Effect of propranolol on the plasma cyclic AMP and cyclic GMP levels to massive doses of glucagon in euthyroid and hyperthyroid subjects. The plasma c-AMP level increases significantly in response to pharmacologica doses (1 mg i. v.) of glucaton. Beta blocking agents somewhat inhibit this increase in both euthyroid and hyperthyroid subjects. Catecholamine release elicited by glucagon thus plays some part in the response. In euthyroid subjects 2 microgram/kg glucagon still produces a significant increase in the plasma c-AMP concentration and propranolol fails to counteract this response. The c-AMP response elicited by identical doses of glucagon is more marked in hyperthyroid than in euthyroid subjects and can be somewhat reduced by propranolol. This indicates that in hyperthyroid patients even low doses of glucagon stimulate the release of catecholamines or enhance the responsiveness of beta receptors. The plasma c-GMP level increases in response to glucagon loading but in a lesser degree than does the c-AMP concentration. The response of c-GMP to glucagon is more protracted than the response of c-AMP and propranolol fails to counteract it.


Comparison of pituitary-adrenocortical response to hypoglycaemia and surgery. The hypothalamic-pituitary-adrenocortical (HPA) responses to the hypoglycaemic stimulus and to operation (laparotomy) are compared. The studies were carried out in eight patients who were subjected to insulin-induced hypoglycaemia on the day before elective abdominal surgery. Plasma corticotrophin (ACTH) and plasma cortisol concentration increases were virtually indentical during the two procedures, which suggests that hypoglycaemia and surgical trauma are comparable stress factors and that the hypoglycaemia test is reliable in predicting the HPA responses to major surgical trauma.


Origin and function of 'rod-like structures' in mitochondria. Both organ culture (choriallantoic membrane) of striped muscle from mouse diaphragm and freeze-drying of myocardial cells presented very characteristic structures in mitochondria. The organ culture evidence 'rod-like structures' in the intracristal spaces of the cristae mitochondriales. It is believed that these structures are the central apparatus responsible for mitochondrial division. On the other hand, the freeze-dried mitochondria presented neither intracristal spaces nor a space in the outer mitochondrial membrane. Because these spaces appeared only after fixation and dehydration, it is discussed if they are really artifacts. The mitochondrial cristae appearing as united structures after the freeze-drying process have been compared to the rod-like structures appearing intracristally after organ culture and conventional preparation techniques.


Ultrastructure of the nerve cells and fibres in the urinary bladder wall of the cat. The nerve elements in the urinary bladder of the cat were studied by electron microscopy. According to their ultrastructure, nerve cell somata can be classified into three types: the large cells with a cytoplasm rich in organelles, several processes and numerous synaptic contacts on their surface; the cytoplasm contained 80- 120-nm granulated vesicles. The second type is poor in cytoplasmic organelles and has very few processes and virtually no synaptic contacts on the soma. The third type contains numerous large 160- to 220-nm 'neurosecretory' vesicles in the cytoplasm. According to the morphology of the vesicle population, four types of nerve processes could be distinguished: Type a, with a dominant population of small (40-60 nm) agranular vesicles. These are thought to be sacral parasympathetic fibres. Type b, with small (40-60 nm) granular vesicles, which may be the noradrenergic sympathetic fibres. Type c, with 80- to 120-nm granulated vesicles, probably of local origin. Typed d, with large 160- to 220-nm 'neurosecretory' vesicles also of local origin. Different types of nerve fibres are converging on the local nerve cells. This suggests that the local circuits can play an important role in coordinating the function of the bladder. Therefore, ganglia may be considered as an elementary functional unit.


A simple large-scale method for separating closed circular form DNA by gel electrophoresis. The covalently closed form of circular duplex SV40 DNA was separated from the open and linear form of SV40 DNA by agarose gel electrophoresis in a large-scale gel system. The closed circular DNA was recovered from agarose gels by re-electrophoresing the gel slices. The recovery of DNA was about 70%. Electron microscopic analysis showed that the recovered DNA did not have doube- or single-stranded breaks. The recovered DNA can be used without further purification for electron microscopy, as a substrate for experiments using restriction endonuclease and as a template for in vitro RNA synthesis.


Metabolic studies and glucagon gel filtration pattern before and after surgery in a case of glucagonoma syndrome. A case of glucagonoma syndrome with necrolytic migratory erythema, glossitis, anemia, hyperglucagonemia and a malignant, pancreatic A-cell tumour in a 68-year-old male is described. Gel filtration of the highly elevated circulating glucagon immunoreactivity (2200 pg/ml) demonstrated 60% pancreatic glucagon and 30% "proglucagon". Metabolic studies before operation demonstrated suppression of the total plasma glucagon concentration on oral glucose tolerance test, unchanged total plasma glucagon concentration during intravenous glucose tolerance test and insulin-induced hypoglycemia. Administration of arginine was followed by a rise in both the pancreatic glucagon and the "proglucagon", whereas alanine increased only the pancreatic glucagon. The plasma somatostatin level was immeasurable preoperatively. Somatostatin infusion completely suppressed the release of the pancreatic glucagon but did not significantly affect the "proglucagon". After removal of the tumour the skin lesions disappeared and the total plasma glucagon values fell to normal levels (120 pg/ml). Also, other abnormal laboratory findings returned to normal, including the preoperatively observed renal glucosuria.


Differences in metabolic responses to beta-adrenergic stimulation after propranolol or metoprolol administration. Isoprenaline, or the beta 2-agonist terbutaline, was infused in healthy male volunteers and the plasma levels of insulin, glucose and free fatty acids (FFA) were determined. Saline, propranolol, or the selective beta 1-receptor antagonist, metoprolol, was administered i.v. prior to the infusion of the beta-stimulants. The two beta-receptor blockers inhibited isoprenaline-induced increase in chronotropy to about the same extent, while the effects on systolic and diastolic blood pressure were in accordance with a selective beta1-blocking effect of metoprolol and a non-selective beta-blocking action of propranolol. Quantitative differences were found between metoprolol and propranolol on the metabolic parameters. The effects can best be described in terms of beta 1- or beta 2-receptors, where effects on plasma FFA and glycerol levels seem to be mainly beta1-mediated. An apparent beta 2-mediated effect was found for insulin release and hepatic glucose output.


Peripheral neuropathy in monoclonal gammapathy with cryoglobulinemia and arteritis. We report a patient with IgM gammapathy, cryoglobulinemia, Raynaud's phenomena, purpura hyperglobulinemica of the legs and polyneuropathy. Endoneural vasculitis with infiltrations of eosinophilic and neutrophilic granulocytes and an extensive loss or Wallerian degeneration of myelinated nerve fibers were seen on histopathologic examination of a sural nerve biopsy specimen. The microscopic picture differed somewhat from that observed previously in cryoglobulinemic vasculitis. Although vasculitis is most often believed to represent an immunologically mediated lesion, we propose an alternate explanation, namely, that the disease manifestations in the present case were secondary to cold-induced effects of the cryoglobulin on the microcirculation.


Hormonal control of glycogen metabolism. In summary, we have presented evidence which relates to the action pathway of hormonal control of glycogen metabolism. In the case of insulin, there are changes demonstrable in the cyclic AMP-dependent protein kinase and also in the phosphoprotein phosphatase, under conditions where no direct relationship to either cyclic AMP or cyclic GMP levels are measurable. Therefore, a new unknown intermediate or second messenger system is again proposed. An insulin-generated labile compound(s) which inhibits the protein kinase has been discovered. This may function as an intermediate. Finally, the fact that the glycogen synthase system clearly differs from phosphorylase in its regulation by covalent phosphorylation is discussed. Synthase is now accepted as a multiply phosphorylated subunit, in contrast to phosphorylase which is singly phosphorylated. The inherent theoretical advantages of multiple phosphorylation over single phosphorylation are considered. The advantages of a multistate over a two-state model of enzyme interconversion are mentioned. The importance of the multiple phosphorylations interacting in a nonlinear manner with the control by cellular metabolites is in the explanation of how a small change in covalent phosphorylation signalled by a hormone can be translated in the cell milieu into a much larger change in rate.


Regulation of insulin receptors in normal and abnormal physiology in humans. Insulin receptors in human tissue undergo marked changes in both their concentration and their affinity for insulin. In general, alterations in receptor affinity are associated with rapidly changing metabolic environments and can occur within hours, whereas alterations in receptor concentration appear to require longer time periods for their induction. The association of a given type of receptor alteration (i.e., change in affinity or concentration) with a given clinical state indicates the presence of distinct modulators of the insulin-receptor interaction. We have presented evidence for 2 specific modulators, i.e., insulin itself and anti-insulin-receptor antibodies. In several clinical states, especially those associated with changes in receptor affinity, receptor alterations are unrelated to either ambient insulin levels or anti-receptor antibodies, suggesting the presence of several as yet unknown mediators of the insulin receptor. The direct metabolic consequences of these receptor events are not well established. In several states, the receptor alteration correlated quite well with the clinical sensitivity of the whole organism to insulin, indirectly implicating the receptor as the major control point for insulin sensitivity. In contrast, specific examples were cited in which receptor events are not consonant with observed biologic responses to insulin, thereby suggesting a predominance of postreceptor processes. Finally, it should be emphasized that the study of hormone receptors and their relationship to disease states is in the formative stage. With new and improved methodology we hope we will be able to investigate the entire pathway of insulin action at its target tissues, from the initial receptor binding to the final biologic effect.


Contrast enhanced CT scan and radionuclide brain scan in supratentorial gliomas. The preoperative contrast enhanced CT and radionuclide brain scans of 60 patients with surgically verified supratentorial astrocytomas were evaluated and compared. Results indicated that the mechanisms of contrast enhancement and radionuclide uptake are identical in the detection of supratentorial gliomas. These diagnostic methods apparently mirror the integrity of the blood-brain barrier and therefore can be useful in assessing the degree of malignancy of supratentorial gliomas. However, lesions with an intact blood-brain barrier will be missed with radionuclide imaging. These parenchymal abnormalities and/or the associated mass effect will be detected with contrast enhanced computed tomography. These findings firmly establish contrast enhanced computed tomography. These findings firmly establish contrast enhanced CT as the primary investigate tool in the suspected brain tumor.


