[Investigations on bloodcultures with three culture media containing Na-polyanetholsulfonate (aerobic iso- and hypertonic and anaerobic isotonic (author's transl)]. By using parallel culture techniques 330 blood specimens steming from patients of an intensive care unit were cultured simultanously in 3 media containing 0.05% Na-Poly-anetholsulfonate. Otherwise having an identical composition the media differed in the following respects : the isotonic medium A and the - by additional content of 10% sucrose - hypertonic medium B were used for aerobic culture. The anaerobic and isotonic medium C contained 2% Proteose-peptone, additionally. Without regards to the isolation of strictly anaerobic bacteria a total of 114 positive bloodcultures was obtained (tab. 1). The use of medium A resulted in 81 positive bloodcultures, that of medium B and C in 93 and 50, respectively (tab. 2). With the combined use of media A + B 103 positive bloodcultures would have been detected, with B + C 102, but with A + C 92 only (tab. 2). Of all 3 media the hypertonic medium B promotes bacterial growth most efficiently, but 13 strains grown in A did not grow in B (tab. 3), a fact that leads to the conclusion that isotonic as well as hypertonic aerobic media are employed in parallel advantageously. The effect of the hypertonic medium was expressed most distinctly with the isolation of grampositive bacteria (tab. 4). As during the period of this investigation the intensive care unit was afflicted by an outbreak of Serratia marcescens the predominance of this species among the other isolated microbes (tab. 5) is not surprising. While no difference of detection-time was observed between A and B, microbial growth in medium C seemed to be slower (fig). It was concluded that the use of 3 media, aerobic isotonic and hypertonic as well as anaerobic isotonic should be employed whenever possible.


[The smallpox vaccination strain MVA: marker, genetic structure, experience gained with the parenteral vaccination and behavior in organisms with a debilitated defence mechanism (author's transl)]. The MVA virus is a lab virus ideally suited for vaccination of both man and animal which can be differentiated from the known Vaccinia strains by the use of numerous biological markers. Its reduced virulence for the chick embryo, for experimental animals and for man is a particularly characteristic feature. With the exception of chick embryo fibroblasts, the MVA virus grows in cell cultures only abortively. This applies particularly to cells of human origin in which the cytopathic effect and plaque formation are completely missing. The restriction analysis of the DNS of the MVA virus demonstrates that its genetic structure differs from that of the CVA basic virus and other orthopox viruses. In contrast to the WHO reference strain Elstree, the MVA virus has a genome shortened by about 9 per cent. The use of the MVA virus for human vaccination is particularly indicated in persons to be vaccinated for the first time and likely to entail a risk (on account of allergies etc.) because it brings about a state of revaccination without complications. The MVA virus can be administered in intracutaneous, subcutaneous or intramuscular injections. Innocuoursness and successful vaccination have been demonstrated in more than 120000 persons. While other Vaccinia strains, such as the Elstree virus, experience a drastic increase of virulence in the immunosuppressed organism (subjected to whole-body irradiation), the MVA virus cannot be activated not even in this situation.


[Detection and persistence of human-pathogenic viruses in chemical sludge (author's transl)]. Virological investigations, using poliovirus type I, were carried out on the detection of enterovirus and their persistence in the chemical sludge from a tertiary treatment process, which could be suitable for agricultural and horticultural applications.--A comparison of six eluents showed that tryptose phosphate broth yielded best results allowing approximately 30% overall recovery with the method described. With sludge of low virus content a concentration was possible with alginate filters and the phase separation method.--Examinations on the persistence of poliovirus show that at 5 degrees C and 10 degrees C the inactivation was slow and that virus was detectable over a 15 week period at 5 degrees C.


Isolation and biological characterization of an adenovirus of rhesus macaques. The etiology of a disease in rhesus monkeys the main clinical manifestation of which was acute conjunctivitis of an epizootic character has been studied. The cytopathogenic agent well propagating in primarily trypsinized kidney cells of monkeys has been isolated when investigating the affected eye mucosa. It was not pathogenic for laboratory animals. The mean diameter of the virions is 75 nm, the buoyant density in CsCl is 1.34 g/cm3, the viral DNA density is 1.706 g/cm3. The biological properties and findings of physicochemical, electron-microscopic, and serologic investigations allow one to allocate the isolated agent to the SV-37 strain, a representative of the adenovirus group.


Preparation and properties of a Met-tRNAf binding factor from rat liver and rat hepatoma. A Met-tRNAf binding factor (IF-2) from the microsomal fraction of rat liver and rat hepatoma ascites cells was partially purified by ammonium sulphate fractionation, DEAE-cellulose and phosphocellulose chromatography. The factor binds [3H]Met-tRNAf only in the presence of either GTP or GMPPCP. Maximal binding takes place at 37 degrees C and in the absence of Mg++. The factor is specific for Met-tRNAf and does not bind Phe-tRNA from rat liver or from E. coli. The ternary complex [Met-tRNAf . IF-2 . GTP1 binds to 40 S ribosomal subunits from rat liver in the absence of mRNA or poly(A, G, U) without GTP hydrolysis. GDP as well as aurintricarboxylic acid inhibit the ternary complex formation. Both factors are rapidly inactivated by N-ethylmaleimide treatment and by preincubation at 45 degrees C. Heat inactivation is partially prevented by GTP and GDP. With regard to the functional properties there are no significant differences between IF-2 from normal liver and hepatoma cells. On the other hand heat denaturation compared to the rat liver factor, which may be due to differences in contaminating proteins.


Identification of the soluble HVP-associated antigen of the lymphoblastoid cell line established from lymphomatous baboon (Papio hamadryas). A new technique (indirect double immunodiffusion) for detection of EBV-associated soluble antigen and corresponding antibodies has been developed. This technique includes three steps: 1) simple double immunodiffusion with extracts of Raji cells (or other EBV-genome positive cells) and human sera containing antibodies against EBV-associated soluble antigen; 2) extensive washing and treatment with anti-human globulin; 3) extensive washing and treatment with tannic acid. Using this test it was shown that the soluble antigen indistinguishable from EBV-associated soluble antigen was present in KMPG-1 cells producing HVP.


Shuttles for translocation of NADH in isolated liver cells from fed rats during oxidation of xylitol. Translocation of xylitol-derived NADH via malate-aspartate and alpha-glycerophosphate shuttles was studied in liver cells isolated from fed rats. In bicarbonate medium amino-oxyacetate, rotenone and antimycin A, were equally efficient in depressing the xylitol removal. Incubation of cells in nonbicarbonate medium did not affect the rate of xylitol removal. In this medium amino-oxyacetate and antimycin A, but not rotenone, inhibited xylitol removal. Xylitol inhibited the lactate accumulation found when the cells were incubated without any exogenous substrates. Glucose was the main end product of xylitol oxidation. In nonbicarbonate medium ketogenesis was high, whereas in bicarbonate medium a low rate of ketone body formation was found. Xylitol had no effect on the rate of ketone body formation in either medium tested. Xylitol markedly decreased the ATP and Pi contents of the cells, but no change in the ATP/ADP x Pi ratio or the rate of oxygen consumption was found. The results suggest that NADH formed during xylitol oxidation is translocated to the mitochondria mainly through the malate-aspartate shuttle and only when this shuttle is inhibited does the alpha-glycerophosphate shuttle transfer NADH. Intramitochondrial reactions which form NADH and FADH2 are also suggested to be important regulators of the activity of the alpha-glycerophosphate shuttle.


Electron microscopic detection of papilloma virus particles in selected koilocytotic cells in a routine cervical smear. A routine cervical smear from a 56-year-old postmenopausal woman showed appearances indicative of papilloma virus infection with atypia. In an attempt to prove the diagnosis, the smear was reprocessed for electron microscopic examination. The reprocessing technique is described. Ultrastructural preservation was poor, and significant shrinkage was observed. In spite of these technical difficulties it was possible to prove that the selected cells in the smear contained papilloma virus particles. The virus particles seen were intranuclear in location and spherical in shape with a diameter of 40 to 50 nm. As was demonstrated in this case, the technique described will prove useful in evaluating the reliability of various diagnostic criteria for identifying viral infections in routine smears. This will apply particularly in cases where cultural confirmation of a reported viral infection is not possible.


Diagnosis of a papillary hidradenoma of the vulva by simultaneous cytology and colposcopy. A case of papillary hidradenoma of the vulva is reported, and the simultaneous use of cytology and colposcopy as diagnostic aids is suggested. The cytologic and colposcopic findings are described in detail. The cytologic findings correspond with the histologic pattern of these benign growths.


Malignant cystosarcoma phyllodes a case report with cytologic presentation. The cytologic findings in a fine-needle aspirate of a malignant cystosarcoma phyllodes of the breast are presented. They are characterized by the presence of mononucleated and multinucleated sarcoma cells and clusters of normal or hyperplastic duct epithelial cells. The histogenesis and subclassification of the stromal portion of this rare neoplasm are discussed.


Effects of prolonged infusions of potassium chloride, adrenocorticotrophin or angiotensin II upon serum aldosterone concentration and the conversion of corticosterone to aldosterone in rats. The temporal relation between alterations in serum aldosterone and in the conversion of labelled corticosterone to aldosterone by incubated adrenal tissue was studied in conscious rats receiving long-term infusions of KCl, ACTH or angiotensin II. When potassium-deficient rats were given KCl, a marked increase in serum aldosterone was observed only after 12 h, i.e. at a time when the conversion of corticosterone to aldosterone had become normal. After 24 h of ACTH infusion into sodium- and potassium-replete rats the serum aldosterone was markedly elevated, whereas the conversion of corticosterone to aldosterone was significantly decreased. After 48 h of continued ACTH infusion the serum aldosterone returned to normal and there was a further decrease in the conversion rate. A 24-h angiotensin II infusion into sodium- and potassium-replete rats induced significant increases in both the serum aldosterone and the conversion. After 48 h of continued angiotensin infusion the serum aldosterone returned to normal while the conversion and the blood pressure remained elevated. These results indicate that the activity of the enzymes involved in the final steps of aldosterone biosynthesis may become rate-limiting for the secretion of aldosterone during potassium deficiency and during prolonged ACTH treatment. On the other hand, the observed transiency of aldosterone stimulation by exogenous angiotensin II was not due to a suppression of the final steps of aldosterone biosynthesis and remains unexplained.


