Safety and rationale for continuation of propranolol therapy during coronary bypass operation. Thirty consecutive patients undergoing coronary bypass were studied. Oral propranolol therapy was maintained up to 4 to 10 hours before operation. Nineteen of the patients had a history of myocardial infarction (MI), 14 had hypoakinetic areas, and 8 had decreased ejection fraction indicating advanced coronary artery disease. Twenty-four-hour urinary epinephrine and norepinephrine obtained the day before operation were markedly increased at 136 +/- 12 microgram per 24 hours (normal, 39 +/- 4 microgram, rho less than 0.01). There were 4 perioperative MIs (13%) and no deaths. Plasma propranolol 1 hour before operation was 43.3 +/- 8 ng per milliliter, indicating good beta blockade. Propranolol was started within 24 hours postoperatively. There were no preoperative, intraoperative, or postoperative complications related to propranolol therapy. We conclude that because of markedly increased adrenergic tone the day before operation and transient hypersensitivity to adrenergic stimulation after withdrawal of propranolol, this agent should be continued through coronary bypass operation.


Perioperative myocardial infarction associated with coronary artery bypass graft surgery: improved sensitivity in the diagnosis within 6 hours after operation with 99mTc-glucoheptonate myocardial imaging and myocardial-specific isoenzymes. The present study was performed to evaluate scintigraphic imaging with technetium 99m-labeled glucoheptonate and serum enzyme levels of creatine phosphokinase isoenzyme (MB-CPK) in the early diagnosis of perioperative acute myocardial infarction associated with saphenous vein bypass graft operations. Myocardial imaging was done in 27 patients (50% of whom were considered high-risk) before operation and again 5 hours after operation. Four of these patients (15%) had both electrocardiographic and serum MB-CPK evidence of acute myocardial infarction, and all 4 had developed positive postoperative scintigrams. Four other patients had only elevated serum MB-CPK, and scintigrams became positive after operation in 3 of them. In addition, serum MB-CPK 6 hours after operation was 83 +/- 21 mIU/ml (mean +/- standard error of the mean) in patients with positive postoperative scans compared with 24 +/- 5 mIU/ml in those patients with negative postoperative scintigrams (p less than 0.001). Myocardial imaging with 99mTc-glucoheptonate in the perioperative period is rapid, safe, and atraumatic. Furthermore, our results suggest that it is a sensitive method for the early diagnosis of perioperative acute myocardial infarction, and, when imaging is combined with serum MB-CPK isoenzyme analysis, the reliability of the diagnosis of acute myocardial infarction is enhanced even further. Only 1 of the patients who showed perioperative myocardial damage had acute hemodynamic compromise or obvious impairment of recovery in the immediate postoperative period, and the 30-day mortality of the total group was 4% (1 of 27).


Ultrastructural integrity of human ventricular myocardium following cardioplegic arrest. The appearance of the ventricular myocardium in 6 patients electing coronary bypass operation was evaluated by electron microscope before and after aortic cross-clamping. Bypassing protocol included the induction of hypothermic cardioplegia by intermittent aortic root perfusion, with potassium chloride added to cold blood serving as the cardioplegic agent. Cross-clamp intervals ranged from 66 to 125 minutes. Ultrastructural alterations following bypass manipulations, and distinct from those observed before cross-clamping, were limited to the presence of extensive myocardiocytic pooling of glycogen. Scrutiny of the intramyocardial capillary bed following perfusion with the cardioplegic solution revealed no abnormalities attributable to, or intensified by, the bypass maneuver. These findings indicate that hypothermic potassium cardioplegia, as specified, is not injurious to human myocardial ultrastructure.


Five-year follow-up of patients undergoing coronary artery bypass. Two hundred eighty-two patients who underwent coronary artery bypass operation between January, 1971, and July, 1972, were followed until the time of death or for 5 years after operation. The angina-free status progressively decreased during the period of follow-up but at 5 years 57% of the survivors were free from angina. The total (early and late) incidence of nonfatal myocardial infarction was 3.3 per 100 patient years of follow-up. Nine (3.2%) of the patients had a repeat coronary artery bypass operation within the first 5 postoperative years. The overall 5-year survival was 86.9%. The expected 5-year survival of the general population, matched by sex and age, is 90.7%. Five-year survival was 97% for single-vessel disease, 87% for double-vessel disease, and 85% for triple-vessel disease.


Anesthetic considerations for aortocoronary bypass graft surgery. Between 1964 and 1978, aortocoronary bypass graft procedures were performed in more than 300,000 patients, and the number seems to increase every year. Nevertheless, the procedure itself can result in perioperative myocardial infarction leading to death. Greater understanding of and constant attention to the myocardial oxygen (O2) supply and demand may reduce the incidence of perioperative myocardial infarction. Some of the factors influencing supply and demand can be controlled pharmacologically. Drugs such as nitroglycerin, nitroprusside, and propranolol can reduce the myocardial O2 demand. Unfortunately, there are few data to elucidate the relationship between myocardial O2 demand and supply as influenced by anesthetic drugs, especially in patients with myocardial ischemia. However, enthusiasm for aortocoronary bypass graft operations has given enormous impetus to laboratory and clinical studies of this subject. Recent developments in anesthetic management afford better means for protection of the ischemic myocardium during and after operation.


Y-grafts and sequential grafts in coronary bypass surgery: a critical evaluation of patency rates. In a series of 584 patients undergoing coronary bypass, 425 patients received Y-grafts, sequential grafts, or a combination of the two. The saphenous veins from the legs frequently had Y- or double Y-branches suitable for bypasses. As many as 5 grafts have been served satisfactorily by a single proximal anastomosis. Simultaneous procedures included 45 left ventricular aneurysmectomies, 18 valve replacements, 7 carotid endarterectomies, repairs of a ventricular septal defect, an acute dissection, and coronary arteriovenous fistulas, with a total surgical mortality of 6 (1.4%). Restudy to determine graft patency was undertaken only in the 59 patients with unsatisfactory surgical results. These patients represent the worst 10% of the series in terms of surgical results. The patency rate for proximal anastomoses was 93%; Y-branchings, 93%; distal end-to-side anastomoses, 89%; and distal side-to-side anastomoses, 89%. Fifty-eight patients (98%) had at least 1 patient graft, and in 47 patients (80%) all anastomoses were patent up to six years after operation. Six patients underwent reoperation without any deaths.


Routine use of autotransfusion following cardiac surgery: experience in 700 patients. An autotransfusion technique has been developed for collection and reinfusion of shed mediastinal blood. This system has been routinely applied in the postoperative management of 592 consecutive adult and 108 pediatric cardiac surgical patients. Two hundred seventy-one adult patients (46%) and thirty-six pediatric patients (33%) actually received autologous blood. Autotransfusion volume ranged from 50 to 21,350 ml per patient. In 1976 at our institution, homologous transfusion requirements averaged 8.4 +/- 0.7 units per adult patient. During 1978, with the routine use of postoperative autotransfusion, bank blood transfusions were lowered to 4.2 +/- 0.3 units per patient (p less than 0.001). In contrast to perioperative autotransfusion techniques, collection and reinfusion of shed mediastinal blood is particularly useful for intravascular volume replacement in patients with serious postoperative bleeding.


Ventricular function and the native coronary circulation five years after myocardial revascularization. Of 531 patients who underwent coronary artery bypass grafting during 1970 to 1973, 181 were restudied by ventriculography and by graft and coronary angiography at least 5 years following operation. Five patterns of postoperative ventricular function were identified: improved ventricular function resulting in normal left ventricular (LV) function; normal ventricular function that was unchanged; abnormal ventricular function that improved but did not reach normal; abnormal ventricular function that remained unchanged; and deterioration of LV function. Patients who regained (40) and those who retained normal ventricular function (49) comprise 49% of the series and patients with deterioration of ventricular function, only 20%. Graft patency and angina relief were significantly better in those with normal LV function than in those with LV deterioration. Progression of disease in grafted coronary arteries was similar in all groups, but was significantly higher in ungrafted coronary arteries (61.3%) in the patients showing deterioration than in either the improved patients or those with an unchanged normal LV (33.3% each) (p less than 0.05). The high incidence of progression of disease in ungrafted coronary arteries in the group with deterioration suggests that low graft patency and deterioration of ventricular function in this group might both be related to intrinsic acceleration of coronary atherosclerosis unrelated to operative intervention.


Pediatric appendicitis. A 20-year study of 1,640 children at Cook County (Illinois) Hospital. Of 1,640 children with acute appendicitis treated at Cook County (Illinois) Hospital between Jan 1, 1957, and Dec 31, 1976, 35% had appendiceal perforation. Overall morbidity was 12.8% and mortality was 0.24%. Antibiotics, transperitoneal drainage, and delayed wound closure were used routinely in children with appendiceal perforation. Antibiotics and transperitoneal drains did not appreciably alter the incidence of intraabdominal abscess formation. Delayed wound closure in patients with appendiceal perforation reduced the incidence of wound infection by 75%.


Thyroid carcinoma. Immunology, irradiation, and lymphocytic infiltration. Patients undergoing thyroidectomies at Evanston (III) Hospital, during a six-month period had immunological studies performed preoperatively. No differential could be found between those with carcinoma or benign pathologic findings. T- and B-cell distribution and lymphocytic response to mitogens varied widely. Quantitative immunoglobulins showed slightly increased levels of IgG in patients with carcinoma and thyroiditis in comparison with those patients with adenomas. Antithyroglobulin antibodies were negative in all patients. Pathology slides from 107 patients with thyroid carcinoma between 1972 and 1978 at Evanston Hospital were reviewed for the presence of thyroiditis, either focal or diffuse. It was found that 50% of all carcinomas had either diffuse or focal thyroiditis. Diffuse thyroiditis was more common in patients with no history of irradiation and papillary carcinoma, and in younger age groups.


[Morphometric and histochemical characteristics of the frog sartorius muscle in ontogeny]. Morphometric and histochemical investigation of musculus sartorius was performed in ontogenesis in Rana ridibunda and Rana temporaria. Muscular composition was characterized according to the type of muscular fibres. Spectrum of lactatdehydrogenase isoenzymes was studied at different developmental stages. As the studies demonstrated, musculus sartorius underwent some essential changes in ontogenesis which manifested themselves in increasing number of muscular fibres and their areas, in changing LDG isoenzymic spectrum. Differentiation of the muscular fibres three types takes place at the 30th stage after P. V. Terentiev and depends on the nerve system maturation.