Viral type A and type B hepatitis: morphology, biology, immunology and epidemiology--a review. Viral hepatitis is one of the most serious infectious diseases in the United States and is of great concern to the public health agencies, hospitals and research laboratories. Progress in our knowledge of this disease has been based on cooperation between specialists in many diverse scientific disciplines employing sophisticated scientific instruments and technics. Close cooperation between clinical pathologists and clinicians is of great importance in diagnosis. Biologic, immunologic, epidemiologic and morphologic studies have resulted in the demonstration that the disease is the result of infection with at least two different viruses, described as type A and type B hepatitis viruses. The first induces type A hepatitis (infectious or epidemic, or MS-2 strain) of longer incubation period, is transmitted parenterally and apparently by inhalation or ingestion of virus-containing material, by venereal means as well as by other means. Extremely sensitive methods are now available for the detection of hepatitis type B infection, based on the results of biochemical, biophysical and immunoelectronmicroscopic studies that resulted in our knowledge of structure and composition of type B virus, and our knowledge of host immune responses to the various components of this virus. Thus it is now known that two antigen-antibody systems are associated with viral hepatitis type B: hepatitis B surface antigen (HBsAg) and antibody (HBsAb) and hepatitis B core antigen (HBcAg) and antibody to it (HBcAb). The test for antibody to HBcAg appears to be a sensitive indicator of viral replication when only subdetectable amounts of HBsAg are circulated. Since the recent discovery and characterization of type A hepatitis virus, great progress has been made in our understanding of the relationship between type A and type B hepatitis viruses. There is no cross immunity between the two viruses, and as is now suspected, there may be at least another virus, described as type C virus, which may play an etiologic role in viral hepatitis. There is no doubt now that type A and type B hepatitis viruses can be transmitted to monkeys; type A to marmosets and chimpanzees, type B to chimpanzees and rhesus monkeys. The two viruses are serologically and immunologically distinct. This knowledge and the results of biologic experiments have laid a solid foundation of meaningful diagnostic procedures for the two types of viral hepatitis. Advances in biophysical and biochemical procedures of treatment of sera of hepatitis B patients have resulted in availability of viral material, noninfectious but immunogenic, for vaccination of chimpanzees. Protective efficacy trials of the vaccine in chimpanzees have demonstrated the vaccine to be fully protective against high doses of infectious hepatitis B virus...


Detection of viral hepatitis type A.

Detection of viral hepatitis type A. Several technics are currently being used to detect hepatitis type A antigen or its antibody. These include immunoelectronmicroscopy, immune adherence, and complement fixation. This paper describes another promising technic, a microtiter solid-phase immunoradiometric assay, in which hepatitis A antigen and antibody are detected. Such a method can be utilized for biochemical and biophysical analysis of purified particles, for the seroepidemiology of type A hepatitis, and as a means for monitoring hepatitis A antigen in cell cultures.


Genetic factors and autoimmunity in viral hepatitis. Whether a patient develops the HBsAg carrier state may depend on his genome. HBsAg subtypes may reflect the viral genome and may be of prognostic significance. Different subtypes predominate in different populations throughout the world. Altered immune response, as in patients with Down's syndrome, may increase the HBsAg carrier rate. Autoantibodies have been used to differentiate various types of hepatitis. There is an increased incidence of histocompatibility antigen HL-A1 and HL-A8 in patients who have chronic aggressive hepatitis. In primary hepatic carcinoma, the HBsAg carrier rate is increased. Because of the suggestion that neonatal hepatitis, biliary atresia and choledochal cyst may all result from infantile obstructive cholangiopathy, with the precise outcome depending on whether other conditions such as alpha 1-antitrypsin deficiency are also present, we have determined HBsAg in 166 children with a variety of diseases, among them Reye's syndrome, alpha 1-antitrypsin deficiency, and renal disorders. The HBsAg carrier rate in the sera of these patients was normal.


Isolation and characterization of hepatitis A virus. This paper presents current isolation technics of hepatitis A virus (HAV) from human and chimpanzee stool, liver, and bile specimens, as well as comparative characterizations of HAV buoyant density properties of human and chimpanzee stool-derived particles. In addition, methods designed for the extraction and purification of HAV from large samples of stool and liver tissues, including agar gel filtration, are discussed in detail.


Blast cell leukemia with IgM monoclonal gammopathy and intracytoplasmic vacuoles and Auer-body-like inclusions. A patient with acute leukemia and an IgM, kappa (IgMkappa) monoclonal gammopathy, Bence-Jones proteinuria, and blasts containing intracytoplasmic vacuoles with peroxidase-positive inclusions is discussed. Special stains, immunofluorescence, and electron microscopy suggested that the vacuoles were autophagosomes containing Auer-body-like inclusions, and that the blast cells did not synthesize the paraprotein. Chemotherapy with cyclophosphamide, vincristine, and prednisone resulted in transient improvement of the leukemia, but the level of the paraprotein was unchanged. Other case reports involving monoclonal gammopathy in association with acute leukemia are reviewed and contrasted with this case.


Radiometric detection of Haemophilus in simulated blood cultures. The radiometric detection of various Haemophilus species was studied in simulated blood cultures and in blood culture media without added blood, but supplemented with nicotinamide-adenine dinucleotide (NAD) or hemin, or both. Haemophilus aphrophilus was the only species studied that was radiometrically detectable without added blood or NAD. All other species studied (Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, and Haemophilus parahaemolyticus) required either added NAD, whole blood, or washed blood cells for growth and radiometric detection. The results of this study and extensive experience with clinical specimens show that the radiometric system is an effective means of rapidly detecting Haemophilus in blood cultures, but it is essential that it be used in conjunction with a subculture three to five days after inoculation.


Cytoplasmic hepatitis B surface antigen and the ground-glass appearance in hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) was identified with aldehyde fuchsin and immunoperoxidase stain and by immunofluorescence in malignant hepatocytes with a ground-glass appearance in only one needle biopsy specimen of a series of biopsies from 130 consecutive cases of hepatocellular carcinoma. The patient was 14 years old. HBsAg was identified by aldehyde fuchsin stain in nonmalignant hepatocytes of 48 (58%) of 83 biopsy specimens that contained nonmalignant liver tissue. The antigen was demonstrable in significantly greater proportions of cases in younger age groups. A similar but not identical age relationship has been found for hepatitis B antigenemia in Hong Kong. It appears that the ability to produce HBsAg declines with age. The usual absence of demonstrable HBsAg in cells of hepatocellular carcinoma may be due to a failure of this characteristic to survive into the malignant cell line, and so does not invalidate the possibility that the hepatitis B virus (HBV) plays a direct role in the pathogenesis of hepatocellular carcinoma. In exceptional circumstances, as when hepatocellular carcinoma appears at an unusually early age, this marker is identifiable in cells of the tumor.


Seasonality and the requirements for perpetuation and eradication of viruses in populations. Perpetuation of a virus in a population is distinct from the ability to persist in a cell culture or individual host. Parameters which determine perpetuation include: 1) the size of the population; 2) the turnover of the population; 3) the proportion of immunes in the population; 4) the transmissibility of the infection; and 5) the generation time between sequential infections. These parameters may be grouped into two composite factors which most directly affect transmission dynamics and perpetuation: (a) population turnover per generation period, and (b) transmissibility or the fraction of susceptibles infected per existing infection. Perpetuation in small populations usually requires either the ability to persist in individuals or rapid population turnover. Conversely, human viruses which initiate only acute infections require larger populations to persist. Seasonal variation in transmissibility can greatly increase the minimum population size in which persistence is possible, and we argue that the population size of 500,000 for measles persistence (described by Bartlett) is primarily a consequence of seasonal variation. Computer modelling can be used to examine the effect of changes in parameters which determine the seasonal cycle of virus perpetuation and fadeout. Finally, human infections are reviewed to indicate those which have been eradicated (smallpox), are on the threshold of eradication (poliomyelitis), are possibly eradicable (measles), or could be candidates for future efforts (hepatitis A and hepatitis B). In developing a strategy for eradication two points are of great potential utility: first, the seasonal trough should be exploited as a time for effective intervention; and, second, containment efforts should be directed at epidemiologically important population groupings such as schools.


Serologically active clinically quiescent systemic lupus erythematosus: a discordance between clinical and serologic features. The significance of abnormal serologic tests in systemic lupus erythematosus (SLE) in the absence of active clinical disease is unclear. In this report we describe a group of 14 patients with SLE in whom a discordance between clinical and serologic features was apparent. These patients had persistently positive lupus erythematosus preparations and antinuclear antibody tests, low serum complement levels and high levels of DNA binding. Their lymphocyte response to concanavalin A (Con A) mitogen was suppressed. They have been asymptomatic and have remained untreated for a mean of four and a quarter years.


Hormonal hyperthermia: endocrinologic causes of fever. Although hyperthermia is a component of many endocrine diseases, it is uncommon for fever to be the presenting manifestation of hormonal disorders. During a four year period we encountered six patients, hospitalized principally because of fever, who were found to have endocrine causes for the fever. In all, the admitting diagnosis was infection; three were suspected of having tuberculosis, two of gram-negative bacteremia and one of endocarditis. Except for asymptomatic bacteriuria in one patient (who remained febrile despite appropriate antibiotic therapy) infection was ruled out in all cases, and fever was attributed to "masked" thyrotoxicosis, triiodothyronine (T3) toxicosis, subacute thyroiditis, primary adrenal insufficiency, secondary adrenal insufficiency and pheochromocytoma. In a seventh patient, extreme pyrexia developed in the setting of the thyroid storm. The importance of hormonal mechanisms in thermoregulation is discussed.


Cytomegalovirus granulomatous hepatitis. Three patients with granulomatous hepatitis due to cytomegalovirus are described. They are compared to the three previously described patients with this disease, and their clinical and serologic characteristics are discussed. Similarities and differences between infectious mononucleosis (Epstein-Barr virus) and cytomegalovirus infections are adduced. That cytomegalovirus may be a cause of granulomatous hepatitis in the adult is stressed.


Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective. Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.


Adrenoleukodystrophy and adrenomyeloneuropathy associated with partial adrenal insufficiency in three generations of a kindred. Four cases of adrenoleukodystrophy (ALD) and one case of adrenomyeloneuropathy (AMN) have developed in a kindred over three generations demonstrating that AMN is a clinical variant of ALD. Pituitary-adrenal function studies were performed in 10 family members, including two affected males and four females identified as carriers of ALD/AMN. No pituitary-adrenal abnormality was found in the carriers. However, basal morning plasma adrenocorticotropic hormone (ACTH) levels were markedly elevated in the two males with ALD and AMN, despite the fact that they had no clinical signs of adrenal insufficiency and that morning plasma cortisol levels and their response to maximal exogenous ACTH stimulation appeared to be normal. In addition, the integrated 24-hour response to the administration were also subnormal in these two cases. Thus, people with ALD and AMN may have subclinical partial adrenocrotical insufficiency. No other endocrinologic dysfunction was identified.