Metabolic effects of glucagon in endogenous hypertriglyceridemia. The metabolic effects of glucagon, administered i.v. in doses of 1 microgram/kg, were evaluated in two groups of patients with endogenous hypertriglyceridemia (Types IV and V according to Fredrickson) with normal and reduced glucose tolerance and in a control group. Glucagon had a lipolytic effect, evaluated as the plasma increase of free fatty acids (FFA) during the first 20 min in normal subjects, but not in the two hyperlipemic groups. A negative correlation was observed between fasting IRI level and FFA mobilization. The ketogenic and hypotriglyceridemic effects of glucagon were demonstrated in normal and hyperlipemic groups. It would seem, therefore, that at the pharmacological doses injected, there is no resistance to the hypotriglyceridemic effect of glucagon in endogenous hypertriglyceridemia.


Changes in mitochondrial redox state following an oral glucose load. Changes in cytosol and mitochondrial redox state after an oral glucose load were studied in the liver of rats. The [NAD+]/[NADH] ratios increased 4-fold in the cytoplasm and 1.5-fold in the mitochondria 60 min after an oral glucose load, when serum IRI was maximally increased. It is suggested that an increase in mitochondrial redox state following an oral glucose load is due to an enhanced rate of removal of NADH by the respiratory chain, possibly due to an elevated level of insulin available to hepatocytes, and that an increase in cytosol redox state depends on an enhancement in mitochondrial oxidation of cytosol reducing equivalent.


[Comparative histoenzymological demonstration of certain digestive enzymes in the intestinal epithelium of the mouse and the chicken during a 24-h-period (author's transl)]. At different times of the day activities of hydrolytic (alkaline and acid phosphatase, esterase) and oxydative (succinodehydrogenase, cytochromoxidase, monoaminoxidase) enzymes were studied in the epithelium of the upper part of the jejunum in the adult female mouse and the adult laying chicken. In both species the activities of the intestinal enzymes showed marked circadian variations with respect to their activity and distribution pattern. The variations did not principally differ in both species. The species' differences were mainly expressed by phase shifts of about 12 h in the occurrence of maximal and minimal activities according to the different phases of the locomotor activity of the mainly night-active mice and day-active chickens.


The effect of acute alloxan diabetes on the sensitivity of the rat skeletal neuromuscular junction to drugs. Preparations from alloxan diabetic rats showed a reduced sensitivity to the neuromuscular blocking action of (+)-tubocurarine but no alteration in sensitivity to the depolarizing neuromuscular blocking drug decamethonium. Physostigmine was less effective in augmenting twitch height in preparations from alloxan diabetic rats and such preparations had a significantly lowered total cholinesterase activity compared with control preparations. An additional observation was a reduction in the effectiveness of the pre-junctionally active agent beta-bungarotoxin in producing neuromuscular blockade in physostigmine-treated preparations from alloxan diabetic rats. All the changes produced by alloxan administration were prevented by treatment with insulin.


Farber's disease (disseminated lipogranulomatosis)--a pathological, histochemical and ultrastructural study--. The first case of Farber's disease in Japan was reported, which was confirmed clinically, biochemically and pathologically. Soon after birth, the patient started developing hoarseness, stridor, fever, muscle hypotonous with retarded psychomotor functions including incapability of sitting alone and head control, joint swelling, subcutaneous nodules, albuminocytologic dissociation in cerebrospinal fluid, nodular corneal opacity, and abnormal findings in electroencephalogram. Lipid analysis on the material obtained from a subcutaneous nodule confirmed the presence of ceramide. Pathologically, the subcutanoues nodules were made up of granulomatous lesions displaying varied histological pictures, i.e., from cellular to fibrous areas depending on the disease progress. In the beginning, cells were mostly spindle-shaped, and as these cells were getting more round and larger, cells manifested the morphology of foam cells. Spindle-shaped cells were positive for periodic acid-Schiff and acid mucopolysaccharide stainings. This particular substance disappeared almost entirely in typical foam cells. Electron microscopically, the cytoplasm of foam cells was filled with membrane-bound storage inclusions which consisted of so-called curvilinear tubular structures. Morphogenesis of the granulomatous lesions and histochemical and ultrastructural correlation of storage cells in this disorder were discussed.


Electron microscopic studies of the effect of ACTH and flavin-adenine dinucleotide on adrenocortical atrophy of rats treated with dexamethasone phosphate. In a previous paper the authors described the morphologic observations that the concomitant administration of ACTH and flavin-adenine dinucleotide (FAD) to hypophysectomized rats exerted a more potent preventive effect on atrophy of the adrenal cortex of the animals than the single administration of ACTH. The present study was made to electron-microscopically observe the effect of concomitant administration of ACTH and FAD on atrophy of the adrenal cortex induced with the administration of dexamethasone (Dx). The zona fasciculata of the adrenal gland of rats treated with Dx+ACTH+FAD was morphologically closer in cell organelles such as smooth-surfaced endoplasmic reticulum, mitochondria and chylomicrons to that of control animals than the counterpart of animals treated with Dx+ACTH only. The zona fasciculata of the adrenal cortex of animals treated with Dx+FAD was morphologically similar to that of animals treated with Dx only. These findings suggested that FAD would potentiate the adrenocorticotropic action of ACTH through its physiologic action.


Syndrome of the sea-blue histiocyte--the first case report in Japan and review of the literature--. A case of the syndrome of sea-blue histiocyte is presented in a 53-year-old Japanese woman, which is the first recorded case in Japan. The patient had hepatosplenomegaly, bleeding manifestations, mild thrombocytopenia, fatty metamorphosis and cirrhosis of the liver, as well as abnormal serum lipid profiles. Her parents were consanguineous and her maternal grandmother with hepatomegaly died of hepatic failure. Histologically, peculiar histiocytes containing numerous, intracytoplasmic sea-blue stained granules on May-Giemsa stain were demonstrated in biopsy materials of the bone marrow, lymph node and liver. The sea-blue granules in these histiocytes proved to have histochemical staining characteristics of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic inclusions of heterogeneous nature, including electron-dense amorphous or variegatedly osmiophilic, frequently laminated materials. Enzyme cytochemically, localization of acid phosphatase activity was demonstrated in and around the intracytoplasmic inclusions. With regard to the pathogenesis of the sea-blue histiocytes in this case, it may be suggested that the existence of the abnormality in lipid metabolism plays an important role in intralysosomal ceroidogenesis in these histiocytes.


Density determinations of human parathyroid glands by density gradients. The densities of human parathyroid glands were measured in density gradient columns of various media. Percoll (an aqueous colloidal solution of polyvinylpyrrolidone-coated silica), equilibrated to 300 mOsm with sodium chloride, was found to be the ideal gradient medium for density measurements of tissues with a density greater than 1.0 g/ml. which includes most parathyroid glands. The densities of the glands varied between 0.96 and 1.06 g/ml. Density measurements in gradients of Percoll were simple and reproducible and were made with an accuracy of approximately 0.001 g/ml. In other gradient media (aqueous solutions of sucrose and Ficoll, and organic solvents) there was a drift in density caused by osmotic or lipid-solving effects of the media. For measurements of densities less than 1.0 g/ml no ideal gradient medium was found, but a silicon oil or carbon tetrachloride/kerosone gradient could be used with somewhat reduced accuracy. It is concluded that the density gradient technique with the use of Percoll is potentially useful as a complement to routine histopathological parathyroid diagnosis, as glandular density is a good indicator of the relative proportions of parenchymal and fat tissue.


Neutralization of aggregated strains of enterovirus 71 and echovirus type 4 in RD and Vero or GMK-AH1 cells. Strains of enterovirus 71 and echovirus type 4 containing aggregates which were poorly neutralized by antibody in cell lines of green monkey kidney origin such as Vero and GMK-AH1, were as easily neutralized as non-aggregated strains when grown in human RD cells, The explanation for this may be a lesser degree of aggregation of viral materials originating from RD cells and/or the use of lower doses of virus for neutralization tests in such cells. The latter was a consequence of a higher sensitivity of RD cells to minimal amounts of virus than that shown by Vero and GMK-AH1 cells. Thus, virus grown in RD, Vero or GMK-AH1 cells reached a titre 10 to 100 times higher in RD cells than in the other cell lines.


Effect of di-(2-ethylhexyl) phthalate on rat liver injured by chronic carbon tetrachloride treatment. The effect of Di-(2-ethylhexyl) phthalate (DEPH), a widely used plasticizer, was studied using histopathological and biochemical parameters on rat liver injured by carbon tetrachloride (CCl4). The mild centrilobular necrosis observed with CCl4 (7.7 mmol/kg subcutaneously and biweekly up to 38 days) and mild congestion and bile duct proliferation produced by DEHP (2.5 mmol/kg intraperitoneally daily for ten days after the day 28 of experiment) were modified into extensive necrosis of the parenchymal cells when the animals received both chemicals. Groups of hepatocytes mostly at the periphery of the lobules also showed coagulative necrosis and some central and portal veins were completely occluded. Alterations in the activity of serum and liver enzymes of the animals receiving both chemicals were not significantly different from those treated with CCl4 alone, except in case of glucose-6-phosphatase (G-6Pase) and SGPT. The characteristic decrease of G-6-Pase and increase of SGPT was less marked. Although the exact mechanism of the chemical interaction between CCl4 and DEHP is not known, the results indicate their combined toxic potentiality.


Primary and metastatic scirrrhous carcinoma of the rectum. Eight cases of scirrhous carcinoma of the rectum are described. Five patients had primary lesions and three had metastases from stomach and breast. Radiographic features were severe rectal narrowing, rigidity, and smooth contours or, more commonly, moderate narrowing, distorted nodular folds, and an irregular serrated contour mimicking inflammatory disease. Difficulties in the radiologic and histologic diagnosis and a short review of pertinent literature are reported.


Prognostic value of a persistently positive technetium-99m stannous pyrophosphate myocardial scintigram after myocardial infarction. Technetium-99m stannous pyrophosphate myocardial scintigrams were obtained in 138 clinically stable patients 32.7 +/- 47.3 weeks (range 6 to 260) after acute myocardial infarction. Of the 138 patients, 74 (54 percent) had a persistently positive scintigram. Patients with such a scintigram were more likely to have severe angina pectoris, compensated congestive heart failure, anterior location of acute myocardial infarction, Q waves and S-T segment elevation in the electrocardiograms, cardiomegaly, left ventricular dyssynergy (dyskinesia or global dyssynergy), and an ejection fraction of less than 50 percent. During a follow-up period of 11.6 +/- 6.9 months after scintigraphy, 42 percent of the patients with a persistently positive scintigram had either a cardiac death, a nonfatal myocardial infarction, unstable angina pectoris or decompensated congestive heart failure compared with 13 percent of the patients with a negative scintigram (P less than 0.001). Of the 14 patients with cardiac death, 13 (93 percent) had a persistently positive scintigram. A persistently positive scintigram not only was the best single predictor of cardiac death and combined end points, but also added significantly to the predictive ability of the other clinical variables, including age, location of acute myocardial infarct, clinical status, electrocardiographic findings, and chest X-ray findings. It is concluded that technetium-99m stannous pyrophosphate myocardial scintigraphy has prognostic value in patients after acute myocardial infarction.


