Ultrasound examination with a two-dimensional recording technique has proved increasingly useful in obstructive biliary disease and in abnormalities of the liver parenchyma causing a reduction in biliary contrast excretion. In particular, hydrops of the gall bladder, cholelithiasis and choledocholithiasis and choledocholithiasis can be demonstrated where there is biliary obstruction. Analysis of various planes of section is particularly useful in showing obstruction due to the head of the pancreas. The introduction of grey scale techniques and focussed transducers of various frequencies and sizes, suggests that there will be further improvements in the sonographic diagnosis of the hilum of the liver and of the intrahepatic biliary passages.


[The use glucagon for endoscopic and radiological examination of the gastrointestinal tract (author's transl)]. In more than 1,000 radiological and endoscopic examinations of the smooth muscle hollow organs of the upper intestinal tract, crysalline glucagon (0.2 to 0.5 mg., average dose 1 u/kg. body weight given at a single intravenous injection) resulted in a significant relaxation and reduction of peristalsis. This effect was less marked in the colon and recto-sigmoid. In five patients with colonic diverticulosis it had no effect. In 150 patients it was found that the onset of hypotonia after injection of glucagon increases from proximal to distal, the duration of maximal reduction in peristalsis decreasing distally. Glucagon is indicated for reducing the tone of smooth muscle hollow organs in order to judge their elasticity and to distinguish between functional and organic causes of a stenosis or increased size of folds. The rapid onset of peristaltic inhibition makes various diagnostic and therapeutic endoscopic procedures simpler or even possible. Compared with the usual atropin-like antispasmodics, glucagon has the advantage of being free from side effects apart from transient hyperglycaemia. Diabetes mellitus requiring insulin is a (relative) contra-indication to the use of glucagon.


[Double-contrast examination of the small bowel without intubation (author's transl)]. A method for tubeless, double-contrast examination of the small bowel is described. Oral contrast medium and capsules which effervesce in the small bowel resulted in double-contrast demonstration of the small bowel in 90 out of 130 patients. Transit through the small bowel was reduced to an average of 78 minutes, due to increased peristalsis resulting from distension by the intralumental gas. For comparison, average transit time in a control group of 83 patients was found to be 126 minutes. The differential diagnosis of stenosing processes and additional information concerning space-occupying lesions was furthered by small bowel hypotonia induced by the intravenous injection of 15 to 45 mg. propantheline bromide (Probanthine) or 1 to 2 mg. glucagon. The method has the following advantages: 1. Improved demonstration of detailed mucosal pattern, 2. Reduced examination time and 3. Simultaneous visualisation of the entire small bowel.


[Cyst of the duodenum with termination of the bile and pancreatic ducts (author's transl)]. The radiological findings in a 27-year old female Turkish patient with a cyst in the wall of the duodenum are described. It caused a sharply demarkated, smooth thumb-print in the duodenum shown by barium meal. An intravenous and intra-operative cholangiogram caused filling of the cyst with contrast through the bile duct. The bile and pancreatic ducts terminated on the medial side of the cyst through the papilla of Vater. The size of the cyst varied, depending on its degree of filling with bile and pancreatic juice. Its position and morphology has been confirmed at operation. Histology showed an external cover of small bowel mucosa and an inner lining of small bowel mucosa interspersed with islands of gastric mucosa. The development of this cyst is explained as a developmental anomaly during recalisation of the embryonic duodenum.


[The demonstration of hererotopic gastric mucosa in the oesophagus with 99mTc pertechnitate (author's transl)]. Scintigraphy of the stomach with 99mTc pertechnitate indicates showing uptake of this substance. One case is described showing that heterotopic gastric mucosa in the oesophagus, as occurs in the so-called Barrett syndrome, can be demonstrated in this way. The examination can be performed rapidly and easily without trouble to the patient.


[Lateral renal scans (author's transl)]. The value of lateral renal scans was evaluated in 26 patients with a firm diagnosis of space-occupying lesions in the kidneys. In 14 patients the lateral view provided information additional to the usual P.A. scan. In seven of these 14 patients, the abnormality was shown better on the lateral than on the P.A. SCAN. In the other seven patients, the abnormality had been shown on the P.A. view, but the lateral scintigram provided more precise information concerning the position and size of the lesion.


[Aortic truama from blunt abdominal injuries (author's transl)]. The radiological and angiographic changes resulting from abdominal aortic trauma after blunt injuries are described in four patients. These include intimal damage as well as perforation.


[Traumatic rupture of the thoracic aorta associated with an aberrant right subclavian artery (author's transl)]. Traumatic rupture of the aorta isthmus is described in a patient with an aberrant right subclavian artery. While the aortic rupture could be diagnosed on plain films of the thorax, only an arch aortogram was able to demonstrate its location and the presence of the anomaly. Left anterior oblique views are to be preferred to the A.P. projection for the arch aortogram.


[Translumbar aortography with curved radiopaque cathter (author's transl)]. The technique for translumbar aortography with radiopaque polyaetylen catheters has been modified by curving the catheter so that the catheter tip after puncture and withdrawal of the canule, will bend in the lumen of the aorta. This is a simple technique to ensure that the catheter tip is placed free intra-luminally and at the same time it permits a better downstream or upstream technique.


[Myelomalacia following vertebral angiography with a femoral catheter (author's transl)]. Cerebral angiography with femoral catheters in two patients was followed by an incomplete cervical transverse myelitis. The complications were thought to be due to high contrast concentration in the cervical spinal vessels because of hypoplasia of one vertebral artery, and to contrast injection into the thyro-cervical trunk.


[The radiology of traumatic pneumatoceles. Pathogenesis and course (author's transl)]. The development and course of traumatic pneumatoceles was followed radiologically in four patients. The interval between the trauma and a recognisable cystic space varied. The patients had in common the fact that they were young, had suffered a serious road accident and developed haemoptysis. In one patient a lobe had to be resected, in the other spontaneous regression occurred within four weeks.


[Origin of the left vertebral artery from the left external carotid artery (author's transl)]. A rare anomaly is described consisting of the left vertebral artery arising from the left external artery. The developmental basis and relationships are discussed.


[Routine use of a catheter technique for cerebral angiography (965 examinations) (author's transl)]. The authors report their experience with routine use of a catheter technique for cerebral angiography. The complication rate is low and the diagnostic yield is increased. They conclude that it is superior to direct puncture of the vessels in the neck and to retrograde brachial angiography.


[The effect of increased performance of modern x-ray tubes on improvements in picture quality, particularly of moving organs (author's transl)]. The deleterious effect of organ movement on radiographic quality is examined. In connection with this, the performance of various focal spots is discussed, particularly of a modern high speed tube with focal spots of 1.2, 1.5 and 1.8, with a resolution in the region of 3 to 6 lp/mm. A detailed discussion of the results is given with examples derived from various techniques used for the stomach and lungs. The results indicate that there is considerable improvement to be derived from high performance tubes with small focal spots. A further significant advance is also due to the high resolution image intensifiers. These have resulted in a marked increase in the use of 70 and 100 mm. film.


[Sarcoidosis of the skeleton. Review of the literature and case report. (author's transl)]. The frequency of sarcoidosis in the skeleton varies between 3 and 36%. Skeletal sarcoidosis is rare in early stages (Löfgren-syndrom), relatively frequent in late stages. The initial phase is characterized by the formation of miliary non-caseating epitheloid-cell granulomas in the bone marrow. The invasion of the bone marrow may either be tolerated by the bone tissue or it initiates a perifocal osteosclerosis or a osteolysis. Correspondingly the X-ray of the skeleton shows normal structure or focal osteosclerosis or osteolysis. Therefore in the first case the sarcoidosis cannot be identified by X-ray. Most frequent locations are the phalanges of the fingers and toes, less common the stem skelton (skull, vertebrae, pelvis) and very rare the long tubular bones. In most cases the skeletal sarcoidosis is well tolerated. Report of a case of osteosclerotic sarcoidosis of the pelvis of a 39-years old woman with generalized sarcoidosis which was diagnozed four years earlier. The X-rays of the phalanges were normal. The biopsy of the iliac crest shows miliary sarcoid granuloma of the bone marrow and accretion of lamellar bone on the surface of the bone trabeculi with a distinct mosaic pattern. Treatment with steroids during the following five years was ineffective.


[The radiological manifestations of fibroxanthosarcomas (author's transl)]. The radiological findings in eight patients with fibroxanthosarcomas are described. In seven patients the primary tumour was in the soft tissues of the extremities or of the trunk. Infiltration of the primary tumour into a neighbouring bone, producing a "motheaten" appearance on the radiograph was seen in one case. A primary tumour in the mediastinum (one case cannot be distinguished radiologically from malignant lymphoma. Pulmonary metastases were found radiologically in five patients; in two they were solitary and in three patients there were multiple round foci measuring up to 8 cm. in diameter. Metastases in the lung hila and mediastinum were found only in the presence of pulmonary metastases (three cases). Pleural effusions developed in an advanced stage of the disease only (three cases). A solitary, purely osteolytic bone deposit was seen in two patients. Multiple metastases in the kidneys were hypo- or avascular, but some showed fine corkscrew vessels. On intravenous urography they could be demonstrated after reaching a considerable size (one case). A deposit in the jejunum presented as a small polyp. Two fibroxanthosarcomas developed as a second tumour within the operative field of a previous malignancy; one of these had been irradiated with 4,500 rads. All primary and secondary tumours showed extremely rapid growth. The palliative effect of radiation and chemotherapy was very variable.


[Intra-osseous angiography of human tubular bone (author's transl)]. After a comprehensive review of the literature dealing with the topography, morphology and histology of the vascular systems in long tubular bones, a method of "intra-osseous angiography" of these bones is described. Serial angiograms of isolated human tubular bones show a branching system running in the long axis of the bone; this corresponds with the vascular pattern seen on retrograde angiograms of the nutrient vein. Histologically these can be identified as venous structures as far as its microcirculatory components. Application of the method to medicine may become a valuable aid in early and differential diagnosis.


