Paramagnetic and crystallographic effects of low temperature ashing on human bone and tooth enamel. Low temperature ashing by excited gas (LTA) causes crystallographic and paramagnetic alterations of the human bone and tooth enamel mineral. On the one hand, LTA induces variations of the alpha lattice parameter. These variations depend upon the nature of the gas used, but are little affected by its degree of excitation. Trapping of gas molecules in the crystal structure is demonstrated. On the other hand, LTA produces two preponderant paramagnetic centers in bone and enamel samples at 20 degrees C. Their inorganic origin clearly indicated. One of the two radicals has been identified as O3- (g1 = 2.002, g2 = 2.010, g3 = 2.016) and the other as (CO3-3 (parallel = 1.996, g = perpendicular 2.003). Variations of the alpha lattice parameter and trapping of paramagnetic gas species do not seem to be directly related.


Some comparative properties and localization of porcine jejunal adenylate cyclase. Cholera toxin is thought to cause intestinal secretion by activating adenylate cyclase and increasing intracellular 3',5'-cyclic AMP concentrations in intestinal mucosa. Cholera toxin causes profuse secretion of fluid into ligated intestinal loops of both pigs and rabbits, but cholera toxin-induced increases in 3',5'-cyclic AMP concentration are much lower in the pig than in the rabbit. Porcine jejunal adenylate cyclase was examined for unusual properties which might account for a lack of 3'-5'-cyclic AMP accumulation after treatment with cholera toxin. The divalent cation requirements, the pH optimum, and the stimulation by fluoride ion were unremarkable. The Km for ATP was 0.11 mM with negative cooperativity indicated by a Hill coefficient of 0.83. Triton X-100 was inhibitory and guanosine diphosphate methylenephosphate stimulated enzyme activity. Adenylate cyclase activity was highest in the basal and lateral membrane fractions of jejunal mucosa and relatively low in brush-border preparations. Pretreatment of pig jejunum with cholera toxin caused a 30-40% activation of the crude and of the partly purified enzyme. A relatively low activation of adenylase cyclase in pig jejunal mucosa, compared with rabbit, may account for the absence of 3',5'-cyclic AMP accumulation after cholera-toxin treatment in the pig.


Lapine rotavirus: preliminary studies on epizoology and transmission. Antibody to rotavirus was found in sera of domestic rabbits, wild cottontail rabbits and Snowshoe hares. Eight out of 187 stools from a rabbitry contained rotavirus, though no clinical symptoms were apparent. The virus extracted from one such stool infected a five week old seronegative rabbit and led to distention and congestion of the colon, excretion of virus in the stool and a serological response to virus. Human and Simian rotaviruses did not replicate in the rabbits.


Characteristics of neonatal calf diarrhea virus ribonucleic acid. The nucleic acids of neonatal calf diarrhea virus were characterized by isopycnic centrifugation in Cs2SO4, electron microscopy, ultraviolet absorbance temperature profiles and polyacrylamide gel electrophoresis. These studies indicated that the neonatal calf diarrhea virus genome consists of 11 segments of double stranded RNA with a total molecular weight of 10.75 million daltons.


Sensitivity and specificity of the fluorescent antibody technique for detection of infectious laryngotracheitis virus. The specificity of a fluorescent conjugate to infectious laryngotracheitis virus was examined using chick trachea organ culture or tissue sections infected with other avian viruses (adenovirus, infectious bronchitis, poxvirus, reovirus, Newcastle disease virus, Marek's disease virus, avian encephalomyelitis and infectious bursal agent) or Mycoplasma gallisepticum. Confirmation of virus replication in these preparations was obtained by either 1) demonstration of virus titre increase or 2) demonstration of fluorescence when using the homologous conjugate. Once either of these criteria had been satisfied, negative results with the infectious laryngotracheitis conjugate were taken to indicate that the conjugate would not present false positive results in differentiated cells infected with these heterologous viruses. The spectrum of reactivity of the infectious laryngotracheitis conjugate was then examined on organ cultures infected with several infectious laryngotracheitis isolates from across Canada. Finally, the conjugate was applied to experimental and natural cases of infectious laryngotracheitis and its efficiency was compared to routine virus isolation methods.