Changes in the fine structure of tanycytes during the annual reproductive cycle of the male little brown bat Myotis lucifugus lucifugus. The hypothalamic arcuate nucleus in the male little brown bat Myotis lucifugus lucifugus was studied with the electron microscope. Animals were killed by intracardial perfusion at each season throughout the year so that the arcuate nucleus could be examined for seasonal variations in morphology. Striking seasonal changes in the fine structure of ependymal tanycytes lining the arcuate nucleus were observed. Tanycytes in animals collected in the fall and early winter exhibited pale processes characterized by a scant internal framework of microtubules and fine filaments. These processes, which were found throughout the arcuate nucleus, exhibited simple irregular shapes. In animals collected between January and June, tanycyte processes contained dense accumulations of fine filaments intermingled with microtubules, and projected long attenuated extensions that often formed multilamellar sheets around axodendritic terminals or other neuronal elements. Tanycyte processes of animals collected in July and August were densely packed with microtubules and fine filaments. The processes radiated elaborate multilamellar extensions that encapsulated axons, dendrites and even entire neuronal perikarya. Multilamellar sheets consisted of as many as 10 or 12 closely spaced gyres. The seasonal variations in tanycyte structure are suggestive of astrocyte-like behaviour. These changes are discussed with respect to seasonal changes in hypothalamic neuroendocrine activity.


Effect of a standardized wheat bran preparation on serum lipids in young healthy males. Feeding of a chemically standardized coarse wheat bran product in a dose of 0.5 g/kg body weight per day over a period of 4 weeks in young healthy male volunteers did cause a significant reduction in total serum cholesterol as well as in total serum triglycerides of 10 and 24%, respectively. Very low density lipoprotein-, high density lipoprotein-, and low density lipoprotein-cholesterol levels tended to diminish during bran feeding. The most marked reduction was observed in the high density lipoprotein- cholesterol fraction. Although the duration of this study was relatively short, it is concluded, that these results could have therapeutic consequences for the dietary management of hyperlipidemia. However, the lowering of high density lipoprotein-cholesterol could also be interpreted as unfavorable since an inverse relationship between high density lipoprotien-cholesterol levels and the occurrence of coronary heart disease has been established.


The effect of coffee consumption on plasma lipids, lipoproteins, and the development of aortic atherosclerosis in rhesus monkeys fed an atherogenic diet. Rhesus monkeys (seven females and six males) were fed ad libitum a diet comparable to that consumed by humans, containing 25% by weight fat (40% of calories) and 0.15% cholesterol (0.3 mg/kcal) for 12 months (phase 1). From the 13th month all monkeys were continued on the diet while four females and three males were given 50% coffee as their fluid intake and the remainder were water controls (phase 2). Major changes in total plasma lipids and lipoprotein profiles occurred within 3 months and generally plateaued thereafter. Total plasma protein remained constant while total plasma cholesterol, phospholipids, triglycerides, and free fatty acid levels increased. After the initiation of coffee, there was no difference between the diet-water group and the diet-coffee group with respect to total protein and lipids in plasma. Total concentrations of plasma lipoproteins varied throughout the study. The pre-beta (very low density lipoproteins) fraction remained constant while the beta (low density lipoprotein) and alpha (high density lipoprotein) fractions, along with their major components, increased within 3 to 6 months, then fluctuated in absolute weight thereafter. The introduction of 50% coffee was without effect on the dynamic changes in these fractions as fluctuations were found in both groups and to the same magnitude. This leads the authors to suspect that such variations are "normal" or are in response to the diet per se. The atherogenic diet induced fatty streaks in the aortas of all monkeys to a greater extent in males than females. However, there were no gross differences in the quantity or distribution of the streaks between control and coffee-drinking monkeys.


Studies on the quality of breast milk during 23 months of lactation in a rural community of the Ivory Coast. Milk samples from 33 women from a rural area of the Ivory Coast were analyzed once a month. In two longitudinal studies covering 23 months of breast feeding, analyses of lipid components and protein were performed. The compositions remained virtually constant over 23 months of lactation except for a decrease of protein concentration during the first 6 months, a rising trend of myristic acid (14:0) and a falling trend of oleic acid (18:1). Infants were growing well on breast milk with nothing else for the first 5 months, but thereafter their growth curves were no longer satisfactory as judged by Western standards: weight for age (percentage of Harvard standards) decreased from 5 to 10 months of age to level off thereafter at a value of 80%. The mothers' weight for height remained constant. In a cross-sectional study, additional determinations were performed: aminograms, lactose, calories, iron, copper, manganese, zinc, and vitamin E. All data were compared with those of the literature. Lauric (12:0) and myristic (14:0) acids were higher, total lipids and polyunsaturated fatty acids lower than those published for Western countries. Plasma composition of the mothers showed lower levels of albumin, lipids, and polyunsaturated fatty acids as well as blood hemoglobin. Possible correlations between various variables such as milk composition, plasma levels, and anthropometry were calculated and discussed.


A nonencapsulated sclerosing lesion of the breast. A histological study of 15 examples of a unique proliferative and tubular lesion (Fenoglio and Lattes) of the breast was performed. Although it consistently lacked infiltration of adipose tissue, the commonality of some of its morphologic features and those of tubular cancer provokes the possibility that these lesions may represent incipient tubular cancers. Nevertheless, such lesions may be satisfactorily treated by simple excision. Since we are certain only about its topographic and clinical behavior, but not its precise biologic nature, we regard the designation nonencapsulated sclerosing lesion most appropriate. Stromal and periductal elastosis was not infrequently encountered in examples of overt sclerosing and blunt ductal adenosis which may mimic, but can readily be distinguished from, the nonencapsulated sclerosing lesion.


Adenovirus hepatitis in an immunosuppressed adult patient. The role of adenovirus as an etiologic agent of hepatic damage has been controversial. A fatal case of adenovirus infection with fulminant hepatitis in a young immunosuppressed adult patient is presented. Intranuclear inclusions were confined to the liver. Electron microscopy revealed crystalline arrays of virions within hepatocytes. This is apparently the first reported case of adenovirus hepatitis occurring in an adult. Adenovirus hepatitis represents another hazard for the immunosuppressed patient.


Acquired cytomegalovirus infection in preterm infants. Small sick preterm infants requiring care in a neonatal intensive care unit for more than 28 days were cultured for cytomegalovirus in urine and/or nasopharynx during two periods lasting a total of 13 months. Sixteen of 51 such infants began excreting the virus at 28 to 148 days of age (mean, 55 days). In 14 of the 16, a recognizable, self-limited symptom complex developed that consisted of respiratory deterioration, hepatosplenomegaly, a remarkable gray pallor, and both an atypical and absolute lymphocytosis. All of the infants with the clinical symptom complex had underlying chronic lung disease and all had received multiple blood transfusions during their hospitalization. Acquired cytomegalovirus may be relatively common in sick preterm infants and should be distinguished from other causes of rapid deterioration.


Preoperative embolization of Wilms' tumors. In two patients with Wilms' tumors, the ipsilateral kidney was nonfunctional. To facilitate initial surgical removal of the tumors, a preoperative transcatheter embolization was performed following diagnostic arteriography. Preoperative embolization of a renal tumor reduces the vascularity of the lesion prior to surgery, and a patient in whom primary surgical removal of the tumor would carry unacceptable risk may be converted into one in whom primary surgical removal is safe.


Hepatoma in a child with neurofibromatosis. A 6-year-old girl had neurofibromatosis and hepatocellular carcinoma (hepatoma). Although neurofibromatosis is a common disorder, hepatic cancers are rare in childhood. Hepatic cancer, Wilms' tumor, and adrenocortical neoplasia are all seen with increased frequency in association with certain congenital anomalies, particularly with hemihypertrophy and various hamartomas. Neurofibromatosis, a hamartomatous disorder, is also seen with these congenital anomalies and it is reported with an unusually high incidence in patients with Wilms' tumor. We therefore suggest that these disorders may be related.


Impact of swine influenza vaccine on serum antibody. Comparison of a 1976 serum survey with one of 1977 has permitted an assessment of the impact of the national swine influenza vaccine program of 1976-1977 on the antibody status of the Michigan population. Prevalence of HI influenza virus antibody in premarital sera collected in 1976 prior to the vaccine program was compared to that in similar sera collected in 1977. Overall prevalence of A/New Jersey antibody (titers greater than or equal to 1:10) in 1976 sera was 22.3%. Little antibody was detected in sera from persons less than 40 years of age and prevalence peaked at age 50. Increased antibody prevalence was found for all age groups in sera collected in 1977 following the vaccine program, and the overall prevalence was 41.6%. Only 3.5% of those under 19 years of age were vaccinated, and post-vaccine prevalence for this group was 10%. This age group, comprising about 30% of the state population, appears to have had least exposure to swine influenza virus, and may be the population segment at greatest risk of infection should strains of this antigenic composition reappear. In contrast, highest prevalence of A/Victoria antibody was found in the 15 to 19 age group, where prevalence was 52%, compared to an overall prevalence at 40%.


Small cell lung cancer. Complete remission and improved survival. Thirty-two patients with limited-stage small cell lung cancer were treated with combined supervoltage radiotherapy and a combination of cyclophosphamide, doxorubicin and vincristine chemotherapy. The goal of obtaining a complete remission, the necessary step which precedes improved survival, was successful in 26 of 27 of completely re-evaluated patients. Fiberoptic bronchoscopy was useful in substantiating complete remission status. Seventeen of the 32 patients remain alive from 8+ to 28+ months (median 16+ months). Ten patients are alive and relapse-free from 12+ to 28+ months (median 19+ months). Transient granulocytopenia (mean nadir 650 cells/mm3) during induction therapy and the associated risk of infection were the most serious toxicities encountered. This therapy produces complete remission on roentgenography and bronchoscopy, symtomatic improvement and improved survival in the majority of patients with limited-stage small cell lung cancer. A portion of these patients may have their disease eradicated.


Feedback-controlled dextrose infusion during surgical management of insulinomas. Through the use of a feedback-controlled dextrose infusion system, we obtained continuous monitoring of the blood glucose level in a patient undergoing surgery for multiple pancreatic beta-cell tumors. In addition, this device infused dextrose at variable rates to maintain a predetermined euglycemic level of 90 mg/dl. Before locating the source of excessive insulin production, the maximum dextrose infusion rate of 400 mg/min was required; but after extirpation of multiple insulinomas, the dextrose-infusion rate declined whereas the blood glucose level rose above the preselected level. These results emphasize the usefulness of a monitoring and infusion system not only in protecting the patient from the hazard of hypoglycemia under anesthesia but also as an aid in determining whether all insulin-secreting tumors have been removed.


