High granulocyte yield with a simple method of filtration leukapheresis. A simple continuous filtration leukapheresis has been devised whereby two Leuko-Pak filters can be charged and eluted within 5 h with approximately 121 of blood in a closed system of tubes. Blood flows by means of gravity without the use of pumps. Without premedication with prednisolone the average yield from 10 donors was 3.66 x 10(10) granulocytes per leukapheresis and after premedication with 150 mg prednisolone orally it was 6.44 x 10(10) granulocytes per leukapheresis. The in vitro function of filter granulocytes was not reduced even after premedication with prednisolone. In comparison with leukapheresis by blood cell separators this modified method of filtration leukapheresis offers the following advantages: 1) the granulocyte yield per litre of whole blood processes is higher, 2) technical assistants in a blood-bank can carry out the method on several donors simultaneously, 3) the method is more economical than leukapheresis by blood cell separators.


Prostaglandin-mediated hypercalcemia: a paraneoplastic syndrome. Evidence has been presented for prostaglandin-mediated hypercalcemia and bone resorption in malignancies of both, experimental animals and man. Occurence of hypercalcemia in cancer patients is known for a long time, but its pathogenesis has been poorly understood so far. Besides ectopic parathyroid hormone secretion by tumors, an osteoclast-activating factor released from leukocytes and direct bone destruction by tumor cells, prostaglandins of the E series have to be considered as one of the candicates involved in the pathomechanism of hypercalcemia and osteoclastic osteolysis in cancer patients. This new concept on the pathophysiology of cancer-associated hypercalcemia has implications for the diagnosis and management of this common complication of neoplastic disease.


Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Perivascular cells in CNS tissue from six multiple sclerosis (MS) patients and a patient with motor neuron disease were examined by light and electron microscopy. Lymph node tissue from one MS patient was also examined. CNS perivascular macrophages in both MA and motor neuron disease were found to closely resemble free macrophages elsewhere in the body except that they often contained unusually large primary lysosomes. Cytoplasmic inclusions consisting of membrane-bound stacks of curved linear profiles, presumed to be a product of myelin degradation, were constantly observed in microglia in MS plaques but were rarely observed in perivascular macrophages in the same area. Unidentified cylindrical bodies were observed within cysternae of rough endoplasmic reticulum in some lymph node cells. Quantitative studies of the perivascular cell population in one MS case revealed, in histologically normal white matter 260 lymphocytes and 178 plasma cells per cubic millimeter of fresh tissue. Typical chronic plaque tissue without obvious inflammatory cell cuffing contained 1772 plasma cells per cubic millimeter of fresh tissue. No plasma cells were observed in the CNS in motor neuron disease. The results of this study suggest that perivascular macrophages in the CNS represent a specialized population of monocyte-derived free macrophages, that these cells differ functionally from microglial cells, and that the digestion of myelin breakdown products in MS requires the participation of both cell types. The results also suggest that in some chronic MS cases there is a large, permanent population of CNS plasma cells that persists, like the elevated cerebrospinal fluid IgG level in this disease, for the life of the patient, that these cells, rather than inflammatory cells in fresh lesions, are the major source of this raised IgG, and that the existence of such a population of cells may indicate the continuing expression of antigens in chronic MS lesions in the absence of fresh lesion formation.


Streptozotocin-induced pancreatic insulitis in mice. Morphologic and physiologic studies. Pancreatic insulitis and diabetes mellitus were induced in Charles River CD-1 mice with five subdiabetogenic injections of streptozotocin. Plasma glucose and immunoreactive insulin levels were measured and animals were sacrificed at intervals for morphologic studies of pancreatic islets and measurements of extractable pancreatic immunoreactive insulin. Light microscopy revealed striking insulitis, 5 to 6 days after streptozotocin injections, with cell necrosis and eventual islet atrophy due to beta-cell necrosis, and numerous type C viruses within many of the surviving beta-cells. Light microscopic immunoperoxidase stains of islet cell hormones and electron microscopy identified relatively increased numbers of alpha- and delta-cells within the atrophic islets 6 and 12 months after streptozotocin injections. Plasma  glucose, plasma immunoreactive insulin, and extractable pancreatic immunoreactive insulin measurements documented the persistence of profound hyperglycemia, as well as the reduction of plasma and pancreatic immunoreactive insulin levels. Immunofluorescence studies demonstrated the absence of circulating islet cell antibodies during both the acute and chronic stages of the syndrome. The pathogenesis of this model of insulin-deficient diabetes is believed to be a cell-mediated autoimmune reaction directed against pancreatic beta-cells altered by subdiabetogenic injections of streptozotocin. The importance of the increased number of type C viruses within surviving beta-cells remains obscure.


Distribution and development of angiotensin converting enzyme in the fetal and newborn rabbit. An immunofluorescence study. The distribution and development of angiotensin converting enzyme (EC 3.4.15.1) were studied in fetal and newborn rabbits, using fixed tissues embedded in paraffin and stained with a fluorescein-conjugated antibody specific for the enzyme. The enzyme was found at the luminal plasma membrane of endothelial cells from the second third of gestation to the neonatal period. In addition, two types of epithelial cells also contained the enzyme, renal tubular and intestinal. The vascular enzyme may play a role in the regulation of its vasoactive peptide substrates, angiotensin and bradykinin, at term.


Colorectal carcinoma in young black patients: a report of eight cases. Colorectal carcinoma in the black population of South Africa is very uncommon when compared with incidence among whites. Even in whites the proportion of patients with colorectal carcinoma under 25 years of age is less than 1% (Hardin, 1972). Eight cases of colorectal carcinoma in black patients under 25 years of age are presented. None had any evidence of premalignant lesions of the colon. The prognosis of colorectal carcinoma in young adults is poor in most series and this group of patients was no exception. Reasons for this poor prognosis are mentioned. A more aggressive approach to the early detection and treatment of the lesion in young patients is essential.


Cholesterol and triglycerides in serum lipoproteins of young persons in Rochester, Minnesota. Cholesterol and triglyceride levels in whole sera and in the major lipoprotein fractions are presented for 2,421 children and youths in Rochester, Minnesota, ranging in age from 6 to 18 years. This cross-sectional study revealed subtle changes associated with puberty and the occurrence of certain additional sex-specific changes related to age. Hyperlipoproteinemia was detected in 101 youngsters; those cases exemplified types IIa (61 cases), IIb (5 cases), III (5 cases), and IV (30 cases). One case of type V hyperlipoproteinemia was observed in a second and comparable population sample of 1,245 young persons.


Computerized axial-tomography in the preoperative evaluation of an angiofibroma. Computerized axial tomography (CAT) of the head provides the otolaryngologist with an effective diagnostic tool. This technique is particularly useful when used in the preoperative evaluation of head and neck pathology and may be used to define the extent of disease and to direct the surgical approach. The case of a 16-year-old male with an extensive angiofibroma involving the paranasal sinuses and nasopharynx is presented as an example of CAT in preoperative planning of the surgical procedure. Computerized tomography was used initially to define the tumor margins. Serial CAT scans were also obtained at intervals during the patient's preoperative estrogen therapy. Evidence was obtained which suggests CAT may be used to monitor the effects of preoperative hormone management of angiofibromas and in the definition of the optimal time for surgery. In the case presented the final CAT scan provided a detailed and accurate description of the tumor margins which were confirmed at surgery. Our experience with a case of an extensive nasopharyngeal angiofibroma demonstrates the CAT scan to be a useful objective diagnostic method for preoperative planning.


Adrenal hemorrhage in the adult.

Adrenal hemorrhage in the adult. Bilateral adrenal gland hemorrhage was found in 22 of 2,000 (1.1%) consecutive general hospital autopsies. Clinical features of these 22 patients with diffuse or focal bilateral adrenal hemorrhage have been analyzed and compared with previous series. In our experience, patients with this postmortem finding rarely manifest features of adrenocortical insufficiency and appear instead to die as a consequence of concomitant overwhelming illness, such as septicemia, body surface burns or cardiovascular catastrophe. Two-thirds of the current series had impaired renal function at the time of adrenal hemorrhage and three patients had pituitary gland necrosis. Experimental and clinical observations indicate that the "stressed" adrenal gland--under substantive endogenous or exogenous ACTH stimulation--is unusually susceptible to hemorrhage. While our own experience indicates that bilateral adrenal hemorrhage can infrequently be implicated as a factor contributing to patients' death, the possibility of adrenocortical insufficiency must be considered in patients at risk for adrenal hemorrhage. Such patients are those who are azotemic and have bacteremia, burns, or recent cardiovascular catastrophe, particularly when the latter is managed with anticoagulant administration. In these patients, unexplained clinical deterioration or the appearance of findings consistent with adrenocortical insufficiency mandate measurement of serum cortisol concentration and institution of stress-level corticosteroid replacement therapy until a diagnosis of acute adrenocortical insufficiency can be established or refuted.


The clinical, radiologic, and pathologic characterization of benign hepatic neoplasms. Alleged association with oral contraceptives. Poor histopathologic documentation and confusing terminology have caused focal nodular hyperplasia (FNH) and liver cell adenoma (LCA) to be categorized together as "benign hepatomas." FNH and LCA are distinguishable grossly, microscopically, and ultrastructurally. In a majority of instances they may be differentiated by combined angiography and liver scan: FNH is hypervascular and exhibits normal uptake on scan whereas LCA is hypovascular and cold on scan. FNH almost always follows a benign course, rarely undergoing hemorrhagic necrosis and rupture. FNH does not possess malignant potential; the prognosis, even if unexcised, is excellent. Resection is indicated only if FNH is symptomatic. LCA often ruptures and its malignant potential remains uncertain; the prognosis is guarded and resection is indicated. The literature reported association between FNH and oral contraceptives is anecdotal. However, the recent marked increase in the incidence of LCA's, their almost exclusive occurrence in young women, and the consistent hormonal history strongly suggests an association between oral contraceptive use and LCA's, although here too, statistical evidence is lacking. Prognostic and therapeutic considerations mandate that a clear distinction be made between FNH and LCA.