Polyphosphate-deficient mutants of Anacystis nidulans. Polyphosphate-deficient mutants of Anacystis nidulans have been isolated by either ethyl methanesulfonate (EMS) or N-methyl nitrosoguanidine (NTG) mutagenesis and penicillin-enrichment techniques. Mutagenised stock was preincubated in a medium lacking sulfate, then transferred to a phosphate-lacking medium before penicillin treatment. Many single-colony isolates, in contrast to wild-type, show little growth in absence of phosphate, and have altered polyphosphate, and have altered polyphosphate kinase levels indicating that the lesions affect either the activity or the expression of this enzyme. In these same mutants radioactive phosphate incorporation is severely retarded. Electron micrographs confirm the absence of polyphosphate granules in some mutants.


Growth of Escherichia coli on glucosamine 6-phosphate: selection of a constitutive hexose phosphate transport system mutant. Glucosamine 6-phosphate was found to be a substrate but not an inducer for the hexose phosphate transport system of Escherichia coli. Wild-type cells grow very poorly on glucosamine 6-phosphate. A mutant was selected that will grow rapidly on glucosamine 6-phosphate because it contains a constitutive hexose phosphate transport system.


Purification and some properties of the citrate synthase from a marine Pseudomonas. Citrate synthase (citrate-oxaloacetate lyase (CoA acetylating), EC 4.1.3.7) has been purified to electrophoretic homogeneity from a marine Pseudomonas. The enzyme was made up of identical subunits, with a molecular wieght of about 53 000, as determined by sodium dodecyl sulphate - polyacrylamide gel electrophoresis. The native enzyme (citrate synthase II, CS II) could be dissociated by dialysis against 20 mM phosphate (Pi), pH 7; the enzyme thus obtained (citrate synthase I, CS I) was still active, but presented different molecular weight and kinetic and regulatory properties. CS II was activated by adenosine monophosphate (AMP), Pi, and KCl, and inhibited by reduced nicotinamide adenine dinucleotide (NADH), being apparently insensitive to adenosine triphosphate (ATP) and adenosine diphosphate (ADP). The inhibition by NADH was completely counteracted by 0.1 mM AMP, but not by 50 mM Pi or 0.1 M KCl. The activation by KCl and Pi, or by KCl and AMP was nearly additive, whereas that by AMP and Pi was not. The activators acted essentially by increasing Vmax, although they also caused a decrease in the Km values. CS I was inhibited by ATP, ADP, AMP, and KCl, and was insensitive to NADH. CS I could be reassociated after elimination of Pi by dialysis, regaining the higher molecular weight and the activation by AMP characteristic of CS II.


Direct observation of fungal aggregates in sand dune soil. The mycorrhizal fungus Glomerus in association with bean hosts, Phaseolus vulgaris L., growing in pot cultures and grass hosts, Calamovilfa longiflora (Hook). Scribn and Andropogon sp. growing on Lake Huron sand dunes produced extensive external mycelium. This mycelium was the dominant factor in the aggregation of soil particles. Light and scanning electron microscope studies indicated that the sand grains were attached to the hyphae. An amorphous deposit was often present at the interfaces of sand grains and hyphae. It appeared to act as an adhesive. Staining procedures indicated that this material contained polysaccharide. Other microogranisms were observed in association with the Glomus hyphae and the amorphous deposits.


Plasma lipids and lipoproteins in Friedreich's ataxia and familial spastic ataxia--evidence for an abnormal composition of high density lipoproteins. A systematic study of plasma lipids and lipoproteins was carried out in 11 cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using 11 healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart.


Possible mechanisms of normal amylase activity in hyperlipemic pancreatitis. Lipemic serum from three patients with acute pancreatitis and type IV hyperlipemia was fractionated into very-low-density lipoproteins and clear serum. Amylase activity (determined by the Phadebas method) in the component fractions did not exceed that in the original lipemic serum. Addition of these fractions or VLDL and chylomicrons from asymptomatic patients with hyperlipemia to nonlipemic serum from patients with "routine acute pancreatitis" did not inhibit amylase activity or alter the electrophoretic mobility of amylase isoenzymes. Therefore the normal amylase activity often observed in hyperlipemic pancreatitis does not result from an inhibition of amylase activity by serum lipoproteins.