Computerized tomography in intracranial hemorrhage. Three hundred patients with intracranial hemorrhage were studied by computerized tomography (CT). Thalamic-ganglionic hematoma was found in 232; the mortality increased from 25% to 70% if ventricular extension occurred in this group. Lobar hematoma occurred in 45 of these patients, with a mortality of 20%, which was not influenced by ventricular extension. Seven had intraventricular bleeding only; of these, two died. In 12 patients with CT evidence of cisternal blood, angiography demonstrated aneurysms; the location of the blood predicted the location of the aneurysm in six. Multiple spontaneous intracerebral hematomas (ICHs) were visualized by CT in five patients. In 29 of 146 cases of ICH, postcontrast study showed enhancement; in 15, this was consistent with neoplasm, angioma, or aneurysm. In 14 with spontaneous ICH, ring enhancement occurred ten days to six weeks following hemorrhage.


Ocular inflammation and hemorrhage as initial manifestations of uveal malignant melanoma. Incidence and prognosis. A consecutive series of 450 eyes enucleated because of a malignant melanoma of the choroid or ciliary body was reviewed in an effort to establish the incidence of ocular inflammation or intraocular hemorrhage as the initial clinical manifestation. Thirty-five patients had these clinical signs initially. Twenty-two (4.9%) initially had ocular inflammations. Eight of these had an episcleritis, and the remaining 14 had some form of uveitis, endophthalmitis, or panophthalmitis. Five of those with episcleritis had tumors in the ciliary body, and all six patients who developed panophthalmitis had necrotic choroidal melanomas. Thirteen patients (2.9%) were initially observed with some form of intraocular hemorrhage. Follow-up information was available for 26 of the 35 patients selected for detailed study. Fourteen patients died of metastatic disease. We believe the relatively poor prognosis of these tumors depends on three factors: cell type, maximal diameter of the tumor, and extraocular extension.


Experimental endophthalmitis treated with an implantable osmotic minipump. A rabbit model of endophthalmitis was used to test the efficacy of an osmotic minipump delivery system as compared to standard intravitreal injection of the antibiotic, Staphylococcus aureus was inoculated into the vitreous cavity, and elimination of microorganisms was compared with use of intravitreal administration of 100 micrograms of gentamicin sulfate by either single pars plana injection or the continuous four-day administration of drugs to the vitreous via pars plana tubing connected to the minipump implanted subcutaneously near the rabbit's ear.


Bacteria in chronic maxillary sinusitis. Sixty-one chronically inflamed maxillary sinuses produced 131 bacterial strains from mucosal pieces that were taken during a Caldwell-Luc operation and cultured aerobically and anaerobically. Sinus secretions showed only 62 and nasal secretions 106 bacterial strains. Fourteen mucosal strains, including 11 Haemophilus influenzae, grew heavily. None of 24 mucosal anaerobes showed heavy growth. Of 52 antral mucosae with culturable bacteria, 37 disclosed mixed and 15 pure growth. The bacteriological characteristics of the diseased sinus and the nose did not correlate. The duration or extent of the disease, the macroscopic appearance of the diseased sinus, or the presence or absence of allergy were unrelated to bacteriological findings, except that H influenzae was concentrated in purulent sinuses. Intraoperative culture of antral mucosa seems to give the most reliable picture of the bacteriological condition in chronic maxillary sinusitis.


Prevalence, pathogenesis and treatment of post-menopausal osteoporosis. About 11% of post-menopausal women with wrist fractures have spinal osteoporosis with compressed vertebrae, and about 25% of postmenopausal osteoporosis patients have had a wrist fracture. The estimated prevalence of post-menopausal spinal osteoporosis is 4% of the female population at age 60 and about 8% at age 80. Osteoporotic patients have lower plasma oestrone and androstenedione levels, lower calcium absorption and higher urinary hydroxyproline than matched controls. Of six treatments tested in three different ways, the least successful were vitamin D2 and 1 alpha-OHD3 and the most successful were hormones with or without 1 alpha-(OH)2D3 and calcium supplements. Calcium and vitamin D given in combination occupied an intermediate position.


Aeromedical implications of the X-Chrom lens for improving color vision deficiencies. A red contact lens (X-Chrom lens) worn on the nondominant eye by 12 color-defective subjects caused significant improvements on the Dvorine, Ishihara, and Hardy-Rand-Rittler pseudo-isochromatic color plate tests. Color vision scores on the Farnsworth Lantern, Color Threshold Tester, and Aviation Signal Light Gun were not improved. Minimal changes were found on the Farnsworth D-15 test, aeronautical chart color identification task, visual acuity, phoria, and stereoscopic depth perception. Control and color-defective subjects perceived a change in the path of a pendulum (Pulfrich test) when viewing through the X-Chrom lens or a monocular red filter. The X-Chrom lens may require extended wearing before its optimum effect becomes apparent.


Arthritis associated with jejunoileal bypass: clinical and immunologic evaluation. Arthritis is a common complication of small bowel bypass, occurring in 5-20% of the postsurgical patients. Thirteen patients with arthritis related to jejunoileal bypass were studied. These patients had a symmetrical polyarthritis, and 8 also had extraarticular connective tissue disease manifestations. Immunologic evaluations were done on these patients and on a control group of 12 age- and sex-matched postintestinal bypass patients without arthritis. The incidence of positive ANA, rheumatoid factors, immune complexes, and antibodies to intestinal flora was the same in both groups. Patients in both groups showed similar changes in numbers of circulating T and B lymphocytes. More patients in the group with arthritis than in the control group had elevated IgA levels (38% versus 8%), but the difference was not significant (P less than 0.05). This study demonstrates that immunologic abnormalities occur after jejeunoileal bypass irrespective of the onset of arthritis or related symptoms. No specific immunologic abnormalities could be associated with the arthritis occurring after small bowel bypass.


Haemopoietic progenitor-cell responses in mice with the transplanted lymphoid leukaemia ABE-8. BALB/c mice bearing the transplanted lymphoid tumour ABE-8 developed increased levels of neutrophil, macrophage and eosinophil progenitor cells in the marrow and spleen. Neutrophil-macrophage progenitors, assayed as granulocyte-macrophage colony-forming cells in agar, increased in number only if invasion of the marrow or spleen by ABE-8 cells was demonstrable. Rises in B-lymphocyte colony-forming cells occurred whether or not there was invasion of the host spleen or marrow. No increase in progenitor cells was found in mice bearing diffusion chambers containing ABE-8 cells. The magnitude of leukaemic infiltration was determined by assaying numbers of leukaemic stem cells in the spleen and marrow using a selective cloning system. This transplanted lymphoid leukaemia appears to be a useful model for analysing the effects of haemopoietic tumours on host haemopoietic tissues.


Histiocytosis X in two infants--treated with topical nitrogen mustard. Two infants suffering from histiocytosis X were treated successfully with a topically applied nitrogen mustard. All cutaneous symptoms disappeared completely within 2 weeks in one case while the skin improved significantly in the other. No irritation or dermatitis was experienced from the treatment. The only side-effect noted was hyperpigmentation.


Liver ribonucleases from the bullfrog, Rana catesbeiana. Purification, properties and changes in activity during metamorphosis. A major and three minor RNAases exhibiting activity at neutral pH were found in bullfrog liver homogenates. These RNAases were purified to electrophoretic homogeneity. Total purification was 1100 to 1600-fold, and the average recovery was 35%. The molecular weight estimated by gel filtration and SDS-urea-polyacrylamide gel electrophoresis was 12,000 for all the components. An antibody against the major RNAase (component B) reacted with the major RNAase to form a single precipitin line on double immunodiffusion and inhibited the activity of the major RNAase but did not cross-react with the other three components and bovine pancreatic RNAase A. Amino acid analyses revealed that the major RNAase differed markedly from the other three RNAase components in the contents of ten amino acid residues, whereas the minor RNAases were similar to each other. The major RNAase was contained in both frog and tadpole liver and its activity in the liver markedly increased at the metamorphic climax.


Studies on factor VIII-related protein. I. Ultrastructural and electrophoretic heterogeneity of human factor VIII-related protein. Human factor VIII-related protein precipitates with specific heterologous anti-bodies directed against purified factor VIII and supports ristocetin-induced aggregation of washed platelets. We purified human factor VIII from cryoprecipitate by subsequent gel filtration on crosslinked large-pore agarose. Factor VIII-related protein appeared as a large aggregate following electrophoresis on 3% polyacrylamide gels in the presence of sodium dodecyl sulfate (SDS). The same material was separated into multiple bands (molecular weight in excess of several millions) following electrophoresis on SDS-1% agarose gels. After complete disulfide reduction of factor VIII-related protein and electrophoresis on SDS-5% polyacrylamide gels a single subunit chain (Mr approximately equal to 200 000) was revealed. Analysis of this protein, in its non-reduced state, by negative contrast electron microscopy showed filaments of markedly variable size. The calculated molecular weight of such filaments ranged from about 0.6.10(6) to 20.10(6). We conclude that size heterogeneity is an essential feature of human factor VIII-related protein.


[Comparative study of D-glyceraldehyde-3-phosphate dehydrogenase from frog and pike skeletal muscles]. The purified preparations of glyceraldehyde-3-phosphate dehydrogenase isolated from frog and pike skeletal muscles were found homogenous under polyacrylamide gel electrophoresis. Their amino acid composition is similar to that of glyceraldehyde-3-phosphate dehydrogenase from other animal species. The interaction kinetics for frog and pike glyceraldehyde-3-phosphate dehydrogenase SH-groups with 5,5'-dithio-bis-(2-nitrobenzoate) (DTNB) were studied. A negative correlation between the thermal stability of the enzyme preparations from pig, pike, lamprey and frog muscles and the reactivity of their SH-groups with respect to DTNB was observed. NAD at saturating concentrations was found to protect the enzyme from lower vertebrates muscles against thermal inactivation in a lesser degree than does the pig muscle enzyme. The weaker protective effect of NAD was observed for lamprey and frog enzyme preparations, which are characterized by a low SH-group reaction ability. Frog and pike apoenzymes are considerably more resistant to trypsin proteolysis than the pig apoenzyme.


[Development of delayed hypersensitivity to sheep erythrocytes after separate and combined administration of the antigen and cyclophosphamide]. The ability to the development of delayed hypersensitivity (DHS) to the appropriate antigen was studied in mice treated with large doses of SRBC and cyclophosphamide at varying time prior to the experiment. Suppression of DHS development induced by administering either the cytostatic alone or a large dose of the antigen was examined at the same periods of time. The combined treatment was shown to induce tolerance according to diverse tests for DHS (skin and macrophage migration inhibition tests). At the basis of this tolerance lies genuine deficiency of the appropriate clone of T cells. Administration of cyclophosphamide alone leads to a slight suppression of DHS, while a large dose of the antigen induces a different form of areactivity due to the suppressor cells whose nature is not yet clear.