Adrenocorticotropin and glucocorticoid concentrations in fetal and maternal plasma of rabbit does continuously infused with cortisol from day 21 to day 24 of gestation. Previous studies have suggested that suppression of fetal rabbit adrenocorticotropin (ACTH) secretion results in impaired development of ACTH-specific adenylate cyclase activity. In order to test this hypothesis we measured fetal and maternal plasma ACTH, cortisol, and corticosterone concentrations in control does and does infused with 0.3 mg of cortisol/hour at 21 to 24 days of gestation. This cortisol infusion regimen significantly depressed maternal and fetal plasma ACTH and corticosterone concentrations but did not change fetal serum cortisol concentrations. These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life.


Desoxycorticosterone in normal pregnancy. II. Cortisol-dependent fluctuations in free plasma desoxycorticosterone. Desoxycorticosterone (DOC) secretion increases during pregnancy. Administration of adrenocorticotropic hormone (ACTH) to women during the third trimester of pregnancy was noted previously to result in marked sodium retention, while aldosterone excretion declined. Since urinary tetrahydrodesoxycorticosterone increased substantially, sodium retention resulting from ACTH was ascribed to enhanced DOC secretion. Surprisingly, the elevated plasma DOC in late pregnancy failed to respond consistently to ACTH. Effects of ACTH upon total plasma concentrations and free indexes of DOC and cortisol were studied in pregnant women in the third trimester. As a result of ACTH, plasma cortisol and the free cortisol index increased strikingly; the plasma free DOC index rose markedly in those subjects in whom the total plasma DOC level was not altered appreciably and was unchanged or even increased slightly in the few subjects in whom the total DOC level decreased. The results support the proposition that the plasma free DOC fraction is increased because of displacement from corticosteroid-binding globulin by the ACTH-induced increment in cortisol. Resultant elevations of free DOC would not be evident from customary measurements of the total DOC concentration but, nonetheless, could contribute to sodium retention and also would be available for hepatic metabolism.


In vitro stimulation of human colostral lymphocytes by cytomegalovirus. Lymphocytes isolated from the peripheral blood and colostrum of 17 healthy donors, 1 to 3 days post partum, were cultured with cytomegalovirus (CMV), strain AD169, as stimulating antigen in a lymphocyte transformation test. The test was performed in microculture utilizing the cell-free supernatant of CMV-infected human fibroblasts and isolated peripheral blood and colostral lymphocytes showing normal reactivity to phytohemagglutinin. Lymphocytes from CMV-seropositive donors were stimulated by the CMV antigen, whereas lymphocytes from both male and female CMV-seronegative donors failed to respond, as measured by incorporation of tritiated thymidine. In those donors from whom utilizable colostrum samples were obtained, two donors lacking peripheral blood lymphocyte (PBL) CMV reactivity also lacked colostral lymphocyte CMV reactivity. The remaining five colostrum donors showed both PBL and colostral lymphocyte reactivity to the CMV antigen, with colostral lymphocyte reactivity in four of five donors exceeding PBL-cytomegalovirus reactivity. There was no clear-cut correlation between the titer of CMV antibody by complement fixation and the amount of tritiated thymidine incorporated into the lymphocytes stimulated with the CMV antigen. These results highlight current knowledge that milk and colostrum contain large numbers of specifically sensitized T-lymphocytes, expressing a selective quota of maternal cell-mediated immunities. We are currently investigating the possibility that CMV-reactive colostral lymphocytes obtained during suckling may be of some protective value to the immunologically inexperienced neonate by transferring an adoptive immunity. This assumes special significance in the light of known transmission of CMV via mothers' milk to neonates.


Reproductive function in aged female chimpanzees. Reproductive function was evaluated in ten female chimpanzees (Pan troglodytes) aged 35-48 years. Forty-eight years is the longevity record for the chimpanzee. Data on cycle frequency and duration was available for seven animals. Most were cycling regularly until death, and all had experienced at least one menstrual cycle within one year of death. After exclusion of periods when the animals were pregnant or in postpartum amenorrhea, the mean cycle frequency (+/- standard error)/year was 9.54 +/- 0.20 in seven animals aged 15-25 (432 cycles analyzed) compared to 8.6 +/- 0.76 in the same animals at age 35 + years (405 cycles analyzed); this effect approached significance (p = 0.072, Mann-Whitney U-test). Cycle length of 16 cycles in each of seven animals aged 15-25 was 32.23 +/- 0.38 days. The same animals when aged over 35 had mean cycle lengths of 35.59 +/- 0.73. This difference was not significant, although cycle lengths clearly increased with age in some individual animals. In five aged animals for which mating data was available, appropriate exposure to a male occurred in 52 cycles, but only two pregnancies occurred; one pregnancy resulted in a live birth at age 38, the other in a stillbirth at age 40. This conception rate was 3.85% compared with 20% in the same animals aged 15-25. These data suggest greatly reduced fertility after age 35, although menstrual cycle frequency remained high. The persistence of menstrual cyclicity until death, which occurred due to natural causes at latest in the fifth decade, is in striking contrast to the human female in which menopause occurs in the fifth decade and death is often postponed for several more decades.


Thyroxine and Na+ transport in toad: role in transition from poikilo- to homeothermy. The effects of thyroxine (T4) on Na+ transport, oxygen consumption (QO2), and Na+-K+-ATPase activity were studied in the urinary bladder and liver of the toad Bufo marinus. In the bladder, T4 in vitro (10(-8) to 10(-6) M) had no significant effect on these parameters during 15 h of incubation. When injected intraperitoneally (approximately 20 microgram/(kg body wt.day) for 6 days), T4 lowered base-line, short-circuit current by 62% (P less than 0.0025) and potential difference by 37% (P less than 0.001), increasing tissue resistance by 40% (P less than 0.02). T4 depressed QO2/DNA (-25%, P less than 0.05) with no significant effect on Na+-K+-ATPase activity. In liver, T4 increased the recovery per cell DNA of mitochondrial proteins by 32% (P less than 0.025), corresponding to an increased QO2 (stage IV) of isolated mitochondria per cell DNA (+54%, P less than 0.01). There was no significant effect on Na+-K+-ATPase activity. These results suggest that, unlike its function in the rat, T4 in the toad does not regulate cellular thermogenesis by inducing Na+-K+-ATPase. This major difference could account at least in part for the transition from poikilothermy to homeothermy. In addition, T4 has a distinct inhibitory effect on Na+ transport in the urinary bladder, which suggests an antagonism to the action of aldosterone.


Time course of the T3- and T4-induced increase in rat soleus muscle mitochondria. Citrate synthase and cytochrome c increase in soleus muscle of rats in response to excess thyroid hormones. The half times of the increase in the levels of citrate synthase and cytochrome c in soleus muscle during induction are greater than the half times of the decline in enzyme levels after cessation of treatment (15 days vs. 7 days for citrate synthase). Denervation of the soleus does not prevent the increase in citrate synthase in response to thyrotoxicosis. This provides evidence that thyroid hormones affect the muscle directly and not via the motor nerves. ATP concentration is reduced in liver, but not in soleus muscle in response to thyrotoxicosis. Creatine phosphate is not significantly altered in soleus muscle. Cyclic AMP is slightly lower in thyrotoxic soleus muscle. Simultaneous treatment with thyroid hormones and propranolol does not affect the increase in citrate synthase in response to excess thyroid hormones. It is concluded that the increase in muscle mitochondria associated with thyrotoxicosis is not mediated via the nervous system or by a cAMP-regulated process.


Induction of delta-aminolevulinic acid synthetase in muscle by exercise or thyroxine. There is evidence that delta-aminolevulinic acid (ALA) synthetase is the rate-limiting enzyme in heme biosynthesis. Accumulation of the apoproteins of the mitochondrial cytochromes appears to be regulated by availability of heme. Exercise and thyrotoxicosis bring about increases in the cytochromes, and in other mitochondrial enzymes, in muscle. In this context, we have examined the effects of exercise and of thyroid hormones on ALA synthetase activity in skeletal muscle. Treadmill running and injection of thyroid hormones both resulted in significant increases in muscle ALA synthetase activity. A rise in ALA synthetase activity was evident within 17 h after a bout of vigorous exercise and 14 h after a single injection of thyroid hormones. The increase in ALA synthetase preceded the increase in cytochrome c, which was used as a mitochondrial marker. These results are compatible with the hypothesis that a relationship exists between heme synthesis and mitochondrial growth in which the rate-controlling step is ALA synthetase activity.


Some aspects of temperature regulation in newborn harp seal pups. Harp seals are born on the drifting ice of the North Atlantic Ocean during arctic winter when temperatures of -20 degrees C, occasionally in combination with wind of 10 m/s, might prevail for days. At birth the pups lack subcutaneous blubber and the wet infantile fur has a conductance value of 30.0 W . m-2 . degrees C-1, as compared with only 2.0 W . m-2 . degrees C-1 when dry. While still wet immediately after birth the pups are nevertheless able to retain body core temperature by shivering. This activity leads to reduction of muscle fat and glycogen stores. Nonshivering thermogenesis commences in thermogenic adipose tissue by virtue of loosely coupled mitochondria. Thermogenic adipose tissue is found at birth both as a subcutaneous layer along the back and as internal deposits around venous plexuses in the neck, on the pericardium, on the kidneys, and the abdominal walls. After about 3 days of suckling the subcutaneous adipose tissue loses its thermogenic function being gradually transformed into blubber, whereas the internal deposits persist at least until the pups venture into water at the age of 3-4 wk.


Physical activity and plasma cyclic adenosine monophosphate levels in manic-depressive patients and healthy adults. Intense exercise for one hour induced a significant increase in plasma cyclic adenosine monophosphate (cAMP) in 5 healthy volunteers. In 44 manic-depressive patients, cAMP levels correlated more strongly with mood ratings than with activity scores. The authors conclude that physical activity is one of the factors which contribute to changes of cAMP levels in affective illness.


A possible cardiovascular effect of lithium. Heart rate rises associated with performance of mental arithmetic tasks were compared in 22 euthymic manic-depressive patients receiving lithium carbonate and 17 drug-free normal controls. The lithium-treated subjects showed a markedly lower heart rate response to the mental arithmetic stimulus. No effect was observed on basal heart rate. The results are consistent with lithium's reported inhibition of noradrenaline-induced rises in adenylate cyclase activity but lack of inhibition of basal adenylate cyclase activity. The biochemical and psychophysiological findings may parallel lithium's unique ability to calm excited behavior without sedating normal behavior.