CCNU-adriamycin therapy in bronchogenic carcinoma. Forty-eight patients with advanced bronchogenic carcinoma were treated with a combination of CCNU and Adriamycin. There was an overall objective response rate of 38%. This consisted of 1 of 12 (8%) patients with epidermoid carcinoma, 5 of 15 (33%) with adenocarcinoma, 2 of 5 (40%) with large cell undifferentiated carcinoma and 10 of 16 (63%) with small cell undifferentiated carcinoma. The overall median survival time (MST) from initiation of therapy was 28 weeks. The MST was 18 weeks for patients with epidermoid carcinoma, 30 weeks for those with adenocarcinoma, 39 weeks for those with large cell carcinoma, and 30+ weeks for those with small cell carcinoma. Objective tumor response was associated with prolonged survival. There were no drug related deaths and toxicity was minimal.


Chemotherapy of small cell carcinoma of the lung with V.P. 16-213. A Phase II study of V.P. 16-213 administered to 47 patients suffering from small cell carcinoma of the bronchus. V.P. 16-213 was given as an intravenous infusion over 15 minutes daily for five consecutive days using 60 mg/m2/d at 14-day intervals. Oral V.P. in 100 mg doses was given twice a week between the intravenous courses. Objective response rate for this drug compared favourably with that of other single agents reported. All but two patients showed a degree of response to treatment and 24 of 47 patients showed a true objective response to treatment. The overall median survival of these patients was 225 days and localized disease 278 days. The quality of survival was such that responders lived relatively normal lives up to the latter stages of their disease. The majority of patients had a marked response in performance status, 37 out of 47  showing an improvement. Three patients are alive and well at more than 27 months. In all cases the side effects were minimal. Alopecia was common and reversible haematological complications occurred. Severe toxicity was not encountered and the drug was well tolerated with supportive antiemetic therapy at onset of treatment.


Ifosfamide in the treatment of recurrent or disseminated lung cancer: a phase II study of two dose schedules. Ifosfamide was administered to 21 patients with recurrent or disseminated lung cancer at a dose of 4.0 gm/M2 iv every 3 weeks. The response rate was 33% with an additional 14% showing no response or stable disease. At a dose of 1.2 gm/M2 daily for 5 days every 4 weeks, 57% of 14 patients responded with 35% showing no response or stable disease. The majority of the patients (28) had epidermoid carcinoma. Two (7%) had complete response with 9 (32%) showing partial responses. Other responses included 1/2 oat cell carcinomas and 3/6 large cell undifferentiated carcinomas. Toxicity was equal in both regimens for nausea, vomiting, increased serum LDH and neutropenia but the 5 day program had significantly less hemorrhagic cystitis. Survival was greatly influenced by response. There was no statistical difference in overall length of response between responders and the non responding/stable disease patients. But these two groups had a very significant survival advantage when compared to those patients with increasing disease. Similarly, there was a significant improvement in response duration for the low dosage regimen. Therefore, the low dose 5 day regimen is recommended because of its response rate, it has less hemorrhagic cystitis and it has better patient acceptance in that it can be given as an outpatient and does not require a Foley catheter.


Amyloid stroma in a tubular carcinoma of palatal salivary gland: a histochemical and ultrastructural study. Amyloid as defined by positive Congo red green birefringence and STB red birefringence was observed in the stroma of a tubular carcinoma of minor salivary gland origin. The amyloid exhibited additional histochemical characteristics of immunamyloid, viz., positive DMAB-nitrate and DC-reactions and spontaneous autofluorescence. Electron microscopic studies of the epithelial tumor cells displayed large amounts of cytoplasmic microfilaments similar to those present in the extracellular amyloid masses. It is suggested that the amyloid is derived from spontaneous assembly or polymerization of cytoplasmic microfibrils of the dying tumor cells as has been proposed for the amyloid associated with the calcifying epithelial odontogenic tumor (CEOT).


Application of a microchemical technique to the elucidation of enzyme activity profiles within single human mammary tumors. An ultramicrochemical technique has been adapted to the evolution of enzyme profiles within individual human mammary tumors. Tandem observation of adjacent stained and lyophilized sections permitted dissection of microgram quantities of freeze-dried material within confirmed regions of malignancy. Enzymes frequently monitored to examine glycolytic, respiratory, and metastatic capacity were microanalyzed successfully: lactic dehydrogenase (LDH), phosphoglucose isomerase (PGI), malate dehydrogenase (MDH), acid phosphatase (AP), aldolase (ALD), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK), alpha-glycerophosphate dehydrogenase (alpha-GOPDH), hexokinase (HK), and phosphofructokinase (PRK). All enzyme activities were higher in infiltrating ductal carcinomas than in fibroadenomas. Extracts of tumor cells mixed in varying proportions with brain or muscle extracts of rat evidenced no modification of expected activity. The technical adaptation described provided a sensitive methodology to resolve problems of relication, profile analysis, sample quantity, and selectivity within heterogeneous tissues.