The purification and polypeptide composition of avian infectious bronchitis virus. Purification of egg-grown infectious bronchitis virus (IBV) by sucrose density gradient centrifugation alone, or sucrose density gradient centrifugation plus pH 8.0 treatment, concanavalin A precipitation or metrizamide density gradient centrifugation, failed to produce any differences in the virus polypeptide pattern following polyacrylamide gel electrophoresis in the presence of SDS(SDS-PAGE). SDS-PAGE of purified IBV on 7.5% acrylamide gels separated 16 polypeptides which were detectable by staining with Coomassie blue or measurement of radioactivity following electrophoresis of (3H)-leucine labelled IBV. The molecular weights of the polypeptides were within the range 15,000-135,000. The polypeptides of egg and chick kidney (CK) cell-grown IBV were identical in both size and number but quantitative differences were detected. In particular the relative proportion of the major 52,000 molecular weight polypeptide was greatly reduced in IBV grown in CK cells. SDS-PAGE of purified IBV and staining with Schiff's reagent to detect carbohydrate revealed four.bands with molecular weights of 128,000, 86,000, 67,500 and 37,000. The 128,000 band did not correspond to any of the detected polypeptides. Use of 5% acrylamide gels for SDS-PAGE of IBV failed to resolve all the minor polypeptides and only seven bands were detected.


Persistent infection with mouse hepatitis virus of low virulence in nude mice. A persisting type of infection with wasting syndrome was established in congenitally athymic nude mice after intraperitoneal inoculation with a mouse hepatitis virus which was not fully pathogenic for heterozygous haired littermates. From the liver, spleen, lymph nodes, and brain of most infected nude mice, the virus was detected at high titers during aperiod from 6 to 35 days postinfection, occurrence of degenerative and necrotic lesions being correlated with virus titers in these organs. The titer of serum neutralizing antibody remained undetectable or very low in most diseases nude mice, whereas some animals resisting the infection could produce antibody at a later stage. In heterozygous haired mice, some lesions were detectable at a very early stage of infection in the spleen and liver, but they seemed to disappear with a marked elevation of the neutralizing antibody titer. Nude mice were able to resist the virus infection when they had previously received transfer of thymocytes from weanling heterozygous littermates.


Comparative studies on cytopathic effects induced by vesicular stomatitis virus in two cell types. Infection of mouse L cells with vesicular stomatitis virus (VSV) leads to an extensive cell fusion, while porcine kidney stable (PS) cells infected with VSV show only cell rounding. Therefore, comparative morphological studies on the infection of the two cell lines were carried out using a transmission or scanning electron microscope and an immunofluorescence microscope. PS cells infected with VSV contrasted to L cells infected with the same virus in the following two points; (1) the principal site of VSV maturation was the intracytoplasmic vacuolar membrane in PS cells and the plasma membrane in L cells. However, it was found that viral glycoprotein was present on the cell surface of infected PS cells; (2) the morphological changes at the cell surface of infected PS cells occurred much earlier and were severer than those at the cell surface of infected L cells. From these observations, we discuss the possibility that the surfaceembrane of PS cells is too sensitive to the VSV-induced cell damage to cause cell fusion.


The prevalence of antibody to hepatitis A virus in two populations in Victoria. Sera collected from a group of 1053 Victorians were tested for antibody to hepatitis A virus by solid phase radioimmunoassay. The group comprised approximately equal numbers of males and females of all ages, 488 of whom lived in Melbourne and 565 in six provincial cities. In both the metropolitan and provincial groups, the prevalence of antibody to hepatitis. A virus was independent of sex and increased steadily with age. Antibody was detected in approximately 20% of children by the age of 10 years, in 40% at 40 years and in excess of 95% above the age of 60 years.


Studies on the kinetic effects of cyclic nucleotides dependent glutamate dehydrogenase. Stopped-flow spectrophotometric studies of the reductive amination of L-ketoglutarate by L-glutamate dehydrogenase showed a biphase time course, which consisted of a rapid first phase lasting 60-100 msec and a slow final phase in which the rate of coenzyme oxidation increased until the coenzyme was depleted. The effects of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) on the time course of both phases were established. The results showed that in the concentration ranges used the cyclic nucleotides accelerate the catalytic reaction. The effect of cAMP was more pronounced as compared to cGMP. In all cases this influence was most clearly expressed in the first phase. Using an Arrhenius plot the activation parameters were calculated. The experiments with cAMP and cGMP at different molar ratios showed that a specific cAMP binding may occur.


Localization of host poly(A)+ mRNA in the ribosome profile of mengovirus-infected Ehrlich ascites tumor cells. The distribution of poly(A)+ mRNA among polysomes, monosomes, and ribosome-free supernatant fractions after mengovirus infection of Ehrlich ascites tumor (EAT) cells was investigated employing sucrose gradient centrifugation of their corresponding postnuclear supernatants. Poly(A)+ mRNA was isolated from sucrose gradient fractions and quantitated in a cell-free protein synthesizing system from uninfected EAT cells. It was also localized by annealing [3H]-poly(U) to the poly(A)-tracts of mRNA present in the sucrose gradient fractions. Both experiments revealed a gradual shift of host poly(A)+ mRNA from large to small polysomes and monosomes, respectively, with the time postinfection. The greatest part of host template RNA appears to remain ribosome-bound and only a fraction seems to be detached from the ribosomes in the course of mengovirus infection. At the end of the infectious cycle, 8 h postinfection, approximately 70% of the poly(A)+ mRNA detected in uninfected cells is still biologically active, but not translated in vivo, in agreement with data from the [3H]poly(U)hybridization experiment.


[Clinical aspects, diagnosis and treatment of organic hyperinsulinism. Experience with 46 operated patients (author's transl)]. The clinical picture of organic hyperinsulinism is presented with reference to experience in 46 operated patients. For the recognition of disease, a careful history is a decisive contribution. The hunger test showed a characteristic hypoglycemic reaction in 100%; the tolbutamide test gave a positive result in 92%. Insulinomas could be localized angiographically in 71%; in one patient this could only be done with an ERCT. The treatment of choice is operation as soon as possible. If possible, enucleation is to be given preference over pancreas resection because of the low complication rate. A search for ectopic (2%) and multiple (12%) adenomas is important. A cure was achieved in 76% of all those operated on. The hospital mortality was about 4%.


Methyl methanesulphonate mutagenesis in L5178Y mouse lymphoma cells. The alkylating agent MMS was toxic to mouse lymphoma L5178Y cells and decreased their growth rate. A dose-dependent induction of thioguanine- and thymidine- but not ouabain-resistant variants was observed. The prolonged period for expression of thioguanine-resistant variants observed with other mutagens was also found in these studies. A comparison of MMS and EMS showed that MMS on a molar basis was approximately 10 times more toxic than EMS. With mutation, however, when evaluated at equal levels of cell killing MMS and EMS induced the same number of thymidine-resistant variants. For thioguanine-resistant variants MMS was approximately 10-fold less efficient than EMS, while for ouabain-resistance MMS, unlike EMBS, produced no variants at all. The ouabain results were further compared with positive results obtained using a modified Luria--Delbrück fluctuation test.


Post-treatment with caffeine and the induction of gene mutations by ultraviolet irradiation and ethyl methanesulphonate in V-79 Chinese hamster cells in culture. The effect of caffeine on V-79 Chinese hamster cells after ultraviolet irradiation or treated with ethyl methanesulphonate was investigated. Caffeine strongly potentiated the killing of both agents, but it had no effect on the induction of mutations at the hypoxanthine-guanine phosphoribosyl transferase locus. The results are consistent with the notion that caffeine slows down an error-prone post-replicative repair mechanism without changing the mutation frequency.


Expression of a bacterial gene turned on by a potent carcinogen. Contrary to mutagenesis, lysogenic induction produced by chemical carcinogens occurs in the majority of a population of lysogenic cells. Such a mass effect can therefore be measured at the biochemical level using an E. coli tester strain in which the galactose operon has been put under the negative control of the lambda repressor. In this publication we show that galactokinase synthesis is turned on by aflatoxin B1 metabolites within an hour after treatment of the tester bacteria. Such a biochemical assay provides a useful means for identifying potential chemical carcinogens.


Search for the uremic toxin. Decreased motor-nerve conduction velocity and elevated parathyroid hormone in uremia. In a retrospective analysis to determine whether secondary hyperparathyroidism in uremia has a role in uremic peripheral neuropathy, we simultaneously measured motor-nerve conduction velocity and serum parathormone level in 42 uremic patients. We compared age-matched groups of nondiabetic uremic patients, divided into three groups according to serum parathyroid hormone, for degree of impairment of motor-nerve conduction velocity, and 12 diabetic patients with uremia. The group with highest levels had a significantly (P less than 0.01) lower conduction velocity (25.3 +/- 4.9 m per second) than the group with normal or slightly elevated parathyroid hormone, who had only mild depression of nerve conduction (45.1 +/- 1.3 m per second). Mean serum calcium and creatinine were not significantly different between groups. Nerve conduction velocity was similarly depressed in 17 patients on additional dialysis studied prospectively and divided into groups according to parathyroid hormone levels. These results suggest a relation between high parathormone levels and uremic neuropathy and implicate parathyroid hormone as a uremic toxin.


Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. We investigated the antihypertensive effect of the angiotensin converting-enzyme inhibitor SQ 14225 in 12 hypertensive patients for periods of three to 24 weeks. Blood pressure decreased in all patients (from 177 +/- 8/110 +/- 2 to 136 +/- 6/88 +/- 2 mm Hg--mean +/- S.E.); oral doses ranged from 400 to 1000 mg daily. Concomitant effects noted were small increases in plasma potassium concentration and pulse rate. One patient experienced a transient febrile reaction. Plasma renin activity rose during treatment, plasma aldosterone decreased, and angiotensin-converting-enzyme activity was virtually eliminated. There was no significant correlation between pretreatment plasma renin activity and degree of blood-pressure fall with SQ 14225. The exact mechanisms contributing to the blood-pressure-lowering effect of this agent remain unclear. SQ 14225 is a promising new antihypertensive agent, effective in patients refractory to traditional medical therapy.


Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D. Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman. The patient had normal serum 25-hydroxyvitamin D (14 ng per milliliter) and markedly elevated serum 1,25-dihydroxyvitamin D (137 pg per milliliter). Vitamin D3, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism. The results suggest that the disorder results from impaired end-organ response to 1,25-dihydroxyvitamin D. We propose that the entity be called vitamin-D-dependent rickets Type II.