Adenoid cystic carcinoma of the salivary glands. A study of ninety-three cases. The present study reviews ninety-three cases of adenoid cystic carcinoma of the major (80 cases) and minor (13 cases) salivary glands occuring in ninety-one patients. This tumor is insidious in its presentation and subsequent clinical course with early perineural lymphatic invasion and late metastases. Many patients remain alive but with recurrent disease. The high incidence of recurrent disease (parotid gland 20 of 47, submaxillary gland 20 of 33, and minor salivary glands 7 of 11) suggests inadequate initial surgery at all anatomic sites. Misdiagnosis (16 cases) on frozen or permanent section has led to less than optimum primary treatment. The frequency of perineural lymphatic involvement with recurrence (11 of 19 cases) suggests that the tumor may be extending along the nerve roots in an anatomic area with extensive nerve distribution (the head and neck). Radical neck dissection, in our studies, has contributed to improved survival rates when the primary site has been the submaxillary gland. The treatment of recurrent disease has been primarily surgical (3 operations per patient), and palliation with prolonged survival has been achieved with radical excision of recurrence. The fifteen year determinate cure rate of 19 per cent in comparable to that reported in the world literature. Radiation therapy has been helpful in palliation but has not been curative. Radiation treatment was used for recurrence in twenty-seven patients, and the average time from radiation treatment to death was 3.8 years.


Elective hepatic resection.

Elective hepatic resection. Significant salvage of patients with a wide variety of cysts and benign tumors of the liver and of some patients with biliary strictures can be achieved by hepatic resection in carefully selected clinical situations with a low operative mortality rate and an acceptable postoperative complication rate. Still to be determined is the role of hepatic resection in metastatic carcinoma and sarcoma of the liver, where survival is modest but measurable, but important palliation can be achieved. Hepatomas should be resected when possible, but hepatic resection for aid in resection of bile duct carcinoma has proved generally unrewarding.


Fluidity and lipid composition of mouse biomembranes during adaptation to ethanol. Showing that ethanol added in vitro increased the fluidity of mouse erythrocyte and synaptosomal membranes and that the same membranes isolated from mice after chronic treatment with ethanol had increased cholesterol and were resistant to ethanol in vitro, the study suggests that the animals had adapted to the chronic presence of the drug by changing their membrane lipid composition to offset the fluidizing effects of ethanol.


Chronic degeneration of aminergic nerve endings and blood-aqueous barrier. Chemical sympathectomy of the anterior segment of the eye was performed in rabbits with 6-hydroxydopamine (6-OHDA) intravitreously injected. The response of the pupillary diameter (PD) and intraocular pressure (IOP) to NE, E and Isoproterenol was determined through instillation of the drugs in the pretreated and control eyes. The results were as follows: 1) Both PD and IOP at different intervals of time from the injection show a sharp decrease in the treated eye. 2) About four weeks after the injection, the instillation of NE and E increases the PD only in the 6-OHDA pretreated eyes, while IP administration is not effective on both control and pretreated eyes. 3) The instillation of the three drugs, while decreasing IOP in the control eyes, does not modify the already low IOP in the pretreated eyes. The authors suggest the presence of a postdenervation supersensitivity affecting only the alpha receptors, since the beta stimulant IP is inactive in both treated and untreated eyes.


The occurrence of uterine stromal and intraepithelial monocytes and heterophils during normal late pregnancy in the rat. The steady decline in plasma progesterone level that occurs during the last week of pregnancy in the normal rat (Wiest, '70) provides good opportunity to study the effect of withdrawal of progesterone on uterine differentiation. Evidence is presented that tissue monocytes, heterophils, and eosinophils are regular components of the normal late gestational uterus and that their number increases as term approaches. Uterine monocytes and heterophils are located in the endometrial and myometrial stroma as well as within the basal intercellular compartment of the luminal epithelium. Stromal monocytes are distributed throughout the attenuated endometrium of late gestation, but are more common immediately beneath the luminal epithelium. In the myometrium, monocytes and heterophils occur, often as perivascular, clusters in the connective tissue septum that separates the two layers of smooth muscle. Eosinophils are present especially in the deep endometrial and myometrial stroma, and increase in number as plasma estrogen rises immediately before parturition. A small population of lymphocytes is regularly present. An important feature of the prepartum uterine stroma is the sparseness of macrophages. Near term, however, the beginnings of monocytic-macrophagic transformation are noticeable as the cell surface becomes more irregular and organelles associated with endocytic activity arise. The prepartum monocytes are positioned in the same histological sites that during the postpartum period of regression will be occupied by macrophages (Padykula and Campbell, '76). Since it is generally accepted that monocytes are precursors of macrophages, this spatial correlation raises the possibility that cellular preparations for regression commence before birth. The possible significance of prepartum monocytic infiltration is discussed in relation to the effect of changing plasma and uterine concentrations of progesterone on uterine collagenase activity. The steady increase in uterine leucocytes which occurs concomitantly with decreasing uterine binding capacity for progesterone supports the hypothesis by Siiteri et al. ('77) that progesterone in high local concentrations has an anti-inflammatory effect.


Formation of concentric saccules in murine parietal cells after injection of diazo-oxo-norleucine. After treatment with various chemical and physical agents, flattened or ring-like saccules may occur in the cytoplasm of parietal cells of the gastric glands of several species of mammals. In the current investigation, similar structures appeared after treatment with high dosages of diazo-oxo-norleucine (DON), a glutamine antagonist. A tentative sequence for their formation is suggested. Saccules formed of unit membrane became abundant in some parietal cells of the treated mice. Single saccules often had narrow lumens and peripheral distensions. The saccules, either singular or several stacked together, became progressively more curved, enclosing a region of cytoplasm that often contained glycogen-like particles and occasionally vesicles or other organelles. Many of the concentric saccules were close to an intracellular canaliculus. Membrane bound cytoplasm containing glycogen-like particles occasionally occurred in the canaliculi, suggesting that exocytosis had occurred. Cytochemistry revealed that glycoproteins were associated with the concentric saccules, probably located on the luminal surface. The glycogen-like particles in all locations stained in a manner characteristic of glycogen. It is suggested that the concentric saccules may form from vesicles of the tubulovesicular system.


Intramammary granular cell myoblastoma.

Intramammary granular cell myoblastoma. Two female patients, age 15 and 21 years, with intramammary granular cell myoblastoma who were without recurrence of the development of additional lesions after one year and eight years, nine months respectively, are reported. Electron microscopic examination of one of our cases disclosed the typical osomphilic granules but no features to support a particular cell of origin. Review of the 52 previously reported cases indicates that this unusual intramammary neoplasm has been encountered with relatively few exceptions in the 20 to 59 year age group and in the upper quadrants. It clinically mimics fibroadenoma or carcinoma and on frozen section examination may be misinterpreted as malignant. None have recurred following adequate excision.


Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis. Angiotensin-converting enzyme assays and gallium-scan results were obtained from 27 patients with biopsy-proven, clinically active sarcoidosis. Twenty-three of these patients had elevated converting enzyme levels, and 22 had positive gallium-scan results. Three of four patients with normal or borderline-elevated levels of angiotensin-converting enzyme also had positive gallium-scan results. Of 156 nonsarcoid patients (pulmonary and other diseases), 27 were found to have elevated serum converting enzyme levels, and 25 of these had negative gallium-scan results. These results indicate that the combination of an assay of angiotensin-converting enzyme and gallium scan increases diagnostic specificity from 83% to 99% without sacrificing sensitivity. We conclude that the concurrent use of angiotensin-converting enzyme assay and gallium scan is of value in the diagnosis of sarcoidosis.


Primary aldosteronism: diagnosis, localization, and treatment. New diagnostic techniques have enhanced the detection of primary aldosteronism. However, the response of blood pressure after operation in unilateral and bilateral adrenal disease is different. We have compared four localizing techniques--adrenal venography, adrenal isotopic scanning, a modified adrenal venous sampling for steroid measurements, and the anomalous postural decrease in plasma aldosterone concentration--in 51 patients with primary aldosteronism, all of whom had undergone operative confirmation. Adrenalectomy resulted in normal blood pressure in 59%, improvement in 25%, and no change in 16%. Correct localization of the lesion was obtained in 47% by the adrenal isotopic scan, in 66% by adrenal venography, and in 91% by the modified adrenal venous hormone technique despite four false-positives. Of the 26 patients with an anomalous postural decrease in plasma aldosterone, 88% had a unilateral lesion.


[Adenylate cyclase activation in KB cells infected by Sendaï virus (author's transl)]. Adenylate cyclase activity is increased in KB cells infected by a little dose of Sendaï virus. The apparent Km for ATP substrate is decreased from 0.7 to 0.4 mM and the activity regulation is changed. This activation may be related to interactions between virus and cell membrane where adenylate cyclase is located.


[Crosti's reticulosis. Report on three cases, one with ultrastructural study (author's transl)]. Crosti's reticulosis is defined as a peculiar form of well-circumscribed, slow developing lymphomas in adults, with a malignant histological picture. Three cases with typical dorsal localisation according to Crosti's first description are reported and the cardinal features of this type of tumour are recalled. One observation includes an ultrastructural study which confirms the malignant nature of histiocytes in this disease. Localisation in back seems not to be exclusive and a study of 32 cases of the literature about other localised cutaneous reticulum cell lymphomas show them similar to Crosti's reticulosis-which authorizes their classification, as was proposed by Thiers in a single group of slow developing circumscribed reticuloses.


Carcinoma of Stensen's duct.

Carcinoma of Stensen's duct. The authors present 2 cases of carcinoma primary in Stensen's duct, one a mucoepidermoid carcinoma and the other an adenoid cystic carcinoma. This is an unusual site for a primary carcinoma and these are apparently the thirteenth and fourteenth cases to be reported in the English literature. The authors review the diagnosis and treatment for primary carcinoma of Stensen's duct.