Plasma cell granuloma (inflammatory pseudotumor) of the spinal cord meninges: report of a case. A case of plasma cell granuloma (inflammatory pseudotumor) arising in the meninges of cervical spinal cord of a 37-year-old Japanese man is presented. The diagnosis was made by analogy with the similar lesions known in the lung. Its histology was characterized by infiltration of three kinds of cells; histiocytes with slight epithelioid appearance, plasma cells with numerous Russell bodies, and lymphocytes. Electron microscopy of the formalin-fixed tissue was useful for the identification of these cells, particularly of histiocytes. Although extrapulmonary plasma cell granulomas have been reported, this is the first case, to our knowledge, of this type "tumor" in the spinal cord meninges. Differential diagnoses have been briefly discussed.


Histopathology and prognosis of Wilms tumors: results from the First National Wilms' Tumor Study. Detailed histological analysis of 427 cases entered on the first National Wilms' Tumor Study revealed that lesions with foci of marked cytological atypism (anaplasia), and those composed predominantly of sarcomatous stroma, were associated with unfavorable outcome. Twenty-five patients had anaplasia, and 24 had sarcomatous lesions of which a total of 28 (57.1%) died of tumor. Three hundred and seventy-eight patients had tumors which showed neither of these features, and only 26 (6.9%) died of tumor. Seven of ten deaths due to tumor in patients diagnosed before two years of age were associated with sarcomatous lesions. Three sarcomatous patterns were recognized, of which one, designated "clear cell" sarcoma, had a predilection for bony metastases. Using criteria defined and illustrated in this paper it is possible to identify in advance those patients likely to do poorly using current therapeutic approaches.


Cystosarcoma phyllodes: a clinicopathologic analysis of 42 cases. A retrospective clinicopathologic evaluation of 42 patients with cystosarcoma phyllodes was undertaken to determine if tumor size, contour, degree of stromal atypia and mitotic activity were reliable indicators of clinical behavior. Excluding size, the latter three determinants showed a positive correlation with prognosis and served as the basis of a classification in which 18 benign, 5 borderline and 19 malignant cystosarcomas were diagnosed. The tumors occurred in women averaging 44.3 years of age who most often presented with a palpable occasionally painful mass with a median diameter of 5 cm. Excision or simple mastectomy were the more frequent forms of therapy. Local recurrences were experienced by 6 patients and occurred in all 3 categories of tumor. Only malignant neoplasms developed systemic metastases which was observed in 4 patients 3 of which have died. On borderline tumor recurred 14 times and eventually proved fatal as a result of contiguous pulmonary involvement. A plea is made to label the stroma of malignant cystosarcomas as to the cell(s) of origin so future investigators may evaluate the effect of various soft tissue patterns on prognosis.


Peritoneoscopy in the staging of 190 patients with small-cell anaplastic carcinoma of the lung with special reference to subtyping. Peritoneoscopy with liver biopsy was routinely done as a pretreatment staging procedure in 190 patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 28.3% with fusiform cell type (WHO II,1), 28.9% with polygonal cell type (WHO II,2), 41.5% with lymphocytelike cell type (WHO II,3) and 1.3% with mixed types (WHO II, 4). Liver metastases were found in 21% of the patients with adequate liver biopsy. In addition macroscopic signs of liver metastases were observed in 9%. No significant differences were observed among the histological subtypes. Liver function tests, such as alkaline phosphatase, LDH and GOT, were of little value in excluding liver metastases. On the other hand, 2 of 3 abnormal liver function tests were highly indicative of liver metastases. In patients with positive liver biopsy, 41% had liver metastases alone and 76% had no other evidence of distant metastatic disease if bone-marrow involvement identified with bone marrow examination is excluded as a staging procedure.


The differences between the primary structures of mitochondrial DNAs from rat liver and ascites hepatoma (AH-130). Rat mitochondrial DNAs (mtDNAs) of ascites hepatoma (AH-130) and normal liver cells (Donryu strain) were digested by various restriction endonucleases and the cleavage patterns compared by agarose gel electrophoresis. Different cleavage patterns were observed between AH-130 and liver mtDNAs when they were digested by HindII and EcoRI. The mtDNA of AH-130 lost one clevage site of HindII and one clevage site of EcoRI. The cleavage patterns of mtDNAs from other organs and strains tested were the same as that of liver mtDNA. From these observations we concluded that the molecular clone of AH-130 mtDNA was different from that of other mtDNAs.