9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Of a series of nucleoside analogues synthesised, 9-(2-hydroxyethoxymethyl) guanine was found to have marked antiviral activity in animal models of herpes virus infections, associated with very low toxicity.


Membrane leakiness after viral infection and a new approach to the development of antiviral agents. Viral development induces changes in the permeability properties of the plasma membrane of the host cell. Here it is shown that, because of this leakiness, inhibitors of protein synthesis normally impermeable to uninfected cells are able to enter infected cells and thereby specifically inhibit viral protein synthesis.


Complete nucleotide sequence of SV40 DNA. The determination of the total 5,224 base-pair DNA sequence of the virus SV40 has enabled us to locate precisely the known genes on the genome. At least 15.2% of the genome is presumably not translated into polypeptides. Particular points of interest revealed by the complete sequence are the initiation of the early t and T antigens at the same position and the fact that the T antigen is coded by two non-contiguous regions of the genome; the T antigen mRNA is spliced in the coding region. In the late region the gene for the major protein VP1 overlaps those for proteins VP2 and VP3 over 122 nucleotides but is read in a different frame. The almost complete amino acid sequences of the two early proteins as well as those of the late proteins have been deduced from the nucleotide sequence. The mRNAs for the latter three proteins are presumably spliced out of a common primary RNA transcript. The use of degenerate codons is decidedly non-random, but is similar for the early and late regions. Codons of the type NUC, NCG and CGN are absent or very rare.


[Etiology and pathogenesis of arteriosclerosis]. Cardiovascular diseases are the leading cause of death in Western countries, with an enormous increase in death rate and involvement of younger age groups during the last decades. This applies especially to coronary heart disease and is mainly caused by first-degree risk factors: hypertension, hyperlipoproteinemia, cigarette smoking, gout, obesity, polycythemia, lack of physical activity, and stress. These risk factors are discussed with special reference to overnutrition and increased cholesterol levels. Recent resuults of research concerning lipids and their relation to atherosclerosis are reviewed.


The movement of plutonium, americium, and curium through the food chain. The actinides, plutonium, americium and curium, are being produced in increasing quantites as the nuclear programme is expanded. As these alpha-particle-emitting elements are hazardous to man there is considerable concern about the movement of these elements through the environment; The uptake of these elements from soil into the plants is low, as is the gastrointestinal concentration factor. Although there are complexing agents in the environment which have been shown to complex these elements there is no evidence that these complexing agents might bring about a concentration of actinides in the food chain of man.


Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice. II. Changes in gene expression during tumor progression. The hybridization properties of in vivo labeled nuclear and mitochondrial ribonucleic acids of an transplantable hepatoma were studied. It was shown that during tumor progression the repression of nuclear genome revelead at its early stages was replaced by the de-repression at its later stages. The hybridizability of mitochondrial RNA with nuclear DNA was not changed.


Experimental hypoglycemizing tumor of B-cells of Langerhans islets produced by the combined action of streptozotocin annd nicotinamide in the rat. Young male and female Wistar-Velaz rats were treated with streptozotocin-nicotinamide combination according to the method of Rakieten and examined periodically for 23 months for fasting and postprandial glycemia, by intravenous, intraperitoneal or intragastric glucose tolerance and tolbutamide tests with the aim to detect in vivo the experimentally produced nesidiomas. One male rat with severe hypoglycemia, apparent first on tolbutamide test after twelve months, later also on glucose tolerance test and fasting hypoglycemia associated with paraplegia with macroscopically and microscopically documented nesidioma is described. The exstirpation of this nesidioma was followed first by normalization and later by development of latent diabetes.


Effect of proteinase inhibitor in experimental tumors. Aprotinin, a wide range proteinase inhibitor, was given alone to tumor-bearing mice and life span and several tumor growth parameters were recordered. Aprotinin showed anti-tumor effects in Hepatoma 22 and Lewis lung carcinoma, remaining ineffective in Sarcoma 37, Leukemia L1210 and Ehrlich ascitic carcinoma.


Percutaneous electro stimulation of the trigeminal nerve in patients with atypical trigeminal neuralgia. In eleven patients with atypical trigeminal neuralgia, following herpes infections or radiation therapy of cancer of the epipharynx, percutaneous electrical stimulation of the trigeminal tract or in the vicinity of the nucleus area was performed. Relief of pain lasting from fourteen days up to six weeks could be obtained.


Sleep patterns in growth hormone deficient children and age-matched controls: developmental considerations. Ten patients with isolated growth hormone (GH) deficiency and 13 age-matched normal controls were studied. All patients were below the 3rd percentile in height and weight. All but 1 subject were studied for 3 or 4 consecutive nights in the sleep laboratory which included monitoring of the EEG, EOG, EMG, and EKG. GH samples were taken during sleep in 6 of the 10 patients. There were no significant differences in the slow-wave sleep (SWS) parameter between the 2 groups, nor was there any difference when all growth hormone patients were compared to controls. The age group comparisons for the percent of rapid eye movement (REM) sleep parameter revealed a significant difference between GH and controls for the youngest group only (p less than 0.05). Similar results were obtained when the GH subjects were grouped according to bone age. A significant decline in SWS was found with increasing chronological age (p less than 0.02), while the REM parameter did not show any significant changes across age categories. None of the patients showed a sleep-related peak in GH secretion. These data are not compatible with the hypothesis of a monotonic relationship between SWS and GH secretion.


Lymphocyte ultrastructure in two cases of neuronal ceroid-lipofuscinosis. Circulating blood lymphocytes from two patients with neuronal ceroid-lipofuscinosis (NCL) were investigated by transmission electronmicroscopy. Ultrastructural examination showed two forms of intracytoplasmic single membrane-limited inclusions. Contents of the first inclusion form were arranged in five distinct patterns: (1) granules, (2) membranous formations, (3) paracrystalline forms, (4) alternating electron-dense/electron-lucent arrangements, and (5) admixtures of these components. These molecular morphologies suggest the usefulness of lymphocyte fine structure as a diagnostic tool in NCL. The second inclusion form contained cylinder-like structures. These structures are not specific for NCL and have been identified in other diseases.


Polyneuropathy from inhalation of N2O cartridges through a whipped-cream dispenser. A generalized toxic polyneuropathy was identified in a 23-year-old woman after excessive intentional inhalation of compressed N2O delivery from cartridges through a whipped-cream dispenser. The chronology of the patient's N2O abuse correlated clearly with two episodes of recurrent polyneuropathy. The toxic effects were limited to the nervous system, primarily involving the peripheral nerves, although some signs suggested a possible effect on the cerebellum or its connections. The findings on sural nerve biopsy were nonspecific, characterized principally by axonal degeneration. Gas chromatographic analysis of the N2O cartridges dispensed through the whipped-cream canister revealed an exposure to N2O and 26 other compounds. Three of these, trichloroethylene, toluene, and phenol, are known neurotoxins.


Neuropathy following abuse of nitrous oxide. A disabling peripheral neuropathy, mainly sensory, developed in three health workers who habitually abused nitrous oxide. The distinctive clinical picture included patterns of numbness that were radicular rather than purely distal, and a "reverse" Lhermitte sign, in the absence of signs of spinal cord involvement. Nerve conduction studies suggested an axonal rather than demyelinative neuropathy. The neurologic disorder improved slowly when the patients abstained from further nitrous oxide abuse.


Differential maternal-fetal response to androgenizing luteoma or hyperreactio luteinalis. Lacl of masculinization in female infants whose virilized mothers have h. luteinalis is in contrast to the common finding of fetal masculinization when maternal virilization occurs with luteoma of pregnancy. From the data at hand, this variation in fetal response cannot be explained by differences in the quantity of androgen production nor by the stage of pregnancy when maternal virilization becomes evident. Steroid analysis from cases of h. luteinalis suggests that the placenta may serve as an androgen barrier by aromatizing steroids before they reach the fetus. Testosterone conversion by the placenta of an anencephalic fetus confirms that conversion to estrogens occurs even without significant fetal adrenal activity. Understanding of the breakdown of this mechanism, with resultant fetal masculinization, will require careful evaluation of the steroid milieu in conditions like luteoma in which fetal masculinization often occurs. Both cystic and solid ovarian hyperplasia are recognized as are complications of pregnancy which require proper identification and conservative management. The significant difference in patients at risk for luteoma and h. luteinalis and the pathological and hormonal differences clearly indicate that these are distinct and separate entities.


[Creatine biosynthesis enzymes in the postnatal development of rats: the role of cyclo-3',5'-AMP and glucagon in the postnatal induction of liver guanidine acetate-N-methyltransferase]. The activity of enzymes of creatin biosynthesis in the rat liver and kidneys has been studied during the postnatal development. The activity of transamidinase of kidneys (E.C. 2.1.4.1.) increases gradually and linearly up to the 20th day after birth, then decreases on the 12th--25th days and increases again up to the level characteristic of the adult organism. The activity of guanidine acetate-N-methyl transferase (E.C. 2.1.1.2.) is rather high during the first days of postnatal development, then decreases and from the 15th day on increases again attaining the maximal level by the 23rd--25th day. The second period of the increase in the enzyme activity begins on the 29th--30th day of postnatal development. The results obtained suggest that the sharp increase of activity of guanidine acetate-N-methyl transferase of the rat liver during the early postnatal development is realized with the participation of cyclic 3',5'-AMP which appears to mediate the glucagon action.


Adenocarcinoma of the palate--diagnosis and management. A case of adenocarcinoma of the palate has been presented. Emphasis has been placed on the surgical management and immediate postoperative care. Frequent postsurgical examination has been stressed to rule out evidence of recurrence or metastasis.


Cyst formation and cavitation in pulmonary metastases from Wilms' tumor. A report of two cases. Two children with pulmonary metastases from Wilms' tumor are presented. In one case the lesions evolved into large cysts and in the other case cavitation occurred within two metastatic nodules. These are extremely rare complications of metastases from Wilms' tumor. The possible mechanisms are briefly discussed.