Hexamethylmelamine: an evaluation of its role in the treatment of ovarian cancer. Hexamethylmelamine (HMM), NSC 13875, a synthetic agent structurally related to triethylenemelamine, has clinical antitumor activity and a role in the treatment of ovarian cancers of epithelial origin. Fifty-four patients, with International Federation of Gynecology and Obstetrics Stage III or IV carcinomas, previously untreated with chemotherapy or irradiation therapy, were treated with HMM (8 mg/kg/day) as a single agent at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, between January, 1973, and May, 1976. The response end points analyzed were complete plus partial response rate, duration of remission, and survival time. The complete and partial responses were verified whenever possible by "second-look" operation. Seventeen patients (31.8%) responded to HMM and three had no evidence of cancer, determined by multiple biopsies at second-look operation. Gastrointestinal, hematologic, and nervous system toxic effects were severe in 10 patients, requiring discontinuation of HMM. This study shows that HMM can induce a complete response and provide an extended disease-free interval without maintenance  chemotherapy.


Primary mucinous sweat gland carcinoma of the eyelid simulating metastatic carcinoma. A 78-year-old man suffered an unusual variant of sweat gland carcinoma of the eyelid. This disorder is seldom recognized, and is frequently confused with inflammation, benign neoplasms, and metastatic carcinomas. On the basis of clinicopathologic and ultrastructural features found by both light and electron microscopy, we diagnosed sweat gland carcinoma of the eyelid. We considered the possibility of metastasis from a primary carcinoma elsewhere in the patient.


Multiple choroidal metastasis from bronchial carcinoid treated with photocoagulation and proton beam irradiation. A 23-year-old man had bilateral multiple choroidal lesions eight years after removal of a bronchial carcinoid tumor. Choroidal biopsy confirmed that the clinical diagnosis and conventional radiotherapy to one eye resulted in rubeosis iridis, neovascular glaucoma, cataract, and vitreous hemorrhage. We were able to destroy the tumors in the other eye by photocoagulation and proton beam irradiation without any adverse effects. The patient is in good health 1 1/2 years after therapy and he has 6/6 (20/20) vision in the eye that was treated.


Cellular toxicity of gentamicin.

Cellular toxicity of gentamicin. Subconjunctival injections of gentamicin induced a lysosomal storage process within the conjunctival fibroblasts in rats, rabbits, and humans. Under electron microscopy, the accumulated substance was composed of a granular material and pleomorphic lamellar structures, corresponding to the presence of complex lipids. In animals, the other ocular tissues as well as the cells reached through the bloodstream remained unaffected, except the proximal convoluted tubules of the kidneys, where important lesions were evident. Although human kidneys were not examined in our study, we believe they might present similar alterations.


Monocyte and granulocyte defect in chronic lymphocytic leukemia. Enzymatically homogeneous populations of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from 5 untreated patients with chronic lymphocytic leukemia (CLL) and 2 patients with CLL in full remission. The cells were then quantitatively analyzed for six leukocytic enzymes and compared with cells from normal subjects. CLL monocytes were deficient in beta-glucuronidase (0.06 units; normal, 0.16), myeloperoxidase (0.07 mg; normal, 0.5 mg), and lysozyme (0.7 mg; normal, 3.3 mg). In 2 cases, CLL neutrophils were severely deficient in lysozyme (1 to 2 mg; normal, 7 mg) and myeloperoxidase (2 to 3 mg; normal, 7 mg). Neutrophil alkaline phosphatase and neutral protease were unaffected. CLL lymphocytes shared with the monocytes the deficiency of beta-glucuronidase (0.03 units; normal, 0.09 units). The 2 CLL patients in full remission carried normal enzyme levels in leukocytes of all three cell lines. The CLL lymphocytes of untreated patients were unresponsive to mitogens but became responsive in remission. The CLL monocytes from both untreated and treated patients transformed into macrophages. The pattern of shared enzyme deficiency among lymphocytes, monocytes, and neutrophils of CLL patients and its normalization in all three cell types under remission suggest that the differentiation of the three leukocytic cell lines may be an enzymatically interlinked process and that the deficiency of these enzymes in leukemia may reflect an interrelated aberrant differentiation of the leukemic cells.


Pathogenesis of reactivated latent murine cytomegalovirus infection. Sixteen weeks after inoculation, murine cytomegalovirus (MCMV) can no longer be detected in the tissues of mice. However, a 2-week course of immunosuppression with antilymphocyte serum and cortisone acetate results in reactivation and dissemination of the latent virus in all animals. In this study of reactivation, MCMV was first detected in the liver, usually during the first week of immunosuppression, and virus replication was shown to be restricted to hepatocytes. Subsequently, a viremia occurred, with spread of infection to other organs. The highest titers of virus were reached in salivary glands in which replication occurred in serous acinar cells. In the lung, virus-specific abnormalities were difficult to detect because of superimposed bacterial and fungal infections. However, interstitial pneumonitis could be produced when cortisone acetate was deleted from the immunosuppressive regimen. Although the site of virus latency has not been defined, this model system will be useful for study of reactivation of latent cytomegalovirus infection.


Superoxide production induced in rabbit polymorphonuclear leukocytes by synthetic chemotactic peptides and A23187. SYNTHETIC FORMYL METHIONYL CHEMOTACTIC PEPTIDES INDUCE THE VARIOUS MANIFESTATIONS OFTHE RESPIRATORY BURST: increased 0(2) consumption, activation of the hexose mono-phosphate shunt, and increased production of superoxide (0(2) (-)) and H(2)0(2). They do soalone but to a much greater extent when in the presence of cytochalasin B. Superoxidegeneration by the chemotactic peptides in the presence of cytochalasin B shows thesame relationship of structure to activity as does the stimulation of chemokinesis andchemotaxis, granule enzyme secretion, and neutrophil aggregation by these sameagents. Carbobenzoxy-phenylalanyl-methionine, CBZ-Phe-Met, competitively inhibitsthe induced stimulation of locomotion, granule enzyme secretion, and neutrophilaggregation caused by the synthetic peptides. It also is a competitive inhibitor of O(2) (-) generation by the same peptides. The structure-activity and the competitive inhibitor studies lead to the conclusion that in polymorphonuclear leukocytes the chemotactic peptides induce superoxide formation and presumably the other manifestations of the respiratory burst by interacting with the same membrane receptor responsible for the stimulation of chemokinesis, chemotaxis, granule enzyme secretion, and neutrophil aggregation. The effectiveness of formyl-methionyl-leucyl-phenylalanine, F-Met-Leu-Phe, in generating 0(2) (-) is greatly reduced but not abolished by removing calcium from the external medium. The calcium ionophore A23187 induces 0(2) (-) generation that requires external calcium and is greatly enhanced by cytochalasin B. From these findings we hypothesize that the proximate cause of the induction of 0(2) (-) formation and other manifestations of the respiratory burst by the chemotactic peptides is the influx into the neutrophil of Ca(2+) and/or possibly Na(+) previously shown to be induced by the peptides.


Effects of thyroid deficiency and sympathectomy on cardiac enzymes. The effects of thyroid deficiency (Td) and of chemical sympathectomy (Sx) were studied on marker enzymes of energy metabolism in cardiac muscle of neonatal and of adult rats. Td prevented the normal development of neonatal body weight, relative heart mass, and cardiac levels of cytochrome c (-22%), citrate synthase (-27%), phosphofructokinase (-20%) and Mg2+- and Ca2+-ATPase activity of purified myofibrils (-33%, -44%). Exogenous thyroxin replacement restored those parameters studied to normal with the exception that it persistently elevated citrate synthase activity significantly above normal control levels. Responses similar to those of Td neonates occurred when adult rats were similarly treated. Sx produced no consistent effects on respiratory and glycogenolytic marker enzymes, but caused a 20% reduction in Ca2+-ATPase activity of both neonatal and adult cardiac myofibrils. These findings suggest that cardiac muscle cells require thyroxin for normal growth and enzyme development. Also, Sx may impair cardiac functional capacity by altering Ca2+ activity of actomyosin ATPase.


Myasthenia in frogs immunized against cholinergic-receptor protein. Frogs immunized with cholinergic-receptor protein developed myasthenia in 116--175 days. The muscular weakness was overcome by subcutaneous administration of 20 microgram of neostigmine. Electromyograms showed a decline in action potential amplitude during a 2-Hz train. Nerve stimulation evoked subthreshold end-plate potentials (EPPs) averaging 10.4 +/- 7.4 mV, but at many junctions no EPP was obtained. Miniature EPP amplitude had a modal value of 0.15 mV compared with 0.35 mV for the controls. The corresponding means were 0.24 +/- 0.23 mV and 0.48 +/- 0.23 mV. Microperfusion with edrophonium (5 mg/l) increased the amplitude of EPPs and miniature end-plate potentials (MEPPS). Postjunctional response tested with 20 muM carbamylcholine was 56% of control. Postjunctional response by carbamylcholine iontophoresis gave 19 +/- 22 mV/nC compared with 76 +/- 50 mV/nC for the controls. The data indicate that the neuromuscular transmission deficits in receptor-immunized frogs are mainly postsynaptic in origin, but there may be additional presynaptic contributions. This amphibian model of myasthenia gravis offers many opportunities and advantages in the study of receptor-immunized animals.


Effect of tolbutamide on plasma renin activity. The effect of tolbutamide on renin secretion in rats was studied in vivo, and in vitro. Administration of tolbutamide in doses of 12.5 and 25 mg/kg body wt ip to two groups of rats produced no significant change in plasma renin activity compared to the control group. In the in vitro experiments renal cortical slices were incubated with increasing concentrations of tolbutamide (0--4 mg/ml). No significant increase in the net renin production was observed, whereas the concentration of cyclic AMP increased significantly in the incubation medium. These findings suggest that in the intact rats tolbutamide does not increase plasma renin activity. In the renal cortical experiments although tolbutamide increased cyclic AMP production, the increase may not have been sufficient to stimulate the net renin production. These results are of biological significance because of the possible effects of tolbutamide and increased plasma renin activity on the cardiovascular system.