EBV-related cytotoxicity of Fc receptor negative T lymphocytes separated from the blood of infectious mononucleosis patients. Epstein-Barr virus (EBV) related specific killing was demonstrated previously in the T cell enriched subpopulations of blood lymphocytes of IM patients. In the present work we demonstrate that the cytotoxic cells belong to the Fc negative T subset. T cells in the blood of IM patients can be divided in 2 categories, 1 Fc positive with non discriminative cytotoxicity and the other, Fc negative with selective cytotoxicity against EBV genome carrying lymphoblastoid cell lines.


Search for disease-related cytotoxicity in mammary tumor patients. Blood lymphocytes from benign and malignant mammary tumor patients ahd healthy blood donors were tested for cytotoxicity against monolayer cell lines, including two which were derived from breast carcinomas. Generally, the T subset was not cytotoxic, and if so this was not restricted to the relevant cell lines. In accordance with previous results 'null' cells were most efficient in the seemingly non-selective cytotoxicity.


Detection of the EBV-determined nuclear antigen (EBNA) in Burkitt's lymphoma and nasopharyngeal carcinoma biopsies by the acid fixed nuclear binding (AFNB) technique. Epstein-Barr virus (EBV) carrying biopsies of Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) were used to examine the question whether the EBV-associated nuclear antigen (EBNA) can be demonstrated by the acid fixed nuclear binding (AFNB) technique, developed previously for the demonstration of EBNA in cultured cell lines [11]. Extracts of 5 BL and 5 NPC biopsies gave a brilliant, EBNA specific fluorescence after binding to acid fixed chicken red cells. Similar extracts of 3 other African tumors that are not known to carry the EBV-genome were negative, in spite of the fact that they were derived from EBV-seropositive patients with relatively high anti-EBV (VCA) antibody titers. Crude extraction and DNA-cellulose purification gave equally active extracts, provided that incubation was carried out at 4 degrees C. These results show that the acid fixed nuclear binding technique can be applied to biopsy material. This may be helpful in searching for EBNA carrying cells in heterogeneous normal and tumor tissues in vivo where the direct in situ ACIF staining for EBNA is known to meet great difficulties.


Immunoreactive beta-endorphin in the rat mammotropic transplantable tumor (MtT-F4). Raised levels of what appeared to be beta-lipotropin (beta-LPH), beta-melanotropic hormone, and beta-endorphin were detected by radioimmunoassay in the plasma of rats bearing the mammotropic transplantable pituitary tumor MtT-F4. The immunoreactivity to anti-beta-endorphin in the assay was displayed by a substance with the molecular weight of beta-LPH, as determined by gel filtration. Isolated cells of MtT-F4 tumor incubated in vitro released immunoreactive beta-LPH and beta-endorphin, with the expected molecular weights, into the incubation medium. These results suggest that the pituitary transplantable rat tumor MtT-F4 secretes peptides structurally related to beta-LPH.


Differences in total mitochondrial proteins and proteins synthesized by mitochondria from rat liver and Morris hepatomas 9618A, 5123C, and 5123tc. Mitochondria were isolated from a slow-growing (9618A) and two intermediate-to-fast-growing (5123C, 5123tc) Morris hepatomas and host livers. The mitochondrial proteins were solubilized and fractionated on sodium dodecyl sulfate:polyacrylamide slab gels. One Coomassie blue-stained band was absent or reduced in amount in all tumors relative to host livers. In addition, a major mitochondrial enzyme present in normal liver, carbamyl phosphate synthetase, was missing or greatly reduced in the slow-growing, highly differentiated hepatoma 9618A, a tumor that is considered to be similar to normal liver in many biochemical and morphological respects. Incubation of mitochondria with [35S]methionine and a suitable amino acid incorporation system resulted in labeling of specific mitochondrial proteins. Autoradiography of the slab gels disclosed four prominently labeled fractions and a number of minor fractions. Preparations from hepatoma 5123tc demonstrated two labeled bands that were absent or greatly reduced in host liver. Host liver preparations displayed a minor band that was absent or greatly reduced in hepatoma 5123C. However, no single change in labeling pattern was common to all three tumors, suggesting the absence of a causal relationship between carcinogenesis and mutations in mitochondrial DNA.