[Experimental investigations regarding the limations of radiological demonstration of fractures of the head  of the tibia (author's transl)]. The discrepancy between the radiological and the morphological finding, which we know from the clinic, could be confirmed in examinations of experimentally produced fractured of the lateral tibial condyle. The depth of the impressions of the tibial plateau and the width of the gap of the fracture can only be shown on additional tomographs and oblique radiographs of the knee-joint. Pure impressions of the tibial plateau up to a depth of 3 mm are totally beyond the radiological methods known for the present.


[Xeroradiographic studies on the capsule and ligaments of the knee joint. 1. Anatomy of the cruciate and lateral ligaments in the xerotomogram]. The suitability of xeroradiography for contrast arthrography was investigated by in vitro studies. Special attention was devoted to the cruciate and lateral ligaments on xero-ty lateral tomography. The anterior and posterior ligments can be evaluated and defined satisfactorily in the antero-posterior view. The lateral ligaments can be seen on xero-tomography without difficulty. The use of xero-tomography promises to improve the radiological diagnosis of injuries of the capsule and ligaments of the knee joint.


[Xeography of the neck and upper airways compared with conventional X-ray techniques (author's transl)]. The soft tissue structure and air containing hollow organs of the pharynx, larynx and upper trachea are particularly suitable for xerographic investigations. The well known edge effect on the one hand and the reduction of marked contrast effects on the other, both of which are specific features of xerography, provide much information and high diagnostic accuracy in the evaluation of abnormalities in the neck. Xerography was compared with lateral views and A.P. tomograms, using conventional radiography without contrast medium, in forty patients. Most had malignant tumours, but some had benign stenoses or injuries due to foreign bodies. Both with respect to total information obtained as well as detailed demonstration of the disease processes, xerography proved superior to radiography. An exception must be made for xerographic examinations of patients with short, thick necks. Accurate demonstration of the depth of malignant tumours and recognition of diseased lateral cervical lymphnodes is almost completely confined to xerography. Since radiation dose is increased by a factor of two to nine times, indications for xerography must be strictly defined, but is acceptable when compared with the radiation dose of routine examinations.


[Xeroadiography in facio-maxillary surgery (author's transl)]. Xeroradiography, which permits simultaneous demonstration of bone, cartilage and soft tissue, is particularly suitable for planning of facio-maxillary operations.


[A complex malformation of the first and second branchial arch and of the first bran-hial arch and of the first branchial cleft. Dysostosis temporo-spheno-facialis (author's transl)]. A complex malformation of the first and second branchial arches and of the first branchial cleft is described; there was also involvement of the axial skeleton and the limbs. The syndrome has been described by us as dysostosis temporo-sphenofacialis and could not be classified with any previously described entity. The reason for this was due to the imcomplete description of previously published cases, but also the large number of possible combinations of changes in various organs which can occur. In order to understand the condition more clearly, the aetiology and pathogenesis of abnormalities of the face and skull have been considered in detail. Adequate and accurate radiographic examination is considered as a pre-requisite to surgery, which can be cosmetic or improve hearing, and which may have good results.


[A contribution to the differential diagnosis of odnotogeneous cysts]. Problems concernint the diagnosis and differential diagnosis of odontogenic cystic lesions of the jaw are discussed with reference to a series of patients and some specially selected cases. The use of isotope examination is often of particular significance in coming to a decision. The position and value of scintigraphy has been demonstrated by referring to the literature and to our own investigations. The often difficult differentiation from certain types of odontogenic tumours is also discussed.


[Acromesomelic dwarfism (author's transl)A1]. Report on two brothers exhibiting the characteristic features of acromesomelic dwarfism first delineated in 1971, in which the shortening of the forearms and hands/feet are pronounced.20


[Radiological meneral equivalent determinations in bone. The problems of build-up factor (author's transl)]. The apparatus for measuring mineral equivalents described by Gebhardt, Heinen and Zwicker in 1973 was subjected to theoretical and experimental investigations; as a result, changes were introduced which significantly improved the basis for exact absorption measurments on phalanges. 1.The CuK alpha radiation (8.5 kV) produced the Hohannson monochromator was replaced by higher energy AgK alpha radiation (22.2 kV). The total spectrum was improved by using a palladium filter and an impulse height discriminator. 2. A slit collimator was used giving a beam area of 3 mm X 0.5 mm with improved paralleism ofthe beam and an incident angle alpha of 0.1 degrees compared with a previous angle of alpha approximately 1 degrees. 3. Correction of attenuation N = No. e-ux by a correction factor B to allow for "build-up factor" in the required area of measurement is no longer necessary. Measurements at four of hydroxyle apatite (Reiss) provide the required mineral absorption. 4.AgK alpha radiation permits measurement of thicker bones such as radius and calcaneus and provides adequate impulses for short periods of measurement which is useful in practice.


[Radiological investigations of over-modelled skulls from New Ireland (Melanesia) (author's transl)]. The authors examined a series of overmodelled and decorated skulls from New Ireland which had been used as cult objects for ritual dances. The results are described briefly with a number of examples. Radiological examination provided no evidence that these had been chosen specifically according to age or sex. Of particular significance for ethnology is the finding of two skulls in which the jaws have been replaced before modelling by adapted pigs' mandibles. The non-destructive radiological investigation of artistic and cultural objects has a particularly long tradition in Berlin (eg. Baessler). With these examples we should like to stimulate further similar work.


[Radiation burden from X-ray diagnosis and new technological developments (author's transl)]. Radiation exposure of the population is expressed nowadays in terms of genetically significant dose and its individual components are compared. The calculations necessary for the present considerations have been carried out. As a basis for evaluating radiation protection, the natural sources of radiation and therir variations are used. The dose of 110 mrem/a for the population of the Federal Republic is subject os considerable variations. Artificially produced radiation contributes a total of 60 mrem/a to the exposure. Of this, most is contributed by medical sources with 50 mrem/a, second is exposure due to atom bomb research. Other sources of radiation, such as occupational exposure, its use in research and technology, and use of nuclear technology, contribute little to total exposure, each producing about 1 mrem/a. The data provided is supported by numerical evidence.


[Premedication with valoron (Tilidin) in internal laparoscopy]. Apart from sufficient experience on the part of the examining physician and adequate technical apparatus, proper premedication can facilitate the procedures for both patient and physician considerably. The paper reports on experience gained in 500 laparoscopies carried out under conditions which were deviated slightly from those hitherto recommended in the literature. The analgesic employed was Tilidine (in Germany: Valoron), and Diazepam was used as a sedative; both of these substances were given intravenously, the vein was kept open for the entire course of the examination. The Tilidine dose was normally 50-100 mg, but under exceptional circumstances as much as 150 mg. Tilidine showed good analgesic effectiveness and tolerance; no case or nausea or vomiting and no sign of respiratory depression of effects on smooth muscle were observed under the conditions stated. The fact that Tilidine is not subject to the restrictions imposed by the German narcotics law is also seen as an advantage. The Diazepam dose was 5-30 mg. Apart from its sedative effect Diazepam also diminishes the tonus of skeletal muscle (important in laparoscopy) and has a relatively long time of elimination (20-48 h). In addition to these two substances, 10-20 ccm of 1% Lidocaine solution with Epinephrine additive was given as a local anaesthetic. The investigators' experience with the above premedication procedure was found to be convincingly positive.


Effects of dehydroepiandrosterone and 16 alpha-hydroxydehydroepiandrosterone on the reduction of glucose to glucitol by the human placenta. The metabolism of glucose by subcellular preparations of human full term placentae has been investigated. It has been shown that in the presence of NADPH two transformation products can be detected of which one has been identified as glucitol. The effects of dehydroepiandrosterone and 16alpha-hydroxydehydroepiandrosterone on the reduction of glucose to glucitol have also been studied. It has been found that at a concentration of DHA 1.2 X 10(-4)M, the reduction of glucose is strongly inhibited (35-51%), while at a concentration of DHA 5.8 X 10(-6)M this reaction is stimulated by 13 +/- 2.3%. 16alpha-hydroxyepiandrosterone at concentrations ranging from 1.2 X 10(-4)M to 3 X 10(-6)M inhibits the formation of glucitol from 63% to 9%.


Male pseudohermaphroditism due to testicular 17-ketosteroid reductase deficiency. A new case of testicular 17 ketosteroid reductase (17 KSR) deficiency without gynecomastia was investigated. Delta4 androstenedione (15.6 ng/ml) was ten times the normal range, unchanged after dexamethasone administration. In contrast, plasma testosterone (4.1 ng/ml) was in the low normal male range and plasma dehydroepiandrosterone (4.2 ng/ml) was normal. Plasma luteinizing hormone and follicle-stimulating hormone were increased (162 and 470 ng/ml LER 907 respectively). After adrenal suppression and human chorionic gonadotropin stimulation, the increase of delta4 androstenedione was in contrast with the inertia of testosterone. In spermatic venous plasma delta4 androstenedione level (293.2 ng/ml) was very high and testosterone level (7.1 ng/ml) a hundred times below the normal mean. Plasma estrone (124 pg/ml) was increased and estradiol (22 pg/ml) was normal. In spermatic venous plasma estrone was elevated and estradiol very low (1380 and 32 pg/ml respectively). It is the third case of 17 KSR deficiency where the lack of E2 increase explains the absence of gynecomastia.


Characterization of the proteinase inhibitors from bull seminal plasma and spermatozoa. Two acid stable proteinase inhibitors are present in bull seminal plasma and washed ejaculated bull spermatozoa. Inhibitor I with a molecular weight of about 8700 (estimated by gel filtration) is a very strong inhibitor of bull sperm acrosin but also inhibits bovine trypsin and chymotrypsin and porcine plasmin; inhibition of porcine pancreatic and urinary kallikrein was not observed. In this respect inhibitor I resembles the well known cow colostrum trypsin inhibitor. Inhibitor II with a molecular weight near 6800 (estimated by gel filtration) inhibits bovine trypsin and chymotrypsin, porcine plasmin and pancreatic and urinary kallikrein as well as bull acrosin. The inhibition specificity of inhibitor II is thus very similar to that of the basic inhibitor from bovine organs (Kunitz-type). In view of the inhibition strength and other characteristics, however, the acid stable bull seminal inhibitors are not identical with the inhibitor from cow colostrum or bovine lung (organs).