Prednisone-responsive aplastic anemia: a mechanism of glucocorticoid action. We performed serial agar cultures (CFU-C) using marrow cells from a patient with prednisone-responsive aplastic anemia and from five patients with prednisone-resistant aplasia. Colony growth was decreased in all patients. Cortisol (10(-7)-10(-4)M) significantly enhanced colony growth in the prednisone-responsive patient but fauled to enhance colony growth in the remaining five patients. Further studies in the responsive patient indicated that (1) colony growth was enhanced by depleting T lymphocytes from the marrow cells, (2) colon growth T-depleted marrow cells was inhibited by autologous peripheral blood lymphocytes (PBL), (3) cortisol failed to enhance colony growth of T-depleted marrow cells, (4) PBL and PBL-conditioned medium inhibited colony growth of both autologous and allogeneic marrow cells, but neither cortisol-treated PBL nor T-depleted PBL were inhibitory. Serial cultures in the responsive patient showed that colony growth normalized during remission when "suppressor" cells were absent and that colony growth was subnormal during a later relapse when cortisol-resistant "suppressor" cells were present. Therefore, in this prednisone-responsive patient, cortisol-sensitive T lymphocytes suppressed granulopoiesis in vitro. Our observations suggest that aplastic anemia in this patient is immunologically mediated and that prednisone therapy enhanced hemopoiesis in vivo by inhibiting the "suppressor" T lymphocytes.


Distinct subtype within the spectrum of hairy cell leukemia. Most cases of hairy cell leukemia represent malignancies of B cells. However, recent findings suggest that there is a spectrum of functional capacities within the entity hairy cell leukemia. Two patients with hairy cell leukemia, whose malignant cells in the peripheral blood showed both T- and B-cell features, are reported. The malignant cells of the spleens showed only B-cell characteristics. The hairy cells of both patients did not adhere to glass and lacked the la antigen. Both patients showed pronounced polyclonal hypergammaglobulinemia and developed frank leukemic blood pictures after splenectomy. Within the spectrum of hairy cell leukemia, these two cases probably represent a distinct subtype.


T-cell subpopulations in chronic lymphocytic leukemia: abnormalities in distribtuion and in in vitro receptor maturation. Purified human thymus-derived (T) lymphocytes were analyzed by detection of Fc receptors for either IgG or IgM in healthy controls and in patients with chronic lymphocytic leukemia (CLL). There was a significant and persistent increase in the numbers of T cells bearing receptors for IgG (Fc gamma) in CLL patients in comparison to the controls. After an in vitro culture period, there was a significantly decreased appearance of cells with IgM receptors (Fcmu) in CLL patients in comparison to the control group. These results indicate an imbalance in circulating T-cell subpopulations for CLL patients. In addition, an in vitro defect in CLL T-cell membrane receptor appearance is present.


Evidence that protease inhibitors reduce the degradation of parathyroid hormone and calcitonin injected subcutaneously. 1 Agents known to delay absorption from a subcutaneous site were tested in chicks for their ability to prolong the hypercalcaemic response to parathyroid hormone (PTH). 2 Polyvinylpyrrolidone was found to enhance the response but gelatine greatly reduced the 2 h hypercalcaemia. 3 The reduction by gelatine was reversed when the protease inhibitor aprotinin was added to the injection vehicle, and hypercalcaemia then persisted for more than 8 h. 4 Of other protease inhibitors studied, epsilon-aminocaproic acid was also found to enhance the hypercalcaemic response to subcutaneous PTH and its fragments but, unlike aprotinin, it was ineffective in the presence of gelatine. 5 By radioimmunoassay and bioassay respectively, it was confirmed that aprotinin raised circulating levels of PTH and also of another peptide hormone, calcitonin, injected subcutaneously. 6 Addition of calcium to the solutions injected subcutaneously abolished the hypercalcaemic response to PTH while injection of calcium and PTH simultaneously but at separate sites left the response unaltered. 7 The two protease inhibitors, epsilon-aminocaproic acid and aprotinin, each restored the response to subcutaneous PTH despite the presence of calcium at the injection site. 8 It was concluded that protease inhibitors injected subcutaneously with PTH and calcitonin in the chick reduced the rate of degradation of these hormones and that the proteases responsible for hormone degradation at the subcutaneous injection site may be released or activated by calcium ions.


Uptake and release of 5-hydroxytryptamine by enteric 5-hydroxytryptaminergic neurones: effects of fluoxetine (Lilly 110140) and chlorimipramine. The effect of fluoxetine on uptake of 5-hydroxytryptamine (5-HT) by enteric 5-hydroxytryptaminergic neurones has been analyzed in order to compare further these neurones with 5-HT neurones of the CNS. In addition, the effects of fluoxetine and chlorimipramine on efflux of [3H]-5-HT from the myenteric plexus were also evaluated. Fluoxetine was found to be a competitive inhibitor of 5-HT uptake by the myenteric plexus and was a more potent inhibitor of 5-HT uptake than was chlorimipramine. However, chlorimipramine enhanced the efflux of [3H]-5-HT more than could be explained by inhibition of 5-HT uptake and, therefore, appears to have the additional action of releasing the amine. These observations, similar to those of others studying central neurones, support the view that enteric 5-HT neurones resemble those of the CNS and are a useful model for the evaluation of drugs.


Mortality in patients with haematemesis and melaena: a prospective study. In a prospective study of death in 817 patients with haematemesis and melaena admitted on 894 occasions, the protocol included admission of all patients to a defined unit, early endoscopy and resuscitation, and planned management. Over the three consecutive two-year periods of the study mortality significantly decreased from 9% to 2.4%. Although the operative rate remained the same, the operative mortality fell from 16% to 1.6%. The fall in mortality was greatest in patients with bleeding gastric ulcers. These results suggest that prospective studies with a defined policy can influence the mortality in patients with upper gastrointestinal bleeding.


Peptide containing vesicles within neuro-neuronal synapses. In the descending part of the classical neurosecretory system, the axon terminals are not differentiated or they take the form of presynaptic elements which then form synaptoids or synapses with pituicytes or adenohypophyseal glandular cells respectively. In contrast, the axon terminals of the ascending part fulfil the criteria of true presynaptic elements which form synapses with other neurones. The presence of neurophysin vesicles in the presynaptic element is a particular morphologic feature of these neuro-neuronal synapses.


[Ophthalmic herpes: treatment of herpetic neuralgia by repeated stellate block]. Eight cases of herpes zoster with severe neuralgic pain were treated by repeated stellate blocks, 5 during the acute stage and the 3 others later on. Of the 5 patients treated during the acute stage 3 were cured, the pain disappearing completely. Four other patients were substantially improved. Only one case was a failure. It is important to begin the injections soon after the beginning of the illness, preferably in the first couple of weeks after the rash appears.


Septic arthritis in childhood.

Septic arthritis in childhood. In the first 4 years (1974 to 1978) of operation of the Children's Hospital of Eastern Ontario, in Ottawa, 50 children were treated for septic arthritis. The neonatal group (birth to 6 months) of three patients had the most severe involvement and the worst prognosis. The early childhood group (6 months to 4 years) of 15 patients was characterized by sepsis due to Hemophilus influenzae. The 32 older children (4 to 16 years), more susceptible to staphylococcal infections, commonly presented with atypical and unusual symptoms. The erythrocyte sedimentation rate was the most reliable laboratory investigation. Positive joint cultures were obtained in 66% of patients. Arthrotomy with drainage was the most reliable form of treatment, particularly in cases of hip joint sepsis. Six patients have substantial residual joint damage with some degree of permanent disability. Early diagnosis of the condition and rapid removal of pus are mandatory for the survival of the joint.


Lung function in diaphragm pacing.

Lung function in diaphragm pacing. Electric stimulation of the diaphragm via the phrenic nerve to induce ventilation has recently been used for the long-term management of chronic ventilatory insufficiency. Since 1973 three patients with inadequate alveolar ventilation have been treated with diaphragm pacing at the Toronto Western Hospital. Two, who had quadriplegia due to lesions of the spinal cord in the upper cervical region and a severe restrictive ventilatory defect, were treated with continuous diaphragm pacing. The third patient required assisted nocturnal ventilation because of primary alveolar hypoventilation. All three patients tolerated the diaphragm pacing well, and pulmonary function tests showed satisfactory gas exchange with the patients breathing room air. This form of therapy seems to be a practical clinical method of managing chronic ventilatory failure in patients with lesions of the upper cervical cord or primary alveolar hypoventilation.


Treatment of hepatic metastases by percutaneous hepatic arterial infusion. Better palliation for patients with hepatic metastases requires improved quality and duration of survival with a low complication rate and acceptable expense. Eligible patients between 1967 and 1977 were treated with a program of systemic chemotherapy until progression of hepatic metastases, then hepatic arterial infusion and subsequent maintenance on systemic chemotherapy. The angiography department was able to place the infusion catheter into the common hepatic artery percutaneously in 85% of all patients. The reasons for failure appeared related to anatomic variations and not to the physical characteristics of the liver cancer. A group of 24 patients with colorectal cancer and another group of 28 patients with 13 different primaries were treated. The colorectal cancer patients attained a median treatment time of 8 months before hepatic arterial infusion, and 9 more thereafter. The median survival of 17 months is much better than that reported for systemic chemotherapy alone. In a group of 28 patients with various primaries treated in the same way, the median survival time was 10 months. The nature of complications and the 6% incidence were the same in both groups. In summary, this is a modality yielding improved quality of life and longer survival with a low complication rate and acceptable costs.


T and B-RFC inhibiting factor in plasma from patients with active Hodgkin's disease. We report the presence of a rosette inhibiting factor (RIF) in the plasma of patients with active Hodgkin's disease. This factor suppresses the rosette forming ability of autologous Active T, Total T, and B lymphocytes with sheep red blood cells, and tends to disappear when clinical remission is achieved. To a lesser extent, the RIF also lowers the Active T, Total T and B-RFC percentages of lymphocytes obtained from normal donors. Although carcinoma and non-Hodgkin's lymphoma patients, as a group, did not exhibit rosette inhibitive properties, certain individuals with these diagnoses did show isolated RIF activity. The RIF could be adsorbed out of plasma using peripheral blood lymphocytes (PBL) from normal controls and appears to be a large heat stable molecule which does not affect PBL viability.