Alkyl methane sulfonate mutation of diploid human lymphoblasts and Salmonella typhimurium. Concentration dependence of mutation in equigenerational exposures to methyl, ethyl, propyl, and butyl methanesulfonates has been determined in diploid human lymphoblasts and Salmonella typhimurium. Forward mutation was measured at the hypoxanthine guanine phosphoribosyltransferase locus in human lymphoblasts and at the putative guanine phosphoribosyltransferase locus in S. typhimurium. Reverse mutation at the his G46 locus was also measured in S. typhimurium. This analysis and previous reports support the conclusion that S. typhimurium and mammalian cells are essentially equisensitive to the mutagenic effects of ethyl methanesulfonate when concentration and exposure time are taken into account. Comparison of forward and reverse mutation assays in S. typhimurium reveals no important differences in sensitivities for the four compounds studied.


Turnover of messenger RNA in transplantable hepatomas and host liver of rats. The turnover of messenger RNA (mRNA) in two intrahepatically transplantable hepatoma (5123 and 19) and host livers of Buffalo rats was evaluated with four different approaches. [14C]Orotic acid incorporation into the rapidly labeled peak between 18S and 4S of total polyribosomal RNA was measured. In vitro RNase assay of [14C]orotic acid-labeled mRNA of polyribosomes was utilized. The decay of mRNA as reflected by disaggregation of free and membrane-bound polyribosomes at intervals after actinomycin D treatment was determined. The incorporation of [14C]orotic acid into polyadenylic acid-mRNA of free and membrane-bound polyribosomes was assayed. The results revealed that the turnover of mRNA of total, free, and membrane-bound polyribosomes was greater in the host livers than it was in the two hepatomas. In host livers the turnover of mRNA of the free polyribosomes was greater than that of the membrane-bound polyribosomes. In the two hepatomas the turnover of mRNA of free polyribosomes was at a similar rate as that of membrane bound polyribosomes. Hepatoma 19, which grow more rapidly and is less differentiated morphologically than is hepatoma 5123, appeared to have a slower turnover of mRNA than did hepatoma 5123. Measurement of RNase activity revealed greater activity in host livers than in hepatomas.


Induction of peripheral neuroblastomas in Syrian hamsters after injection as neonates with JC virus, a human polyoma virus. Neuroblastomas developed in 10 of 31 Syrian hamsters inoculated intraocularly with JC virus, a human polyoma virus. The latent period was 6 to 11 months. Primary tumors occurred in the abdominal cavity, pelvis, mediastinum, and neck region. The origin of one tumor from the adrenal gland was demonstrated. Metastases were seen in the liver, bone marrow, and lymph nodes. Two neuroblastomas arising in this experiment were transplanted serially in weanling hamsters, and a tissue culture cell line was established from one of the transplanted tumors. T-antigen was detected in three of five primary tumors tested and in the transplanted tumors. Antibody against T-antigen was demonstrated in sera from five of six animals with neuroblastomas. Neuroblastomas also developed after combined s.c. and i.p. injection of JC virus.


Radioimmunoassay for protein p28 of murine mammary tumor virus in organs and serum of mice and search for related antigens in human sera and breast cancer extracts. The main protein of the core of murine mammary tumor virus, with a molecular weight of 28,000 (p28), was solubilized by deoxycholate treatment of the virus and purified by Ultrogel ACA-54 filtration and hydroxyapatite chromatography. This protein was used as labeled antigen in a highly specific and reproducible radioimmunoassay. Organ extracts of uninfected C57BL mice did not contain p28, but organ extracts of infected RIII mice did contain the antigen. Despite the high content in the mammary gland, the level of p28 in the other organs was identical in male and female mice. Sera of uninfected mice and the majority of the sera of infected mice did not contain the antigen. The investigation included 338 human sera (50, normal; 157, breast cancer; 77, polycystic disease; 32, benign mastopathy; 12, fibroadenoma; 10, at risk of developing breast cancer). None contained an antigen related to p28. Eight of 24 extracts of human breast cancer gave results that appeared weakly positive, possibly as a result of proteolysis. Extracts of healthy breast tissue and the serum from the breast arterial and venous blood of corresponding patients were negative.


Yoshi 864 (1-propanol, 3,3'-iminodi-, dimethanesulfonate [ester], hydrochloride): a phase II study in solid tumors. Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting.