Action of intracellular proteinases on mitochondrial translation products of Neurospora crassa Schizosaccharomyces pombe. Gel electrophoretic analysis of mitochondrial membranes from Neurospora crassa shows the presence of a polypeptide fraction with apparent molecular weights of 7000 - 1200, which is synthesized on mitochondrial ribosomes. This fraction comprises between 10 and 50% of total mitochondrial translation products. Evidence is presented that the major part of this fraction is derived from components with higher apparent molecular weights by proteolytic activity. The proteolytic activity is located in vesicles which are co-isolated with mitochondria upon differential centrifugation. The activity is strongly enhanced by application of detergents such as sodium dodecylsulfate and Triton. Proteins synthesized on mitochondrial as well as cytoplasmic ribosomes are subject to proteolytic breakdown. This proteolysis can be blocked by addition of inhibitors such as diisopropylfluorphosphate to isolated mitochondria. Similar observations were made with Schizosaccharomyces pombe. In Neurospora, the amount of mitochondrial translation products with apparent molecular weights of less than 12000 is low in mitochondria from cells treated with cycloheximide for 1 h and high in mitochondria from cells treated with cycloheximide for 5 min. This observation is explained by the finding that proteinase activity in mitochondrial preparations decreases exponentially with a t1/2 of 20 min during preincubation of cells with cycloheximide. Procedures are described to remove or block contaminating proteinase activity. The results appear to be relevant for the interpretation of many data obtained from experiments in which this puzzling kind of artifact has not been sufficiently considered.


Cryopreservation of human lymphocyte function as measured by in vitro assays. Methods are described by which cryopreserved cells can be utilized in a number of in vitro assays. On a per cell basis, nearly total recovery of function can be demonstrated for lymphocyte transformation (mitogens, antigens and MLC) and rosette-forming cells. Excellent recovery of mononuclear cell production of leukocyte migration inhibitory factor was also observed. Highly reproducible activity was recovered on a per lymphocyte basis in lymphocyte cytotoxicity but with a definite decrement in the percentage recovery. Both for longitudinal studies of immune function and for standardization of these assays in one or more laboratories such cryopreserved cells are ofimmense value and should be widely utilized.


A measure of primary sociobiological functions. The Index of Independence in Activities of Daily Living (Index of ADL) is a scale whose grades reflect profiles of behavioral levels of six sociobiological functions, namely, bathing, dressing, toileting, transfer, continence, and feeding. Its hierarchical nature makes it possible to rank the overall functional status of people in an ordered manner, to make comparisons among them as individuals or groups, and to detect changes over time. Developmental studies have encompassed children as well as adults, the mentally retarded as well as physically disabled, and noninstitutionalized as well as institutionalized people. In view of relationships to behavior of primitive societies and parallelisms between the order of index functions and patterns of child growth and development, the Index of ADL appears to be based on functions of sociobiological primacy. This concept is supported by twenty years of methodological and applied observations. The Index has been used to produce predictive information about chronic conditions and to evaluate the benefits of long-term services. It has been used in profiled measures of severity of illness. As a screening measure and survey measure, it has contributed information about health needs and outcomes which is useful for management, planning, policy making, research, and techning.


Fibrinolytic activity in cystic lesions of jaw bones. The fibrinolytic activity in the tissues of cystic lesions of jaw bones was investigated by the semiquantitative method of Astrup. The specimens examined were ameloblastoma (9 cases), follicular cyst (8 cases) and radicular cyst (14 cases). High fibrinolytic activity was observed in ameloblastoma, while in radicular cyst the activity was variable. It is suggested that in radicular cyst inflammatory episodes play an important role in activating local fibrinolysis, while in ameloblastoma the tissue itself has a great capacity to induce locally activated plasmin.


Possible side effects of glucose, fructose, sorbitol and xylitol in man. It is concluded that there are no specific and dramatic side effects of glucose substitutes, apart from the increase in uric acid synthesis. All other side effects are noticed with glucose as well. The danger of lactic acidosis is not indicated, provided a normal dose of fructose or other carbohydrates is used. With respect to sorbitol and xylitol, lactic acidosis was not considered a serious side effect until now. No facts are known to establish the hepatotoxicity for fructose or for another glucose substitute. The danger of hyperglycemia is smaller with the glucose substitutes as compared to glucose. Therefore, the glucose substitutes are an alternative to glucose under certain conditions.


Degree of sulfation in mucopolysaccharide sulfates in normal and stone-forming urines. Mucopolysaccharides were extracted from both normal and stone-forming urines, and those from the stone-forming samples showed a higher degree of sulfation than those from normal urines, as determined by sulfate analysis and electrophoretic measurement. The sulfated mucopolysaccharides from stone-forming urines formed insoluble calcium salts, whereas those from normal urines generally remained soluble in the presence of calcium ion. Rachitic rat cartilage was found to have more highly sulfated mucopolysaccharides than normal rat cartilage. Highly sulfated mucopolysaccharides appear to be a significant factor in calcium stone formations.


[Biochemistry and function of glycosaminoglycans of the skin]. The basic defects of a number of genetic disorders affecting the connective tissue have been elucidiated during the last few years. A similar progress in understanding the pathobiochemistry of other dermatological diseases is expected. The present review summarizes our knowledge about structure, synthesis, degradation, macromolecular organization and possible function of glycosaminoglycans, which are an important constitutent of the ground substance in the skin. The difficulties of relating the clinical symptoms of diseases with the basic defects are examplified for the mucopolysaccharidoses.


[Chloracne, porphyria cutanea tarda, and other poisonings due to the herbicides]. In 80 industrial workers producing herbicides (2,4,5-trichlorphenoxyaceticacidsodium and sodiumpentachlorphenolate) in Czechoslovakia the following signs of intoxication caused by 2,3,6,7-tetrachlordibenzodioxin were found: Dermatological: Chloracne and Porphyria cutanea tarda. Internal: Disorders of the metabolism of porphyrins, fats, carbohydrates, plasmaproteins. Neurological: Mainly lesions of the peripheral neurone. Psychiatric: Neurasthenic syndrome and organic lesions. Differences from the usual course of chloracne were observed. Porphyria cutanea tarda acquisita was most obvious, one patient suffered and died from severe atherosclerosis, hypertension and diabetes. Many patients developed polyneuropathy, as verified both by EMG and autopsy. Two patients died from bronchogenic carcinoma.


Natural history of autologous blood clot embolization in swine. Previous studies of the natural history of embolized clots in dogs have demonstrated rapid lysis, presumably because the canine fibrinolytic system is very active. The fibrinolytic activity in swine, however, is similar to humans, and for this reason the pig was chosen for our study. The gluteal branches of the external iliac artery in nine domestic swine were embolized with either unmodified or modified (heat-formed, Amicar) autologous clot. In addition, three pigs were embolized with unmodified autologous clot to branches of the gastrosplenic artery. The lysis of clot emboli in both groups was followed by serial angiography at 48 hours and 14 days. Clot lysis as assessed by euglobulin lysis and plasmin generation was not activated by the experimental technique. Necropsy was performed on the animals in the second group. Partial or total obstruction of all arteries was present 48 hours after embolization and only 50% of arteries were recanalized at 14 days. At necropsy, organized partially occluding clot was demonstrated in the splenic artery of all 3 embolized swine. It is concluded that: 1)swine provide an excellent animal model for studying the natural history of arterial embolization; 2)Amicar or heat-formed clot shows no advantage over simple autologous clot in retarding intra-arterial clot lysis, and 3)simple autologous clot is an effective material for temporary intra-arterial occlusion.


[Scarification artefacts in the test reaction in an expert opinion of occupational dermatosis]. A patient is reported, who tried to simulate a positive patch test reaction by scratching one of the patch-tests. When reading the results of patch-testing, the possibility of manipulation has to be considered, especially when dealing with compensation cases. Certain modifications of the test are proposed to avoid these problems.


[Diagnosis and therapy of bromoderma tuberosum]. After taking bromine-containing drugs two patients developed bromoderma on the leg. This diagnosis was confirmed by high bromine-levels in the blood. Topical occlusive treatment with glucocorticosteroids was successfull.


The histochemistry of mucosaccharides in some organs of germfree rats. In order to study the histochemical nature of mucosaccharides in germfree animals, the organs in natural contact with bacteria (stomach, small and large intestine) and those naturally remote from bacteria (tracheal and ear cartilage and aorta) were studied by means of light microscopic methods for mucosaccharides in germfree and conventional rats. In the stomach (surface and foveolar cells) of germfree rats the histochemical reactions for acid and neutral mucosaccharides were apparently less intense than in that of conventional rats, whereas in the small and large intestine (goblet cells) of germfree rats the reactions were significantly more intense than in those of conventional rats. In the cartilage (intercellular matrix, lacunar border and chondrocyte cytoplasm) and aorta (interelastic spaces) of germfree animals the reactions were less intense than in those of conventional animals. In  addition, some differences in the histochemical nature of mucosaccharides between the organs of germfree and conventional rats were noted, as revealed by the effects of chemical modifications and digestions with enzymes upon the histochemical reactions studied.


Fine cytochemical detection of acid mucopolysaccharides in growing hyphae of Neurospora crassa. The presence of mucopolysaccharides (MP) in Neurospora crassa hyphae was detected in samples of cultures from 4 h to 5 days. Using a modification of the method of Rothman (1969), acid MP were identified by electron microscopy in vesicles located at the apex, septae, and throughout the cytoplasm of the hyphae. The size, number, and localization of these vesicles was related to the stage of growth of the fungus. The mechanisms of release and transport of these macromolecules are compared to the process of secretion in cells endowed with a better developed endoplasmic reticulum and Golgi system. The specificity of the method was evaluated histochemically. The structures displaying greater electron density corresponded to the Alcian blue positive areas.