Immunologic evaluation of patients with advanced head and neck cancer receiving weekly chemoimmunotherapy. Patients with advanced head and neck cancer have significant reduction in their circulating lymphocyte mass which is reflected in decreased numbers of T cells, Fc receptor cells, and in derangements of T lymphocyte functions, i.e., decreased responsiveness to several dilutions of phytohemagglutinin and lack of development of delayed hypersensitivity to 2,4-dinitrochlorobenzene (70% of patients were DNCB (-)). A population of phagocytic cells capable of decreasing lymphocyte responsiveness to mitogens were demonstrated. Removal of these cells resulted in an increment in lymphocyte responsiveness. Immunological impairment seemed to correlate with patients' ability to become sensitized to DNCB. Those patients who were DNCB (+) had less derangement in their immunological parameters. Weekly administration of Corynebacterium parvum in conjunction with chemotherapy did not have a discernible effect on patient's immune reactivity.


Defective monocyte chemotaxis in mycosis fungoides: lack of essential helper lymphocytes. The effect of lymphocytes on monocytes chemotaxis in vitro was studied using lymphocyte fractions prepared by glass bead column separation and mononuclear cell fractions prepared by Ficoll-Hypaque separation. The diminished monocyte chemotaxis in ten patients with mycosis fungoides was corrected in vitro by the addition of normal lymphocytes. This helper effect was not mediated by soluble factors. Lymphocytes from mycosis fungoides patients did not inhibit chemotaxis by monocytes from mycosis fungoides patients did not inhibit chemotaxis by monocytes from normal donors. No cell directed chemotactic inhibitor, differences in LDCF production in vitro or differences in circulating chemattractants were found. These data support the conclusion that the abnormal monocyte chemotaxis seen in mycosis fungoides is due to lack of essential helper lymphocyte function and represents an abnormal mononuclear cell interaction which may be important in the establishment of the mononuclear cell infiltrate in mycosis fungoides.


Effect of operation and radiotherapy on antibody-dependent cellular cytotoxicity. A subpopulation of human lymphocytes bearing receptors for the Fe portion of IgG causes lysis of nucleated target cells in the presence of antibody. The reaction is known as antibody-dependent cellular cytotoxicity (ADCC) and the effector cells have been called killer (K) cells. We have measured K cell activity quantitatively in the peripheral blood of cancer patients using 51Cr labeled murine mastocytoma target cells and hyperimmune rabbit antimastocytoma antibody. ADCC was the same in males and females, was not affected by eating, smoking or the presence of infections, but was decreased in those over 65 years, during pregnancy, and in those with cachexia, or severe sepsis associated with nonmalignant diseases. It was normal in those with cancers being treated for cure and in those with benign diseases, but was decreased in those with advanced cancers. Operation did not produce a significant change in those who were not immunodepressed; in those who were immunodepressed before operation it caused a significant decrease maximal by the fifth day with recovery by the 15th day. Radiotherapy caused a decrease in K cell activity, maximal at 4 weeks, that persisted for 12 weeks with recovery after that time in those who did not have residual tumor. The values did not return to normal in those who had persistent tumor or distant metastases.


Presence of suppressor cells in spleens of mice bearing a weakly immunogenic syngeneic tumor. Spleen cells of C57BL/6J mice bearing a poorly immunogenic syngeneic tumor T241 have been shown to suppress the mitogen-induced proliferative responses of normal spleen cells. However, no suppressive effect of these cells was observed on the generation of cytotoxic cells following immunization in vitro against H-2 histocompatibility antigens. The suppressor activity disappeared rapidly after the removal of the primary tumor. Spleen cells of tumor-bearing mice also suppressed the mitogen-induced stimulation of normal spleen cells of mice of different H-2 loci. Removal of phagocytic cells with carbonyl iron treatment had very little effect on the suppressor activity. Suppressor activity was enhanced following fractionation of cells through nylon wool columns. The suppressor population was found to resist anti-immunoglobulin serum and complement treatment, but treatment with anti-thymocyte serum and complement drastically reduced the suppressor activity. These results indicate that cells with suppressor activity have characteristics of T-lymphocytes.


Possible mechanisms of action of lithium on augmentation of in vitro spontaneous myeloid colony formation. To understand the possible mechanisms of lithium carbonate-induced neutrophilia, the in vitro effect on human myeloid progenitor cells was examined. A significant increase in spontaneous colony formation (15 of 24 experiments) was observed with the addition of lithium. Increased colony formation seldom occurred when human placental conditioned media as a source of colony-stimulating activity (CSA) was simultaneously added to the cultures. Further data suggest that lithium requires an adherent marrow cell population for this action and that increases in CSA-containing cultures may be due to suboptimal CSA concentrations. Lithium was shown to release CSA from marrow cells and adherent cell population prepared from human bone marrow. Lithium possibly increases spontaneous human myeloid colony development indirectly through CSA release by adherent cells.


Treatment of osteogenic sarcoma. I. Effect of adjuvant high-dose methotrexate after amputation. Thirty-nine patients with extremity osteogenic sarcoma and no discernible metastases were treated with amputation and postoperative adjuvant high-dose methotrexate with leucovorin rescue. One half of the patients were also randomized to receive bacillus Calmette-Guérin by a multiple-puncture technique. Results have been analyzed with a minimum followup of 10 months and a median followup of 27 months. Actuarial analysis estimates that 38% of current protocol patients remain continuously free of disease for 24 months compared to only 17.4% of historical control patients (P = 0.029; one-sided generalized Kruskal-Wallis test). Bacillus Calmette-Guérin administered by a multiple-puncture technique had no effect on disease-free interval. Minor differences between current protocol and historical control patients with regard to race, age, histologic type, and site and size of primary tumors do not affect the difference in disease-free interval between these two patient groups. However, current patients had somewhat lower grade lesions and consideration of the patients with grade III and IV lesions only, lessens the difference between current and historical control patients (P = 0.11; one-sided generalized Kruskal-Wallis test). High-dose methotrexate was administered with virtually no morbidity and no deaths. The small differences observed in this study between protocol patients treated with surgery plus high-dose methotrexate and historical control patients treated with surgery alone point to the need for a prospective randomized study to establish the role of high-dose methotrexate in the adjuvant treatment of patients with osteogenic sarcoma.


High-dose methotrexate for advanced breast cancer. High-dose infusions of methotrexate with citrovorum factor rescue were evaluated in 27 patients with advanced recurrent breast cancer who had previously been treated with various Adriamycin-containing regimens. Eight of 27 patients (29%) achieved objective tumor regression with a median duration of response of 26 weeks. Nineteen patients had previously received standard doses of methotrexate (less than 50 mg/m2/dose), while eight patients had had no prior exposure to methotrexate. The response rates observed in these two groups of patients were similar. Except for two drug-related deaths, toxic effects were acceptable. Myelosuppression was mild, transient, and noncumulative. Gastrointestinal toxic effects did not appear to be dose-related and were mild in most instances. Central nervous system dysfunction with lethargy, fatigability, confusion, and disorientation was the most significant toxic effect of this high-dose methotrexate therapy and was observed in six (22%) of the patients. In two patients treatment with this program was discontinued because of the development of renal dysfunction. High-dose methotrexate with citrovorum factor rescue appears to be an effective regimen in patients with advanced refractory breast cancer. However, in view of the enormous cost necessitated by this treatment approach, we do not feel further studies would be worthwhile.


The predominantly nonhydrolytic action of alpha amylases on alpha-maltosyl fluoride. Crystalline alpha amylases from a number of sources utilized alpha-maltosyl fluoride as a glycosyl donor and acceptor at high rates (approximately 10 to approximately 1550 mumol/min/mg of protein, for 30 mM substrate). All enzymes catalyzed conversion of this compound into maltooligosaccharides in preference to causing its hydrolysis. Maltotetraosyl flouride and maltooligosaccharides of d.p. 3 to 6+ accounted for 75--93% (by weight) of early reaction-products. At a late stage, the yield of maltooligosaccharides was 2--5 times that of maltose, with chains as long as 12 D-glucosyl residues formed by one amylase (from Asp. oryzae), which utilized alpha-maltosyl fluoride as a donor and as an acceptor at extremely high rates. These results indicate that alpha amylases have a substantial capacity for binding two molecules of this small substrate in a distinctive way, with the C--F glycosylic bond of one and the free C-4 hydroxyl group of the other located in the region of the enzyme's catalytic groups, therby favoring glycosylation of the suitably positioned acceptor over solvent water. Hydrolysis is assumed to prevail when only a single substrate molecule or segment binds to alpha amylase with a (1 linked to 4)-alpha-D-glucosidic linkage of glycosylic C--F bond positioned at the catalytic center. The present demonstration that glycosyl-transfer reactions can be dominantly expressed by alpha amylases, given an appropriate substrate, illustrates the inadequacy of the usual characterization of these enzymes as hydrolases that produce overwhelming hydrolysis of all substrates.


Effect of serotonin on prolactin- and MSH-secreting cells in the eel. Comparison with the effect of 5-hydroxytryptophan. As parachlorophenylalanine appears to reduce release of prolactin (PRL) and melanocyte-stimulating hormone (MSH) in the eel, a stimulating serotoninergic control of these adenohypophysial secretions was suspected. Eels were therefore injected with serotonin (5-HT) (7.5--20 mg/kg) and compared with eels injected with the precursor of serotonin, 5-hydroxytroptophan (5-HTP) (20 mg/kg). In both cases, a darkening of the skin was observed, more rapid and intense with 5-HTP than with 5-HT. Similarly, MSH cell degranulation is more completely in 5-HTP-treated eels, which show simultaneously an unexplained dilatation of the swim-bladder not elicited by 5-HT treatment. In both cases, PRL cells are stimulated, and the nuclear area of PRL and MSH cells increases significantly. These results suggest that a serotoninergic pathway stimulates PRL and MSH release in the eel. An antagonism between the serotoninergic system and the dopaminergic system previously demonstrated in the same species seems apparent, but the interaction of other organs or factors, such as the pineal, are considered.


Moulting in Rana esculenta: development of mitochondria-rich cells, morphological changes of the epithelium and sodium transport. The present study concerns moulting of the skin in Rana esculenta in vivo and in vitro. The evolution of mitochondria-rich cells (MRC) and changes in the epithelium during moulting were followed. The greater part of the MRC are lost during moulting, either because they remain attached to the old stratum corneum or because they are left in contact with the external medium and degenerate. The cells thus lost leave deep impressions in the new stratum corneum which disappear progressively. Before an MRC is shed, a cell of the stratum intermedium contacting it differentiates to form a new MRC to replace the old. Isolation of the skin triggers moulting in the excised pieces. This moulting does not cause changes in the short-circuit current or in the transepithelial resistance. Aldosterone (10(-6) M) added in vitro to the serous side appeared to facilitate the detachment of the slough, however, no clear-cut moult-inducing effect of the hormone was seen.