Glycosaminoglycan synthesis by Wilms' tumor. Wilms' tumor contains approximately 1 mg hyaluronic acid and approximately 0.3 mg sulfated glycosaminoglycan per g tissue. Minced tumor and cells cultured from the tumor incorporate labeled acetate and glucosamine into hyaluronic acid and sulfated glycosaminoglycans. A particulate enzyme preparation derived from the tumor catalyzed the transfer of GlcUA or GlcNAc from UDP-GlcUA or UDP-GlcNAc at a rate of approximately 20 nmol/hr/mg protein to produce high molecular weight hyaluronic acid chains. The urine and plasma of a Wilms' tumor patient contained approximately 20 mg hyaluronic acid and 8 mg sulfated glycosaminoglycan/100 ml, respectively. It appears that this higher than normal level of circulating glycosaminoglycan is synthesized by the Wilms' tumor.


Effects of adrenocortical steroids and of adrenocorticotrophic hormone on (Na+-K+)-ATPase in immature cerebral cortex. The effect of cortisol, methylprednisolone, and ACTH on (Na+-K+)-ATPase activity in developing cerebral cortex has been measured. Stimulation of (Na+-K+)-ATPase by these agents has been found in whole brain homogenates of kittens as early as age 8 days, and in whole homogenates and light microsomal fractions in young rats at 14 and 28 days. (Na+-K+)-ATPase activity in animals treated with corticosteroids or ACTH for 4 days was found to be 15--30% higher than activity in littermate controls. Brain potassium concentrations was increased in 14-day-old rats treated with methylprednisolone.


The role of catecholamines in lung liquid absorption at birth. We have examined the effect on lung liquid secretion of catecholamines infused in chronically catheterized fetal lambs in utero. Isoproterenol and epinephrine inhibited secretion, an effect which increased with gestation and, in fetuses near delivery, caused absorption of lung liquid. In 7 out of 8 experiments nor-epinephrine had no effect on secretion. This pattern of response and the fact that the inhibitory effect could be blocked by propranolol indicate a mode of action involving beta-adrenergic receptors.


Nutrient intake and serum cholesterol level in normal children 6 to 16 years of age. A study of 103 healthy, white schoolchildren who were between 6 and 16 years of age revealed no positive correlation between the level of serum cholesterol and the mean daily amount of total calories, cholesterol, fat, saturated fat, or sugar in the diet.


A case of short rib polydactyly.

A case of short rib polydactyly. A patient with neonatal dwarfism had many characteristics of the Majewski syndrome, except for a cleft lip and abnormalities of internal organs. Absence of these anomalies and presence of more severe pathological changes in bone suggest either a wider spectrum for this disorder or a separate entity.


Sleep and memory: reproduction of syntactic structures previously evoked within REM sleep-related reports. 7 subjects, aged 19 to 25 yr., who evoked syntactic verbal material in the report made after awakening during REM sleep, were asked to reproduce it a few minutes later. No big differences had been obsered between the two recalls; all recalled verbal materials, many sentences and kernel-sentences reappeared. These results indicate a good consolidation of the material obtained after awakening during REM sleep.


Psychophysiological correlates of the spontaneous K-complex. A pilot study covering three nights and two studies were carried out to investigate the psychophysiological correlates of the spontaneous K-complex in relation to intense psychotherapy. The pilot study produced evidence that the K-complex was not consistent and stable within or across nights and that its variability might be sensitive to psycho-emotional influences. In the first major study 2 subjects were recorded non-consecutively over a 3-wk. period during experience of intensive therapy while in the second 6 subjects were studied before and after two therapeutic sessions. Results indicated that nights after therapy differed significantly from baseline nights and a significant interaction took place between subjects and therapy on one or more variables of the K-complex and several eye movement indices. Some relationship to length of time in therapy was also noted. These findings were interpreted to indicate a possible relationship between complete expression of feeling and the occurrence of phasic events in the sleeping EEG.


[Diffuse polymorphous inclusions in a patient treated with perhexiline maleate (author's transl)]. Case report of polyneuritis and liver dysfunction induced by perhexiline maleate in a 64 years old male patient. The ultrastructural study of nerve, liver, muscle and skin biopsies shows polymorphous, membrane bound, often multilamellar, lysosome-like inclusions, the content of which is probably complex lipids. The histochemical study of liver reveals a lipid storage, consisting mainly of triglycerides and of smaller amount of phospholipids and free fatty acids, the pattern of which is abnormal. The biochemical study of nerve tissue shows a decrease of phospholipids levels and some qualitative disturbances in gangliosides. These changes, some of which are similar to those reported in amphiphilic drug intoxications, are prevalent in high lipid metabolism cells such as hepatic and Schwann cells.


Characterization of N6, O2-dimethyladenosine from nuclear RNA of Novikoff hepatoma. A modified nucleoside was isolated from low molecular weight nuclear RNA of Novikoff hepatoma, the nucleotide sequence of which was reported earlier. The structure of this novel nucleoside was shown to be N6, O2'-dimethyladenosine (m6Am) by mass spectrometry of its trimethylsilyl derivative and by comparison with the mass spectra of N6- and O-2' monmethyl model compounds. The complete characterization was carried out using 0.04 A260 units (2 microgram) of m6Am.


Polynucleotide kinase from a T4 mutant which lacks the 3' phosphatase activity. Polynucleotide kinase from E. coli infected with the PseT 1 mutant of bacteriophage T4 has been isolated. The PseT 1 enzyme purifies similarly to normal polynucleotide kinase and effectively transfers the gamma phosphate of ATP to the 5' terminal hydroxyl of DNA and RNA. The PseT 1 and normal enzymes require similar magnesium ion concentrations, have the same pH optima and are both inhibited by inorganic phosphate. However, the PseT 1 enzyme is totally lacking the 3' phosphatase activity associated with normal  polynucleotide kinase. The PseT 1 enzyme is a useful tool for the preparation of oligonucleotides with 3' and 5' terminal phosphates for use as susbstrates for RNA ligase.


Properies of tRNAPhe from yeast carrying a spin label on the 3'-terminal. Interaction with yeast phenylalanyl-tRNA Synthetase and elongation factor Tu from Escherichia coli. The 2-thioketo function of tRNAPhe-C-s2C-A in which the penultimate cytidine residue is replaced by 20thiocytidine can serve as a site of specific attachment of spin label. By alkylation of tRNAPhe-C-s2C-A with iodoacetamide or its spin label derivatives tRNAPhe-C-(acm)s2C-A or tRNAPheC-(SL)s2C-A are formed. The enzymatic phenylalanylation of these tRNAsPhe revealed that the 2-position of the penultimate cytidine can be modified without impairing this enzymatic reaction but there exists a sterical limitation for the subsituent on this position beyond which the tRNAPhe:phenylalanyl-tRNA synthetase recognition is not possible. Both Phe-tRNAPhe-C-(acm)s2C-A as well as Phe-tRNAPhe-C(SL)s2C-A form ternary complexes with EF-Tu.GTP. The part of the 3'-terminus of tRNAPhe where the additional substituents are attached is therefore not involved in the interaction with this elongation factor. This could be also demonstrated by ESR measurements of spin labelled tRNAsPhe. The correlation times, tauc, for tRNAPhe-C-(SL)s2C-A, Phe-tRNAPhe-C-(SL)s2C-A and Phe-tRNAPhe-C-(SL)s2C-A.EF-Tu:GTP are essentially identical indicating that the structure of the 3'-end of tRNAPhe is not influenced significantly by aminoacylation or ternary complex formation.


Effect of freezing on incidence and levels of Clostridium perfringens in mechanically deboned chicken meat. Paucity of information about the effect of plant practices on microbiological condition of comminuted chicken meat prompted this investigation. Commercially deboned chicken backs and necks were analyzed for levels of aerobic organisms, incidence and levels of Clostridium perfringens vegetative cells and spores before and after 4-6 weeks at -23 degrees C. Initially vegetative cells were isolated more frequently than spores. Frozen storage significantly reduced incidence and levels of vegetative cells and spores but did not affect levels of aerobic organisms. After frozen storage (a common industrial practice), with good food handling practices, C. perfringens should pose no undue hazard when comminuted chicken meat is incorporated into other food products.


Immunosuppression in chickens by passive transfer of preparations of specific immunoglobulins. The immunosuppressive effects of passive transfers of specific immunoglobulin preparations obtained from immune or hyperimmune sera were evaluated in chickens which were challenged with sheep red blood cells. The data indicate that IgY, fractionated from immune sera, and IgY and IgM, fractionated from hyperimmune sera, when passively administered at the doses employed in this study resulted in antibody-mediated suppression.


Oncogenicity of the C-type virus HL-23V in marmosets and characterization of virus isolated from an HL-23V-induced marmoset tumor: comparison with simian sarcoma virus type 1. Dog thymus cells chronically infected with HL-23V, a C-type virus isolated from human acute myelogenous leukemia cells, produced both transforming and nontransforming virus indistinguishable from simian sarcoma virus type 1 (SSV-1/SSAV-1) and induced fibromas in newborn marmosets. All inoculated marmosets developed anti-HL-23V antibodies. A cell line established from a tumor biopsy produced transforming virus identical to SSV-1 and HL-23V at early passages. However, at later passages the cell line and a cell line established from residual tumor tissue removed at autopsy, produced virus which was neutralized only at low dilutions of anti-SSV-1 serum (1:32) relative to SSV-1 (1:1,024). This virus (BFV) was also distinguished from SSV-1 and HL-23V by XC tests, and by membrane immunofluorescence and serum cytotoxicity tests.


The influence of dibutyryl cGMP on the rabbit auricle. Dibutyryl cGMP, like acetylcholine, shortens and reduces repolarization and overshoot of the action potential, slightly hyperpolarizes the cell and decreases the force of the contraction in the atrial working muscle. It suggests that cGMP may mediate the action of acetylcholine in the atrial working fibres.


Studies with the baboon endogenous virus and its pseudotype of murine sarcoma virus in marmosets. Three marmoset species (Saguinus oedipus oedipus, S. fuscicollis, Callithrix jacchus) failed to show evidence of infection or disease following inoculation of baboon endogenous type-C virus (BaEV). Cells infected with a Kirsten murine sarcoma-BaEV pseudotype (MSV[BaEV]) produced a progressive fibrosarcoma in S. o. oedipus and tumors in S. fuscicollis and C. jacchus which regressed. Tumor formation is believed to be due to growth of inoculated, virus-infected cells and not transformation of marmoset cells. S. o. oedipus showed the best serum neutralizing antibody response to BaEV and MSV(BaEV), S. fuscicollis a moderate response and C. jacchus no response.