Asymptomatic urethral gonorrhea among men in public New York City Social Hygiene Clinics. Cultures were made from the urethra of 2,370 male Social Hygiene Clinic patients who were not directly associated with gonorrhea by signs, symptoms or epidemiology were cultured for N. gonorrhoeae. Of these asymptomatic individuals, 37 or 1.6% were found to be urethrally infected. Gram stain smear examinations of urethral specimens from these men were positive in about one-half of the cases.


Mucopolysaccharidosis in a cat.

Mucopolysaccharidosis in a cat. A young adult female Siamese cat born of a mother-son mating was referred because of dwarfism, facial abnormalities, severe skeletal deformities, multifocal neurologic deficits, and retinal atrophy. Cats of similar appearance had been observed in a previous litter of the same parents. Metachromatic inclusion bodies were demonstrated in circulating leukocytes. The urine contained a high concentration of mucopolysaccharide, as detected by the toluidine blue spot test. The uronic acid content of the cetylpyridinium chloride-precipitable mucopolysaccharide in the urine was 17 times greater than that in the urine from a control cat of the same age and breed.


Escape synthesis of D-serine deaminase in lambda dsdC integration lysogens. Heat shock of lysogens that contain lambda thermosensitive repressor mutants integrated into the dsdC gene results in escape synthesis of d-serine deaminase at a high differential rate.


Neurospora crassa cytoplasmic ribosomes; ribosomal ribonucleic acid synthesis in the wild type. The biosynthesis of ribosomal ribonucleic acid (rRNA) In wild-type Neurospora crassa growing at 25 degrees C was investigated by continuous-labeling and pulsechase experiments using [5-3H]uridine. The results of these experiments suggest the following precursor-product relationships: the first RNA molecule to be synthesized in significant quantities is the 2.4 X 10(6)-dalton (2.4-Mdal) ribosomal precursor RNA. This RNA is cleaved to produce two species of RNA with weights of 0.7 and 1.4-Mdal. The former is the mature 17S rRNA of the 37S ribosomal subunit. The 1.4-Mdal RNA is subsequently cleaved to produce the mature 1.27-Mdal (25S) and 61,000-dalton (5.8S) rRNA's of the 60S ribosomal subunit. In the maturation process, approximately 15 to 20% of the 2.4-Mdal ribosomal precursor rRNA molecule is lost. As in other eukaryotes that have been examined, 5S rRNA is not derived from this precursor molecule.


Depression of uracil uptake by ammonium in Neurospora crassa. The mechanism of uracil uptake and one aspect of its regulation were studied in germinated conidia of Neurospora crassa. Uracil was found to be taken up by a transport mechanism that did not exhibit Michaelis-Menten kinetics. Rather, the kinetic patterns indicated two separate systems or a single transport mechanism with negative cooperativity. Cytosine and thymine inhibited uracil uptake, but uridine did not. The mutant strain uc-5-pyr-1, which failed to transport uracil, was used in reversion studies and to map the uc-5 locus. Spontaneous reversion rates at the uc-5 locus were found to be approximately 2 x 10(-8), indicating that the uc-5 lesion results from a single mutation. Loss of the uracil transport function through a single mutation favors the model of a single transport mechanism with negative cooperativity. Uracil uptake was significantly decreased in the presence of NH 4+, and evidence is presented for repression by NH4+ of a uracil transport system. Growth rates of pyrimidine-requiring and wild-type strains measured in the presence and absence of NH4+, with uracil as the pyrimidine supplement, showed that NH4+ decreased the growth rates of the pyrimidine-requiring strains significantly, while having no effect on wild-type growth rates.


Permeability measurements on mitochondria from wild-type and poky strains of Neurospora crassa. The permeability properties of isolated Neurospora mitochondria were determined by measuring the rate at which the mitochondria swell in isotonic solutions of various organic and inorganic molecules. Like mammalian mitochondria, wild-type Neurospora mitochondria were impermeable to sucrose and only slightly more permeable to most inorganic ions (K, Na, Cl). Their permeability to K was greatly increased by valinomycin and by monensin. In addition, the mitochondria contain specific systems mediating PO4 uptake and PO4- malate, fumarate, and succinate exchange. Mitochondria from the maternally inherited poky strain of Neurospora, previously demonstrated to possess defective ribosomes and a grossly cytochrome chain, showed a slight but significant increase in permeability to inorganic ions. They contained, however, the specific uptake and exchange systems for phosphate and dicarboxylate anions, a result suggesting that these systems do not depend upon mitochondrially synthesized polypeptides.


Membrane-associated, energy-linked reactions in Bdellovibrio bacteriovorus. Disrupted cells of Bdellovibrio bacteriovorus exhibited adenosine triphosphatase activity, 60 to 80% of which was in the soluble fraction. Dicyclohexylcarbodiimide did not inhibit the adenosine triphosphatase activity in membrane particles. The particles did not show energy-linked transhydrogenase activity. The activity of non-energy-linked transhydrogenase as well as the rate of oxygen consumption were higher in membrane particles of the host-independent strain than in the host-dependent strains. The uptake of amino acid uptake was inhibited by cyanide and by carbonyl cyanide p-trifluoromethoxyphenyl hydrazone. Valinomycin, in the presence of K+, did not inhibit the uptake, and only partial inhibition was exerted by arsenate and dicyclohexylarbodiimide. Sulfhydryl reagents inhibited amino acid uptake.


A novel adenosine triphosphatase isolated from RNA polymerase preparations of Escherichia coli. I. Copurification and separation. Adenosinetriphosphatase (ATPase) [EC 3.6.1,3] activity has been found to exist in most preparations of DNA-dependent RNA polymerase [EC 2.7.7.6] obtained from Escherichia coli by a number of purification procedures so far established. Electrophoretic analysis on polyacrylamide gels demonstrated that ATP hydrolysis and RNA synthesis were catalyzed by two distinct enzyme proteins. It appears that the two enzymes are associated or have similar molecular properties. Separation of the two enzymes, the object of the present work, was achieved by three independent methods: ion exchange chromatography on a phosphocellulose column, electrophoresis in glycerol gradients, or high-salt glycerol gradient centrifugation.


A novel adenosine triphosphatase isolated from RNA polymerase preparations of Escherichia coli. II. Enzymatic properties and molecular structure. An adenosinetriphosphatase (ATPase) [EC 3.6.1.3] copurified with the DNA-dependent RNA polymerase [EC 2.7.7.6] from Escherichia coli was isolated to apparent homogeneity and some of its functional as well as structural properties were examined. Although the novel ATPase exhibited metal requirements similar to those of Mg2+, Ca2+-ATPase, its response to NaN3 and antisera appeared completely different from that of the Mg2+, Ca2+-ATPase. The purified ATPase was found to be a large protein with a molecular weight of 9.3X10(5) daltons, composed of identical subunits of 7X10(4) daltons. When viewed under an electron microscope, the ATPase appeared to be very similar to material previously misidentified as the RNA polymerase. The physiological role of the novel ATPase, however, remains unclear.


Calcium binding and ATPase activities of heart sarcolemma. Rat heart sarcolemma prepared by the hypotonic shock-LiBr treatment method was found to bind calcium by a concentration-dependent and saturable process. The calcium binding values at 50 muM and 1.25 mM Ca2+ concentrations were about 30 and 250 nmoles/mg protein, respectively. Both Mg2+ and ATP inhibited calcium binding and no evidence for energy-linked calcium binding with sarcolemmn was found. z sn the other hand, maximal ATP hydrolysis by heart sarcolemma was seen at 4 mM Mg2+ or Ca2+. The Ca2+-ATPase LEO) of Ca2+ failed to stimulate ATP hydrolysis in the presence of various concentrations of Mg-ATP. These results indicate the absence of a "calcium pump" mechanism in the heart sarcolemmal membrane preparation employed in this study.


Functional role of soluble mitochondrial ATPase subunits. A preparation of soluble mitochondrial ATPase (coupling factor F1) containing no gamma and delta minor subunits has been isolated. The minor-subunits-deficient F1 was found to be competent in ATP hydrolysis. However, it did not demonstrate a "coupling" effect in EDTA-submitochondrial particles. A portion of the ATPase activity of EDTA particles, stimulated by the minor-subunits-deficient F1, was insensitive to oligomycin. ATPase activity of Na+-particles was changed only slightly by this F1. It is suggested that gamma and delta subunits are necessary to form specific contacts between the F1 molecule and components of the mitochrondrial membrane.


Genetic analysis of mitochondrial biogenesis and function in Saccharomyces cerevisiae. Different mitochondrial mutants have been isolated that affect mitochondrial ribosome function. These mutants were used to establish most of the known methods and principles of mitochondrial genetics in yeast. Another class of mitochondrial mutants have been shown to affect mitochondrial ATPase and, more specifically, the "membrane factor" of mitochondrial ATPase. These mutants might be very useful in studying the energy-conserving function, and the interaction between the hydrophobic and hydrophylic parts, of the ATPase complex. New types of mitochondrial point mutations, concerning cytochrome a-a3 or b, will soon open up new fields of investigation. The biochemical and genetic analysis of numerous mutants belonging to that category and recently obtained [31] is being currently pursued in Tzagoloff's and Slonimski's laboratories.