Sodium-coupled chloride transport by epithelial tissues. There is compelling evidence that active Cl absorption by a variety of epithelia, widely distributed throughout the animal kingdom, is the result of an electrically neutral Na-coupled transport process at the luminal membrane and that the energy for transcellular Cl movement is derived from the Na gradient across that barrier. These co-transport processes are found predominantly in "leaky" or "moderately leaky" epithelia and permit these tissues to absorb Na and Cl with high degrees of efficacy. In addition, there is a growing body of evidence that cyclic AMP and Ca-induced electrogenic Cl secretion by a wide variety of epithelia may involve electrically neutral, Na-coupled Cl entry across the contraluminal membrane and that the energy for these secretory processes is derived from the Na-gradient across that barrier. A model for electrogenic Cl secretion that accounts for the available data is presented.


Time course of the renal response to triiodothyronine in the rat. Experiments were carried out to compare temporal changes in glomerular filtration rate (GFR), filtered Na+ load, and renal cortical (Na+ + K+)-adenosine triphosphatase (Na-K-ATPase) activity in the hypothyroid rat after administration of a single dose of triiodothyronine (T3) (50 microgram/100 g body wt). The cortex showed an increase in Na-K-ATPase at 24 h and progressive increases to a peak of 62% at 48 h. GFR and filtered Na+ load showed no changes at 24 and 48 h. At 72h, however, significant increases of 62 and 63% (per rat) were observed in GFR and filtered Na+ load, respectively. The results show that the early increase in Na-K-ATPase activity upon T3 treatment precedes the increases in GFR and filtered Na+ load, suggesting a direct effect of T3 on the regulation of Na-K-ATPase activity in the hypothyroid rat kidney cortex, rather than a secondary response to a primary increase in filtered Na+ load as proposed previously.


Development of angiotensin-converting enzyme in fetal rat lungs. Angiotensin-converting enzyme (ACE) catalyzes rapid hydrolytic cleavage of angiotensin I to form angiotensin II (AII). Inasmuch as converting enzyme activity is present at birth and increases postnatally to adult values it was of interest to determine the prenatal development of ACE. Converting enzyme activity was determined in the 20,000 x g supernatant fraction of lung homogenates using hippuryl-L-histidyl-L-leucine (HHL) as substrate. Hippuric acid liberated by the hydrolysis of HHL was quantified spectrophotometrically. ACE activity was first detectable at 18 days of gestation and increased fourfold prior to birth (21 days gestation). Pulmonary ACE activity of 1-day-old animals was twice that of fetuses at day 20 of gestation; however, this increase did not appear to result from ventilation alone. The Michaelis-Menten constant for fetal ACE (2.0 mM HHL) was not different from that calculated for ACE of adult rat lungs (2.6 mM). These data were interpreted to indicate that the age-related increase in ACE activity was due to greater ACE content as opposed to further activation of preexisting enzyme. This increase in fetal ACE activity may play an important role in preparing the renin-angiotensin system for postnatal function.


alpha-Sympathetic control of glucose output of mouse liver perfused in situ. Electrical stimulation of perivascular nerve bundles of mouse liver perfused in situ at constant flow resulted in an increase of glucose production that was maximal at 20 Hz. The neurally induced glucose output was inhibited significantly by the beta-blocker propranolol, and to a considerably greater extent by the alpha-blockers, phenoxybenzamine and phentolamine. The effect of 20-Hz electrical stimulation could be matched by an infusion of norepinephrine at a concentration of 5 X 10(-7) M. It is suggested that the carbohydrate metabolism of the liver is controlled by its own nerve supply rather than by circulating catecholamines and that alpha-adrenergic receptors have a greater effect than beta-receptors on hepatic glucose production resulting from electrical and catecholamine stimulation.


Effects on rat parotid amylase and Ca of alpha- and beta-adrenergic sympathetic stimulation. The roles of alpha- and beta-adrenergic receptors in the regulation of the secretion of amylase and calcium from rat parotid gland were studied by using direct electrical stimulation of the sympathetic innervation to the gland in the presence of selective adrenergic blocking agents. When phenoxybenzamine was administered intraperitoneally 25 min prior to nerve stimulation, the highest [Ca] (12-14 meq/liter) and amylase activity (1,000 mg/microliter) in the evoked saliva were observed. On the other hand, stimulation of the nerve in the presence of propranolol evoked a saliva that contained the lowest [Ca] (5-6 meq/liter) and amylase activity (170 mg/microliter). Furthermore, salivary flow (4.27 +/- 0.42 microliter/min X g) induced by sympathetic nerve stimulation in the presence of phenoxybenzamine was higher than that induced by sympathetic nerve stimulation in the presence of propranolol (2.55 +/- 0.39 microliter/min X g). Therefore, it was concluded that beta-adrenergic receptors play the major role in the regulation of salivary flow and the secretion of amylase and calcium, whereas alpha-adrenergic receptors play a minor role in the regulation of these parameters.


Cation-anion gap and choleretic properties of rat bile. To investigate whether bile contains choleretic anion(s) other than bile salts (BS) that could account for the observed cation-anion gap in bile, the choleretic properties of bile were investigated in the rat. Infusion of bile increased bile flow significantly more than did taurocholate (TC) (P less than 0.005). By contrast, TC increased BS excretion more substantially (P less than 0.01). This effect was dose dependent for both bile and TC. The choleretic principle had a molecular weight of less than 1,000 as estimated by ultrafiltration of bile. Infusion of bile that had been chromatographed on BioBeads SM-2 still elicited choleresis, whereas bile that had been chromatographed on Dowex 1 x 50W did not. Administration of bile in vivo did not affect Na+-K+-stimulated ATPase activity in liver plasma membrane fractions. These results suggest that bile contains anion(s) other than 3-hydroxy-BS, which increase bile flow in a dose-dependent fashion without affecting the permeability of the biliary tree. This putative choleretic appears to be anionic in nature, heat stable, and has an apparent molecular weight of less than 1,000. This finding suggested that bile salt-independent bile flow partly depends on the excretion of a currently undefined anion.


Development of secretory mechanisms in rat pancreas. Mechanisms and development of secretory function were studied in rat pancreas in vitro. Amylase release from term fetal pancreas was refractory to stimulation by carbamylcholine chloride (carbachol) and cholecystokinin-octapeptide (CCK-OP), but was significantly augmented by calcium ionophore (A23187), DBcAMP, 8-Br-cGMP, and theophylline. The latter agent when combined with either cyclic nucleotide analogue further increased secretory responses. At 1 day and 8 days postnatally, responsiveness to carbachol and CCK-OP had been acquired because amylase secretion stimulated by these agents was brisk and at a level comparable to that found in mature tissue. Increasing extracellular calcium concentrations from 1.23 to 5.28 mM had no effect on basal amylase release in either the fetal or 8-day pancreas. No changes in intracellular cAMP concentrations were found at any age under experimental conditions used. Similarily, in fetal tissue, no changes in cGMP concentrations were found in response to carbachol or A23187. However, at 8 days of age, both agents produced two- to four-fold increases in tissue cGMP levels at 1, 2, and 5 min of incubation. These studies confirm that responsiveness to carbachol and CCK-OP is a maturational process in the pancreas that lags behind the development of intracellular processes involved in stimulus-secretion coupling.


Effect of altered intestinal water transport on rabbit ileal blood flow. A method is described for measuring ileal blood flow in the anesthetized (pentobarbital sodium) rabbit by the intraventricular injection of microspheres (15 micrometer) labeled with cerium-141 or chromium-51; with this method the amount of labeled microspheres lodging in the tissue is proportional to the blood flow. Blood flow to the ileal mucosa plus submucosa could be separated from flow to the ileal muscularis propria plus serosa by this technique. Simultaneous and sequential injections of radiolabeled microspheres gave similar measurements of ileal blood flow and did not affect ileal water absorption. Increasing ileal water absorption by treatment with the glucocorticoid methylprednisolone (3 mg/100 g per day for 3 days) increased blood flow to both compartments of the ileum and also to the colon, liver, and kidneys; methylprednisolone treatment did not alter blood flow when studies were performed before the methylprednisolone-induced increase in ileal water absorption had occurred. In contrast, intestinal secretagogues that induced both active ileal secretion (purified cholera toxin and serotonin) and passive ileal secretion (hypertonic mannitol) did not affect ileal blood flow. These studies indicate that increased ileal water absorption is associated with increased ileal blood flow, whereas intestinal secretion is not necessarily associated with an alteration in ileal blood flow.


Involvement of renal alpha- and beta-adrenoceptors in release of renin by carotid baroreflex. In anesthetized vagotomized dogs with renal arterial pressure constant, carotid sinus hypotension (BCO) caused a reflex rise in systemic arterial pressure, a fall in renal blood flow, and a similar increase in renin release from both kidneys. Unilateral alpha-adrenoceptor blockade with phenoxybenzamine resulted in an increase in basal renal blood flow, a depression of basal renin release, and an abolition of the responses to BCO in the treated kidney. The untreated kidney responsed to BCO as before. Nonblocked and alpha-blocked kidneys released similar amounts of renin when renal blood flow was mechanically reduced by aortic constriction. Administration of propranolol to the nonblocked kidney prevented the release of renin but not the hemodynamic changes resulting from BCO. The experiments demonstrated that under certain conditions carotid sinus hypotension produced alpha-adrenoceptor-mediated changes in the kidney sufficient to cause increased renin release. A step in the renin release mechanism subsequent to the alpha-adrenoceptor-mediated changes in sensitive to propranolol.


Research on the psychosocial treatment of schizophrenia: a summary report. The authors present an overview of research on psychosocial treatments for schizophrenia. Findings from studies of five therapeutic approaches--individual psychotherapy, group psychotherapy, family therapy, milieu therapy, and community support systems--are discussed in detail. The usefulness of each type of therapy is critically assessed on the basis of available data from controlled outcome studies. The authors make recommendations regarding high-priority areas to be addressed in future studies of psychosocial treatment.


Beta-adrenergic receptor function in affective illness. In a study of beta-adrenergic receptor sensitivity, the authors determined the response of cyclic AMP synthesis to in vitro addition of norepinephrine (NE) and isoproterenol (IP) in leukocytes of patients with affective illness and schizophrenia and of normal controls. IP-stimulated increase in 3H-cyclic AMP synthesis in depressed patients was significantly lower than in normal subjects and schizophrenic patients. These results suggest that beta-adrenergic receptor sensitivity is reduced in depressive illness.


Reduced cyclic AMP production in the blood platelets from schizophrenic patients. The authors assessed alpha-adrenergic receptor function in blood platelets from chronic schizophrenic patients and normal control subjects. The number of receptors was measured by the specific binding of the alpha-adrenergic antagonist [3H]dihydroergocryptine to the platelets. A physiological response of the platelets to agonist occupancy of the alpha-adrenergic receptors was measured by the norepinephrine inhibition of prostaglandin E1(PGE1)-stimulated cyclic AMP (cAMP) production. cAMP production in male schizophrenic patients was lower than in normal male subjects. alpha-Adrenergic receptor function was similar in patients and normal control subjects of both sexes. Normal male subjects had about 1.5 times the number of alpha-adrenergic receptors as normal females and generated about 1.8 times the quantity of PGE1-stimulated cAMP.