Differences in expression of surface marker characteristics on Epstein-Barr virus-transformed human and simian lymphoid cell lines. Human lymphoblastoid cell lines transformed in vitro by the Epstein-Barr virus (EBV) had receptors for fixed complement detectable by a rosette test. EBV transformed cells derived from cotton-topped marmoset leukocytes did not express this receptor. Evidence is presented that both human and marmoset cell lines arose from precursor cells which have complement receptors. Our findings suggest that transformation of marmoset leukocytes by EBV results in the loss of a differentiated surface marker.


Characteristics of cell lines established from Epstein-Barr virus induced marmoset tumors. The inoculation of a cotton-topped marmoset with B95-8 strain of EBV resulted in the induction of a multifocal lymphoma and lymphoblastoid cell lines were established from liver, spleen and mesenteric lymph node tumors. The cell lines were remarkably similar to each other with respect to the presence of EBV and its expression, the surface properties of the cells and their stability, and the functional products of the cells. Karyotypic examination of the cell lines revealed the common loss of a single chromosome. The slight differences noted in karyotypes suggest some divergence from a tumor stem cell and imply a clonal origin. Thus, EBV-induced lymphomas in cotton-topped marmosets resemble Burkitt's lymphoma in man.


Susceptibility of marmosets to Epstein-Barr virus-like baboon herpesviruses. Epstein-Barr virus (EBV)-like herpeviruses, strains of Herpesvirus papio (HVP), have recently been isolated from lymphomatous (HVP-L) and from normal baboons (HVP-N). Both HVP isolates infect some species of marmosets, HVP-L inoculated adult animals develop a mild to severe and sometimes fatal lymphoproliferative disease whereas newborn marmosets of the same species do not develop a measureable disease after inoculation with HVP-l. HVP-N infects adult marmosets but does not cause disease.


Spontaneous infectious diseases of marmosets. The various species of marmosets are susceptible to a wide variety of infectious agents of which only a few have been fully characterized. Little is known concerning spontaneous disease in their natural habitat, and often deaths in the laboratory go unexplained. In captivity, Herpesvirus-T infection appears to be the most important viral infection, but serious disease may also follow infection with measles virus (rubeola) and an unidentified paramyxovirus. Bacterial diseases are multiple, but rarely occur as epizootics. Various species of Salmonella, Yersinia, Klebsiella, and Diplococcus are among the more frequent pathogens. Mycoses and parasitic infections are also numerous, but most do not result in major losses.


Transfer factor and its protective effect against herpesvirus infections of marmosets. Using skin test response and lymphocyte blastogenesis as indicators of cell-mediated immunity, we have been able to demonstrate in vivo transfer of cell-mediated immunity to marmosets both with dialyzable transfer factor (TFd) prepared from a human donor and transfer factor (TF) from baboon whole cell lysates. We were able to protect marmosets with TFd from fatal Herpesvirus hominis type 1 (HVH-1) disease. When TFd was administered prior to challenge with HVH-1, 50% of the marmosets survived. Of the untreated control animals and those first treated on day 0 or postinfection, 100% succumbed to disseminated HVH-1 disease. In addition, when TF prepared from TFd-treated marmosets which had survived HVH-1 disease, was given to other marmosets, it conferred protection from subsequent HVH-1 challenge.


Tests in rufiventer and other marmosets of susceptibility to human hepatitis A virus. The rufiventer marmoset proved equally satisfactory to S. mystax for studies of human hepatitis A virus. C. jacchus, C. argentata, S. weddelli, and S. oedipomidas oedipus were not satisfactory. Livers of rufiventer marmosets produced satisfactory CR326 strain hepatitis A antigen for immune adherence tests both in amount and specificity. Rufiventer marmosets infected with human hepatitis A virus showed enzyme elevations and high titers of viral antigen in their livers as early as seven days after viral inoculation, indicating that a primary viral infection can cause hepatitis without need for a secondary autoimmune response to liver tissue.


Experimental infection of marmosets with hepatitis A virus. Saguinus mystax marmosets were experimentally infected with two strains of human hepatitis A virus. One of these strains of HAV was successfully subpassaged in this species of marmosets. In another experiment, the 1.32 and 1.41 g/cm3 buoyant density species of HAV derived from an infected chimpanzee stool were shown to be infectious in three species of marmosets. The value of the marmoset as an experimental model for hepatitis A infection was demonstrated by these studies.


Overview of viral oncology studies in Saguinus and Callithrix species. Marmoset monkeys are highly susceptible to tumor induction by type C sarcoma viruses and primate lymphotropic herpeviruses. Six experimental models were reviewed, three sarcoma models induced by Rous, feline or simian sarcoma viruses and three models of lymphoproliferative disease induced by Herpevirus saimiri, H. ateles or Epstein-Barr virus. Relative susceptibility of cotton-topped (Saguinus oedipus oedipus), white-lipped (S. nigricollis, S. fuscicollis subspecies) and commone (Callithrix jacchus jacchus) marmosets to the different viruses was compared.


Species-specific cellular DNA-binding proteins expressed in mouse cells transformed by chemical carcinogens. Mouse cells transformed by DNA and RNA tumor viruses and by chemical carcinogens have been examined for the presence of specific DNA-binding proteins by DNA-cellulose chromatography. Using mouse DNA-cellulose we have obtained single-stranded DNA-binding proteins from two clones transformed by chemical carcinogens. Simian virus 40 transformants also have a DNA-binding protein [the tumor (T) antigen] that binds to mouse and human DNA with comparable affinity. Mouse sarcoma virus-transformed cells and two other chemically transformed clones showed no difference in DNA-binding protein pattern compared to the untransformed parental cell. The DNA-binding proteins isolated from the chemically transformed cell clones are between 25,000 and 30,000 daltons by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. These cellular "T proteins" bind to the homologous mouse cellular DNA with a higher affinity than to heterologous human cellular DNA.


[In vitro thyroid hormone reception by the adenohypophysis and hypothalamus of male rats of different ages]. In studying the thyroid hormone binding with the water-salt extracts of the adenohypophysis and the hypothalamus of male rats after Schreiber it was shown that with ageing there occurred in the adenohypophysis a redistribution of T4 and T3 binding in the direction fo an increase of the T4/T3 coefficient, and a reduction of the relative T3 binding, the latter bordering with the significant one. Some reduction of the T4/T3 coefficient, both in comparison with the rest of the tissues under study and in age aspect, was peculiar to the posterior hypothalamus. In the rats-tumour-carriers some changes in the thyroid hormone binding (reduction of the T4/T3 index in the posterior hypothalamus and its sufficiently high values in the adenohypophysis and the anterior hypothalamus) were similar to those observed in normal and ageing rats.


Insulin and epidermal growth factor-urogastrone: affinity crosslinking to specific binding sites in rat liver membranes. Both insulin and human epidermal growth factor-urogastrone (EGF/URO) can be covalently linked to specific rat liver membrane binding sites by glutaraldehyde coupling followed by sodium borohydride reduction to yield affinity-labeled membrane constituents sufficiently stable for solubilization and further analysis by various techniques. Solubilization of membranes covalently labeled with (125)I-labeled insulin yields a component with chromatographic properties identical to those of a soluble insulin receptor characterized in previous studies. A second soluble insulin-binding component that is not revealed by the affinity-labeling method and that has not yet been reported can also be detected. Membranes similarly labeled with (125)I-labeled EGF/URO yield one major and two minor ligand-specific soluble (Triton X-100) affinity-labeled components, as detected by chromatography on Sepharose 6B. Further analysis of the EGF/URO-labeled components by affinity chromatography on concanavalin A-Sepharose, by disc gel electrophoresis, and by enzymatic digestion suggests that the major specific binding component for EGF/URO in liver membranes is a glycoprotein subunit of approximately 100,000 daltons that possesses a 20,000-dalton portion inaccessible to proteolytic cleavage when the subunit is anchored in the membrane. The affinity labeling approach described should prove of use for the study of other polypeptide receptors that, like the EGF/URO receptor, lose their ligand recognition property subsequent to membrane solubilization.


[Effect of large doses of reserpine on the hypothalamo-hypophyseal-adrenal system in Itsenko-Cushing's disease]. The results of study of the hypothalamo-hypophysio-adrenal system in patients with Itsenko-Cushing's disease under the influence of high reserpine doses are presented. An increase of plasma ACTH and cortizol level and disturbance of the 24-hour rhythm of their secretion was noted in the patients. High reserpine doses led to the fall of ACTH and cortizol secretion, without any normalization of their secretion rhythm in the course of 24 hours. A test with metopyron carried out before and after the reserpine prescription pointed to the increase of the ACTH reserve under the influence of high reserpine doses.


[Mechanisms of neuromuscular transmission disorder in rats with alloxan diabetes]. A microelectrode intracellular leading off of the postsynaptic potentials of isolated skeletal muscles was carried out in rats with alloxan diabetes of short duration (1--5 weeks), but manifest (blood sugar level from 150 to 350 mg%). A significant disturbance of the neuro-muscular synaptic transmission in this case was wholly caused by the reduction of the excitatory capacity of the presynaptic terminals. There was seen a reduction of the frequency of the miniature potentials of end plates (PEP), and a reduction of quant PEP composition. A distinct reduction of the intensity of the mediator synthesis, without any significant suppression of the fractional acetylcholine secretion was revealed in determination of the dynamic characteristics of the mediator transformations. This served as the cause of a deficiency of the fraction of a mediator ready for use in the animals suffering from diabetes.


A simple model of DNA superhelices in solution. Closed circular DNA molecules in aqueous solution take the form of interwound superhelices over a wide range of superhelix densities. We describe a very simple model of such a superhelix in which twisting and bending forces are in balance, subject both to topological constraints and to a limitation on the distance of closet approach of the interwound duplexes of the superhelix. The model is consistent with some of the observed physical properties of closed circular DNA, and suggests that there may be severe limits to the range of allowable geometries for the superhelix structure of minimum energy.