Relationship between configuration, function, and permeability in calcium-treated mitochondria. Low levels of calcium (100 nmol/mg) added to beef heart mitochondria induced a configurational transition from the aggregated to the orthodox state and a simultaneous uncoupling of oxidative phosphorylation. The primary effect of calcium was to cause a nonspecific increase in the permeability of the inner membrane, resulting in entry of sucrose into the matrix space and the observed configurational transition. The uncoupling and permeability change induced by calcium could readily be reversed by lowering the calcium:magnesium ratio in the presence of either substrate or ATP. The configurational state, however, remained orthodox. This, along with studies of hypotonically induced orthodox mitochondria in which the membrane remained coupled and impermeable until after the addition of calcium, led to the conclusion that coupling was related to the permeability state of the inner membrane rather than the configurational state. Phosphate, arsenate, or oleic acid was found to cause a transition similar to that induced by calcium. Studies with the specific calcium transport inhibitors, EGTA, ruthenium red, and lanthanum revealed that endogenous calcium is required for the anion-induced transitions. A single mechanism was further indicated by a common sensitivity to N-ethylmaleimide. Strontium was ineffective as an inducer of the transition, even though it is transported by the same mechanism as calcium. This indicates that there are additional calcium-binding sites responsible for triggering the transition. Magnesium and calcium appeared to compete for these additional sites, since magnesium competitively inhibited the calcium-induced transition, but had no effect on calcium uptake. Calcium was found to potently inhibit the respiration of all NAD+-requiring substrates prior to the transition. Strontium also produced this inhibition without a subsequent transition. ATPase activity was induced at the exact time of transition with calcium and was not induced by strontium. This suggests that calcium-induced ATPase uniquely required the transition for activity, in contrast to the ATPase induced by uncoupler or valinomycin. The results of this work indicate that mitochondria have a built-in mechanism which responds to low levels of calcium, phosphate, and fatty acids, resulting in simultaneous changes, including increased permeability, inducation of ATPase, uncoupling of oxidative phosphorylation, and loss of respiratory control.


Phospholipid-protein interactions in the Ca2+-adenosine triphosphatase of sarcoplasmic reticulum. Ca2+-adenosine triphosphatase from sarcoplasmic reticulum has been delipidated by gel filtration through a Sephadex G-200 column equilibrated with buffer containing cholate. The delipidated Ca2+-adenosine triphosphatase had negligible adenosine triphosphatase activity, but up to 50% of the ATPase activity was restored when the delipidated enzyme was recombined with phosphilipids. It was shown with the delipidated preparation that the phosphorylation of the enzyme by either ATP or Pi was entirely dependent on phospholipids. Among the purified phospholipids, phosphatidylcholine reactivated the adenosine triphosphatase activity better than phosphatidylethanolamine. Vesicles capable of translocating Ca2+ were reconstituted from delipidated Ca2+-adenosine triphosphatase and phosphatidylethanolamine, but not with phosphatidylcholine alone. We conclude that the firmly bound phospholipids which are purified together with the adenosine triphosphatase protein are not essential for the pump since they can be substituted by phosphatidylethanolamine isolated from soybeans.


Ethanol metabolism by a transplantable hepatocellular carcinoma. Role of microsomes and mitochondria. 1. Ethanol metabolism in slices or homogenates of transplantable hepatocellular carcinoma HC-252 (HC-252) was 50 to 60% of the rate found in host liver slices or homogenates when they were expressed per gram of tissue wet weight and 70 to 80% of the liver when the rates were expressed per milligram of tissue protein. At 10 mM ethanol, the activities of alcohol dehydrogenase in tumor and liver supernatants were comparable. 2. Tumor microsomes did not oxidize ethanol in the presence of a NADPH-generating system, indicating the absence of the microsomal ethanol-oxidizing system and catalase-mediated peroxidation of ethanol. The HC-252 microsomes were contaminated with catalase, and acetaldehyde production occurred in the presence of a H2O2-generating system (xanthine oxidase). The virtual absence of ethanol oxidation and drug metabolism (aminopyrine demethylase and aniline hydroxylase) in HC-252 microsomes may be due to the low activities of NADPH-cytochrome c reductase, NADPH oxidase, and NADPH-dependent oxygen uptake. 3. Microsomal oxidation of ethanol was present in Morris hepatoma 5123C, a well-differentiated tumor of intermediate growth rate, while activity was negligible in microsomes from Morris hepatoma 7288CTC, a less differentiated tumor. Microsomal NADPH oxidase was present in the well differentiated tumor 5123C but was lacking in the less differentiated tumor 7288CTC. Several microsomal, mitochondrial, and cytosolic properties of HC-252 are similar to those of Morris hepatoma 7288CTC but differ from those of the more differentiated 5123C tumor and normal liver. 4. The content of mitochondrial protein in HC-252 was only 25% that of liver, and oxygen consumption per gram of tumor was only 28% that of the liver. When corrected for the mitochondrial protein content, oxygen uptake in tumor HC-252 and liver homogenates was comparable. Isolated tumor and liver mitochondria displayed comparable State 4 and 3 rates of oxygen consumption with succinate and glutamate as substrates. The activities of the reconstituted malate-aspartate and alpha-glycerophosphate shuttles were only slightly lower in isolated HC-252 mitochondria compared to liver mitochondria, when shuttles were reconstituted with purified enzymes. 5. Antimycin inhibited alcohol metabolism,and pyruvate stimulated alcohol metabolism, much less in tumor slices than in liver slices, suggesting the presence of an augmented mitochondria-independent, cytosolic mechanism for oxidizing reducing equivalents in the tumor. These factors suggest that oxidation of NADH is the limiting factor in ethanol metabolism. Whereas, in the liver mitochondrial reoxidation is predominant, in HC-252, cytosolic reoxidation of NADH also plays a major role.


Mechanism of ATP hydrolysis by sarcoplasmic reticulum and the role of phospholipids. Exchange of sarcoplasmic reticulum phospholipids with dipalmitoyllecithin inhibits the (Mg2+ + Ca2+)-activated ATPase activity below 40 degrees by inhibition of the decomposition of phosphoprotein intermediate. The rate of phosphoprotein formation and the steady state concentration of phosphoprotein measured by rapid kinetic techniques are affected to a lesser extent. The inhibitory effect of dipalmitoyllecithin on ATPase activity is probably related to the viscosity of the hydrocarbon region of the membrane which inhibits the conformational change leading to calcium translocation and the eventual cleavage of phosphoprotein.


Modification of the alkali light chains of skeletal myosin inhibits actin binding and adenosine triphosphate cleavage. Heavy meromyosin treated with the ATP analog, 6,6'-dithiobis(inosinyl-5'-yl imidodiphosphate), (slppNHp)2, in the presence of adenyl-5'-yl imidodiphosphate at 0 degrees loses its EDTA-ATPase activity and actin binding ability in a parallel manner. Studies with myosin show that under the above conditions (slppNHp)2 reacts preferentially with the single cysteines of the alkali light chains (Mr = 20,700 and 16,500) suggesting a role for these subunits in regulating actin-myosin interaction and ATP cleavage.


Comparative roentgenographic study of the asymptomatic and symptomatic lumbar spine. A comparative roentgenographic study was carried out on 217 asymptomatic patients between forty and seventy years old and 387 symptomatic patients in the same age range. Spondylosis (osteophyte formation) did not appear to have any direct relationship to low-back pain. Degenerative disc disease appeared to be a major cause of low-back pain. Spondylolysis and spondylolisthesis occurred more frequently in the symptomatic than in the asymptomatic patients. Routine roentgenograms of the lumbosacral spine were useful in evaluating patients seen for treatment of low-back pain.


Density-dependent changes in the amount of sulfated glycosaminoglycans associated with mouse 3T3 cells. The relative amount of sulfated glycosaminoglycans associated with the cell layer of parent and SV40-transformed Swiss mouse 3T3 cells was determined from the incorporation of labeled sulfate (35SO4) into macromolecular material. In cultures of SV40-transformed cells, the glycosaminoglycan content per cell was constant over a wide range of densities. In cultures of parent 3T3 cells, the glycosaminoglycan content per cell increased directly with density, the highest values being found in contact-inhibited cultures. At high cell densities, the glycosaminoglycan content of 3T3 cells was several-fold higher than that for SV40-transformed cells. Most of the density-dependent increase in glycosaminoglycans of 3T3 cells was accounted for by chondroitin sulfate (dermatan sulfate) which was over 6-fold higher in confluent cultures than in low density cultures.


Selective medium for isolation of Treponema hyodysenteriae. Pure cultures of six pathogenic isolates of Treponema hyodysenteriae, the colonic mucosal scrapings of seven pigs with acute swine dysentery, and feces from seven unaffected pigs were diluted in phosphate-buffered saline and plated on Trypticase soy agar with 5% citrated bovine blood (TSA) and TSA with various levels of spectinomycin (TSA-S). The plates were incubated at 42 degrees C in a vented GasPak jar with a cold palladium catalyst and either 80:20 H2-CO2 by evacuation and refilling or a H2-CO2 generator envelope. Viable cell counts of the six pathogenic isolates were not altered by plating on TSA-S with 400 mug of spectinomycin per ml (TSA-S400) as compared with TSA alone. Dilutions of colonic mucosal scrapings from seven pigs with acute swine dysentery showed numbers of T. hyodysenteriae to be unchanged when plated on TSA-S400. Flora other than T. hyodysenteriae present in acute swine dysentery was inhibited, on the average, by 99.99%. Plating of dilutions of feces of unaffected pigs on TSA-S400 showed inhibition of flora that averaged more than 99.9%. Pathogenicity of T. hyodysenteriae was not altered by isolation or serial passage on TSA-S400.