The effect of vaccination on titres of antibody to rotavirus in colostrum and milk. The continued presence of antibody to rotavirus in the gut of the neonatal ruminant has been shown to be important in protecting against clinical disease associated with rotavirus infections. This effect is dependant upon the amount of antibody included in the diet. Titres of antibody to rotavirus may be relatively high in ruminant mammary secretions immediately after parturition but decline rapidly over the course of the first day. The influence of vaccination on the titres of antibody, the concentrations of immunoglobulin and their respective of decline in the mammary secretion following parturition has been studied. Ewes vaccinated two to three weeks prior to mating with an inactivated preparation of lamb rotavirus produced colostrum and milk after the subsequent pregnancy which contained significantly higher titres of antibody to the virus than did the mammary secretions from non-vaccinates. The antibody activity appears to be associated with IgG and it is suggested that vaccination may be of value in the alleviation of neonatal diarrhoea associated with rotavirus infection in cattle and sheep.


Benign pleomorphic adenoma of the larynx. A case report. Minor salivary gland tumors of the larynx are relatively rare. Morphologically the majority of them are adenoid cystic carcinomas and the overwhelming location is the subglottic larynx. Benign pleomorphic adenomas are rare minor salivary gland tumors of the larynx which usually occur at the glottic and subglottic levels. We present only the sixth case of a supraglottic benign pleomorphic adenoma that we could find in the literature. A preoperative laryngogram localized the tumor to the supraglottic larynx and the intact mucosa suggested a specific differential diagnosis. The tumor was removed by a lateral pharyngotomy with retention of good laryngeal function. The relatively asymptomatic presentation of our case is a somewhat unusual finding which, however, was previously noted in similar case reports.


The detection of rotavirus specific antibody in colostrum and milk by ELISA. The blocking method of ELISA for the detection and titration of rotavirus-specific antibody in colostrum is described. The results obtained were positively correlated with those of a neutralizing antibody test. On one farm colostrum samples were obtained over a period of 18 months. No relationship was found between the titer of colostrum obtained shortly after calving, and the development of rotavirus-associated diarrhoea in calves. On a second farm only samples obtained during the calving season were tested. Within this restricted period high colostral antibody titers appeared to reduce the incidence of diarrhoea among calves and to delay the onset of rotavirus excretion in the faeces. These results are discussed in relation to the rapid decline in antibody content of colostrum after calving.


[Response to ACTH of human adrenocortical cells isolated from normal glands and from adrenocortical adenoma (author's transl)]. The low sensitivity of adrenocortical adenoma to ACTH, documented in vivo, and in vitro, results from decreased cAMP generation in response to ACTH while distal steps of biosynthesis of cortisol are even more active in these tumoral cells than in normal adrenocortical cells.


Inhibition of the evoked release of acetylcholine by the porphyrin precursor delta-aminolevulinic acid. The effect of delta-aminolevulinic acid (ALA) on neuromuscular transmission were studied. High concentrations (0.6 to 18 mM) of ALA caused significant reductions in the amplitudes of curarized end-plate potentials (epps). Changing the ratio of calcium to magnesium in the bathing solution allowed the quantal content of the epps to be directly measured. Under these conditions, ALA reduced the quantal content of epps without affecting the depolarization produced by a single quantum of acetylcholine. It was concluded that ALA, in high concentrations, inhibits the release of acetylcholine evoked by a nerve impulse but is unlikely to be the cause of the neurological defects of acute porphyria.


Low trimethoprim susceptibility of anaerobic bacteria due to insensitive dihydrofolate reductases. All the 28 Bacteroides fragilis strains investigated were susceptible to sulfamethoxazole (minimal inhibitory concentration < 16 mug/ml) and resistant to trimethoprim (TMP; minimal inhibitory concentration > 4 mug/ml). Synergism between sulfamethoxazole and TMP was present in all strains at a ratio of 1:1. The few clostridia investigated proved more resistant to both compounds. Dihydrofolate reductases from B. fragilis, C. perfringens, and some other anaerobic species were isolated. Inhibition profiles with six structurally different inhibitors revealed major differences in all enzymes. For 50% inhibition, the enzyme from B. fragilis and all clostridia required concentrations of TMP which were between several hundredfold and 1,000-fold higher than those required for the enzyme of Escherichia coli, whereas the enzyme from Propionibacterium acnes only needed a threefold higher concentration. In vitro activities of TMP were seen to correspond to the activity at the enzymatic level in B. fragilis and P. acnes, but correspond to a much lesser extent to the activity at the enzymatic level in clostridia, where a poor penetration is assumed to be involved. Dihydrofolate reductase inhibitors other than TMP were found to be as active as TMP both at the enzyme and in vitro. In B. fragilis, higher concentrations of exogenous thymidine were required for increasing the minimal inhibitory concentration of TMP than in E. coli and probably also in C. perfringens.


Effects of nucleoside analogs on Epstein-Barr virus-induced transformation of human umbilical cord leukocytes and Epstein-Barr virus expression in transformed cells. Two methods of assay, measuring (i) stimulation of host cell DNA synthesis by [(3)H]thymidine incorporation and (ii) morphological transformation in microtiter plates, were employed to determine what effect treatment during infection with adenine arabinoside or 5-iodo-5'-amino-2',5'-dideoxyuridine has on Epstein-Barr virus (EBV) (B95-8)-induced transformation of human umbilical cord leukocytes. It was found that adenine arabinoside inhibited EBV-induced transformation in a dose-dependent manner in both assays, beginning at drug concentrations (<2 mug/ml) which had little effect on either spontaneous or phytohemagglutinin-induced host cell DNA synthesis. Adenine arabinoside was more effective in inhibiting morphological transformation than EBV-induced host DNA synthesis. Adenine arabinoside treatment was also effective in reducing both EB viral capsid antigen expression and production of biologically active extracellular transforming virus in EBV-transformed cells. In contrast, 5-iodo-5'-amino-2',5'-dideoxyuridine, which inhibited herpes simplex virus replication, had little effect on EBV-induced transformation as measured by either method of assay. However, 5-iodo-5'-amino-2',5'-dideoxyuridine was found to be effective in inhibiting viral capsid antigen expression and production of extracellular transforming virus in EBV-transformed cells.


Enveloped virus inactivation by fatty acid derivatives. The enveloped bacteriophage phi6 has been shown to be a valuable model system for the preliminary screening of compounds that might be expected to inactivate herpes simplex virus and other enveloped mammalian viruses. A variety of fatty acid derivatives that form fluid micelles in aqueous media have been found to be potent inactivators of phi6. The chemical nature of the polar head group, the length of the alkyl chain(s), and the extent and geometry of unsaturation are all important parameters in determining the antiviral effectiveness of this class of compounds.


Extreme sensitivity of enveloped viruses, including herpes simplex, to long-chain unsaturated monoglycerides and alcohols. Unsaturated monoglycerides and alcohols of chain lengths of 16 or 18 carbons were found to be extremely potent inactivators of two enveloped viruses, herpes simplex virus type 2 and bacteriophage phi6. The lipid-containing bacteriophage PM2 was also inactivated by some of these amphiphilic molecules. Treatment of herpes simplex virus type 2 with these compounds at concentrations as low as 0.2 muM reduced virus survival to 50% in 30 min, making these agents the most potent inactivators of herpes simplex viruses discovered that are not cytotoxic to mammalian cells. Detailed characterizations of the effects of unsaturated monoglycerides and alcohols on bacteriophages phi6 and PM2 showed that the inactivated phi6 virion remained nearly intact but that PM2 was almost completely disrupted by the inactivating treatment. Some of the compounds inactivate the viruses even at low temperature (0 degrees C). Excess amounts of diglycerides and phospholipids interfere with the inactivating abilities of some of the unsaturated monoglycerides and alcohols against phi6 and PM2. Our findings suggest that the unsaturated monoglycerides and some of the unsaturated alcohols should be further studied as potential antiviral agents, particularly for application to herpesvirus-infected areas of the skin and accessible epithelium.


Mechanism of aminoglycoside antibiotic resistance in anaerobic bacteria: Clostridium perfringens and Bacteroides fragilis. Cell-free amino acid incorporation using ribosomes from strains of either Clostridium perfringens or Bacteroides fragilis was shown to be susceptible to inhibition by streptomycin and gentamicin. Ribosomes bound dihydrostreptomycin as effectively as ribosomes from Escherichia coli. No inactivation of streptomycin or gentamicin was detected by cell extracts of either anaerobic bacterial species. B. fragilis, grown without added hemin, menadione, and fumarate, and C. perfringens did not show any time-dependent accumulation of dihydrostreptomycin or gentamicin at concentrations tested. Decreased resistance to aminoglycosides and time-dependent uptake of dihydrostreptomycin at 500 mug/ml was observed with B. fragilis grown with hemin, menadione, and fumarate. With the last additions, cytochrome b was detected by cytochrome spectra of B. fragilis. These results demonstrate that anaerobic bacteria unable to carry out oxygen- or nitrate-dependent electron transport are resistant to streptomycin and gentamicin because of failure to transport aminoglycosides. The induction of fumarate-dependent electron transport in B. fragilis is associated with some aminoglycoside transport that is of poor efficiency relative to bacteria with electron transport to oxygen or nitrate.


Influence of suspending media upon the susceptibility of Pseudomonas aeruginosa NCTC 6750 and its spheroplasts to polymyxin B. The lytic and bactericidal actions of polymyxin B on whole cells and spheroplasts of Pseudomonas aeruginosa varied markedly with the suspending media, and there was little correlation between them. Relative rates of lysis of these preparations and also of Bacillus megaterium protoplasts suggested that polymyxin causes progressive damage to the cytoplasmic membrane, such that membrane permeability towards various ions increased as follows: K(+) > Na(+) > NO(3) (-) > Cl(-), Ca(2+), H(2)PO(4) (-)/HPO(4) (2-). Impermeant compounds, such as NaCl and sucrose, protected whole cells against lysis but not against death. It is suggested that lysis of whole cells by polymyxin is a secondary effect, resulting from entry of solutes normally excluded by the cytoplasmic membrane and the fragility of the damaged outer membrane. Because the degree of lysis varies with the external solutes, it should be treated with caution as a descriptor of polymyxin activity.


Spread to the nipple and areola in carcinoma of the breast. In 40 breasts with primary carcinoma, the nipple and areola were cut horizontally in order to investigate the frequency of intraductal and invasive cancer. In 20 of these breasts the nipple and/or areola were found to be involved at a depth of 1 cm (50%; 95% confidence limits: 33.8-66.2%). Eleven neoplasms were purely intraductal, eight intraductal as well as stromal, and only one purely stromal. By means of clinical or physical findings, it was not possible to select the breasts in which the nipple and/or areola were not involved. It is concluded that the general use of surgical methods preserving the nipple and areola in treating breast cancer leaves a focus of invasive or intraductal carcinoma in about half the patients. The implications of this are not known.