Interaction of ligands with the opiate receptors of brain membranes: regulation by ions and nucleotides. This study shows that nucleotides, as well as ions, regulate the opiate receptors of brain. GMP-P(NH)P and Na(+) reduce the amount of steady-state specific [(3)H]dihydromorphine binding and increase the rate of dissociation of the ligand from the opiate receptor. In contrast, Mn(2+) decreases the rate of ligand dissociation and antagonizes the ability of Na(+) to increase dissociation. The effects of GMP-P(NH)P on steady-state binding and dissociation are not reversed by washing. Only GTP, GDP, ITP, and IMP-P(NH)P, in addition to GMP-P(NH)P, increase the rate of dihydromorphine dissociation. The site of nucleotide action appears to have high affinity: <1 muM GMP-P(NH)P produces half-maximal increases in ligand dissociation. GMP-P(NH)P- and Na(+)-directed increases in dissociation have also been found for the opiate agonists [(3)H]etorphine, [(3)H]Leu-enkephalin, and [(3)H]Met-enkephalin and the opiate antagonist [(3)H]naltrexone. Mn(2+)-directed decreases in dissociation have been found for the agonist [(3)H]-etorphine and the antagonist [(3)H]naltrexone. Although the plasma membrane receptors for a number of other neuro-transmitters and hormones are also regulated by guanine nucleotides, the opiate receptors appear unique because only they show nucleotide regulation of both agonist and antagonist binding.


Enrichment of special Novikoff hepatoma and regenerating liver mRNA by hybridization to cDNA-cellulose. Total polysomal poly(A)+ RNA of Novikoff hepatoma and of 18-hr regenerating rat liver were compared by analysis of their in vitro translational products on two-dimensional isofocusing/sodium dodecyl sulfate gels. This technique resolved the translated proteins sufficiently to permit detection of quantitative and some qualitative differences between the two mRNA populations. Excess cDNA from regenerating liver or Novikoff hepatoma, covalently linked to cellulose, was used to adsorb the complementary mRNA sequences from Novikoff hepatoma or regenerating liver. As shown by two-dimensional gel electrophoresis, the translated products of the bound mRNA fractions contained proteins common to both tissues. Novikoff hepatoma mRNA which did not bind to regenerating liver cDNA was enriched in sequences encoding for proteins 11/5.1, 15/6.8, 40/8.2, and 65/5.1 (shown as molecular weight/pI). These polypeptides were not detectable in the translational products of regenerating liver mRNA. Regenerating liver mRNA that was not bound to Novikoff hepatoma cDNA was enriched in sequences coding for proteins 12.5/4.9, 13.5/7.4, 17/8.2, 24/5.5, and 46/6.4; these proteins were not found in the translational pattern from Novikoff hepatoma. These results show that adsorption of mRNA to solid-phase cDNA provides a valuable technique for differentiating mRNA species in related tissues and for corresponding enrichment of these specific mRNAs.


Participation of spectrin in Sendai virus-induced fusion of human erythrocyte ghosts. Fusion of washed human erythrocyte ghosts could be induced by the addition of Sendai virus after they were loaded with bovine serum albumin and resealed. Antispectrin antibody purified on a spectrin-Sepharose column and sequestered in the ghosts at 4-5 mg/ml together with the albumin was highly inhibitory for the virus-induced cell fusion, whereas Fab fragments prepared from the same antibody were without effect. The virus-induced aggregation of intramembrane particles of human erythrocytes was also inhibited by the same concentrations of the antispectrin antibody. The virus-induced agglutinations of the ghosts and release of bovine serum albumin from the ghosts (which might be caused by fusion of the viral envelope to the erythrocyte membrane) were not inhibited by the sequestered antibody. Therefore, the antibody seems to inhibit fusion at the last step--i.e., fusion between adjacent erythrocyte membranes. Similarities and differences of the mode of participation of spectrin in the virus-induced fusion and in other membrane-linked phenomena of human erythrocytes are discussed.


Regulation of adenylate cyclase activity mediated by muscarinic acetylcholine receptors. Carbachol, an activator of muscarinic acetylcholine receptors of NG108-15 hybrid cells, inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] rapidly and reversibly and slowly evokes a 200-300% increase in adenylate cyclase activity over a period of 24-30 hr. Both the inhibition of adenylate cyclase and the gradual increase in enzyme activity are dependent on muscarinic acetylcholine receptors and the receptor activator. Withdrawal of carbachol results in a gradual return of adenylate cyclase activity to control levels over a period of 6 hr; the half-life for decay of enzyme activity is 1.6 hr. These results show that muscarinic acetylcholine receptors mediate both transient and long-lived effects on adenylate cyclase activity that resemble those of opiates.


Genetic regulation of galactokinase in Tetrahymena by cyclic AMP glucose, and epinephrine. We have found evidence that transcription of the galactokinase (ATP:D-galactose 1-phosphotransferase; EC 2.7.1.6) gene is inhibited, in the animal-like protozoan Tetrahymena, by dibutyryl adenosine 3':5'-cyclic monophosphate, glucose, and epinephrine. The specific activities of galactokinase in Tetrahymena cells grown in defined media with galactose or glycerol as the principal carbon source are equivalent; the specific activity in glucose minimal medium is [unk] the value. Thus, while there seems to be no specific induction of the enzyme by the substrate, galactose, there is a strong "repression" by glucose. This repression by glucose is mimicked, in glycerol-grown cells, by the addition of millimolar amounts of dibutyryl adenosine 3':5'-cyclic monophosphate or phosphodiesterase inhibitors such as caffeine and theophylline. When glucose-grown cells are washed and resuspended in carbohydrate-free medium, the galactokinase specific activity increases by as much as 10-fold within 12 hr. This increase is blocked by dibutyryl adenosine 3':5'-cyclic monophosphate and by epinephrine (synthesized by Tetrahymena, and previously shown to activate a membrane-bound adenylate cyclase in extracts of this organism), as well as by inhibitors of mRNA synthesis, maturation, and translation. Our results suggest that glucose and epinephrine can regulate transcription of the galactokinase gene by modulation of cyclic nucleotide levels. The observation that the nonmetabolized sugars 2-deoxyglucose, 2-deoxygalactose, and alpha-methylglucoside are as effective as glucose suggests that the sugar itself, or an immediate metabolite such as the 1-phosphate derivative, may be the effector.


Proteases induce secretion of collagenase and plasminogen activator by fibroblasts. We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2-24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or alpha-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16-48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10(6) cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continued presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, alpha(1)-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.


Establishment of clonal human placental cells synthesizing human choriogonadotropin. Seven clonal human placental cell lines were established by transformation of human first-trimester placental cells with simian virus 40. These transformed cells synthesized native human choriogonadotropin (chorionic gonadotropin) (hCG) as well as the free alpha and beta subunits of hCG. The amount of native hCG synthesized by these cells was, however, lower than the amount of free beta subunit. (Both hCG and the beta subunit are detected by the radioimmunoassay for beta subunit, but only hCG is detected by the radioreceptor assay.) The alpha and beta subunits produced by these transformed placental cells were heterogeneous in size; the sizes of the predominant alpha and beta species, however, corresponded to those of urinary alpha and beta subunits, respectively. The seven cell lines transformed by simian virus 40 had chromosome numbers from the near diploid to the near tetraploid range. Fluorescent staining demonstrated the Y chromosome in all the transformants. Furthermore, B-type glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase; EC 1.1.1.49) was present in all seven lines. These characteristics ruled out possible HeLa contamination of the transformed lines. Regulation of the synthesis of alpha and beta subunits plus hCG in these transformed human placental cells differed from the regulation in choriocarcinoma cells.


Inhibition of cholesteryl ester formation in human fibroblasts by an analogue of 7-ketocholesterol and by progesterone. The synthesis of cholesteryl esters in cultured human fibroblasts is catalyzed by a microsomal acyl-coenzyme A:cholesterol acyltransferase (EC 2.3.1.26). The acyltransferase activity is enhanced when fibroblasts take up cholesterol contained in plasma low density lipoprotein. In the current studies two steroids, SC-31769 (an analogue of 7-ketocholesterol) and progesterone, were shown to inhibit acyltransferase activity in cell-free extracts of human fibroblasts. When added to intact cells, these steroids inhibited the incorporation of [(14)C]oleate into cellular cholesteryl [(14)C]oleate and reduced the accumulation of cholesteryl esters in fibroblasts exposed to low density lipoprotein. The inhibition of cholesteryl ester formation in intact cells by SC-31769 and progesterone was readily reversible. Neither compound inhibited the incorporation of [(14)C]oleate into [(14)C]triglycerides or [(14)C]phospholipids. When incubated with fibroblast monolayers at a concentration of 1 mug/ml, SC-31769 suppressed the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating); EC 1.1.1.34], the rate-controlling enzyme in cholesterol synthesis. In contrast, progesterone had no effect on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity at concentrations as high as 25 mug/ml. The availability of two types of steroid compounds that inhibit the acyltransferase activity and cholesteryl ester synthesis in human fibroblasts should prove useful in further studies of the regulatory mechanisms responsible for cholesteryl ester accumulation in human cells under normal and pathologic conditions.


Chimeric mice derived from human-mouse hybrid cells. Mouse teratocarcinoma cells from the OTT6050 ascites tumor were established in tissue culture and selected for 5-bromodeoxyuridine (BrdUrd) resistance. The embryonal carcinoma cells grew without a feeder layer, remained deficient for thymidine kinase (EC 2.7.1.75), and differentiated like the original tumor into various tissues after subcutaneous injection into 129 mice. We fused the BrdUrd-resistant mouse teratocarcinoma cells with HT1080-6TG human diploid fibrosarcoma cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and selected for hybrid cells in hypoxanthine/aminopterin/thymidine medium. The resulting hybrid cells segregated human chromosomes quickly and retained one to three human chromosomes including chromosome 17 that carries the human genes for thymidine kinase and galactokinase (EC 2.7.1.6). Single hybrid cells from five independent clones containing human chromosome 17 were injected into mouse blastocysts bearing several genetic markers that affect the coat color phenotype and strain-specific enzyme variants in order to detect tissue differentiation derived from the injected cells. After the injection of single hybrid cells into a total of 103 experimental blastocysts that had been surgically transferred to pseudopregnant foster mothers, 49 mice were born and 2 of them clearly revealed coat mosaicism. In 2 of 17 mice thus far analyzed, the injected hybrid cells proved to be capable of participating substantially in development of seven different organs. However, human gene products have not yet been detected unequivocally in those tissues and weak human-specific galactokinase activity could be recovered only from two mosaic tissues. Our results demonstrate that, after in vitro culture and selection, at least some of the human-mouse hybrid cells still retain their in vivo potential to differentiate and become functionally integrated in the living organism. It now seems feasible to cycle mouse teratocarcinoma cells carrying human genetic material through mice via blastocyst injection to study human gene expression during differentiation.