The glycosaminoglycans of the human artery and their changes in atherosclerosis. The changes in levels of glycosaminoglycans (GAGs) of the intima and media of the human artery in atherosclerosis were determined by a recently introduced two-dimensional electrophoresis technique that permits direct measurments of each of these macromolecules. To identify the arterial GAGs, they were fractionated by chromatography on a DEAE-Sephadex A-25 column, and the resulting three fractions (hyaluronic acid [HA], heparan sulfate [HS], and the partially separated chondroitin sulfates B [CSB] and C [CSC]) were analyzed for their electrophoretic mobilities by this electrophoretic method, for their digestability by highly specific hydrolases (leech hyaluronidase, heparinase, and chondroitinases ABC and AC) and for their iduronic acid content. From these studies we concluded that normal and atherosclerotic human aortas contain CSB, CSC, HA, and HS. Further, we demonstrated that CSB is a hybrid consisting of approximately 40% CSA and 60% CSB and that CSC appears to be a polymer consisting essentially of glucuronic acid and N-acetylgalactosamine-6-sulfate. Classical CSA as well as chondroitin (CH) were not present in detectable amounts. In the relatively normal intima, the mean concentrations of the GAGs were found to be 4.7, 20.9, 1.3, and 5.1 mg/g of dry, defatted, decalcified tissue for CSB, CSC, HA, and HS, respectively. With the progression of atherosclerosis, there was a pronounced decrease in the total GAG content (from 32 to 18 mg) associated with a decrease in the CSC and HS levels but without a change in the HA concentrations. Of particular interest, however, was the increase in the CSB level. In the media whose total GAG content averaged approximately 20 mg, no significant changes in these GAG levels were noted with the progression of the disease except for that of CSC. These findings may be important in explaining the increased lipoprotein and collagen deposition in the diseased aorta.


[Treatment of an invading fibroma of the abdominal wall by extensive removal and parietal reconstruction by epiplooplasty associated with Marlex's prosthesis]. The authors discuss the treatment of a desmoid tumour of the abdominal wall and propose an original technique of extensive parietal repair by epiplooplasty associated with inert prostheses.


Immunological mechanisms in the reaction between drugs and the skin. Many reactions in the skin caused by drugs would appear to be due to immunological mechanisms. Simple chemical sensitizers become antigenic after combination with carrier proteins. The bonds between the hapten and the protein are not necessarily covalent, and it is likely that weaker linkages such as hydrogen bonding or Van der Waal's forces may be involved. Reactions may be due to humoral antibody or cell-mediated immunity. Experimental models are discussed in which there is competition between B suppressor cells and T effector cells. In these situations, drugs that affect the suppressor cell system specifically can reverse a state of immunological tolerance or increase the intensity of a chemical sensitivity. Finally, the mechanism of fixed drug eruptions is discussed. It is suggested that the actions which follow the systemic absorption of the chemical and always occur at this same site are due to B cells or B cell products that remain from a previous delayed hypersensitivity reaction to the same antigen. These cells would have arrived initially as part of the non-specific inflammatory infiltrate. The initial reaction may even have been subliminal in intensity.


Circadian rhythm of stimulated lymphocyte blastogenesis. A 24 hour cycle in the mixed leukocyte culture reaction and with SKSD stimulation. The in vitro measurement of stimulated T lymphocyte blastogenesis by the incorporation of 14C-thymidine can be shown to be an acceptable and precise measurement with highly significant variations in blastogenesis over a 24 hr period. This circadian rhythm for human T lymphocyte blastogenesis has been demonstrated with specific antigen (SKSD) and in mixed leukocyte culture (MLC). The hours of peak reactivity were different for the SKSD stimulation and the MLC reaction. This biologic cycle in T cell reactivity has significant implications for the immunologic response.


Community-based residential care for the minimally impaired elderly: a survey analysis. Foster home care for the elderly, as an alternative to living independently, living with relatives or living in an institution, has been a neglected area of investigation, although such care is a nationwide phenomenon. This survey of all licensed Family Care Home operators in the Louisville, Kentucky area provides baseline data regarding the characteristics of providers of adult foster care and the recipients. Data were obtained from 183 persons caring for minimally impaired adults in their own homes and on 422 residents in these foster home settings. Of the residents, 69.5 percent were aged 65 or over. Care providers are described on the basis of age, race, sex, educational level, family size and composition, previous employment, reasons for entering the business, and problems encountered. Residents are described on the basis of age, race, sex, physical condition, care required, and outside contacts. Foster home care for the aged can furnish many advantages if the resident is properly placed and support services are provided. This form of care deserves much greater emphasis in future research of the provision of services for the elderly.


Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. II. Electrolyte permeability increase in the target cell membrane concomitant with programming for lysis. In a previous study of the mechanism of specific target cell lysis by alloimmune cytolytic T lymphocytes (CTL), we established that the target cell becomes irreversibly programmed to lyse within a few minutes after contact with the CTL. We here show that at each point in time, the level of specific release of the potassium analog, 86Rb equals the percentage of target cells which have been programmed to lyse. It is also shown that specific release of 86Rb is more rapid than that of a small metabolite of similar weight, 14C-nicotinamide, which in turn is specifically released more rapidly than 51Cr. Thus, an electrolyte-permeable lesion is produced in the target cell membrane within minutes of contact with the CTL. Since measurements of 86Rb release, unlike measurements of programming for lysis, do not involve exposure of the cells to EDTA and vigorous shearing forces, the present observations corroborate and extend, by an independent and gentler method, our previous conclusion that the CTL effects crucial and irreversible changes in the target cell within minutes after contact. The present results are consistent with the possibility that the first, and perhaps the only damage administered directly by the CTL is a membrane lesion permeable to electrolytes and possibly to small molecules.


The formation of stable E-rosettes by human T lymphocytes activated in mixed lymphocyte reactions. The aim of the present study was to determine whether activation of human T-lymphocytes affects their interaction with sheep red blood cells (SRBC). Less than 3% of the E-rosettes formed by freshly isolated peripheral blood lymphocytes (PBL) and SRBC are stable and do not disintegrate after incubation at 37 degrees C. In contrast, about 30% of PBL kept in culture for 5 days in the presence of mitomycin C-treated allogeneic lymphocytes were found to form stable E-rosettes. Whereas no rosettes were formed by freshly isolated PBL incubated with human red blood cells at 24 degrees C, 15% of the cells recovered from mixed lymphocyte reactions (MLR) formed such rosettes. When responder PBL were maintained in culture in the absence of allogeneic stimuli the proportion of cells forming stable E-rosettes depended on the serum present in the medium. Less than 5% of the responder cells kept in medium containing human serum or in serum-free medium formed stable E-rosettes, whereas 18% of the cells maintained in medium containing fetal calf serum formed stable E-rosettes. The proportion of cells forming stable E-rosettes increased before any increase in DNA synthesis was detectable in MLR. Indeed, a high proportion of cells forming stable E-rosettes appeared in MLR taking place in serum-free medium, without any accompanying increase of DNA synthesis. Depletion of cells forming EAC'-rosettes from responder PBL increased the proportion of cells forming stable E-rosettes in MLR. Exposure of the cells recovered in MLR to specific anti-T sera inhibited the formation of both stable and regular E-rosettes. Exposure of the cells recovered in MLR to anti-Ig serum had no effect on the formation of regular rosettes. Anti-Ig serum strongly inhibited the formation of stable E-rosettes by cells grown in medium containing human serum, but had no effect on the formation of stable E-rossettes by cells grown in either serum-free medium or in serum containing fetal calf serum. It is concluded that activated human T lymphocytes are characterized by their capacity to form stable E-rosettes, resistant to incubation at 37 degrees C, and by their capacity to acquire an immunoglobulin coat, possibly by binding immunoglobulin molecules present in their environment.


Human transfer factor: fractionation and biologic activity. Human transfer factor (TF) was fractionated by exclusion chromatography and the fractions were tested for biologic activity in vivo and in vitro. Specific TF activity in vivo was found to reside in the major UV-absorbing peak (Fraction III). Fraction III eluted at 2.7 X V(O) and transferred tuberculin, candida, or KLH-reactivity to previously negative recipients. Fraction III from nonreactive donors was ineffective. When the fractions were tested in vitro, we found that both the mitogenic activity of whole TF and the suppressive activity to mitogen activation when present in TF was found in Fraction I. Fraction III contained components responsible for augmentation of PHA and PWM responses. In addition, Fraction III contained the component responsible for antigen-dependent augmentation of lymphocyte transformation. Fraction IV was suppressive to antigen-induced lymphocyte transformation. These data suggest that TF preparations contain components which can affect immune reactions in both specific and nonspecific ways.


Nicotinamide: suppression of lymphocyte transformation with a component identified in human transfer factor. The component in human transfer factor (TF) (Fraction IV, from exclusion chromatography on Sephadex G-25) responsible for suppression of antigen-induced lymphocyte transformation was previously identified as nicotinamide. Commercially available nicotinamide was subsequently shown to produce suppression of antigen-induced responses in vitro previously observed with TF Fraction IV. Nicotinamide was found to be nontoxic at the highest concentrations employed (10(-2)M) and suppressive over a relatively broad range (10(-5) to 10(-2)M. The suppression appeared to be related to the magnitude of antigen- or mitogen-induced transformation and was apparent even when nicotinamide was added as late as 48 hr after stimulant addition.


Leukocyte migration inhibitory factor (LMIF) production in unidirectional mixed lymphocyte cultures. Puromycin treatment of lymphocytes was used to develop a one-way test for leukocyte migration inhibitory factor (LMIF) production in the mixed lymphocyte culture (MLC) reaction. Lymphocytes incubated with this protein synthesis inhibitor induced a vigorous mediator production by nontreated allogeneic cells, being themselves unable to respond to stimulator cells. When puromycin-treated cells were stimulated with the mitogens PHA, ConA, or PWM, overall protein and DNA synthesis were significantly decreased with concomitant abolishment of LMIF production. Viability of stimulator lymphocytes was found to be essential for generation of the mediator in MLC reaction.


Standardisation of the mixed lymphocyte reaction. The mixed lymphocyte reaction has been optimised with Ficoll--Triosil separated lymphocytes: 100,000 responding cells with 100,000 mitomycin-C-blocked stimulating cells, in 0.2 ml of TC 199 with 10% AB-negative known normal serum in Cook microplates. After incubation at 37 degree C for 120 h, 2 muCi of [3H]thymidine was added, harvesting after a further 15 h at 37 degree C. A pool of stimulating cells, freshly separated from 5 normal subjects (usable up to 36 h  if kept at 4 degree C), produced a Gaussian normal range of increment in CPM from 17,000--88,000, with a between-batch coefficient of variation for triplicates of 22%. For tests against stimulating cells from a single donor a transformation index above 1.64 was significant.