Japanese encephalitis virus in mosquito salivary glands. Culex tritaeniorhynchus and C. pipiens mosquitoes were infected with Japanese encephalitis virus either by intrathoracic injection or by membrane feeding. The virus maturation sites and the process of virus particle concentration in salivary gland cells were studied by electron microscopy. Occurrence of mature virions was primarily associated with intracytoplasmic viral matrices which were extraordinarily large and had a perinuclear location in C. pipiens mosquitoes. The other sign of virus replication was the proliferation of small spherical vesicles throughout the cytoplasm. It appeared that mature virions were entrapped in intracellular vacuoles and later released into the apical cavity of salivary gland cells through the fusion of these vacuoles with the apical plasma membrane. This process seemed to be associated with primary resynthesis of saliva in mosquitoes following blood feeding activity. Another type of shedding involved virus particles either singly or in mass being released directly through the apical plasma membrane. All of these events occurred only in cells of the lateral lobes of the salivary glands, which fact was confirmed by immunofluorescent staining of infected glands. The median lobe of mosquito salivary glands may have a minor or no role in the transmission of Japanese encephalitis virus.


Clinical and laboratory features and treatment of visceral leishmaniasis in hospitalized patients in Northwestern Ethiopia. The clinical and laboratory features, and the response to treatment of visceral leishmaniasis were studied in 18 hospitalized patients. Clinical and laboratory findings were similar to those in patients with kala-azar in the Sudan and East Africa. Fever, heptosplenomegaly, relative lymphocytosis, leukopenia, low platelet counts, and severe anemia were common findings. Pentostam (sodium stibogluconate) was used to treat 17 patients and Neostibosam (ethylstibamine) for one. Three patients died. Four out of the 18 patients had not visited any known endemic area but the significance of this finding has not been fully evaluated.


Interaction of neuromuscular blocking effects of neomycin and polymyxin B. Neomycin and polymyxin B produce neuromuscular blocks with distinct features by different mechanisms of action. In eight anesthetized cats the authors studied their interaction by examining the neuromuscular block produced by an equipotent mixture. Values of onset, potency, dose-response relations, duration and reversibility of block, the train-of-four and tetanic responses during block, the frequency-block relationships, and the posttetanic twitch behavior were well approximated by averaging the corresponding values previously reported for each antibiotic. Edrophonium, 0.2 mg/kg, reversed the block by 8 to 35 per cent. 4-Aminopyridine, 0.6 mg/kg, completely reversed the block and caused a long-lasting overshoot of the twitch response. The authors conclude that neomycin and polymyxin B are additive in neuromuscular effects, not only in terms of potency and duration, but also in terms of the characteristics of the blocks produced.


Failure of naloxone and naltrexone to antagonize halothane anesthesia in the dog. The effects of two narcotic antagonists, naloxone and naltrexone, on minimum alveolar anesthetic concentration (MAC) were studied during halothane anesthesia in the dog. Following induction of anesthesia, MAC was determined in duplicate. Each dog was then given one of the two narcotic antagonists and MAC was redetermined in duplicate: five dogs were given naloxone, 3 mg/kg IV, followed by an intravenous infusion of naloxone, 0.025 mg/kg/min; five dogs received naltrexone, 5 mg/kg IV. MAC was unaffected by the narcotic antagonists. Failure of narcotic antagonists to reverse halothane anesthesia suggests that the endogenous opioid peptides are not involved in the anesthetic state produced by halothane.


Modifications of the immunofluorescence assay for feline leukemia virus group-specific antigens. Observations and minor modifications are presented concerning the immunofluorescence assay for feline leukemia virus (FeLV) group-specific antigens (GSA) in blood cells of cats. Data are given regarding absorption of goat FeLV GSA antiserum in vivo in cats, absorption of the antiserum in vitro with feline blood cells, and the comparative efficacy of various chemical fixatives in preservation of FeLV GSA for immunofluorescent staining. The best results were obtained with in vitro absorption of antiserum and methanol fixation of FeLV GSA in blood smears.


Isolation and identification of a bovine adenovirus type 3 with an adenovirus-associated virus. A bovine adenovirus with agglutinating activity was isolated from feedlot calves and classified as serotype 3. The agglutinating activity was shown to be the property of an adenovirus-associated virus (AAV). The AAV was isolated from the bovine adenovirus by isopycnic centrifugation in CsCl; the AAV had a density of 1.4 g/cm2. This AAV is serologically related to bovine AAV-TR-15, but is distinct from bovine parvovirus-1 and primate AAV types 1 to 4, using counterimmunoelectrophoresis and hemagglutination-inhibition.


Indirect solid-phase microradioimmunoassay for detection of pseudorabies virus antibody in swine sera. An indirect solid-phase microradioimmunoassay (IRIA) was developed for detection and quantitation of antibodies to pseudorabies virus (PRV) in swine serum. Qualitative results of the IRIA compared closely with results of the serum neutralization test (NT) and the microimmunodiffusion test (MIDT). The IRIA was more sensitive than the NT for detection of antibodies to PRV in swine serum. The IRIA result is expressed numerically. With the IRIA and NT, antibody to PRV was first detectable in 3 experimentally infected pigs at 9 days after inoculation. With MIDT, antibody was detected in the 3 experimentally infected pigs at 9 days after inoculation. With the MIDT, antibody was detected in the 3 experimentally infected pigs at 7, 8, and 9 days after inoculation. The IRIA results are obtainable within a few hours; the NT and MIDT require 48 hours for completion.


Isolation of bovine adenovirus type 7 from calves with pneumonia and enteritis. Bovine adenovirus type 7 was isolated from a 10-month-old calf with fibrinopurulent pneumonia and from 2 newborn calves with pneumoenteritis. The viruses were isolated on calf lung and adrenal gland cell cultures and were identified as serotype 7 by immunoelectron microscopy and serum-neutralization tests.


The influence of cell type and lymph node metastases on survival of patients with carcinoma of the lung undergoing thoracotomy. We studied 202 cases of bronchogenic carcinoma treated surgically between January 1, 1966 and December 31, 1970. Over all, adenocarcinoma was the most common cell type (36.1 per cent). Of 151 patients whose carcinomas were successfully resected, and who lived for at least 30 days postoperatively, 88 had lymph nodes free of cancer. Not surprisingly, 5-year survival was related to lymph node metatases and cell type. The best over-all 5-year survival rate was for large cell carcinoma; it was 52.0 per cent without nodal involvement. Similar figures for epidermoid carcinoma were 29.0 per cent over all, and 26.3 per cent without lymph node involvement; for adenocarcinoma, 19.3 per cent over all, and 32.0 per cent without nodal involvement. For the entire group of 151 patients, the 5-year survival rate was 27.8 per cent over all, and 36.4 per cent without nodal metastases. Among resected patients with mediastinal lymph nodes positive for cancer, the 5-year survival rates were 1 of 10 patients with large cell carcinoma, 1 of 19 patients with adenocarcinoma, and 3 of 12 patients with epidermoid carcinoma. This suggests that in patients with epidermoid carcinoma, the presence of mediastinal lymph node metastases is not, in itself, an absolute contraindication to resectional therapy.


Growth of herpes simplex and cytomegalovirus in cultured human alveolar macrophages. In laboratory animals, macrophages play a central role in controlling certain viral infections. Because the adult human lung is more susceptible to infection with cytomegalovirus than herpes simplex virus, we compared the replication of these two viruses in vitro in human alveolar macrophages. The growth of herpes simplex virus in alveolar macrophages was extremely limited, peak titers being only 1.8-fold greater than adsorbed virus titers. Cytomegalovirus, on the other hand, replicated in normal adult alveolar macrophages to the same extent as in permissive tissue culture cell. These data suggest that the human alveolar macrophage may play a central role in the control of lung infection with herpes simplex virus.


Fine structure of the Legionnaires' disease bacterium. In-vitro and in-vivo studies of four isolates. We obtained four bacterial isolates from patients with Legionnaires' disease and examined them for in-vitro and in-vivo fine-structure characteristics. All isolates had an outer membrane, cytoplasmic membrane, and intracellular membrane structure. Numerous intracellular inclusions were seen, particularly from in-vivo specimens, and appeared membrane-limited. Fine-structure analysis did not reveal the presence of a definitive peptidoglycan structure. Isolation, purification, and chemical analysis of Legionnaires' disease bacterium pepdoglycan established molar ratios of alanine-glutamic acid and muramic acid-glucosamine. Diaminopimelic acid was absent in the Legionnaires' disease bacterium peptidoglycan. The Kellenberger procedure for fixation appears to be the best method for the fine-structure determination of Legionnaires' disease bacteria.


Gastrointestinal hormones in clinical disease: recent developments. With the advent of radioimmunoassay and immunocytochemical methods, the peptides of the gastrointestinal tract have been identified and measured. Gastrinoma and insulinoma syndromes have been wall characterized. The pancreatic cholera syndrome and some of the evidence that the major manifestations of this disease may be mediated by vasoactive intestinal peptide have been re-examined. Pancreatic polypeptide seems to be an ideal peptide for study of vagal-cholinergic mechanisms that regulate hormone release; it also appears to be a tumor marker for several types of pancreatic endocrine tumors, particularly those of pancreatic cholera. Secretin and cholecystokinin are important regulators of pancreatic exocrine secretion and have been used to test pancreatic function, but there is little evidence that they account for clinical disease. Glucagon-secreting tumors produce a clinical syndrome of diabetes mellitus and distinctive skin lesions, which can be cured by tumor resection. Hormone-secreting tumors may provide insight into normal gut physiology.


The Cushing syndromes: changing views of diagnosis and treatment. Cushing's syndrome is the common clinical presentation of three unique disorders that give rise to hypercortisolism. In most cases neoplasms underly each of these disorders. Clinical features are highly variable and not accounted for by cortisol alone; indeed, the multihormonal basis for much of the clinical syndrome remains uncertain. Demonstration of sustained, excessive cortisol production is essential and depends on a pattern of repeated measurements and several different procedures. Plasma adrenocorticotropin, although not helpful in establishing the diagnosis, has proved valuable in differentiating the three major entities that cause hypercortisolism. The renewed significance of pituitary microadenomas and their improved detection by sella tomography has accompanied recent, impressive advances in transsphenoidal microsurgery. This may become the preferred treatment for pituitary Cushing's syndrome in the adult, particularly where the appropriate equipment and skills are available; for children, external pituitary irradiation seems to offer safe and effective therapy.