2-acetamido-2-deoxy-alpha-D-galactosidases of Clostridium perfringens. Separation and characterization of an exoglycosidase and an oligosaccharidase. Two distinct 2-acetamido-2-deoxy-alpha-D-galactosidases have been separated from filtrates of cultured Clostridium perfringens by electrophoresis in 6.5% poly(acrylamide) gels. One of the enzymes had a mobility of 0.32--0.36 (relative to Bromophenol Blue) and was identified as the exoglycosidase, 2-acetamido-2-deoxy-alpha-D-galactosidase. It appears to be the same enzyme as that reported in 1972 by McGuire et al. The second of the two enzymes, having a relative mobility of 0.42--0.46, corresponds to the oligosaccharidase reported in 1972 by Huang and Aminoff. The A-specificities of human type-A erythrocytes and of water-soluble glycoproteins having A-activity are both destroyed by incubation with the 2-acetamido-2-deoxy-alpha-D-galactosidase, but not on incubation with the oligosaccharidase. A concomitant rise in blood-group O(H) activity, as indicated by the use of a lectin from Ulex europeus, occurred in the A-erythrocytes treated with the exoglycosidase 2-acetamido-2-deoxy-alpha-D-galactosidase.


Studies on antiviral glycosides. Synthesis and biological evaluation of various phenyl glycosides. A variety of analogues and derivatives of phenyl glycosides were synthesized for examination of their biological activities and of the relationship between structure and antiviral activity. For antiviral activity, a 6-deoxy-6-halogeno-D-glucose residue was most suitable for the carbohydrate moiety and p-alkylphenyl groups for the aglycone moiety. Based on these results, p-(sec-butyl)phenyl 6-chloro-6-deoxy-beta-D-glucopyranoside and p-(sec-butyl)phenyl 6-deoxy-6-iodo-beta-D-glucopyranoside were prepared, and the former compound was found to be the most potent antiviral substance, in this series, against influenza and Herpes simplex virus. The anomeric configuration of phenyl glycosides did not contribute to the antiviral activity.


Effects of propranolol on baroreflex sensitivity in borderline hypertension. Patients with borderline hypertension have reduced baroreflex sensitivity, but the mechanism is not known. These patients reportedly have increased beta-adrenergic activity. Since beta-adrenergic activity has been reported to antagonise baroreflex sensitivity, this study was undertaken, first to determine if propranolol increases baroreflex sensitivity in borderline hypertension, and secondly to test the hypothesis that increased beta-adrenergic activity might contribute to reduced baroreflex sensitivity in these patients. The effect of beta-adrenergic blockade on baroreflex sensitivity was studied in 11 patients with borderline hypertension and was compared with that of six age-matched control subjects. Baroreflex sensitivity was significantly increased by propranolol, 0.2 mg.kg-1 intravenously, in patients with borderline hypertension. However, after propranolol baroreflex sensitivity was still lower in the patients with borderline hypertension than it was in control subjects (P less than 0.01). The results suggest, first that increased beta-adrenergic activity is not a major factor contributing to decreased baroreflex sensitivity in borderline hypertension and, second that increased baroreflex sensitivity produced by propranolol might contribute to the anti-hypertensive effect of this drug.


Immunocytological detection and localization of a peptide reacting with an alpha-endorphin antiserum in the corticotropic and melanotropic cells of the trout pituitary (Salmo irideus Gibb). In the pituitary of the trout, the corticotropic and melanotropic cells display a strong immunocytological reaction with alpha-endorphin antiserum. This reaction persists even when alpha-endorphin antisera treated with beta-1-24ACTH or alpha-MSH are used. In the absence of pharmacological tests on the endorphic potencies of the compounds involved in the immunoreaction, it is not yeat clear whether this reaction is due to the presence of an alpha-endorphin-like peptide or simply an immunologically related peptide without the properties of endorphin. However, the presence of such peptides in the fish pituitary is interesting from the comparative point of view.


[Desensitization of adrenal tumor cells Y1 by ACTH and dibutyryl cyclic AMP]. The steroidogenic responsiveness of mouse adrenal tumor cell line (Y-1) to ACTH and db cAMP declines after stimulations by these compounds. The desensitization induced by ACTH appears early and is more pronounced than that induced by db cAMP. After removal of the hormone or the nucleotide, the recovery of cell responsiveness to both stimuli isprogressively restored. Full responsiveness is recovered within 24 hrs.