Genetic and cellular aspects of xenogeneic mixed leukocyte culture reaction. The nature of the antigens stimulating xenogeneic lymphocytes was studied using "primed LD typing". Human lymphocytes were sensitized in vitro against mouse spleen cells and restimulated with spleen cells of mouse strains sharing non-H-2 antigens or various regions of H-2 with the initial stimulating strain. The largest thymidine uptake was caused by restimulation with cells from the specific primary stimulator or an H-2-identical strain. Species-specific antigens or strain-specific antigens carried in the C57BL/10 background account for less than 15% of the total stimulation; a non-H-2 antigen associated with the Mlsalpha genotype caused moderate restimulation, amounting to 25% of the average H-2 response. Within H-2, the strongest restimulation was caused by antigens controlled by the I-A subregion; the K and D regions caused moderate, the I-C and S regions very weak, and the I-B subregion no restimulation. Thus, the genetic control of antigens stimulating xenogeneic and allogeneic MLC responses requires T cells and adherent cells, but in the human-mouse MLC, both cell types must come from the human responder; the majority of the proliferating cells are T cells. It is suggested that allograft and xenograft reactions are fundamentally identical processes, and that the relative vigor of alloaggression may be explained by secondary potentiating mechanisms depending on species-specific interactions between aggressor and target cells.


In vitro studies on the T-lymphocyte population of human milk. Human milk lymphocytes (ML) can be partially purified and propagated in vitro as a means of assessing their immunological function. When exposed to a variety of stimuli known to activate T lymphocytes, ML respond in a unique manner that indicates a selected population of immunocompetent cells. ML are hyporesponsive to to nonspecific mitogens and respond in a reduced manner to histocompatibility antigens on allogeneic cells. In most cases, they are completely unresponsive to C. albicans although blood lymphocytes from the same patients respond to the antigen. The Kl capsular antigen of E. coli induces significant proliferation in lymphocytes obtained from milk, but fails to stimulate blood lymphocytes. This dichotomy of reactivity does not appear to result from suppressive factors or cells in milk or insufficient adherent cell function. Rather it appears to reflect the accumulation of particular lymphocyte clones in the breast and the local nature of mammary tissue immunity at the T-lymphocyte level.


Three HLA-D region antigens defined by primed LD typing. We have recently described a new method, primed LD typing or PLT, for specific identification of HLA-D antigens. Highly discriminatory PLT cells have been developed which clearly differentiate between cells of individuals that restimulate strongly and those that restimulate weakly. Seven such discriminatory PLT cells have been used to define three antigens called PL1, PL2, and PL3; two more PLT cells may define antigen(s) PL4.


The effect of membrane stabilizing agents on induction of the immune response. I. Effect of lymphocyte activation in mixed lymphocyte reactions. The effect of three membrane-stabilizing agents, chlorpromazine, imipramine, and lidocain, on in vitro activation of cellular responses was studied using the one-way MLR. Cellular activation was found to be depressed by these drugs. However, the degree of suppression paralleled the decline of viable cells in the cultures. It is concluded that drug-induced inhibition of MLR was due solely to the toxicity of the compounds.


Murine t factors: an association between alleles at t and at H-2. Lymphocytes from tx-mutant mice have a definite and consistent pattern of reactivity in MLR. Cells from t-mutant mice within a complementation group usually fail to stimulate each other, while cells from mutants in different complementation groups stimulate each other strongly. This indicates that tx-mutant types are associated with certain H-2 haplotypes, and that members of any give complementation group share the same H-2 haplotype.


[Studies on the mechanism of activation of lymphocyte membrane ATP-ases by concanavalin A (author's transl)]. The ouabain-sensitive and ouabain-intensitive ATP-ases of intact lymphocytes, and of the lymphocyte microsomal fraction and a purified plasma membrane fraction, are all activated by concanavalin A. The Na+, K+, and Mg+-dependence of the plasma membrane ATP-ases were defined at different substrate concentrations. Enzyme activation was rather greater at lower K+ concentrations. From these studies it appears improbable, but not impossible, that concanavalin A exerts an allosteric effect on the ATP-ases.


Wall structure of the Neurospora hyphal apex: immunofluorescent localization of wall surface antigens. Antisera have been raised in rabbits against three wall fractions from Neurospora crassa. Fractions were separated according to Mahadevan & Tatum (1965), i.e. fraction I, glucan-peptide-galactosamine complex; fraction III, laminarin-like glucan; and fraction IV, chitin. Distinct patterns of immunofluorescent staining were obtained using an indirect staining method. Hyphae stained with antiserum to fraction I showed maximum fluorescence in the apical and/or subapical regions: in both cases, fluorescence showed a sharp decrease with distance behing the subapical region. Hyphae stained with antiserum to fraction III showed faintly fluorescent tips with fluorescence increasing with distance from the tip. Hyphae stained with antiserum to fraction IV showed faint fluorescence, equivalent to levels of autofluorescence, except at the sites of hyphal fractures. Antisera were also raised against whole walls from 24 and 120 h cultures. Hyphae stained with antisera against whole walls which had previously been absorbed to remove antibodies to fractions I, III, and IV showed preferential staining of apices. The uncharacterized tip antigen(s) thus revealed was also demonstrated on immunodiffusion plates. This pattern of immunofluorescence was compared to the fluorescence of apices after staining with an optical brightener. Enzymic dissection procedures did not generally give reliable results with apices from 24 h cultures. Untreated apices appeared amorphous, while a drastic chemical treatment revealed randomly oriented microfibrils which were shown to be alpha-chitin. The apical hyphal walls were significantly thinner than those from more mature hyphal regions.


TVR and vibration-induced timing of motor impulses in the human jaw elevator muscles. In order to investigate myotatic reflex involvement in jaw muscle control, an analysis was made of the motor responses induced by mechanical vibration (120-160 Hz) of the jaw elevator muscles in healthy subjects. As seen in torque measurements and mean-voltage electromyographic (EMG) recordings, the vibration caused involuntary reciprocal changes in jaw muscle tone, the contraction force increasing in jaw elevators and decreasing in antagonistic jaw opening muscles. This tonic vibration reflex (TVR) elicited from the jaw elevators exhibited many characteristics similar to those previously described for limb muscle tonic vibration reflexes: it varied in strength from one subject to the next independently of the briskness of the jaw elevator tendon jerks; it had a gradual onset with successive recruitment of jaw elevator motor units firing largely out of phase with one another and at rates much lower than the vibration frequency; it was susceptible to voluntary control--when allowed visual feed-back from the torque meter all subjects were able to suppress the TVR and keep mean contraction force constant. The results indicate that with respect to the tonic motor response to sustained inflow in the Ia afferent nerve fibres, the jaw elevators do not differ markedly from other skeletal muscles. Independently of whether a TVR was present or not, the vibration caused a timing of the motor unit discharges in the jaw elevators that could not be controlled voluntarily and that showed up in gross EMG recordings as a marked grouping of discharges synchronous with each wave of vibration. A similar but less distinct grouping of the gross EMG pattern was seen in limb muscles exposed to vibration, the dispersion increasing with the peripheral conduction distances of the reflex arcs. It is suggested that contrary to the TVR, which depends on the sustained mean level of the Ia afferent input, the timing phenomenon depends, like the tendon jerk, on the degree of synchrony in the afferent Ia volleys. Monosynaptic projections may well be involved in the dynamic timing of motor discharges during tonic firing, but this does not imply that the TVR or the tonic stretch reflex is dependent upon such projections.


Arterial hypertension and the work environment: some considerations affecting its compensability. Hypertension can be considered work-related and, therefore, compensable when it[occurs] causes cardiac disease in occupational groups for whom cardiac ailments are legislated as being work-incurred and in workers exposed to certain nitrate explosives. In legal circles job related stresses are often invoked as a cause of hypertension and judicial precedent has accepted the medically unproven theory that hypertension develops after an exposure for long hours over a period of several years to the exasperations, frustrations, pressures, strains, and stresses of work. Apportionment of liability between industrial and non-industrial factors is a legal concept with negotiations often open to forensic debate. This could be minimized if epidemiologic information permitting the calculation of attributable risk were available. Also desirable is a better understanding of the possible contributions of common physical hazards e.g., noise and vibration, to sustained hypertension.


The effect of anti-inflammatory compounds on the biochemical changes in the Arthus reaction. The effect of anti-inflammatory drugs on the biochemical changes in the Arthus reaction have been studied and correlated to changes in the pathology of the reaction. In the Arthus reaction all the non-steroidal anti-inflammatory drugs inhibited the migration of cells into the lesion and reduced the lysosomal enzyme concentration at the Arthus site. The steroids did not inhibit the cellular inflitration or the total lysosomal enzyme concentration in the skin but did reduce the concentration of cathepsin D in the oedema fluid. In addition, prednisolone and, to a lesser extent, hydrocortisone reduced the degree of oedema formation. The results suggest that non-steroidal anti-inflammatory drugs inhibit the Arthus reaction by reducing the cellular infiltration whereas anti-inflammatory steroids act by preventing these cells secreting their lysosomal enzymes and thus causing tissue damage.


Polycystic disease of kidney, liver and pancreas; a possible patholgenesis. 5,6,7,8-tetrahydrocarbzzole-3-acetic acid (AH 2835) given to maternal rats throughout their gestation produces an experimental model of the autosomally inherited human infantile polycystic disease Potter type I in the rat foetuses. The affected animals have cystic lesions in their kidneys, liver and pancreas like those seen in the human. Evidence is presented for the aetiology of the experimental lesion being related to the action of AH 2835 on the specific activity of the ouabain sensitive (Na+ + K+)-ATPase of absorptive epithelia. It is noted that two cystic kidney diseases, the ocngenital nephrotic syndrome and infantile polycystic disease Potter type I are both inherited as autosomal recessive traits and are therefore likely to be caused by enzyme abnormalities, and that the compound AH 2835 can be used to produce experimental models of both of these diseases.