Clinical conditions mistaken for metastatic cancer to the choroid. Thirteen patients who were referred to the Oncology Unit with the diagnosis of metastatic cancer to the choroid were studied and found to have other conditions. All of the patients were female. Nine of the 13 had a history of systemic cancer of which 6 were breast cancer. Five patients were currently being treated with chemotherapeutic agents for their systemic cancer. Three of the 13 patients had bilateral fundus lesions. The most common diagnostic entities confused with metastatic disease were either inflammatory or hemorrhagic lesions of the retina. The preceding history of cancer in the patient with a puzzling fundus lesion may predispose the referring ophthalmologist to suggest a diagnosis of metastatic cancer to the choroid.


Fibrous histiocytoma: benign and malignant variants. Twenty cases of benign and malignant fibrous histiocytoma are presented. Six were benign, 11 malignant fibrous, and 3 pure malignant histiocytomas. These tumours arise from tissue histiocytes and have a wide range of histological appearances. The characteristic histological features are described and the variable clinical picture and different lines of treatment and management are discussed.


The experimental production of diarrhoea in colostrum deprived axenic and gnotoxenic calves with enteropathogenic Escherichia coli, rotavirus, coronavirus and in a combined infection of rotavirus and E. coli. We attempted to produce diarrhoea experimentally in the newborn calf by orally injecting 17 colostrum-deprived calves with two serotypes of Escherichia coli Ent+ K99+, a rotavirus and a coronavirus. With E. coli alone, a dose of 2 x 10(8) bacteria administered 24 hours after birth causes a mild attack of diarrhoea, whereas 1 x 10(10) bacteria leads to dehydration and death. An inoculation of rotavirus is followed by diarrhoea which always contains large quantities of rotavirus. These animals were anorectic for a time, but none was dehydrated or died. With coronavirus, there were large quantities of watery diarrhoea, which led to dehydration and death. The inoculation of rotavirus, not lethal in itself, followed by a similarly non lethal inoculation of E. coli in doses of 3 x 10(8) to 2 x 10(9) led to dehydration and death. The authors conclude that dehydration and death of the animal can caused by large doses of E. coli or coronavirus or by two non-lethal doses of rotavirus and E. coli administered one after the other.


[Lesions of the auditory nerve in leprosy (author's transl)]. A study of 260 male patients in the Alexandria leper colony showed that 15% of them had uni- or bilateral perception deafness. The lesion was of the retro-cochlear type and has to be related to lesions of the peripheral nerves.


Scanning electron microscopy of abomasium and intestine of gnotoxenic calves infected either with rotavirus, coronarivus or enteropathogenic Escherichia coli or with rotavirus and E. coli. Neonatal calf diarrhoea induced with several agents of infection was studied by scanning electron microscopy. In a gnotoxenic calf infected with E. coli K99+ Ent+, slight lesions of the small intestine were observed and desquamation or puffiness of microvilli occurred. In rotavirus-infected calves, the abomasum was covered with abudant mucous film and appeared to be desquamated. In the small intestine, no desquamation of epithelium was observed. Inoculation of the rotavirus and E. coli induced severe diarrhoea. The whole digestive tract, even the abomasum and colon, was eroded. Coronavirus induced marked lesions in all levels of the intestine. These results demonstrate unequivocally the pathogenic properties of the three infectious agnets, the synergistic effect of E. coli and rotavirus. Furthermore, the importance of the abomasum in neonatal diarrhoea is emphasized.


Cell-mediated cytotoxicity against hamster cells transformed by avian sarcoma viruses. 1. Description of the reaction. The presence of new antigens on hamster cells transformed by avian sarcoma viruses was investigated by in vitro cellular microcytotoxicity assays using spleen cells obtained from immunized hamsters as effector cells and monolayers of transformed cells as targets. The effect of a number of variables was studied especially the concentration of effector cells and of target cells. Probit analysis has been used to statistical interpretation of data. Spleen cells obtained from hamsters immunized with RSV transformed rat cells have allowed the demonstration of new antigens on transformed hamster cells. These antigens have been also detected, in certain conditions, using effector cells obtained from hamsters immunized with RSV transformed hamster cells.


Cell-mediated cytotoxicity against hamster cells transformed by avian sarcoma viruses. 2. Sensitivity of different subclones. The presence of new antigens on different subclones of hamster cells transformed by avian sarcoma viruses was investigated by an in vitro cellular microcytotoxicity assay. The RS 2/3 and RS 2/10 subclones derived from the RS 2 clone, transformed with a Schmidt-Ruppin strain of RSV were highly sensitive to the cytotoxic action of spleen effector cells obtainled from hamsters immunized with RSV-transformed rat cells. The RS 2/6 subclone was sensitive only when 1,000 target cells were seeded and the RS 2/7 subclone was not susceptible to the cytotoxic action of effector cells. The RB 12/1 subclone, derived from the clone RB 12, transformed with a Bryan strain of RSV was poorly sensitive. The comparison between the sensitivity to XC-sensitized spleen cells of the different subclones and their other known properties was discussed.


Behavioural and pituitary-adrenal characteristics of pigs differing by their susceptibility to the malignant hyperthermia syndrome induced by halothane anesthesia. 2. Pituitary-adrenal function. Pituitary-adrenal function was investigated in two groups of Pietrain pigs differing by their susceptibility to the malignant hyperthermia syndrome induced by halothane, and in Large White pigs (LW). Plasma basal levels of glucocorticoids, measured by a protein binding technique, and plasma ACTH concentrations, determined by radioimmunoassay, did not differ according to halothane susceptibility but were higher in LW pigs compared with Pietrain pigs. The reactivity of the pituitary-adrenal axis to such stressors as exposition to a novel environment or shaking was the same for all experimental groups. The same was true concerning plasma levels of glucocorticoids and ACTH after injection of dexamethasone and response of the adrenal cortex to a standard dose of ACTH. These results demonstrate that LW pigs have a higher tonic secretion of ACTH than Pietrain pigs, but with identical phasic response to stimulations. Halothane susceptibility by itself appears to have no influence of pituitary-adrenal function.


Regulation of gastric acid secretion.

Regulation of gastric acid secretion. The three stimulants of gastric acid secretion likely to have physiological roles in regulation of secretion are acetylcholine, gastrin, and histamine. Acetylcholine is released by vagal and intramucosal reflex stimulation, acting directly on the parietal cell. Gastrin is released by peptides and free amino acids in the stomach and is the only known hormonal stimulant of acid secretion. Release of gastrin by acetylcholine may occur. However, cholinergic control of gastrin release is complex since under certain conditions anticholinergic drugs may actually enhance gastrin release. Factors regulating histamine release have not been defined, but studies with H2-receptor antagonists leave little doubt that histamine has an important role in acid secretion. Studies with isolated parietal cells indicate that histamine, gastrin, and acetylcholine each appear to act at separate receptors on the parietal cell. Anticholinergic agents specifically prevent the cellular actions of acetylcholine, cimetidine specifically inhibits stimulation by histamine, and neither inhibitor blocks the small direct response to gastrin. Furthermore potentiating interactions occur between histamine, gastrin, and cholinergic agents which may account for the interdependence of secretagogue action observed in vivo. Direct potentiating interactions occur between histamine and gastrin and histamine and carbachol but not between carbachol and gastrin. However, in the presence of histamine, carbachol, and gastrin, a three-way potentiation does occur. By interfering with the potentiating interactions between stimulants, anticholinergic agents and cimetidine display an apparent cross-specificity in vitro that resembles the effects of these agents in intact mucosa. The mechanisms underlying these interactions are unknown, but the actions of histamine appear to be mediated through increased production of cyclic AMP and cyclic AMP analogs, which mimic the interactions involving histamine itself. The secondary effectors for acetylcholine and gastrin and the mechanisms for amplification of the response to combinations of stimulants remain to be elucidated.


Cardiac heat production.

Cardiac heat production. The energy production (heat + work) of cardiac muscle must be interpreted in terms of the major ATPases underwriting cardiac contraction; these are the Ca2+ and Na+-K+ transport ATPases and actomyosin ATPase. It is possible to apply the classical phenomenological subdivisions to cardiac energy production; when this is done, certain properties immediately distinguish cardiac muscle from skeletal muscle. Little or no temporal distinction exists between initial (anaerobic) and recovery (oxidative) metabolism. Even at temperatures as low as 20 degrees C most of the recovery heat is released within the time course of a single contraction. Cardiac muscle is characterized by a high resting heat rate, the magnitude of which varies between species and depends on the metabolic substrate. In isometric contractions there is a slightly curvilinear relationship between developed force and heat production. There is a tension-independent or activation component, the magnitude of which reflects the prevailing level of contractility and is probably associated with calcium release and retrieval. In isotonic contractions energy production is maximal when the muscle is heavily loaded but falls steeply when the size of the load is reduced. The enthalpy:load relation is probably similar to that found in twitch contractions of skeletal muscle working at room temperature or above; but, unlike for skeletal muscle, there are families of such curves: At any instant of time the relation depends upon the prevailing physiological conditions (e.g. stimulus rate, substrate supply, humoral agents, extracellular ionic concentrations, initial length). Cardiac energy production can be estimated by a variety of other techniques (such as high-energy phosphate utilization, oxygen consumption, and changes in tissue fluorescence related to pyridine nucleotide oxidation levels). At the present time there is considerable agreement between heat measurements and results obtained with these different techniques. We should like to conclude on a cautionary note. First, there is considerable variability in the properties of cardiac muscle from different species. Significant variations occur at nearly all levels of cellular function--e.g. shape of action potential, electrical and mechanical dependence upon stimulus history, mechanisms of excitation-contraction coupling, actomyosin ATPase activity, metabolic regulation, and differential sensitivity to anoxia or ischemia. Second, the types of contractions readily studied in isolated papillary muscles (i.e. isometric or isotonic twitches) may not necessarily be the best mechanical paradigms for understanding myocardial energetics in vivo. The particular geometric demands of individual research techniques require the use of a wide variety of myocardial preparations from a wide variety of species. This necessarily produces a pastiche view of cardiac muscle rather than an integrated picture of some hypothetically typical mammalian myocardium.