Noninvasive breast carcinoma: frequency of unsuspected invasion and implications for treatment. One hundred twenty-nine biopsies from 121 patients with a frozen or paraffin section diagnosis of noninvasive breast carcinoma were studied. Eight women had bilateral noninvasive carcinoma. Seven biopsies reported as intraductal on frozen section contained invasive carcinoma on paraffin section. Of the remaining 122 biopsies proven to have noninvasive carcinoma on paraffin section, 39 (34%) were reported at frozen section and as noninvasive carcinoma, 24 (20%) as atypical and 59 (48%) as benign. Intraductal carcinoma (IDC) was identified more often at frozen section (45%) than was lobular carcinoma in situ (19%). Among 41 patients who had bilateral carcinoma with invasive disease in one breast, 76% of contralateral noninvasive carcinoma was LCIS. After excisional biopsy, carcinoma was found in 56% of 103 mastectomy specimens, including invasive carcinoma in 6% of breasts with IDC and 4% with LCIS. Residual noninvasive carcinoma was usually of the same type found at biopsy (90% IDC and 88% LCIS) and involved quadrants other than the biopsy site in 33% with IDC and in 80% with LCIS. When the frozen or paraffin section diagnosis of a generous excisional biopsy was noninvasive breast carcinoma, there was a substantial risk that foci of the same type of noninvasive carcinoma were also present in other quadrants. However, occult foci of invasive carcinoma were quite infrequent and the risk of axillary metastases was very low. Adequate treatment for noninvasive carcinoma requires elimination of all residual foci of noninvasive disease. At present this can best be accomplished by total mastectomy if the operation is properly performed. To insure removal of the axillary extension of the breast and for staging, in continuity dissection of the lowest axillary lymph nodes is also prudent.


[First Madagascan myxovirus B isolated during an influenza epidemic in Antananarivo (June-August 1977)]. The authors study an influenza epidemic at Antananarivo, during the austral winter 1977. A virologic work confirmed the diagnostic of influenza with the isolation of two influenza B virus strains. An epidemiologic survey was also carried out in consultant people at the Work Medecine Department and Hygiene Municipal Service to evaluate its influency on morbidity and mortality.


Facilitatory effect of naloxone and involvement of specific ligand-opiate receptor system in the antinociceptive effects of non-opioid drugs. The facilitatory effects exerted by naloxone on a nociceptive reaction (jumping) in the hot plate test was not modified by three phosphodiesterase inhibitors, theophylline, Ro-20-1724 and I.C.I. 63197 which had on themselves different effects on the latency of jumping. The facilitatory effects of naloxone were not diminished by neuroleptics, cholinergic agonists or miscellaneous drugs (baclofen, indomethacin, ketoprofen, n-dipropylacetate, diazepam and potassium chlorazepate). Naloxone antagonized the antinocieceptive effects of neuroleptics in different patterns. No competitive component could be observed with haloperidol, whereas such a phenomenon was apparent with benperidol. Pimozide was an intermediary case. The antinociceptive effects of two cholinergic agonists, arecoline and eserine were antagonized by naloxone and stereospecifically by the (-) isomer, Mr 2266. The (+) isomer, Mr 2267 was inactive. The antagonism by the opioid antagonists of the antinociceptive effects of cholinergic agonists appeared to be of a competitive type. Thus the facilitatory effects of naloxone did not apparently involve activation of adenyl cyclase or the mediation of dopaminergic or cholinergic (neural) structures. The antinociceptive effects of benperidol and pimozide but not of haloperidol might result from the triggering of specific opiate receptors and those of cholinergic agonists from such a triggering and/or from release of endogenous ligands.


Effects of cyclic AMP and of protein kinase on the calcium uptake by various tracheal smooth muscle organelles. The role of cyclic AMP, if any, in the regulation of smooth muscle tone is not understood. In the present study the effects of cyclic AMP and of protein kinase on the uptake of calcium by "microsomal", "plasma" and "mitochondrial" preparations obtained from bovine tracheal smooth muscle were examined. Cyclic AMP and protein kinase had only a slight and variable effect on the uptake of calcium by microsomes, and no effect on the uptake of calcium by the plasma membrane or the mitochondria. These findings are not compatible with a role of cyclic AMP and protein kinase in the control of the uptake of calcium by the subcellular organelles of tracheal smooth muscle.


Pulmonary cytomegalovirus infection: detection by Gallium 67 imaging in the transplant patient. Cytomegalovirus (CMV) infeciton is a frequent complication during the first few months following renal transplantation. The diagnosis is sometimes difficult but may be made by viral culture, a fourfold rise in the CMV antibody titer, or by demonstration of the CMV inclusions in the affected tissue. An increased pulmonary uptake of galliulm citrate Ga 67 has been demonstrated following renal transplantation in two patients, each of whom had a fourfold rise in CMV complement fixing antibody titer, one of whom additionally had CMV inclusion bodies in a lung biopsy specimen prior to clinical or radiological demonstration of the pulmonary involvement. Gallium imaging, therefore, appears to be a valuable noninvasive test for early diagnosis of CMV pulmonary infections.


Viral pericarditis in patients receiving hemodialysis. Four patients with end-stage renal disease in whom pericarditis developed while they received intermittent hemodialysis therapy were evaluated for viral infection. We found high or rising serum antibody titers to influenza virus A (three patients) and coxsackievirus B (one patient). Cardiac tamponade occurred in three patients, requiring pericardiectomy in two; each patient eventually recovered. Viral pericarditis may be an important cause of "uremic" pericarditis in chronically dialyzed patients.


Inappropriate antidiuretic hormone complicating histiocytic lymphoma. The syndrome of inappropriate antidiuretic hormone (IADH) often causes the hyponatremia that may be seen in patients with malignant disorders. Most physicians correctly associate IADH with small cell carcinoma of the lung. We describe two patients in whom IADH was caused by histiocytic lymphoma. One patient was thought to have small cell carcinoma of the lung on the basis of marrow infiltration and the IADH. When the proper diagnosis was made and therapy instituted, both patients responded, with rapid resolution of their disease and the IADH. The identification of the neoplasm that produces the IADH is important, since histiocytic lymphoma may mimic small cell carcinoma of the lung, yet may be very responsive with newer treatment regimens.


Metabolism of cyclic AMP in non-pathogenic Mycobacterium smegmatis. The intracellular concentration of cyclic AMP reached a maximum in 3.5-day old cultures of Mycobacterium smegmatis grown in the presence of glycerol as the main source of carbon. Glucose-grown cells exhibited decreased cyclic AMP levels at all stages of growth. When M. smegmatis cells were incubated with various metabolites, pyruvate increased whereas glucose, ctric acid, succinic acid and lactic acid decreased intracellular cyclic AMP levels. No cyclic AMP was detected in the incubation medium. The presence of a cyclic AMP-binding protein was demonstrated in cell-free extracts of M. smegmatis.


[Hypertrophic and exudative gastropathy in the child]. A case of transient hypertrophic and exsudative gastritis, diagnosed in a 4 year-old female is reported. In the light of the recent data published, the authors comment on the particularities of the disease in childhood. The disparity of symptoms, the frequency of mild anaemia and of eosinophilia, a past history of allergy or a concomittant viral infection, the diffuse anatomic changes without polyps and lastly, a transient course of the disease with spontaneous recovery are the most striking features which characterize this entity in childhood.


Pulmonary alveolar proteinosis and cytomegalovirus infection. We report a case of pulmonary alveolar proteinosis (PAP) and cytomegalovirus (CMV) infection occurring in a 5-year-old boy with acute lymphoblastic leukemia. The association of PAP and CMV infection is rare, but the possible etiologic role of CMV in the production of PAP is raised. Pulmonary alveolar proteinosis is being reported with increasing frequency in immunocompromised patients, and this disease may be difficult to distinguish from other causes of diffuse lung disease both clinically and radiologically. Pulmonary alveolar proteinosis, either alone or in combination with CMV infection, should therefore be considered in the differential diagnosis of diffuse lung disease in these cases.


Goblet cell carcinoid tumor of the appendix. Report of five cases and review of the literature. Five cases of goblet cell carcinoid tumor of the appendix showed characteristic histologic features that justified classification of these lesions as mucinous variants of carcinoid tumor. The tumor has low-grade malignancy, and metastases are uncommon. Resemblance to mucinous adenocarcinoma of the appendix is striking, and the features that help to differentiate the two lesions are delineated.


Diffuse metanephric adenoma after in utero aspirin intoxication. A unique case of progressive renal failure. Diffuse persistent glomerular immaturity and focal proximal tubular ectasia were seen in bilateral open renal biopsy specimens for an infant with fluid and salt depletion and slowly progressive renal failure. Subsequently, diffuse tubulopapillary renal adenoma subtotally replaced each kidney, thereby, necessitating renal transplantation. Origin of diffuse metanephric adenoma from persistent primitive epithelium of the proximal nephron is postulated and partly substantiated. We propose that this case of persistent proximal nephronic epithelial immaturity and diffuse metanephric adenoma is a variant of nephroblastomatosis and that in this case, a first trimester suicide attempt with aspirin may have initiated the maturation defect that preceded neoplastic transformation.


Male breast carcinoma. An ultrastructural study. A case of infiltrating ductal carcinoma of the male breast was studied by electron microscopy. The ultrastructure of the tumor is similar to that described in the female breast. Myofibroblasts are the preponderant cells in the stroma. Their significance and possible relation to hormonal stimuli are discussed.


Low-grade mucoepidermoid carcinoma of the breast. Two cases of primary breast carcinoma morphologically identical to low-grade mucoepidermoid carcinoma of salivary gland origin occurred. To our knowledge, this article represents the first description of this tumor type in the breast. Both lesions were well circumscribed, wholly or partially cystic, and composed of intimately associated, well-differentiated, squamous and mucinous glandular epithelium. It is suggested that these may represent an indolent tumor type in the breast analogous to their behavior in the salivary gland.


Percutaneous decompression of benign and malignant biliary obstruction. Percutaneous transhepatic catheterization of the biliary tree was performed in 41 patients with obstructive jaundice. In 39 patients, the catheter was successfully advanced past the obstructing lesion into the distal common duct and duodenum to establish internal biliary drainage. The remaining two patients had the obstructed biliary tract drained externally. Chronic internal catheter drainage was instituted in five patients with stricture and ten with malignant obstruction as a means of palliating symptomatic jaundice. Twenty-two patients had marked reduction in serum bilirubin levels and pruritus, eight patients had moderate decreases in serum bilirubin levels, and six patients did not improve despite adequate catheterization due to hepatic parenchymal disease. This procedure effectively decompresses the severely obstructed biliary tree prior to surgery and can also palliate patients with unresectable malignant biliary obstruction and stent high-risk, benign strictures.