CSTRIP, a fortran IV computer program for obtaining initial polyexponential parameter estimates. A new exponential stripping program, CSTRIP, has been developed. This program overcomes the problems associated with the use of previously published techniques and enables the rapid economical calculation of initial polyexponential parameter estimates. Values for the coefficients and exponents of the exponential terms are calculated as well as estimates of lag times. An exhaustive search procedure ensures that the results are comparable to, or better than, those obtained by manual residual methods.


Puerperal laparoscopic sterilization.

Puerperal laparoscopic sterilization. Two hundred and ninety-seven consecutive puerperal laparoscopic sterilization cases during a five-year period are reviewed. There were six failures to complete the laparoscopic sterilization. A single case of anesthetic cardiac arrest constituted the only major complication. There has been no mortality. Two subsequent pregnancies occurred in this series, and their follow-up operative findings are reviewed.


[Angiocardiographic study after complete correction of interventricular communications treated by banding of the pulmonary artery. 20 cases (author's transl)]. An angiographic study after complete correction in twenty children who had previously undergone banding of the pulmonary artery revealed a certain number of complications. The considerable percentage of residual V.S.D, the persistance of notable narrowing in the region of the zone of banding, and infundibular hypertrophy are mainly due to surgical difficulties. Two cases of pulmonary valve incompetence were detected with the appearance of thickened valves, which were isolated or associated with a "domeshaped" valve appearance. Kowledge of these complications enables reduction as far as possible of the indications for banding of the pulmonary artery.


Interrelationship between excessive levels of circulating androgens in blood and ovulatory failure. The association of excessive circulating androgens in blood and ovulatory failure in women is well documented in a variety of clinical conditions. The restoration of ovulatory function by wedge resection of the polycystic ovary, by the administration of glucocorticoids or removal of tumors of the adrenal or ovary--measures that also reduce the level of circulating androgens--is also well documented. In view of the many hypotheses of adrenal and ovarian abnormalities and disorders of the hypothalamic-pituitary axis in the human, resulting in hirsutism and ovulatory failure, a normal intact rat model was developed to study the effect of androgens on ovulation. The administration of a weak androgen, dehydroepiandrosterone (DHA), to immature rats resulted in a single precocious ovulation followed by ovulatory failure. The conversion of DHA to estrogens appeared to be the principle mechanism for the precocious ovulation. The steps appeared to be an elevation in blood estradiol, followed by the depletion of cytoplasmic estradiol receptors of the hypothalamus and pituitary and the gonadotropin surge leading to ovulation. These events appeared to be similar to those occuring in the adult cycling rat, in precocious puberty induced by the administration of pregnant mare serum gonadotropins and during the onset of natural puberty. The role of estrogens in inducing the precocious ovulation was further supported by the absence of precocious ovulation in animals in which the conversion of DHA to estrogens was blocked or by administering androgens that could not be converted to estrogens. In contrast, the subsequent ovulatory failure could not be explained entirely by the conversion of DHA to estrogens. There was a considerable time lag between the withdrawal of DHA treatment and the replenishment of pituitary and hypothalamic cytoplasmic estradiol receptors. Unlike those of the cycling animal, the receptors were not replenished when the levels of circulating  estradiol in blood receded. The replenishment occurred only after the circulating levels of androstenedione, DNA and progesterone were reduced. Receptor replenishment in the hypothalamus and pituitary was followed by increases in the levels of circulating gonadotropins, particularly LH, with subsequent restoration of cyclic ovulatory function. The ovaries in the acyclic androgen-treated rat were responsive to gonadotropins. The pituitary responded to LH-RH administration, but the sensitivity was reduced. In the adult rat, ovulatory failure and the formation of polycystic ovaries took place with doses of DHA as low as 7.5 mg per kg of body weight. Attempts are being made to obtain further insights into the mechanism of androgen-induced ovulatory failure by studying the effect of androgens and progesterone on the steroid receptors and their function in the hypothalamus and the pituitary. Furthermore, a direct effect of DHA on the ovary, causing follicular atresia and cystic changes, is also being explored.


Chromosome survey of total population of mentally subnormal in North-East of Scotland. A cytogenetic survey of the complete population of mentally subnormal in the North-East of Scotland has been undertaken. A register for the mentally subnormal within the region already existed, and all persons recorded, whether they resided at home or in subnormality hospitals or other institutional care, were included. The total number recorded was 3020 and of these 2770 were examined cytologically. In all 297 (10.7%) were shown to have a chromosomal abnormality, and of these Down's syndrome accounted for 250 (9%). Within this category was an unexpected excess of males. Deletions and supernumeraries comprised the remaining autosomal anomalies. Increased numbers of sex chromosome abnormalities among high grade mentally subnormal individuals were confirmed for both sexes. The survey has shown that abnormal chromosome complements contribute significantly to the causation of mental retardation, and has also provided estimates which cannot be obtained from hospital surveys alone.


Reciprocal translocation, 4q-; 21p+, giving rise to Down's syndrome. A reciprocal translocation is described, t(4;21)(q27;p11), which occurs in a balanced carrier mother and her Down's syndrome child, 47,XX,t(4q-;21p+),+21. A review is presented of Down's syndrome associated with reciprocal translations involving chromosome No. 21.


A transmissible plasmid determining lactose fermentation and multiple antibiotic resistance in a strain of Klebsiella pneumoniae. In a wild strain of Klebsiella pneumoniae the plasmid that determined lactose fermentation also determined resistance to chloramphenicol, ampicillin, tetracyclines, streptomycin, spectinomycin, and sulphonamides. The plasmid transferred at a very low rate to Escherichia coli K12 and Salmonella typhi. By implanting other transfer factors in the strain the rate of transfer and the recipient range were increased. Plasmid transfer from the modified strain to Salm. typhimurium and Salm. gallinarum was detected in the alimentary tract of experimentally infected chicks fed diets containing ampicillin.


Reduction cystoplasty in prune belly syndrome. Reduction cystoplasty is a useful procedure to treat a large, poorly functioning bladder in boys with prune belly syndrome who are candidates for urinary tract reconstruction. The technique includes elliptical resection of all anomalous urachal tissue and sufficient detrusor dome to reduce bladder capacity to average size and to create a spherical detrusor. Improved detrusor function and a satisfactory of excellent result can be expected.


Long-time observations on the Blalock-Taussig operation IX. Single ventricle (with apex to the left). This report concerns a 20 to 28 year follow-up of patients with a single ventricle with pulmonary stenosis and levocardia, a malformation which is frequently combined with a transposition of the great vessels. Only 24 cases were found among the 1037 cyanotic patients with decreased pulmonary blood flow operated on between January 1, 1945 and January 1, 1951. Of the 18 patients who survived surgery, one has been lost to follow-up, eight have lived for more than 20 years, and six for more than 25 years after their initial operation. The results of a Blalock-Taussig operation for a single ventricle are less satisfactory than for a tetralogy of Fallot. Two patients who were living at the close of the study have had no further surgery. Seven patients have had a second operation and four patients have had a third. Progressive cardiac enlargement has been common. The period of enlargement has varied from 10 months to more than 20 years. Three patients have had subacute bacterial endocarditis; two had multiple attacks. One patient died of a brain abscess and one of a purulent meningitis. Three women and four men have married. All four men have A.B. degrees and are gainfully employed.


[To the definition of the reduction of ability in the law of incometax (author's transl)]. Out of jurisdiction and commentaries by the Federal minister of finance and the minister of labour and social affairs it is proved, that the characteristic of externally recognizable, permanent loss of bodily mobility is existent not only for one-eyedness but as well as for reduction of visual acuity, provided (reduction of ability) of 25% or more is present. This statement is good for reductions of Personal income tax as well as Wage tax. The estimation of the degree of disability is to be made according to "leads on the medical expertise on the state provision for the deserving", Edition 1973.


Ultrastructural comparison of the interface between epithelium and stroma in basal cell carcinoma and control human skin. Comparative ultrastructural studies of basal cell carcinomas, seborrheic keratoses, actinic keratoses, and control nontumor skin from human patients demonstrate structural differences between invasive and noninvasive tumor cells. Compared to the other specimen groups, biopsies of basal cell carcinomas reveal a decrease in hemidesmosomes and an increase in actin-like microfilaments in cells at the margins of the tumors. Benign tumors, i.e., seborrheic keratoses and actinic keratoses, have hemidesmosome areas and microfilament contents resembling control nontumor skin. The most striking hemidesmosome areas and microfilament contents resembling control nontumor skin. The most striking increase in microfilaments is in the most infiltrative "morphea" variants of basal cell carcinoma. These findings, in the context of other published reports, suggest that increased microfilaments are related to enhanced motility of invasive carcinoma cells in vivo and that decreased hemidesmosomes may be related to loss of cell to substratum or "anchorage" dependence of growth in malignant cells.


A comparative study of extracellular sulfated glycosaminoglycans synthesized by rabbit corneal fibroblasts in organ and confluent cultures. The extracellular sulfated glycosaminoglycans synthesized by explants of rabbit cornea and sclera, and by confluent cultures of corneal fibroblasts after incubation in medium containing 35S-sulfate were compared. The glycosaminoglycans isolated from corneal explants differed considerably from those obtained from confluent corneal fibroblast cultures and scleral explants. Only the corneal explants secreted into the nutrient medium a population of enzyme-resistant 35S-sulfate-labeled glycosaminoglycan that eluted from Dowex 1-X2 (Cl-) at a 3 M sodium chloride concentration, and which was resistant to testicular hyaluronidase, chondroitinase ABC, and nitrous acid degradation. With time, corneal explants gradually synthesized less of this fraction with these attributes of keratosulfate. If the corneal epithelium and endothelium remained on the corneal explants the total incorporated 35S-sulfate was approximately double that obtained when the cornea was striped of these cells.