Atrial pacing induced left ventricular dysfunction: reversibility after aortocoronary bypass surgery. Three patients with angina pectoris were studied before and after aortocoronary bypass surgery. Angiographic studies were performed with and without atrial pacing. Preoperative atrial pacing in all three patients resulted in angina and/or ST segment changes accompanied by regional left ventricular contractile abnormalities, decreased ejection fraction, as well as decreased left ventricular end-diastolic and stroke volumes. After surgery with all grafts patent, atrial pacing at similar heart rates did not produce an ischemic response. Left ventricular contractile pattern remained normal, and there was no change in ejection fraction though end-diastolic and stroke volumes decreased. These studies demonstrate that aortocoronary bypass surgery can abolish both the ischemic response and left ventricular dysfunction that accompany atrial pacing.


Methotrexate-induced oral mucositis and salivary methotrexate concentrations. We examined the plasma and saliva levels of methotrexate (MTX) achieved during the treatment and rescue periods of ten patients receiving 42-h MTX infusions followed by citrovorum rescue. Saliva MTX levels were generally 1%--2% of the simultaneous plasma levels. Four patients developed severe oral mucositis; three patients developed mild to moderate oral toxicity, and three others had no evidence of mucositis. MTX levels in the patients with severe mucositis were not higher and did not persist longer than the levels achieved in patients with mild or absent toxicity. Attempts at reducing the severity of oral mucositis with topical citrovorum mouthwashes or with atropine to suppress salivation were unsuccessful. MTX-induced oral mucositis is not related to salivary MTX concentrations, and the use of topical citrovorum therapy or the suppression of salivation does not appear to ameliorate this toxicity.


Blood pressure in unanesthetized bacterially infected rabbits: effects of antipyretic drug therapy. It has previously been determined that an intraperitoneal infusion of a combination of antipyretic-anti-inflammatory drugs, sodium salicylate and acetaminophen, increases the survival rate of rabbits injected with Pasteurella multocida, a gram-negative bacterium. To determine whether the increased survival rate was attributable to antihypotensive effects of the drug therapy, aortic arch blood pressure was measured continuously in unanesthetized rabbits before and after an injection of bacteria. The results of this investigation revealed that the injection of bacteria produced a fall in mean arterial pressure of 13 mm Hg in both drug- and saline-infused rabbits. These results exclude the possibility that the increased survival rate of rabbits injected with P. multocida, when infused with sodium salicylate and acetaminophen is attributable to the prevention in the fall in mean arterial pressure.


The relevance of 25-hydroxycalciferol measurements in the treatment of hypoparathyroidism. In twenty-one patients with chronic hypoparathyroidism a close correlation was observed between the prescribed dose of ergocalciferol and mean serum 25-hydroxycalciferol levels. In the 75 serum specimens examined, a significant correlation was found between 25-hydroxycalciferol levels and calcium concentrations. The measurement of serum 25-hydroxycalciferol levels is of potential clinical value in the prediction of hyper- or hypocalcaemic episodes and in monitoring patient compliance.


Lymphocytes forming stable E-rosettes in acute and chronic hepatitis. Lymphocytes forming E-rosettes with sheep erythrocytes which do not disintegrate at 37 degrees C have been demonstrated in increased numbers in peripheral blood of patients with acute type B hepatitis (6--20% of lymphocytes) and with HBsAg negative active chronic hepatitis (9--28% of lymphocytes). They were not increased in patients with HBsAg positive active chronic hepatitis. Such lymphocytes were adherent to nylon wool and a large proportion of them had FcIgG receptors (21--69%). These are properties of a subpopulation of T lymphocytes having suppressor function.


Coronary arterial bypass operations without antibiotic coverage. In this study, six of 693 consecutive patients in 29 months who underwent only myocardial revascularization, without prophylactic systemic therapy with antibiotics, experienced infection of a clean wound. This incidence of infection (0.86 percent) in such patients is the lowest reported in the literature. Prevention of infection of clean mediastinal wounds in patients undergoing only myocardial revascularization is related to preoperative preparation of the skin and local antibiotic irrigation of the wound, rather than to prophylactic systemic therapy with antibiotics.


A comparison of computed tomography and air ventriculography in diagnosis of progressive hydrocephalus of infancy. We have compared the efficacy of computed tomography (CT) and air ventriculography (VGM) in the diagnostic evaluation of progressive nontumoral infant hydrocephalus where both examinations have been done without significant interventing time or treatment in infants under 12 months of age. CT alone was judged to be adequate for diagnosis and treatment 21 of 30 cases reviewed, provided that cerebrospinal fluid studies were available to complete diagnosis where necessary, and provided that the question of ventriculocisternal communication was not a factor in treatment selection. The ability to visualize cerebran aqueduct and 4th ventricle on CT was not always a reliable indicator of ventriculocisternal communication. CT was most adequate as the sole radiographic study in cases of myelodysplasia with Arnold-Chiari malformation, and in premature infants with intraventricular hemorrhage.


Congenital midline porencephaly: a new brain malformation associated with scalp anomaly. 5 cases of dysgenetic hydrocephaly associated with scalp anomalies are described. This brain-scalp anomaly complex is characterized by congenital hydrocephalus, alopecia or cephalocele in the parietal midline and symmetrical defect of the bilateral posterior cerebral mantle along the midline. Midline septal structures of the cranial cavity and tentorium cerebelli were also defective and replaced by a huge dorsal CSF cavity. Histological features of the covering membrane of the dorsal cyst indicate that this new brain anomaly is the consequence of a porencephalic process and we postulate the 'midline porencephaly'. Cerebral angiography is the most valuable method for the diagnosis of this anomaly and its venous phase reveals dysgenesis of the galenic drainage as well as of the dural sinuses.


[Continuous tissue fibrinolytic activity of the large bowel and its effect on wound healing]. 1. Fibrinolytic activity of colonic tissue samples rapidly decreased after wounding, independent of the plasminogen content of the plates. 2. Resorption of aprotinin into the colonic wall after IP application was found to be minimal. Bursting pressures and wall tensions were not altered by the drug.


[The effect of the spleen on tumor growth in mouse lines with various spleen sizes]. Selectively raised laboratory mice differ according to spleen size in their immunologic behavior against various tumors. A small spleen and splenectomy reduce tumor growth, whereas a large spleen or additional transfer of tumor antigen-specific spleen cells ("suppressor cells") stimulate tumor incidence.


[Therapy of low-output syndrome in patients following cardiopulmonary bypass with sodium nitroprusside and dopamine]. In 12 patients with low output after open-heart surgery the therapeutic effect of vasodilatation with sodium nitroprusside (SNP) and dopamine was studied. All patients underwent aortocoronary bypass operations. After cardiopulmonary bypass, the cardiac index (CI) was 2.2 liters/min.m2. The pulmonary wedge pressure (PCWP) was about 20 mm Hg. Application of SNP lowered mean arterial pressure to 82 and PCWP to 13 mm Hg. Then PCWP was elevated to the control level by tranfusion of blood. This therapy increased CI by about 30% without positive inotropic intervention. Additional application of 5 micrograms dopamine/kg.min improved the CI to 3.8 liters/min.m2.


[Quantitative and functional response of a lymphatic subpopulation during adjuvant intermittent chemo-immunotherapy in breast cancer]. In this study, an attempt was made to describe and evaluate in vitro immune parameters in patients with breast cancer undergoing modified radical mastectomy and adjuvant chemoimmunotherapy. T and B lymphocytes and their in vitro functions were markedly reduced by intermittent combination chemotherapy with adriamycin and cyclophosphamide. Laevamisole was not found to influence immune parameters, neither when given between chemotherapy treatments nor when given after chemotherapy. Lymphocytes expressing Fc receptors and mediating antibody-dependent cell-mediated cytotoxicity were less affected and were even found to be elevated in some patients prior to initiation of therapy. Whether or not antibody-dependent cell-mediated cytotoxicity plays a role in patient defense against tumors remains to be investigated.


Immunologic changes in regional lymph nodes of melanoma patients. In tumor-draining lymph nodes, humoral immunity is diverted from individually specific, cytotoxic anti-membrane AB to less specific anti-cytoplasmic AB with progression of the disease. Auto-anti-anti-bodies and suppressor cells seem to be involved in  the failure of control of metastasis.


[Current aspects in the endothelialization of artificial prostheses (experimental studies in rats)]. The interaction between the blood and the inner prosthetic wall after grafting with the autoalloplastic SPARKS prostheses was examined by light and electron microscopy as well as by autoradiography. The results indicate that intercellular bridges are missing, and therefore that those cells that line the inner surface of the prosthesis are no real endothelial cells, as observed with the electron microscope. The authoradiographic findings demonstrate that blood monocytes definitely contribute to the construction of the new inner surface. We showed that although there is a possibility of transformation, the results is not a real endothelial cell, as shown by electron microscope. Nevertheless this cell apparently can fulfil its function.


[A new therapeutic concept for the selection of liver cirrhotics with recurrent bleeding esophageal varices for selective shunt]. Analysis was made of almost 600 patients who received shunt operations between January 1, 1952 and January 1, 1975 because of liver cirrhosis and repeated bleeding from gastroesophageal varices. The emergency portosystemic shunt was abandoned owing to its 50% lethality; the portocaval shunt was also discontinued, because of an encephalopathy rate of 25%. The splenorenal shunt (Linton) and coronary-caval shunt (Gütgemann) gave comparatively satisfactory results. A more recent introduction was the mesocaval interposition shunt (Drapanas). We also developed new criteria of indication for a shunt operation: elective shunt, liver volume 1000--2500 ml, portal vein perfusion 15%--40%, avoidance of celiac trunk and hepatic artery stenosis. Using only the types of shunt operation and criteria of indication here recommended, lethality among 65 patients operated on between January 1, 1975 and July 1, 1978 was only 6%, delayed lethality only 3%. The rate of encephalopathy was reduced to 5%. The 5-year life expectancy should increase to more than 70%. Thus, support is provided for the proposed therapy concept and criteria for shunt indication.


Improved sensitivity of the BTPABA pancreatic function test in animals with meals of raw egg white. An indirect exocrine pancreatic function test (PFT) which measures the ability of a test to hydrolyze a chymotrypsin-labile peptide (N-benzoyl-L-tyrosyl-PABA), was carried out in rats and swine with simulated partial exocrine pancreatic insufficiency. When spray-dried egg white (SDEW), which contains an inhibitor of chymotrypsin, was administered as a test meal with the PFT, the degree of pancreatic insufficiency was more pronounced. The results suggest that SDEW or raw egg while may be useful as a test meal to be given in conjunction with the PFT in humans in order to accentuate moderate degrees of pancreatic insufficiency and improve the sensitivity of this indirect test of pancreatic function.