Purification of nuclear antigens in Novikoff hepatoma. Nuclear antigen in Novikoff hepatoma chromatin was partially purified and characterized. As indicated by complement fixation assay, this antigen was present in chromatin of embryonic livers and several transplantable tumors. It was not detected in normal tissue chromatins of the same animals. For its immunological specificity this protein antigen (molecular weight 45,000-60,000) had to be complexed with DNA. Preliminary experiments indicate that specific nuclear protein antigens are also present in human tissues and spontaneous malignancies.


Transforming activity of Epstein-Barr virus obtained by superinfection of Raji cells. Epstein-Barr virus obtained by superinfection of Raji cells with Epstein-Barr virus recovered from P3HR1 cells (HRI virus) transformed human lymphocytes, but it did not superinfect Raji cells. A human lymphoblastoid cell line, HLB, established by such transformation contained 22 Epstein-Barr virus genomes per cell and Epstein-Barr virus-associated nuclear antigen, and a few cells contained early or viral capsid antigen complexes. Chromosomal analysis revealed that HLB-cells were diploid with normal female karyotypes. Replication of Epstein-Barr virus DNA and inhibition of host cell DNA synthesis were observed in HLB cells after superinfection with HR1 virus.


Differences in behavior and prognosis between leukemic and lymphomatous forms of a transplantable hamster lymphocytic neoplasm induced by simian virus 40. A lymphocytic leukemia of probable monoclonal derivation, induced in a Syrian golden hamster by the oncogenic DNA simian virus 40, was adapted to grow in the allogeneic host either as leukemia or as lymphoma. The leukemia, which was produced by transplanting subcutaneously neoplastic lymphocytes that had circulated through and/or proliferated in lymph nodes and spleen, was characterized by dissemination with systemic manifestations and poor prognosis. The lymphoma, which was produced by transplanting subcutaneously neoplastic lymphocytes that had proliferated at subcutaneous sites of cell implantation, was characterized by localization and favorable prognosis. Evidence indicates that the tissue environment the neoplastic lymphocytes encounter during circulation and/or proliferation regulates their subsequent behavior in the intact host. Since the leukemic and lymphomatous forms of this animal model resemble very closely the analogous human lymphocytic neoplasms, it can serve as a means to elucidate the factors responsible for the differences in their behavior and to determine how these differences may influence prognosis and response to therapy.


Protein kinase activity associated with the avian sarcoma virus src gene product. Incorporation of phosphorus from [gamma-32P]ATP into protein was catalyzed by specific immunoprecipitates from avian sarcoma virus (ASV)-transformed avian and mammalian cells. This incorporation was observed only when antiserum from tumor-bearing rabbits able to specifically precipitate the ASV sarcoma gene product, p60src, was used to immunoprecipitate antigens from transformed cell lysates. Immunoprecipitates of extracts from normal cells or cells infected with a transformation-defective ASV mutant showed no activity in this assay, nor did any immune complexes formed with normal rabbit serum and any of the cell extracts tested. The expression of the protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) was growth temperature-dependent in cells infected with an ASV mutant temperature-sensitive for the transformation. These results on an enzymatic activity associated with the ASV transforming protein are discussed in terms of protein phosphorylation as a mechanism for viral transformation.


Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus. Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the "estrogen-dominated" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In "progesterone-dominated" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [(3)H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [(3)H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [(3)H]oxytocin binding; the concentration of specific [(3)H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon the continuous de novo synthesis of oxytocin receptors. In contrast, progesterone, like actinomycin D, appears to act at the nuclear locus to repress synthesis of oxytocin receptors.


Morphological and biological features of MC-29 virus-induced liver tumors in chicken. Further comparative studies on the biological and biochemical features of virus-derived transplantable and chemically induced hepatomas may contribute to the knowledge of human hepatomas. Evidence for the reprogramming of gene expression found in chemically induced transplantable hepatomas [22] was also found in this virus-derived hepatoma.


Hydrochloric acid and cyclic 3'.5'-adenosine monophosphate content of rodent gastric juice after halothane administration. Pulmonary aspiration of gastric contents during general anesthesia has always been a serious problem. Morbidity and mortality depend on the volume and acidity of the aspirated material. The anesthetic agent itself might affect gastric acid secretion. The effect of halothane (5, 10 and 20 mg/kg intravenously) on HCl secretion and cAMP content of gastric juice in pyloric and cardiac ligated male Sprague-Dawley rats was investigated. Compared with the control group, halothane significantly increased both HCl secretion and cAMP content of gastric juice, but to a lesser degree at the higher doses (p less than 0.05).


Effects of opiates on cAMP in homogenates and slices of rat striata. In slices of rat striata, incubated in a depolarizing medium (53 mM K+), morphine decreased by concentration of cAMP even in concentrations as low as 0.5 micron. This effect was inhibited by naloxone. Levorphanol, but not dextrorphan, induced a similar effect as morphine. In tissue, homogenized in a hypotonic medium, morphine (5-50 micron) also slightly decreased the concentration of cAMP, which was antagonized by naloxone. Neigher slices nor homogenates of morphine-withdrawn rats showed any alteration in the concentration of cAMP.


General pharmacology of ergot alkaloids. Ergot alkaloids possess a wide and divergent spectrum of central and peripheral pharmacodynamic actions. They interfere with different receptor sites to stimulate and/or inhibit effector structures. The concept of partial agonism on alpha-adrenoreceptors has replaced the ancient hypothesis of direct stimulation of vascular and uterine smooth muscle. The mechanisms which are considered to be relevant for the therapeutic use of dihydroergotamine, a potent drug increasing venous tone, and of bromocriptine, a specific inhibitor of prolactin secretion, are discussed in more detail.


Ergot alkaloids and cyclic nucleotides in the CNS. Ergotamine and dihydroergotamine show a higher blocking effect towards the dopamine-induced stimulation of adenylate cyclase activity than to the apomorphine-induced stimulation. This could reflect a possible specificity of the compound to dopaminergic receptor. Bromocriptine blocks in a more competitive way the activation of adenylate cyclase induced in vitro by dopamine, but increases the levels of cAMP in rat striatum in vivo. This effect is blocked by haloperidol and reserpine when given together with bromocriptine. On the base of the biochemical observation and various behavioral data the drug has been used in the treatment of parkinsonism with contrasting results and of Huntington's chorea. Moreover, bromocriptine induces a marked decrease of cGMP levels in cerebellum such as haloperidol and chloropromazine while apomorphine and other dopaminergic drugs increase the levels of cGMP. At the dose of 1 mg/kg, bromocriptine as well as DH-ergotoxine markedly reduces the levels of striatal DOPAC.


Pituitary hormones and ergot alkaloids.

Pituitary hormones and ergot alkaloids. From the data presented it appears that ergot drugs are both a useful tool for use in the study of neuroendocrine control of pituitary hormone secretion and a valid pharmacologic weapon for treatment of hyperprolactinemic states, GH and, probably, ACTH and MSH hypersecretion. In fact, they are capable of a long-lasting disruption of PRL secretion from a normal or tumoral pituitary gland, are unable to affect directly the somatotrophs of an intact AP, but inhibit GH and, possibly, ACTH secretion from a hyperplastic or tumoral gland. Ergolines also exert clear-cut PRL-lowering effects and are capable of suppressing GH secretion in acromegaly. The intimate mechanism(s) and hence site(s) of action of some of these compounds await clarification.


The role of the corpus callosum in the interhemispheric transmission of epileptic electrical activity. In acute experiments on 49 curarized adult rats without general anaesthesia, we studied the transmission of discharges of cortical penicillin foci between the two hemispheres after transecting the corpus callosum. Projected discharges of the cortical penicillin focus appeared in the contralateral hemisphere later than in the controls and had a very different shape. The interhemispheric response of the experimental rats consisted of a small positive and a small negative deflection with long latent periods. Focal discharges could be triggered by electrical stimulat;on of the contralateral hemisphere only irregularly and for short periods of time. In rats with a transected corpus callosum, two symmetrical cortical foci at first behaved independently of each other; their synchronization then slowly improved, but never attained 100 per cent. The corpus callosum is the preferential pathway for interhemispheric transmission of focal activity. Transection of this pathway makes the transmission conditions much worse, but further connections, with a longer conduction time and lower efficacy, gradually come into action.


[Granular cell myoblastoma of the mammary gland and its differentiation from mammary carcinoma (author's transl)]. Report of a case with granular cell tumor of the mammary gland. These tumors are observed infrequently and are important because of the difficulty to differentiate those lesions from carcinoma of the breast. The accurate diagnosis is possible by cytology and microscopy.


The pleural tail sign.

The pleural tail sign. The pleural tail sign is widely thought to indicate malignancy. However, of 18 patients with the tail sign, 9 had benign disease. Bronchioloalveolar carcinoma was the most common malignant tumor, but adenocarcinoma, squamous-cell carcinoma, and metastatic adenocarcinoma of the colon were also found. The location of nodules and the radiographic characteristics of the pleural tails did not help differentiate benign from malignant lesions. However, nodules 2 cm or larger were malignant while those 1 cm or smaller were benign. Histologically, pleural tails reflected thickened, fibrotic connective tissue septae with indrawing of the visceral pleura. Their occurrence with neoplasm reflects desmoplastic reaction or scar carcinoma.


The evaluation of ependymal and subependymal lesions by cranial computed tomography. Lesions of the ventricular ependyma and its derivatives can be visualized by CT scans, and their nature and extent can be determined. Generalized enhancement of the ependyma following the administration of intravenous contrast media can be seen with spendymoma, medulloblastoma, metastatic dysgerminoma, glioblastoma multiforme, and ependymitis. Localized ependymal enhancement can often be identified in the presence of acute ventriculitis, vascular anomalies or malformations, cerebral infarctions with luxury perfusion, and vascular neoplasms.