Research on cholesterol, steroidal hormones and liposoluble vitamins by thin layer chromatography in some adipose organs of anuran amphibians. II. Liposoluble vitamins. By means of thin layer chromatography and selective detection, vitamin A acetate, vitamin E and vitamin E acetate, vitamin D3 and cholesterol were identified in the prepericardic body, adrenal tissue, fat bodies and testis of Bubo bufo, as well as in the prepericardic body of Rana esculenta. On the contrary, liposoluble vitamins could not be isolated from the adipose tissue occurring in the thoracic cavity of Rana esculenta, or in Bufo bufo muscles. The results are discussed in correlation with the histological structure of the prepericardic body and the presumptive identification therein of steroid hormones. Lastly, the functional analogy between the prepericardic body and fat bodies in anuran amphibians and the brown adipose tissue of mammals is also postulated.


Liver resection for hepatic adenoma.

Liver resection for hepatic adenoma. Between 1970 and 1978, eight hepatic adenomas were resected. Four of the eight patients took oral contraceptive pills before the hepatic adenoma was identified; one patient was male. Four patients had evidence of bleeding at the time of presentation. The original histologic diagnosis in the first five patients was malignant hepatoma. There has been no known recurrence of tumor and all patients are well. The use of oral contraceptives in these patients has been prohibited. Formal anatomic resection is recommended for hepatic adenoma when this procedure can be done without mortality or serious morbidity; however, in the future, less drastic treatments, such as occlusion of the hepatic arterial circulation to the tumor or discontinuation of oral contraceptives, may prove as effective as tumor resection.


Biochemical data on subtotally hypophysectomized Xenopus laevis (Daudin) adult specimens treated or not with prolactin. Xenopus laevis (Daudin) adult specimens were submitted to hypophysectomy. Although the operation resulted subtotal, it served the purpose of removing the prolactin-producing cells, whereby the involvement of endogenous prolactin in osmoregulation phenomena was excluded. In the operated animals treated with ovine prolactin the following metabolic parameters, which are closely dependent upon interrenal activity, were estimated: 1) intestine alkaline phosphomonoesterase activity (E.C. 3.1.3.1); 2) liver glycogen level; 3) glucose-6-phosphatase (E.C. 3.1.3.9.) and phosphoenolpyruvate carboxykinase (E.C. 4.1.1.32.) in the liver; 4) blood glucose level; 5) blood ammonia and urea levels; 6) carbamoylphosphate synthetase activity in the liver (E.C. 2.7.2.a); 7) muscle sodium and potassium levels. The above metabolic parameters were found to be pressed by subtotal hypophysectomy and after subsequent prolactin treatment showed the tendency to go back to values similar to those of control animals.


The susceptibility of cell lines of Aedes aegypti (Linn.), Aedes albopictus (Skuse) and Aedes pseudoscutellaris (Therobald) to infection with blutongue virus. Bluetongue virus multiplied in cell lines derived from Aedes albopictus and Aedes pseudoscutellaris cells. Virus reached a maximum titre in the Ae. pseudoscutellaris cells three days post inoculation, and in Ae. albopictus cells six days p.i. Virus growth was demonstrated in both cell lines at 27 degrees C and 37 degrees C. Significant titres of virus were still present in the Ae. albopictus cells after five subcultures at 27 degrees C over a period of six weeks. No cytopathic effect was observed in either cell line. A third cell line derived from the mosquito Ae. aegypti did not support the growth of Bluetongue virus.


Ultrastructural changes in small intestinal epithelium of neonatal pigs infected with pig rotavirus. The small intestine of piglets orally infected with rotavirus was examined by electron microscopy 18, 24, 48 and 60 hours after infection. At 18 and 24 hours after infection columnar epithelial cells covered the villi. Infected epithelial cells tended to be less electron-dense than uninfected cells and were more numerous at 24 hours after infection. Two types of rotavirus particle were seen, usually within dilated cisternae of the RER: non-enveloped particles measuring 50 to 60 nm and enveloped particles measuring 65 to 75 nm. Non-membrane bound viroplasm containing electron-dense cores was encountered outside the cisternae 18 and 24 hours after infection. Tubular structures measuring 44 to 56 nm were often found in nuclei of infected cells. Single-membraned (44 to 55 nm) and double-membraned tubules (70 to 80 nm) associated with viral manufacture were found in the cytoplasm of infected cells. At 48 and 60 hours after infection a proportion of villous epithelial cells were cuboidal. Virus particles were detected in only a few epithelial cells and nuclear and cytoplasmic tubules were not seen. At all times after infection some infected cells showed a reduction in the number and size of the microvilli comprising the brush border.


Further study on the three-dimensional structure of the core of Marek's disease virus and herpesvirus of turkey. Three-dimensional structures of the core of Marek's disease virus and herpesvirus of turkey were examined by the tilting apparatus of an electron microscope. Various types of the core found in the infected cells were considered to represent developmental stages of the viruses. The basic structure of the core consisted of a toroid surrounding a cylindrical mass, which was clearly demonstrated by tilting the core in two directions. A cylindrical mass spooled by more than two toroids, which seemed to constitute a spiral band of 10 to 20 nm, was demonstrated. The maturation process of the cores of the viruses was also discussed.


Physical characterization of a stomatitis papulosa virus genome: a cleavage map for the restriction endonucleases HindIII and EcoRI. The genome of stomatitis papulosa virus (a parapoxvirus) was cleaved with the restriction endonucleases HindIII and EcoRI, each giving rise to 6 fragments respectively. Double digestion with both enzymes resulted in 8 bands, two of which contained DNA fragments in double molar concentrations as revealed by reciprocal digests of isolated DNA fragments. The genome size, estimated by summation of the molecular weights of the fragments, is approximately 86 X 10(6) daltons, some 30 X 10(6) daltons smaller than vaccinia virus (an orthopoxvirus) DNA. The cleavage sites of HindIII and EcoRI endonucleases were mapped on the genome by analysis of reciprocal digests of isolated DNA fragments and by cross-hybridization experiments. This yielded two mapped segments which were then oriented relative to one another by cleavage of isolated partial digestion products. The terminal restriction fragments show rapid renaturation after alkali denaturation and subsequent neutralization, indicating that stomatitis papulosa virus DNA contains terminal cross-links analogous to those found in vaccinia virus DNA.


Cell mediated immunity to bovine rhinovirus type 1 in calves. Calves experimentally infected with bovine rhinovirus type 1 developed a mild respiratory disease and exhibited a cell mediated immune (CMI) response, as determined by leukocyte migration inhibition (LMI) and lymphocyte blastogenesis tests. The CMI response to the virus was detected by day 3 post-inoculation using direct and indirect LMI tests. It persisted through day 28, with maximal responses occurring between days 4 and 14. Measurement of cellular immunity by blast transformation, however, was not evidenced until day 12. The humoral antibody response was minimal with serum neutralizing titers ranging from 1:4 to 1:16 and this response was not evident until 3 weeks after inoculation.


Comparison of the morphology of three coronaviruses. The morphology of three coronaviruses, avian infectious bronchitis virus strain Connecticut (IBV Conn), human coronavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV3), were examined by negative staining. Significant differences were found in the sizes of the three coronaviruses. Furthermore, three types of surface projection of the same lengths, but varying widths and morphology, were observed. Both IBV Conn and HCV 229E had bulbous projections characteristic of coronaviruses, although the projections of HCV 229E were somewhat thinner than those of IBV Conn. On the other hand, MHV3 particles had thin, cone-shaped surface projections, that were completely unlike typical coronavirus projections. The significance of these results is discussed.


Loss of virulence in a small plaque mutant of the infectious bursal disease virus. A variant strain Cu-1 M was established from the infectious bursal disease virus strain Cu-1. This variant strain forms smaller plaques than the wild type; it has a retarded growth rate, does not lead to an overt disease in chickens and causes only minor lesions in the bursa of Fabricius. Infection with this strain induces solid protective immunity against infection with the virulent virus.


Structural polypeptides of the enteropathogenic bovine coronavirus strain LY-138. The bovine coronavirus strain LY-138 was purified by differential as well as velocity and isopycnic centrifugation in sucrose or CsCl gradients. The substrate for purification was contents of the small intestine of experimentally inoculated calves. This strain is highly enteropathogenic, but it could not yet be propagated in cultured cells. Intact virions had a density of 1.245 g/cm3 in CsCl and 1.185 g/cm3 in sucrose. A spherical core-like structure with an average diameter of 82 nm remaining after treatment with chloroform had a density of 1.299 g/cm3 in CsCl and 1.201 g/cm3 in sucrose. Seven distinct bands of polypeptides and 4 shoulders were detected after electrophoresis of SDS-solubilized virions in polyacrylamide gels. The approximate molecular weights ranged from 110,000 to 36,000. Four of the bands gave a PAS positive reaction. These 4 glycoproteins and an additional protein with an approximate molecular weight of 70,000 were removed by chloroform treatment. The remaining core-like structure contained the 2 polypeptides VP3 and VP7.


Differences in antibody responses in varicella, herpes zoster and after vaccination. Difference in antibody responses between varicella and herpes zoster was reconfirmed by complement fixation (CF) test and by platelet aggregation (PA) test. Rise in PA antibody level was observed only in patients with herpes zoster, but not in patients with varicella, while the increase in CF antibody was demonstrated in both types of the diseases. Among 235 healthy children, CF antibody was detected in 42 children and out of these 25 also had PA antibody. Sera of 116 individuals who were vaccinated with a live vaccine comprised of varicella-herpes zoster virus (VZV) were tested for CF and PA antibodies. Within six months after vaccination, 81.3 per cent of the vaccinees demonstrated the rise in CF antibody alone, and only one vaccinee possessed low level of PA antibody. Six months to 1 year after vaccination, CF antibody in 12 out of 13 vaccinees fell to undetectable level. Later than 1 year after vaccination, 9 out of 28 vaccinees possessed CF antibody. Two out of these 9 vaccinees also had PA antibody. The PA antigens prepared from viruses isolated either from a varicella patient or a herpes zoster patient responded similarly to the sera of herpes zoster patients, but no response was detected with sera of varicella patients. PA and CF antibody titers of herpes zoster patients showed a high degree of correlation.