Gastrointestinal bleeding due to chronic portal vein thrombosis in ulcerative colitis. The authors report the case of a patient suffering from ulcerative colitis, who had several episodes of digestive hemorrhage due to portal hypertension. Portal hypertension was secondary to chronic portal vein thrombosis. This diagnosis was made on the venous phase of celiac and mesenteric angiography. The authors review the published cases of ulcerative colitis with portal vein thrombosis and discuss the possible etiologic factors: hypercoagulability, thrombocytosis, and intraabdominal sepsis.


Gastric infarction: a complication of selective vasopressin infusion. This report describes a case of massive gastric hemorrhage, initially controlled by selective arterial vasopressin infusion. Infusion was followed by extensive necrosis of the gastric wall which necessitated subtotal gastrectomy. Gastric necrosis following arterial infusion is rare and in this case appears to be due to migration of the infusion catheter into a peripheral branch of the left gastric artery in a patient whose gastric circulation had been compromised by prior surgery. The complications related to the use of arterial infusion for the control of gastric hemorrhage are discussed and the literature is reviewed.


Hepatic infarction and gallbladder necrosis complicating arterial embolization for bleeding duodenal ulcer. A case of severe duodenal hemorrhage in a septic renal allograft recipient is presented in which successful occlusion of the gastroduodenal artery by Gelfoam emboli also resulted in severe hepatic infarction and gallbladder necrosis. These complications were caused by reflux of emboli from the gastroduodenal artery into the distal branches of the hepatic artery.


A procedure for measuring gastric bleeding caused by drugs. Seven subjects were given one day's treatment with full doses of either aspirin, ibuprofen, or placebo, and then their stomachs were washed out three times at intervals of 10 min, for five successive days. The blood in the recoveries was estimated chemically. After compensating for gastric emptying, the rate of bleeding was expressed as ml blood per day. Relative to placebo, one day's treatment with aspirin increased the rate of blood loss significantly at day 1, median 2.7 ml/day, and not thereafter. A corresponding dose of ibuprofen did not produce any significant bleeding. The procedure gives specific information about gastric bleeding. It can measure rates of bleeding down to 0.01 ml/day.


Herpes simplex esophagitis: a cause of upper-gastrointestinal bleeding. Two patients with hemorrhagic esophagitis secondary to esophageal invasion with herpes simplex virus, type 1, are reported. Microscopic examination of the esophageal mucosa revealed multinucleated cells and intranuclear inclusions which are typical of herpes simplex infection. Herpes virus was cultured from each patient. Thus, hemorrhagic esophagitis due to esophageal invasion by herpes simplex virus may be a more frequent cause of upper-gastrointestinal bleeding than previously recognized.


Factitial bleeding: successful management with psychotherapy. A young female nurse presented with unusual upper and lower-gastrointestinal bleeding, shown to be factitial. Following detection, she was successfully confronted and treated with psychotherapy. A plan for successful management of the Munchausen syndrome is discussed.


[Severe megaloblastic anaemia by triamterene in a patient with alcoholic liver cirrhosis (author's transl)]. Mucosal ulceration and severe bone-marrow insufficiency with marked megaloblastic transformation occurred during treatment with triamterene in a patient with decompensated alcoholic liver cirrhosis and malnutrition. When the triamterene-containing preparation was stopped and folinic acid administered the haematological picture improved, but the patient died, with signs of hepatocellular insufficiency, of gastro-intestinal bleeding. The serum folic-acid level was markedly reduced due to the chronic malnutrition, while the vitamin B12 level was within normal limits. This observation indicates that when the pool of folic-acid coenzymes is reduced, triamterene can cause megaloblastic anaemia due to its folic-acid antagonism. Triamterene should, therefore, be given to patients with borderline folic-acid reservoirs, chronic alcoholism or during pregnancy, only under careful serial control of the blood picture.


[Necrotizing fascitis (author's transl)]. Necrotizing fasciitis is a rare and little known infectious disease of the skin with a mortality, despite modern antibiotic treatment, of 25--50%. A case of the disease in a 63-year-old woman is described. Treatment consisted of wide incision and drainage of the subcutaneous abscess, with regression of the clinical signs and symptoms. There has been no recurrence. Determination of the anti-DN-ase-B titre was of diagnostic value in this instance.


Effect of lidoflazine on membrane currents and contraction in voltage-clamped frog atrial fibers. The effect of lidoflazine on action potential, membrane currents and contraction of frog atrial fibers was tested using the double sucrose voltage clamp technique. Lidoflazine was found to decrease the sodium conductivity of the heart cell membrane, probably by blocking the sodium channels. The availability of the sodium system at resting potential was slightly enlarged by lidoflazine and the recovery from inactivation was prolonged in most of the preparations tested. A small decrease of the slow inward current and a reduction of phasic and tonic tension was observed. The outward current at higher depolarizations was increased by lidoflazine resulting in a shortened action potential duration. The data suggest that lidoflazine's antifibrillatory properties are less pronounced than those of classical antiarrhythmic agents; but the slight antifibrillatory and negative inotropic effect might be helpful in the treatment of angina pectoris.


Effect of diazepam on cerebral 5-hydroxytryptamine synthesis. In the brains of normal and reserpinized rats both diazepam and amino-oxyacetic acid (AOAA) decreased the 5-hydroxytryptophan (5HTP) accumulation induced by the decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD 1015). In reserpinized animals, the action of diazepam was antagonized by picrotoxin and bicuculline in doses which did not themselves influence the NSD 1015-induced rise in 5HTP. In conclusion, diazepam probably depresses 5HT synthesis via GABAergic mechanisms and this effect is not dependent on a functionally intact monoaminergic synaptic transmission.


Vestibular function of saccule in cats as indicated by the response of Deiters' nucleus to static tilts. In ketamine anesthetized cats, the contralateral labyrinth, the ipsilateral utricle, the ipsilateral horizontal and anterior semicircular canal nerves were completely destroyed, leaving the ipsilateral saccule intact. Neurons in the Deiters' nucleus, driven by electrical stimulation of the superior saccule, were responsive to static tilts in the antero-posterior direction. Results suggest that the saccule is capable of conveying information on head positional changes in the antero-posterior direction and that such information is retained at the level of the Deiters' nucleus.


[Effect of the orbital-frontal cortex on several autonomic functions]. It is not only the cortex of orbito-insular complex ("vagal" zone) but also the proreal cortex (frontal zone) which take part in regulation of respiration, blood pressure, rhythmical heart activity. Cortico-fugal impulses spread along two tracts from the proreal gyrus: to the trunk vegetative centers directly and indirectly -- through the orbital gyrus. The experiments with combined destruction of main efferent tracts of the orbito--frontal cortex showed the forebrain medial bundle to be the principal morphological tract of the orbito-frontal cortex projecting to the trunk vegetative centers.


[Study of the "stimulus--excitation" function in the peripheral portion of the frog taste analyzer]. The intensity of glossopharyngeal nerve afferent discharges in the frog was studied during stimulation of gustatory receptors by caffeine, acetic acid, saccharose and sodium chloride ranging widely in the concentration changes. It was shown, that the function "stimulus-exitation" for the summary discharges in response on the coffeine and acetic acid was being logaryphmic. The character of off-effects dependence on the concentration of bitter and sour stimuli. Was proved to be the same. The curve "stimulus-exitation" for the saccharose was "S" shaped, but for the sodium chloride it might be described by the power function with the exponent equal 0,8.


[Effect of the rest interval on the contractile activity of the myocardium]. Isolated strips of the heart auricles and ventricles of frogs at high stimulation frequencies revealed rest potentiation which depended both on the stimulation rhythm and on the duration of rest interval. Amphibians as well as warm-blooded animals and fish seem to display a possibility of Ca++ entering a cell during the period of rest via non-electrogenic calcium canals, but in amphibians this mechanism of the myocardium activation is compansatory, rather.


[Radioimmunological detection of soluble immune complexes in serum (author's transl)]. Immune complexes could be measured in sera with the use of plastfixed Clq and 125J-labeled anti-Ig-antibody. The sensitivity of the system is 0.1 microgram aggregated human IgG, the working range is between 0.1 and 10 micrograms per 0.5 ml. In 58% of the sera from patients with systemic lupus erythematosus was found an increase in the immune complex content.


Effects of antiinflammatory agents and prostaglandins on acid and bicarbonate secretions in the amphibian-isolated gastric mucosa. Effects of antiinflammatory agents and prostaglandins on H+ and HCO-3 secretions and electrical properties were investigated in the amphibian-isolated gastric mucosa. Gastric HCO-3 transport was studied in Rana temporaria fundus, in which H+ secretion had been inhibited with the histamine H2-receptor antagonists metiamide or cimetidine (10(-3) M), and in Necturus antrum, which secreted HCO-3 spontaneously. Hydrocortisone (100-500 microgram/ml) had no effect on H+ or HCO-3 secretion in the fundus. Indomethacin (10(-4) M) was a considerably more potent inhibitor of HCO-3 secretion than of H+ secretion in the fundus and also inhibited HCO-3 transport in the antrum. Fenclofenac (3 x 10(-3) M) almost abolished fundic HCO-3 transport and also depressed H+ secretion. There was a marked fall in transmucosal potential difference and a decrease in electrical resistance in fenclofenac-treated mucosae whereas indomethacin had less effect on electrical properties at the concentrations used here. The prostaglandins, E2, 16,16-dimethyl E2 and I2 all inhibited H+ secretion but only 16,16-dimethyl E2 stimulated HCO-3 secretion. The inhibitory action of indomethacin on HCO-3 secretion was prevented by co-administration of 16,16-dimethyl PGE2 (10(-6) M). It is proposed that the inhibitory action of nonsteroidal antiinflammatory drugs and the stimulatory action of some prostaglandins on HCO-3 secretion contributes to their ulcerogenic and anti-ulcer actions on the gastric mucosa.


Characteristics of isolated intestinal mucosal lymphoid cells in inflammatory bowel disease. Immunologic characteristics of intestinal mucosal lymphoid cells from patients with inflammatory bowel disease and controls have been compared. Mononuclear cells isolated by enzymatic means from intestinal tissues involved with inflammatory bowel disease were present in greater numbers, with increased proportions of macrophages and B-lymphocytes, particularly cells bearing intrinsic membrane immunoglobulin G. Synthesis of immunoglobulin G, measured by radioimmunoassay, was increased tenfold in inflammatory bowel disease, while immunoglobulin A synthesis per 10(6) cells was unchanged. "Null" or K-lymphocytes were absent from all populations, and antibody-dependent cellular cytotoxicity (a K-cell-mediated function) was not demonstrable. Taken together, the results fail to support a role for antibody-dependent cellular cytotoxicity or a defect in secretory immunoglobulin A, but rather focus attention upon possible forms of immunoglobulin G-mediated tissue damage in the pathogenesis or perpetuation of inflammatory bowel disease.