Pitfalls in the radiographic diagnosis of angiofibroma. Radiographic findings previously thought pathognomonic for juvenile nasopharyngeal angiofibroma are anterior bowing of the posterior wall of the maxillary antrum on plain films or tomography, and a dense homogeneous blush on angiography. Two patients presented with nasopharyngeal masses which mimicked angiofibroma radiographically: one mass was a lymphoepithelioma and the other was a fibrous tumor. Constitutional symptoms and atypical physical findings should alert the physician to a diagnosis other than juvenile nasopharyngeal angiofibroma.


99mTc-pyrophosphate bone imaging in osteopoikilosis, osteopathia striata, and melorheostosis. Technetium-99m pyrophosphate bone images were contrasted with radiographic findings in two patients with osteopoikilosis, one with osteopathia striata, and one with melorheostosis. Despite the striking radiographic findings, scans were normal in osteopoikilosis and osteopathia striata. In melorheostosis, focal increased radiopharmaceutical accumulation appeared in each radiographically abnormal area. Technetium-99m pyrophosphate bone images should prove helpful when superimposed osseous disease must be differentiated from osteopoikilosis, osteopathia striata, or melorheostosis.


Juvenile nasopharyngeal angiofibroma. A report of seven cases. Seven cases of biopsy-proved juvenile nasopharyngeal angiofibroma are presented. All patients were males. Examination under anesthesia and tomography and angiography were very rewarding in determining the full extent of tumor. Selective carotid angiography revealed a characteristic early arterial phase with reticulated vessels, and a homogeneous blush continuing into the venous phase without early draining veins. The tumor has a strong predilection for young males. Chromosomal studies and estimation of 17-ketosteroids in 4 patients were normal. None of the patients demonstrated sexual underdevelopment. All were treated by external radiotherapy with 3000 rads in 15 fractions in three weeks with good results. There were no undue side effects.


The effect of dihydroxy-2-aminotetraline (DATs) on dopamine and beta type adenylate cyclases. A number of DATS have been studied for agonist activity with dopamine (DA) and beta (beta) type adenylate cyclases and the most potent ones were found among the 6,7-DATs and the 5,6-DATs, respectively. None of the compounds tested possessed antagonist activity. The observed activities were not expected on the basis of structural analysis of model compounds such as apomorphine and 6,7-dihydroxy-1-benzyltetrahydroisoquinoline. A new view was constructed which suggests that the nitrogens of the DAT compounds were positioned better than those of the model compounds with regard to their binding sites.


Effect of endotoxin on uterine cycle AMP in pregnant mice. The effect of endotoxin (LPS) on uterine cAMP was determined by measuring the levels of cAMP and cAMP phosphodiesterase after challenge. Two LPS preparations, isolated from wild type (WT) and Re chemotype mutant cells of Salmonella typhimurium were used. The pattern of termination differed with WT LPS resulting in expulsion of the fetuses, and Re LPS primarily causing the resorption of the fetuses. The animals challenged with WT LPS showed a decrease in uterine cAMP when the mice were starting to expel the fetuses while the Re LPS treated group maintained control levels of cAMP. Cyclic AMP phosphodiesterase also decreased in WT LPS and not the Re LPS group. These results suggest the possibility that uterine cAMP is involved in the expulsion of the fetuses.


alpha and beta-adrenoceptors in chicken airways. Isolated chicken bronchus (which had been partially contracted to carbachol) relaxes to isoproterenol and epinephrine but contracts weakly to phenylephrine. Propranolol (a beta-adrenoceptor blocker) antagonizes isoproterenol and reverses epinephrine-induced relaxations to feeble contractions. Phenylephrine-induced bronchoconstrictions and constrictions to epinephrine (in the presence of beta-blockade) were blocked by phentolamine. The results of this study showed the predominance of beta-)inhibitory) adrenoceptors and some alpha-(excitatory) adrenoceptors in the bronchus of the adult domestic fowl.


Glomerulonephritis in malignant extra-renal neoplasms. Experimental study on mice using the method of immunofluorescence. Histologic and immunofluorescence studies were done in the murine kidneys (strain C3HAvy) suffering a spontaneous cancer of the liver. Proliferative glomerulonephritis has been found in 17 animals and memranproliferative glomerulonephritis with "wire loop" appearance in 6 animals. The glomeruli of all animals presented immune complex deposition in the mesangium and along the glomerular basement membrane. Furthermore, heavy intensity of IgG complex deposition was observed in animals with membranproliferative glomerulonephritis. The latter animals had developed a poorly differentiated liver cancer.


[The Hoffmann reflex in the normal new-borns. Post-natal evolution of the conduction velocity of the alpha motor and the Ia sensitive fibres of the ulnar nerve (author's transl)]. The conduction velocities of the alpha motor fibres and the IA sensitive fibres of the ulnar nerve have been studied in a group of full term newborn babies and during the neonatal period. At birth the average conduction velocity of the alpha motor fibres is 25,7 m/sec (sigma = to 2,4 m/sec) that of the IA afferent fibres is 35 m/sec (sigma = to 3,2 m/sec). The post natal evolution of the conduction velocity as a function of age has been established for both types of fibres. The time required for nervous conduction between the olecranon process and the wrist diminishes clearly in the course of the first two years because of a discordance between the augmentations of the length and of the diameter of the nerve fibers. The evolution of this conduction time as a function of the age and of the length of the forearm, has been established for the period between birth and the age of six years. The Hoffmann reflex in the inferior limb is present in all infants at birth; its latency is 14,2 msec; the ratio R = to Hmax/Mmax x 100 = to 55,75 p. 100 is identical to that found in the adult. A Hoffmann reflex exists in 66 p. 100 of the population studied in the ulnar nerve. Its latency is 11,1 msec; R = to Hmax/Mmax is equal to 30 p. 100. This reflex disappears progressively during the development.


Hormonal stimulation of intestinal brush border enzymes release. The rat small bowel was perfused in vivo and ex vivo in the absence of biliary and pancreatic secretion. Intraluminal release of sucrase, alkaline phosphatase, aminopeptidases and enterokinase was significantly increased after administration of pentagastrin, caerulein and glucagon at doses ranging between 1 pg and 10 microgram. This suggests that there is a direct hormonal stimulation of the intestinal mucosa. This effect might at least partly be mediated through cyclic AMP since dibutyryl derivates of this cyclic nucleotide exerted a significant stimulatory effect on intraluminal release of proteins, sucrase and enterokinase, although the pattern of enzyme was quite different from the effect produced by the three peptides.


[Proliferation of L 929 mouse fibroblasts and synthesis of active peptidyl prolyl hydroxylase in these cells in monolayer culture under the influence of D-penicillamine, azathioprine, aurothiopolypeptide, oxyphenbutazone and prednisolone (author's transl)]. L 929 mouse fibroblasts were cultured as monolayer using MEM Eagle medium after addition of bovine serum albumin, antibiotics, antimycotica, ferrous nitrate and ascorbic acid. In 24 hours distances cell number was counted. At the same time peptidyl prolyl hydroxylase activity was determined and related to the protein concentration in the cells. The proliferation of the cells followed a typical curve. The cell number decreased after trypsination, then increased logarithmically, finally reached a stationary phase. Enzyme activity showed a correspondent curve. Active enzyme did not appear until near the end of the log phase. After addition of the mesenchyme active substances in therapeutical concentrations proliferation and synthesis of active peptidyl prolyl hydroxylase in the cells were significantly decreased. The results are discussed in relation to the characteristics of collagen synthesis and proliferation of connective tissue cells under physiological, pathophysiological and therapeutical conditions.


Cyclic nucleotide metabolism in experimental bronchial constriction in rabbits. In anesthetized, spontaneously breathing rabbits, intratracheally administered isotonic saline, acetylcholine (Ach) and histamine (His) induced an increase of airway resistance up to 183, 571, and 312%, respectively, compared with untreated controls. This was accompanied by a decrease of the arterial pO2. Bilateral cervical vagotomy led to nearly complete inhibition of the saline- and Ach-induced bronchoconstriction, whereas the His effect was only reduced to 202%. Vagotomy did not improve the arterial pO2. While the bronchoconstrictive effects of isotonic saline and Ach revealed a significant linear correlation with the increased cGMP/cAMP ratio, His did not cause an alteration of the cGMP/cAMP ratio to a degree that corresponds to its bronchoconstrictive activity. These data indicate that (1) bronchoconstriction-inducing agents may act (a) by stimulation of the parasympathetic nerve or (b) by contracting smooth muscles directly; (2) alveolar ventilation is not regulated by the parasympathetic nerve, and (3) bronchoconstriction induced by parasympathetic stimulation is associated with or mediated by an increase of the cGMP/cAMP ratio.


Bleeding from cecal ulcers in renal transplant patients. Cecal ulcerations represent a high percentage of causes of gastrointestinal bleeding in renal transplant patients. A close association of these lesions with cytomegalovirus (CMV) infection has been found, even though a cause-effect relationship has not been established. All of these patients are usually critically ill, and a progressive deterioration leading to death is the rule. Our experience suggests that the decrease of immunosuppressive drug therapy, followed by the nephrectomy of the transplanted kidney if signs of rejection are present, and right hemicolectomy are the best therapy. Angiographic procedures are of importance to determine the site of bleeding, stabilize the bleeding with the use of vasoconstrictor drug therapy, and to plan the surgical treatment.


Origin of intranuclear inclusions in myeloma cells. The mechanism of inclusion of the cytoplasmic dense bodies into the nucleus of myeloma cells was studied by transmission electron microscopy. The findings in different cells suggest that the inclusion of the electron-dense bodies is a result of an interaction between the nuclear envelope and the endoplasmic reticulum. The ability of the nuclear membrane to form an extension into the cytoplasm and the connection with the cisternae of endoplasmic reticulum enables the movement of the dense bodies towards the nucleus. The proposed mechanism does not support the concept of a simple invagination of the bodies into the nucleus or that they are produced in the nucleus itself.


[C-cells of the thyroid gland].

[C-cells of the thyroid gland]. In the human thyroid gland, the C-cell system reacts in physiologic and pathologic conditions as an entity and represents an independent endocrine organ. Its special features are its embryology, which relates it to other derivatives of the neural crest, the special histologic methods needed to demonstrate its disseminated C cells, and the obscure physiologic role of its hormone, calcitonin. Although there exist many histopathologic findings, the only C-cell disease of clinical interest is medullary carcinoma, which in its familial form is usually associated with pluriglandular syndromes.