The influence of different adjuvants on the production of IgD and IgE antibodies. The aim of this study was to investigate the relationship between the synthesis of IgD and IgE antibodies upon the administration of antigen. Different adjuvants were used in order to find the optimal way of inducing in rats the synthesis of IgD and IgE antibodies. Ovalbumin was used as antigen. Fair amounts of IgE antibodies were produced using Al(OH)3 or Bordetella pertussis and Al(OH)3 as adjuvant. Only small quantities of IgE antibodies were formed when either Freund's complete adjuvant (FCA) or no adjuvant were used. IgD antibodies are formed upon the immunization with ovalbumin and FCA or B. pertussis in combination with Al(OH)3. Using Al(OH)3 alone as adjuvant or antigen alone resulted in only very minute quantities of specific IgD. Total serum IgE levels raised in the rats immunized with Al(OH)3 or B. pertussis and Al(OH)3. Total serum IgD was increased after immunization with ovalbumin and B. pertussis in combination with Al(OH)3.


The biosynthesis and metabolism of prostaglandins. With improved techniques for isolation and identification of materials, thromboxane (TXA2) and prostacyclin (PGI2) derivatives are now recognized as more abundant in some tissues and more potent than PGE2 and PGF2alpha. The rapid appearance and disappearance of these autacoids can be regulated at many points along the enzymatic path. Two important features affecting the rate of overall prostaglandin formation are the availability of non-esterified substrate and the availability of hydroperoxide activator for the cyclooxygenase. The fate of the endoperoxide formed by this reaction then depends upon the different relative amounts of the synthases and dehydrogenases in each type of synthesizing cell. Important future developments will indicate ways in which the amounts of these enzyme activities are altered and the ways in which the prostaglandin receptors interact with cellular adenyl cyclase and adrenergic receptors.


Cellular mechanisms of prostaglandin action. The human platelet and erythrocyte differ quite dramatically in relation to the arachidonic acid cascade. The platelet synthesizes its own characteristic products, while the erythrocyte lacks cyclo-oxygenase activity but possesses other metabolic enzymes. In these and other cell types the metabolites are potentially determined by the cascade enzymes, the availability of cofactors, the presence of specific activators and inhibitors, and the selective binding or transport of intermediates. Endogenously synthesized metabolites may have intracellular actions or may be released and exert their effects extracellularly. Study of the cellular mechanisms mediating these effects, like study of the fast-acting hormones, has focused primarily on the cyclic nucleotides and calcium. Considering the diverse activities of several metabolites in the platelet however, these mechanisms seem to need reevaluation or refining. The released cascade metabolites may also act as intercellular signals over a short range. The range depends on their chemical stability in the absence of protective carriers and their selective uptake and metabolism by surrounding cells. Additionally, the effects will reflect the selective interaction of responsive cells with the spectrum of metabolites released. Answering these questions of complex intercellular interactions requires the identification and classification of characteristic responses and the metabolic profile of individual cell types in each tissue. Consequently, this type of analysis may best be done with isolated cells, such as the platelet and erythrocyte.


[Development of an accelerated method of determining the antibiotic sensitivity of Cl. perfringens type A]. An express method for determination of antibiotic sensitivity in the strains of Cl. perfringens of type A using Soviet dry nutrient media and antibiotics is proposed. The criteria for estimation of the level of the antibiotic sensitivity of the causative agent of gas gangrene in short periods on the basis of comparison of the data of the antibiotic agar diffusion procedure and the antibiotic MIC were worked out. Twelve antibiotics and 45 collection strains of Cl. perfringens of type A were used in the experiment. The antibiotic agar diffusion method with the use of the nutrient media, microbial load and cultivation conditions developed by the authors is recommended for tentative determination of the antibiotic sensitivity in Cl. perfringens of type A for 4 hours. The use of the agar diffusion method and determination of the antibiotic MIC provided complete estimation of tha antibiotic sensitivity of Cl. perfringens of type A within not more than 24 hours.


Fluid accumulation in mouse ligated intestine inoculated with Clostridium perfringens enterotoxin. Clostridium perfringens enterotoxin, when inoculated into the ligated intestinal loop of mice, caused marked distension due to fluid accumulation. The increase in weight of the intestinal loop was proportional to the log dose of enterotoxin within a range from 1 to 16 micrograms. The fluid accumulation was arrested by washing the loop with saline or by injection of the specific anti-enterotoxin serum into the loop 5 or even 30 min after inoculation of the enterotoxin. A significant increase in weight of the loop was found as early as 10 min after inoculation of the toxin. These results may suggest that entergotoxin is neither bound firmly to the mucosal membrane nor permeates into the cells of the intestinal wall. The mouse intestinal loop test is economical, simple to perform, and applicable for quantitative determination of the enteropathogenic activity of C. perfringens enterotoxin.


Unsuitability of polioviruses as indicators of virological quality of water. Polioviruses could not be detected in about 50% of sewage samples despite routine administration of live attenuated poliovirus vaccine to the infant population.


Persistence of herpes simplex virus types 1 and 2 in infected individuals. During a 23-month period, 18 patients with facial or genital herpetic lesions were examined; culture specimens from each patient were obtained three times per week for virologic studies. The isolated viruses were identified, and the average duration of herpesvirus in lesions was determined. Herpes simplex virus type 1 (HSV-1) was isolated from facial lesions for a mean duration of 3 1/2 days. In contrast, herpes simplex virus type 2 (HSV-2) was isolated from genital lesions for a mean duration of 5 1/2 days. The duration of viral persistence in lesions of patients with mild primary infection did not seem to differ from that in patients with recurrent infection.


Mitochondrial oxidative activity in human rheumatoid synovial lining cells. The activities of two mitochondrial enzymes, succinate dehydrogenase and cytochrome oxidase, have been measured by quantitative cytochemistry and microdensitometry in the synoviocytes of rheumatoid and non-rheumatoid synovial lining cells. Although both tended to be higher in the former, there was no statistically significant difference in the activities of either enzyme in these tissues. However, when cytochrome oxidase activity was measured without exogenous cytochrome c, the activity in the rheumatoid synoviocytes was highly significantly elevated. It is suggested that these findings may indicate only that the cytochrome c-cytochrome oxidase complex in the rheumatoid cells is more stable, possibly because of the increased availability of phospholipids in these cells.


Cerebrospinal fluid lymphocyte transformations in meningitis. Cerebrospinal fluid lymphocytes from 13 patients with nonsuppurative meningitis were cultured with antigens derived from Mycobacterium tuberculosis, Sporotrichum schenckii, and herpes simplex. When CSF lymphocytes from five patients with infections associated with these organisms were incubated with "correct" antigen there was increased incorporation of thymidine. The levels were higher than those seen when the cells were incubated with different antigens or when CSF lymphocytes from patients with other causes for their meningitis were cultured with these antigens. A compartmentalization of antigen-specific cells was suggested as CSF lymphocytes had greater stimulation than did peripheral blood lymphocytes from the same patient when incubated with the correct antigen. Transformational assays of CSF lymphocytes may provide a valuable diagnostic aid in certain cases of chronic meningitis.


Enzyme inhibition by tobacco smoke: a comparison of the effects of four filters. The effects of four types of cigarette filters on the inhibition of glyceraldehyde-3-phosphate dehydrogenase by aqueous solutions of the free gas phase of tobacco smoke have been studied. Commercial cellulose acetate-charcoal filters or experimental wool filters containing a polyethyleneimine-quaternary ammonium additive were particularly effective in removing the inhibitor(s) from smoke under prescribed experimental conditions. Inhibition was dependent in all cases on both the age and the amount of free gas phase solution as well as contact time. Transient enzyme activation was observed. It is suggested that hydrogen sulfide is the main inhibitor present in the gas phase of cigarette smoke.


Pseudohypoparathyroidism: report on a family with four affected sisters. A family consisting of a mother, a father with probable pseudopseudohypoparathyroidism (PPHP), two normal daughters, and four daughters with pseudohypoparathyroidism (PHP) have been observed for more than 15 years at North Carolina Memorial Hospital (NCMH). The studies performed on family members included (1) roentgenographic examinations of the chest, skull, hands, and soft tissues; (2) serum calcium, phosphorus, and immunoreactive parathyroid hormone measurements; (3) urinary cyclic adenosine 3'5'-monophosphate determinations following parathyroid injection; and (4) HLA and blood-type determinations. We review the genetic aspects of PHP. The findings in this family suggest an autosomal dominant mode of transmission in PHP.


Changes in signal transmission by neurons of the cat lateral geniculate nucleus by acute deafferentation and early degeneration. 1. The responses of single principal cells of the cat lateral geniculate nucleus (LGN) were recorded extracellulary from the optic radiation (OR) axons or intracellularly from the LGN. Electrical stimuli at different frequencies were applied to the optic tract (OT) to test the transneuronal and the synaptic signal transmission in the LGN. 2. The effect of acute deafferentation (by photocoagulation of the retinal receptive field) or of synaptic degeneration induced 2-4 days prior to the recording time on the LGN neuron signal transfer was studied. Immediately after deafferentation, the synaptic signal transfer by LGN neurons exhibits signs of hyperexcitability leading to multiple neuronal discharges. This acute deafferentation hyperexicitability is probably caused mainly by the disapperance of lateral inhibition mediated by LGN interneurons. The deafferentation hyperexcitability disappeared during electrical stimulation of the OT at frequencies greater than 10/sec. 3. With progressing degeneration of the synaptic terminals during the 2nd to 4th day after interruption of the optic nerve axoplasmic flow, the synaptic signal transfer by LGN neurons gradually deteriorates and ceases at the end of the fourth day. The signs of this deterioration (larger temporal scatter, increased exhaustability and reduced upper frequency limit of the transneuronal signal transmission and gradual reduction of the EPSP amplitude in D-neurons) were quantitatively investigated. 4. The neurophysiological data obtained at different levels of synaptic terminal degeneration are well correlated with morphological changes found within the degenerating synaptic terminals.


[Structure of inclusion bodies and electron microscopic virus detection in naturally occurring inclusion body hepatitis in chickens]. Electron microscopy was used to examine the liver of chickens with spontaneous inclusion body hepatitis. Eosinophilic inclusion bodies only were established from two flocks, mainly amphophilic from one flock, and primarily basophilic from another two flocks. Eosinophilic inclusion bodies were predominant in broiler chickens with dystrophic fatty degeneration of the liver, while basophile inclusion bodies were recorded primarily from parental or laying-hen chickens with reduced metabolic stress of the liver and more focal necrosis. The eosinophilic inclusion bodies consitsed of a filamentous matrix, with virus particles not safely detectable. The amphophilic inclusion bodies contained parvovirus particles, most likely adenoassociated virus, while the basophilic inclusion bodies inclused parvoviruses or adenoviruses (in flock NO. IV) or adenoviruses only (in flock No. V) in an amorphous chromatin matrix. The presence of parvoviruses in field material was taken to suggest a possible role of those pathogens in inclusion body hepatitis.