A controlled comparison of continuous intraarterial and intravenous infusions of vasopressin in hemorrhage from esophageal varices. Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown to be effective in controlling hemorrhage from esophagogastric varices. Intravenous infusions of vasopressin (IVV), which can be initiated rapidly and require less sophisticated equipment and personnel, have also been reported to control variceal hemorrhage. We undertook a controlled clinical trial to compare these two routes of administration. Twenty-two cirrhotic patients with massive hemorrhage from varices were randomized to receive either IVV or IAV. Intraarterial vasopressin was begun at 0.1 U/min and increased progressively as needed to 0.2, 0.3, 0.4, and 0.5 U/min. Intravenous vasopressin was begun at 0.3 U/min and increased progressively as needed to 0.6, 0.9, 1.2, and 1.5 U/min. Hemorrhage was controlled in 5 of 10 episodes (50%) with IVV and in 6 of 12 episodes (50%) with IAV. Seven of the ten episodes treated with IVV (70%) ended fatally compared with 9 of 12 treated with IAV (75%). Side-effects and complications occurred with similar frequency in the two groups. The two routes of administration are equal in effects, side-effects, and complications. We recommend that IVV, which can be administered more easily, be given a brief therapeutic trial early in the management of hemorrhage from varices.


Mesenteric vascular occlusion and varices complicating midgut malrotation. Long-standing complete obstruction of the superior mesenteric artery and vein and recurrent gastrointestinal bleeding from varices within the bowel were encountered in a child as a complication of midgut malrotation and volvulus. This condition is unusual, but should be considered in cases of gastrointestinal bleeding, or when small bowel biopsy is contemplated for the evaluation of diarrhea or malabsorption in cases of malrotation.


Active and suppressor T cells: diminution in a patient with dyskeratosis congenita and in first-degree relatives. Active, total and nonspecific suppressor T cells were studied in a 15-year-old black male with dyskeratosis congenita syndrome, a precancerous mucosal disease, and in 7 siblings and several other relatives in three generations. The propositus and 1 elder sister, products of a second-cousin marriage, died with dyskeratosis congenita. The mother had dermatomyositis, and the maternal grandmother and her sister reportedly had rheumatoid arthritis. Studies of available siblings, father, and grandparents revealed a high incidence of deficiency in number of active and/or suppressor T cells, sometimes severe enough to result in a decrease in total T cells. The patient had many stigmata of precocious aging, as did the sibling who died with the same syndrome. The laboratory data suggest that a defect in cell-mediated immunity, involving mainly or exclusively suppressor T cells, is associated with, and is presumably the cause of, precocious aging; perhaps an abiotrophy in this cell subpopulation results in physiologic aging.


Effects of fusion in pairs on the development of anurans Rana dalmatina and Rana esculenta. Of 252 heterospecific, parabiotic pairs of Rana dalmatina and R. esculenta, fused during embryonic life, 87 died because the larva of R. dalmatina died at the beginning of its circulation. Later 89 pairs died when the R. esculenta larva died suddenly at the beginning of its independent feeding. Seventy-one pairs survived at the end of the metamorphic climax. Death in the first case is considered to result from some toxic effect, in the second from an immunological reaction. In the surviving pairs the duration of larval development in the rapidly developing species, i.e., R. dalmatina, was extended from two months to about four months, and in the more slowly developing species, i.e., R. esculenta, was reduced from about five months to about four. These changes in developmental rates are discussed in terms of changes in the concentration of the hormones controlling the rate of development due, in turn, to the parabiosis of embryos with different genetic constitution.


[Combined surgical treatment for coronary heart disease as well as heart valve diseases and carotid artery stenosis]. This is an account on combined procedures in 124 patients suffering from arteriosclerotic vessel disease. In order to judge the proceedings and the results the patients were divided up into two groups. in 15 patients (group I) a carotid endarterectomy combined with an aorto-coronary bypass operation was performed; once a subclavian artery stenosis was resected at the same time. One patient of that group died after 31 days (7%). In group II 108 heart valve operations were performed together with a coronary artery revascularisation. Early and late mortality divided up as follows: aortic stenosis 6/44 (14%) respectively 2/44 (5%); aortic insufficiency 1/14 (7%) resp. 0; combined aortic disease 1/8 )13%) resp. 0; mitral stenosis 1/11 (9%) resp. 0; mitral insufficiency 6/26 (23%) resp. 2/26 (8%); combined mitral valve disease 1/2 (50%) resp. 0; three times both valves (aorta, mitral) were replaced without mortality. In our opinion combined procedures, resection of supraaortic artery stenosis respectively cardiac valve operations and aorto-coronary bypass are indicated especially since the functional long-term results are excellent. Though one should consider the high operative risk in patients with mitral insufficiency and combined mitral valve disease.


[The pathophysiology of tourniquet shock]. In rabbits a tourniquet shock was produced by 4-hour unilateral ischemia of one hind leg. By measuring the tissue oxygen tension on the surface of the ischemically damaged muscle, the liver and kidney the regional rate of perfusion of these organs in the state of shock was investigated. Additionally morphological examinations of muscle, liver, kidney and heart were carried out. In therapeutic trials with a proteinase inhibitor (Trasylol), prednisolone and streptokinase, Trasylol proved to prolong the time of survival significantly.


An integrated system for computerized patient records. A community mental health--mental retardation center developed a computerized problem-oriented record system specifically for use in a full-service community mental health center. It is based on an integrated set of clinical forms that covers all levels of a client's involvement with the center, beginning with his contact as a prospective client and including intake, treatment planning, treatment, and discharge. Most of the forms are computer-generated. Special features of the system include its capability to prompt the clinician about scheduled treatment sessions, follow-ups, and other activities and a scale that rates the client's level of functioning and is keyed to a specially developed master problem list. The authors describe each of the clinical forms used in the system.


Stimulation of murine bone-marrow colony formation by conditioned medium from human fetal liver cells. A substance that stimulates growth of colonies of mononuclear granulocytic cells derived from the bone marrow of mice was produced by incubating fetal liver cells (conditioned medium). This substance appears to have the same properties described elsewhere as colony-stimulating factor (CSF). The enhanced stimulatory ability of the conditioned medium from human fetal liver cells compared to medium not conditioned suggests that fetal liver is a potent source of colony-stimulating factor.


Role of complement in the expression of delayed-type hypersensitivity in rats: studies with cobra venom factor. The hypothesis was tested that delayed-type hypersensitivity (DTH) to the complement-activating bacterium Listeria monocytogenes is initiated by complement-derived mediators that attract sensitized lymphocytes to reaction sites. To this end DTH and acquired resistance to L. monocytogenes were measured in rats injected with cobra venom factor, a potent inactivator of C3. Treatment with cobra venom factor reduced the hemolytic power of serum to less than 0.5% of the control value. Such decomplemented animals expressed both DTH and antimicrobial resistance, although expression of DTH was reduced (ca. 50%) when compared with complement-sufficient controls. The observed depression of DTH in cobra venom factor-treated rats was associated with a reduction in the number of recently activated lymphocytes (lymphoblasts) and macrophages that accumulated in DTH reaction sites. The above findings are explained, in part, by inhibition of inflammation during the early postinduction period. Supporting evidence came from measurements of labeled lymphoblast sequestration in saline injection sites and the slower accumulation of macrophages in nitrocellulose filters that were implanted subcutaneously in complement-depleted rats. The ability of cobra venom factor-treated rats to express DTH and protect themselves against a Listeria challenge seems to exclude C3-dependent factors as essential mediators in the attraction of antigen-reactive lymphocytes to reaction sites.


Response of congenitally athymic (nude) and phenotypically normal mice to Cryptococcus neoformans infection. A Cryptococcus neoformans infection in congenitally athymic (nude) mice and phenotypically normal heterozygote BALB/c mice was used to determine how T lymphocyte-deficient mice compared with normal mice in restricting proliferation of C. neoformans and to determine whether a correlation exists between delayed-type hypersensitivity and resistance to C. neoformans. Although nude mice displayed the ability to maintain cryptococcal population levels lower than did the phenotypically normal animals during the first 14 days of infection, the resistance was not sufficient to control the infection during the remainder of the 35-day experimental period. Heterozygote mice began to demonstrate positive delayed-type hypersensitivity responses by day 14 postinfection; however, nude mice were unable to mount delayed-type hypersensitivity responses. The appearance of the delayed-type hypersensitivity response in the heterozygote mice was concomitant with the reduced rate of proliferation of C. neoformans observed in those animals from days 14 to 35. Because anticryptococcal antibody titers and cryptococcal antigen levels were equivalent in both groups of mice, T-lymphocyte function was considered to be responsible for the resistance observed in the heterozygote mice. The mechanism by which cryptococcal populations were reduced was not addressed; however, the mouse model system used in these studies would be an ideal tool for studying those mechanisms. Nude mice were able to produce antibodies against cryptococcal cells, indicating that at least one component of C. neoformans is a T-independent antigen. The antibody response was predominantly immunoglobulin M in nude and heterozygote mice. Cryptococcal antigen levels were extremely high in both groups of animals and appeared to increase as C. neoformans cell numbers increased.


Effects of cannabinoids on host resistance to Listeria monocytogenes and herpes simplex virus. Previous investigations from our laboratories have demonstrated that cannabinoids possess immunosuppressive properties. The present studies were designed to determine whether these agents decrease host resistance to infections with Listeria monocytogenes and herpes simplex virus type 2. Host resistance was measured by changes in the 50% lethal dose of the pathogen in cannabinoid-treated and control mice. The effect of cannabinoids on resistance to L. monocytogens was dose dependent. Delta-9-tetrhydrocannabinol at doses of 38, 75, and 150 mg/kg suppressed resistance to infection by 10-, 17-, and 657-fold, respectively. Marijuana extract was less active but significantly reduced resistance to L. moncytogenes at all tested doses. Resistance to systemic herpes simplex virus type 2 infection was decreased 96-fold by delta-9-tetrahydrocannabinol, although marijuana extract was inactive. The doses and regimen of treatment with cannabinoids that produced significant decreases in host resistance were similar to those which caused suppression of delayed-type hypersensitivity to sheep erythrocytes. The possible mechanisms and public health aspects of the decreased host resistance produced by marijuana extract and its cannabinoids are discussed.