Stability and immunogenicity of empty particles of foot-and-mouth disease virus. Three strains of foot-and-mouth disease virus were shown to contain significant amounts of naturally occurring 75S, empty particles as well as the infectious, 140S full particles. One of these strains--A Pando (1970)--was studied in detail. The empty particles from this virus strain were shown to have an observed sedimentation coefficient of 67S in 0.04 M phosphate buffer; they were labile in SDS, non-infectious and probably RNA-free and, on heating, they broke down to 12S subunits as did the 140S particles. The empty particles differed from the full particles in their polypeptide composition since they contained VP0, but there was no evidence for a diminished content of VP4. The 75S particles were shown to be present in significant amounts and to be stable to AEI inactivation. At 4 degrees C they were stable for at least two years. In guinea pigs they were as immunogenic as the 140S particles. The antisera raised against the 75S particles had the same serological specificity in neutralization tests as sera prepared against the 140S particle. It was concluded that the 75S particles from the A Pando (1970) strain of FMD virus may provide as important a contribution as 140S particles to the immunogenicity of inactivated vaccines prepared from this virus strain.


Enhanced antiglobulin-mediated neutralization of herpes simplex virus-IgG complexes by complement and heterologous anti-immunoglobulin. The ability of IgG anti-Fc and anti-Fab to neutralize infectious herpes simplex virus-IgG (HSV-IgG) complexes was determined. When limiting amounts of antiglobulin were used, antibody directed against the Fab portion of human IgG was significantly more effective than anti-Fc antibodies in neutralizing the HSV-IgG complexes. The detection of viral bound antibody was enhanced by the incorporation of heterologous antiglobulin or complement in the antiglobulin neutralization test. Specifically, HSV-IgG which had been incubated with rabbit antihuman globulin was further neutralized by goat antirabbit IgG or guinea pig serum complement. This augmented neutralization test could prove useful in detecting small amounts of antibody bound to virus in infectious isolates from patients or experimental animals with viral diseases.


Amyotrophic lateral sclerosis. Impairment of neuromuscular transmission. Neuromuscular transmission was studied in the ulnar-hypothenar group in 55 patients with amyotrophic lateral sclerosis. A decremental response was found in 67.0%. The decrement was larger and present more often in muscles showing atrophy. In addition, muscles with frequent fasciculations showed a larger decrement than the ones with rare fasciculation. A temperature effect similar to that in myasthenia gravis was observed, with a reduction of the decrement following local cooling of the muscles. Administration of edrophonium chloride improved the synaptic defect. Posttetanic exhaustion was observed as well. It is thought that the defect of neuromuscular transmission is due to a decreased trophic function of the neuron followed by morphological changes at the endplate.


Facial myokymia. Pathological features.

Facial myokymia. Pathological features. Pathologic examination in a case of facial myokymia showed edema and mild astroglial proliferation of the ipsilateral seventh nerve nucleus; gliomatous tumor involvement occurred rostral to this nucleus. These findings give circumstantial support to functional deafferentation as the cause of facial myokymia.


Clostridium perfringens corneal ulcer.

Clostridium perfringens corneal ulcer. A corneal ulcer caused by Clostridium perfringens developed in a 76-year-old woman with Sjögren's syndrome. Experimental C perfringens keratitis was induced in rabbits by the intrastromal injection of 10(7) organisms. In both our patient and the experimental animals, a bullous lesion overlay the affected area of the cornea. This may be a specific lesion in clostridial infections of the cornea. Clostridium perfringens should be regarded as an opportunistic corneal pathogen, and anaerobic cultures should be performed in all cases of suspected bacterial corneal ulcer.


Congenital fibrous lesion of the temporal bone. A neonate had a destructive, fibrous lesion of the temporal bone. There was x-ray evidence of disseminated, lytic disease. A histologic diagnosis of malignant fibrous histiocytoma was made. No treatment was given, yet the child survived with spontaneous resolution of her lesions. We briefly discuss malignant fibrous histiocytoma and propose congenital generalized fibromatosis as an alternative diagnosis to explain the child's recovery.


Alcoholic neuropathies.

Alcoholic neuropathies. Peripheral neuropathy is a common and potentially incapacitating complication of prolonged overuse of alcohol. As a relatively early feature of chronic alcoholism, its early identification is of value in the prevention of other and more dangerous consequences of alcohol abuse. With vigilance, peripheral neuropathy is easily diagnosed before gross incapacity has resulted, but its management entails all the problems encountered in the treatment of chronic alcoholism.


Thyroid-hormone modulation of the number of beta-adrenergic receptors in rat fat-cell membranes. Adipocytes from thyroidectomized rats contain 3 times less [3H]dihydroalprenolol-binding sites (beta-adrenergic receptors) than adipocytes from euthyroid animals. This alteration is not solely due to cell-size differences, but also to a thyroidectomy-induced defect in beta-adrenergic receptor density per adipocyte surface area, a defect that is furthermore corrected by tri-iodothyronine treatment.


Changes in cAMP concentrations during chronic cardiac hypertrophy. Mild pulmonic stenosis in the dog, where right ventricular peak systolic pressure was increased approximately 150% at the time of sacrifice, induced 100% or more increase in right ventricular free wall weight by 3 weeks postoperative. Accompanying cardiac hypertrophy at these postoperative times, there was a decrease in both tissue PO2 levels and cAMP concentrations in the hemodynamically stressed ventricle, the right ventricle. Myosin ATPase activity was elevated as well as the velocity of contractile element shortening. The hemodynamically nonstressed left ventricle did not hypertrophy at these early postoperative times.


Growth and metabolism of fucosylated plasma-membrane glycoproteins in mouse neuroblastoma N2a cells. The presence of 1.0mm-dibutyryl cyclic AMP (N(6),O(2')-dibutyryladenosine 3':5'-cyclic monophosphate) and 1.5mm-theophylline completely inhibits the growth of mouse neuroblastoma N2a cells by 24-36h. When compared with N2a cultures without inhibitors (controls), the proportion of cells in S phase, measured by radioautography with [(3)H]-thymidine, was decreased from 55 to 12%. In addition, the presence of the inhibitors decreased apparent [(3)H]fucose incorporation into glycoproteins by 50%, and removing the inhibitors resulted in a rapid recovery of both DNA synthesis and glycoprotein metabolism. Measurement of intracellular acid-soluble radioactive fucose revealed that decreased fucose uptake could account for the apparent change in incorporation. Removing dibutyryl cyclic AMP and theophylline from the medium resulted in a rapid uptake of radioactive fucose to within control values, which illustrated that the inhibitors decreased transport of the carbohydrate, although the cells remained viable. Treatment with dibutyryl cyclic AMP and theophylline also reversibly inhibited glycoprotein degradation. Plasma membranes isolated from growing cells and from growth-inhibited cells labelled with [(14)C]fucose and [(3)H]fucose respectively were co-electrophoresed on sodium dodecyl sulphate/polyacrylamide gels. These displayed no apparent differences in synthesis of specific membrane glycoproteins. Electrophoresis of plasma membranes isolated from cultures pulse-chased with [(14)C]fucose and [(3)H]fucose was used to discern turnover patterns of specific plasma-membrane glycoproteins. High-molecular-weight glycoproteins exhibited rapid rates of turnover in membranes from growing cells, but moderate turnover rates in growth-inhibited cells and cells reversed from growth inhibition. These data indicate that growth arrest of N2a cells results in alterations in the metabolic turnover of plasma-membrane glycoproteins.


Calcium-dependent protein modulator of cyclic nucleotide phosphodiesterases from mouse epidermis. 1. A heat-stable modulator protein was partially purified from mouse epidermis. The protein stimulated modulator-depleted cyclic AMP phosphodiesterase from bovine brain in the presence of Ca2+. 2. DEAE-cellulose chromatography of epidermal extracts demonstrated the presence of two main phosphodiesterase activities that hydrolysed both cyclic AMP and cyclic GMP. A minor peak was eluted between 0.1 and 0.3 M-sodium acetate and a major peak was eluted between 0.3 and 0.45 M-sodium acetate. 3. Cyclic AMP phosphodiesterase activity eluted at low salt concentrations was markedly activated by the epidermal modulator protein in the presence of Ca2+. Storage of the enzyme led to a decrease in its sensitivity to the protein modulator. 4. Treatment of mouse skin with the tumour promoter 12-O-tetradecanoylphorbol 13-acetate, which leads to an increase in epidermal cyclic nucleotide phosphodiesterase activity, did not alter the amount of modulator present in soluble epidermal extracts. The tumour promoter decreased the amount of modulator extractable from particulate epidermal preparations with Triton X-100.


The effects of cortisol, corticotropin and thyroxine on the synthesis of glycerolipids and on the phosphatidate phosphohydrolase activity in rat liver. 1. Male rats were injected daily for 5 days with 0.15m-NaCl, corticotropin, cortisol or l-thyroxine and the rates of glycerolipid synthesis were measured in the livers after intraportal injection of [(14)C]palmitate and [(3)H]glycerol. 2. Injection of all three hormones decreased the rates of body-weight gain. 3. Cortisol treatment increased the weight of the liver relative to body weight. 4. Thyroxine treatment increased the relative rate of triacylglycerol synthesis from [(3)H]glycerol and decreased the relative accumulation of (3)H and (14)C in diacylglycerol. It did not significantly alter the accumulation of these isotopes in phosphatidate nor the activity of the soluble phosphatidate phosphohydrolase in the total liver. However, this activity increased by 1.5-fold when expressed relative to the soluble protein of the liver. The increased triacylglycerol synthesis appears to be related to a general increase in the turnover of fatty acids in the liver. 5. Treatment with cortisol and corticotropin increased the relative rate of triacylglycerol synthesis from [(3)H]glycerol, decreased the accumulation of (3)H in phosphatidate and increased the flux of both isotopes from phosphatidate to diacylglycerol. This appeared to be caused by the increased activity of the soluble phosphatidate phosphohydrolase that was observed in the livers of the cortisol-treated rats. 6. It is proposed that cortisol could be directly or indirectly involved in increasing the activity of hepatic phosphatidate phosphohydrolase in starvation, diabetes, laparotomy, subtotal hepatectomy, liver damage, ethanol feeding and in obesity. This enzyme adaptation could contribute to the potential of the liver to increase its synthesis and accumulation of triacylglycerols or to secrete very-low-density lipoproteins.