Mechanisms of resistance to infection with Coccidioides immitis in mice. Serum from vaccinated mice was ineffective in neutralizing the infectivity of arthrospores of Coccidioides immitis for recipient mice. However, a T-cell-enriched lymphocyte population was effective in preventing a lethal infection. Spleen cells from immune mice were passaged through nylon wool columns resulting in a T-cell enriched, B-cell-depleted population as shown by the susceptibility of the cell population to anti-theta serum and the inability of the cells to transfer adoptively an immune response to ovalbumin. Whereas transfer of 5 x 10(7) unfractionated immune spleen cells was required to protect 100% of the recipients against a lethal infection with C. immitis, 7 x 10(6) T-cell-enriched immune spleen cells were sufficient for the same level of protection. Thus, transfer of resistance to infection was achieved with fewer cells after the removal of B cells from the transferred spleen cells. The results confirm that T cells are crucial in transferring resistance against infection with C. immitis in mice.


Mitogenic activity of staphylococcal peptidoglycan. Staphylococcus aureus peptidoglycan displayed a marked dose-dependent mitogenic activity for mouse splenocytes and human peripheral blood lymphocytes in vitro, as measured by increased [3H]thymidine incorporation. Similarly it was mitogenic for athymic nude mouse spleen cells, whereas no blastogenic effect was observed in T cell-enriched and B cell-depleted mouse lymphocyte cultures. These data demonstrate that peptidoglycan-responding cells in mouse spleen cell cultures are B lymphocytes.


Immunoregulatory responses in experimental disseminated histoplasmosis: depression of T-cell-dependent and T-effectory responses by activation of splenic suppressor cells. The cellular immune responses of mice with disseminated histoplasmosis are markedly diminished in association with the generation of potent immunosuppressor activity by spleen cells. The zenith of suppressor activity was observed during most active infection, from 1 to 3 weeks after inoculation. During this time there was: (i) depression of the delayed-type hypersensitivity response to sheep erythrocytes and histoplasmin, (ii) impairment of concanavalin A- and histoplasmin-induced blastogenic transformations by splenocytes in vitro, (iii) depressed cytotoxic activity of spleen cells from infected mice, and (iv) marked suppression by splenocytes from infected mice of the primary antibody response to sheep erythrocytes by normal spleen cell cultures. With resolution of the infection by week 8, there was a shift of immunoregulatory function from dominant suppressor activity to expression of helper activity. At this time, delayed-type hypersensitivity responses to the above antigens were vigorous; furthermore, the cytotoxic activity and plaque-forming cell response of splenocytes from 8-week-infected mice were equal to or greater than normal control values. The shift in the immunoregulatory response from a suppressor to a helper mode indicated that the net amount of help or suppression measured at any given time during infection represented the algebraic sum of both helper and suppressor activities mediated by different populations or subpopulations of cells within the splenic microenvironment of infected mice.


Adjuvant activity of 6-O-mycoloyl derivatives of N-acetylmuramyl-L-seryl-D-isoglutamine and related compounds in mice and guinea pigs. Adjuvant and antitumor activities of synthetic-6-O-mycoloyl-N-acetylmuramyl-L-seryl-D-isoglutamine and 6-O-mycoloyl-N-acetylmuramyl-glycyl-D-isoglutamine were examined in comparison with those of 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine. Synthetic 6-O-mycoloyl-N-acetylmuramyl-L-seryl-D-isoglutamine was active as an adjuvant for the induction of delayed-type hypersensitivity to m-[4-(4'-arsono-phenylazo)-phenyl]-N-acetyl-L-tyrosine in guinea pigs and for cell-mediated cytotoxicity in allogeneic mice. 6-O-mycoloyl-N-acetylmuramyl-glycyl-D-isoglutamine was inactive as an adjuvant for the induction of delayed-type hypersensitivity in guinea pigs; however, it was active for cell-mediated cytotoxicity in allogeneic mice. 6-O-mycoloyl-N-acetylmuramyl-L-seryl-D-isoglutamine and 6-O-mycoloyl-N-acetylmuramyl-glycyl-D-isoglutamine were not pyrogenic in rabbits. The antitumor activity of these 6-O-mycoloyl-N-acetylmuramyldipeptides was examined preliminarily by using transplantable syngeneic mouse tumors.


Infectious agents in immunodeficient murine models: pathogenicity of Actinomyces israelii serotype I in congenitally athymic (nude) mice. Nude (Nu/Nu) and heterozygous (NU/+) mice were infected with Actinomyces israelii serotype I by either intranasal instillation or intravenous injection. Lung clearance data and 50% lethal dose values indicated that T-lymphocytes were not necessary for pulmonary clearance or prevention of systemic actinomycosis. However, T-lymphocyte deficiency may play a role in the localized cervicofacial form of actinomycosis.


Protein synthesis and secretion by activated human lymphocytes. Human peripheral blood mononuclear cells showed increased synthesis and secretion of protein in response to stimulation by mitogens. Protein secretion in response to concanavalin A (Con A) correlated with cellular proliferation and originated from the proliferating cells. Selective depletion of either B lymphocytes or monocytes did not lead to a reduction in the total protein secreted, suggesting that the T lymphocyte was the cell contributing most of the synthetic activity. It is concluded that the measurement of newly synthesized and secreted protein by Con A activated mononuclear cells is a measurement of the T-lymphocyte response.


Predicted secondary structures of four penicillin beta-lactamases and a comparison with two lysozymes. We have predicted the secondary structures of four beta-lactamases (Bacillus cereus, Bacillus licheniformis, Staphylococcus aureus, and Escherichia coli R-TEM) by the statistical method of Chou & Fasman as well as by the information theory method of Garnier et al. The secondary structures of all four beta-lactamases are of the alpha/beta type (Levitt & Chothia's nomenclature), with helices at N- and C-termini. There are about eight short regions each of alpha-helical (30--50%) and beta-strand (10--20%) structure separated by about 20 reverse turns. The conformation of the Gram-positive and Gram-negative beta-lactamases are generally similar although a few differences are predicted between the S.aureus and E.coli structures. Surprisingly, the two bacilli structures differ significantly in three short regions. In all four enzymes the region near the catalytically-implicated tyrosine has similar secondary structure. The secondary structure of hen egg white lysozyme, a penicillin-binding enzyme, as well as T4 phage lysozyme, has similarities to the N-terminal half of the penicillin-destroying beta-lactamases.


Calculation of the dose-rate dependence of the decentric yield after Co gamma-irradiation of human lymphocytes. The dose relation for dicentrics after in vitro Co gamma-irradiation of human lymphocytes with dose rates of 50 and 1.7 rad/min fit the linear-quadratic function y=alpha D + beta D2. Compared with 50 rad/min, after 1.7 rad/min alpha D was unchanged, whereas beta D2 was decreased by 36 percent. By applying the mean interaction time t approximate to 110 min for primary breaks, determined in an earlier experiment, and Lea's G-function, a theoretical dose relation for 1.7 rad/min can be calculated from the corresponding experimental curve. Thus, from calibration curves with conventional dose rates dose-effect curves for low dose rates can be derived without the need for time-consuming chromosome analyses.


The role of cortisone acetate in liver RNA synthesis of gamma-irradiated rats. The possible role of induced endogenous glucocorticoid levels stimulated by ionizing radiation and their subsequent effect on rat-liver RNA was investigated in adrenalectomized rats using an intraperitoneal injection of cortisone acetate immediately prior to exposure to gamma-radiation (1800 rad). Adrenalectomized rats were divided into four groups: (1) control rats, (2) irradiated rats, (3) nonirradiated rats treated with cortisone acetate (10 mg/rat), and (4) irradiated rats which received cortisone acetate immediately before irradiation. Newly synthesized RNA was measured by an intraperitoneal injection of 8 muCi (6-14C) orotic acid either immediately after irradiation or 40 min prior to killing. All the rats were killed 6 hours post-irradiation. The results of these investigations indicate that (1) newly synthesized (40 min labelling) RNA increased in irradiated adrenal-intact rats, but not in adrenalectomized animals; (2) cortisone acetate by itself stimulated RNA synthesis whether the radioactive precursor was administered 6 hours of 40 min prior to killing; and (3) irradiation of adrenalectomized rats pre-treated with cortisone acetate induced more RNA synthesis than did cortisone alone. The results of this study support the suggestion that ionizing radiation may induce rat-liver RNA synthesis, at least in part, via stimulated adrenal secretion of glucocorticoids.


Effects of ionizing radiation and partial hepatectomy on messenger RNA synthesis. Newly synthesized messenger RNA, as measured by a 40 min uptake of the radioactive precursor (6-14C) orotic acid, was studied in the regenerating livers of non-irradiated and gamma-irradiated (1800 rad) adrenal-intact and adrenalectomized rats 24 aand 48 hours after partial hepatectomy. Two groups of rats, one with and one without adrenal glands, were each divided into four subgroups: (1) control rats, (2) irradiated rats, (3) partially hepatectomized rats and (4) irradiated, partially hepatectomized rats. The radioactive profile of polyribosome formation and distribution was determined by sucrose density gradient centrifugation (10--40 per cent). The result of this study indicates that ionizing radiation decreases the synthesis of newly formed messenger RNA in re generating livers of adrenal-intact rats. However, adrenalectomy largely abolished that inhibition. These data suggest that the decrease in messenger RNA synthesis may be explained by the disturbance of adrenal hormones induced by partial hepatectomy and ionizing radiation.


Excision repair of gamma-ray-induced alkali-stable DNA lesions with the help of gamma-endonuclease from Micrococcus luteus. gamma-Endonuclease Y, an enzyme that hydrolyses phosphodiester bonds at alkalistable lesions in gamma-irradiated (N2, tris buffer) DNA, has been partially purified from Micrococcus luteus. The enzyme has a molecular weight of about 19 000, induces single-strand breaks with 3'OH-5'PO4 termini and contains endonuclease activity towards DNA treated with 7-bromomethylbenz(a)anthracene. gamma-Endonuclease Y induces breaks in OsO4-treated poly(dA-dT) and apparently is specific towards gamma-ray-induced base lesions of the t' type. The complete excision repair of gamma-endonuclease Y substrate sites has been performed in vitro by gamma-endonuclease Y, DNA polymerase and ligase.


The triplet-state charge-transfer reaction between p-nitroacetophenone and guanosine monophosphate: a possible mechanism for electron-affinic radiosensitization. Using flash photolysis it has been observed that the triplet state of p-nitroacetophenone reacts rapidly with guanosine monophosphate to give the p-nitroacetophenone radical anion, and presumably the guanine radical cation is also formed in this reaction. From this observation, it is predicted by theory that a similar reaction will occur between p-nitroacetophenone and the triplet state of guanosine monophosphate. Because guanine is excited to its triplet state when DNA is irradiated with X-rays, it is suggested that the charge transfer reaction between p-nitroacetophenone and the triplet state of guanine contributes to the radiosensitizing action of p-nitroacetophenone.