[Periodate oxidation of lymphocyte membrane glycoconjugates]. Mouse spleen cells free of erythrocytes were suspended in PBS at a concentration of 2 X 10(7) cells/ml and mixed with an equal volume of sodium periodate in PBS for 10 min. at 4 degrees C to give a final concentration of periodate ranging from 10(-4) M to 5 X 10(-3) M. The cells were then washed and suspended (60 X 10(6) ml) in PBS containing 3H-labelled sodium borohydrate and incubated for 30 min, at 23 degrees C. Following this, the cells were washed and the pellets treated with H2SO4 0.1 N for 60 min. at 80 degrees C. Compounds liberated by such treatment, were identified by chromatography as derivates of sialic acid. The data provide direct evidence that the mitogenic effect of sodium periodate is associated to the oxidation of the sialic acid residues on the lymphocyte membrane.


[Purification of calf thymus adenosine diphosphate ribose polymerase]. Calf thymus poly ADPR polymerase has been purified to electrophoretic homogenity. The enzyme has a molecular weight of 120,000 +/- 10,000 dalton. The substrate affinity is very high (apparent Km 82.5 micrometer). The presence of exogenous DNA does not appear to be a requisite for enzymatic activity of the purified enzyme.


[Susceptibility to avian tumor viruses: determination of chick phenotypes]. The genetic cellular susceptibility to avian sarcoma viruses (RSV) of subgroups A, B, C and E has been determined in one week old Chicks. Fibroblasts from pin feathers were grown in vitro and tested by focus formation after infection. This technique will allow, for the first time, the study of the influence of the host phenotypes (susceptibility or resistance to the different subgroups of RSV) upon the immune response to a given virus.


[Tumor specific surface antigen in the culture medium of a rat cell line transformed by Rous sarcoma virus]. TSSA is detected on transformed cells by a mixed hemadsorption reaction. The medium of cultures of Rat cells transformed by Rous sarcoma virus (Prague strain, sub-group C) contains a soluble factor which specifically inhibits this reaction. This factor thus possesses the antigenic activity of TSSA which is associated with the presence of a component of molecular weight 42,000 by polyacrylamide gel electrophoresis.


[Cell transformation in vitro by transfer of isolated metaphase chromosomes]. Human and murine cells can be transformed in vitro following transfer of chromosomes (transfection) isolated from tumour (HeLa) or SV40-transformed (WI98VaD) human cells. An abortive transformation of Mouse cells is observed in soft-agar medium. An instability of the transformed phenotype is exhibited by the transfected human cells, following the isolation of colonies growing in soft-agar or low-serum medium. Nevertheless, two transformed cell lines (809 ch. VaD, Cl.5P and Cl.6P) could be established in culture.


[Characterization of the partial inhibition, by deficiency in serum factors, of multiplication of SV3T3 transformed fibroblasts]. Partial inhibition, by serum starvation, of multiplication of SV3T3 transformed fibroblasts was studied by cultivating cells in a medium containing 1% of serum. Two different and successive states are described: a first step, with a rate of multiplication for 24 hrs, which is lowered (2 instead of 3 in a normal medium containing 10% of serum) but which remains constant (i.e. exponential multiplication), the observed inhibition being reversed by normal medium; a second step, where the rate of multiplication for 24 hrs, decreases very fast, and which is not reversible.


[Effects of hexamethylenebisacetamide on the differentiation of embryonal carcinoma cells]. HMBA induces differentiation in the whole population of some multipotential embryonic carcinoma cells. Morphological, biochemical and immunological changes can be observed even after short treatment. The cells lose the embryonal F9 antigen without acquiring H-2 antigens.


[Effect of periodate oxidation of glycoconjugates of lymphocyte membranes on the immune response in vitro]. Mouse spleen cells treated with sodium periodate for 10 min. at 4 degrees C are stimulated to undergo blastogenesis and to incorporate thymidine. The effect of such treatment on the antibody response in vitro induced by Sheep red blood cells has been evaluated. Periodate-induced proliferation is accompanied by a marked inhibition of the immune response to this antigen. At concentrations leading to mitogenesis, no cytotoxic effect of periodate was observed and treated cells survived well on tissue culture. Cell recoveries from samples treated with periodate at the optimal mitogenic dose, were markedly enhanced when harvested at different days after culturing wheras lower antibody forming cells numbers wereconsistently observed during the culture period.


[Effects of bilateral dorsolateral pontine tegmentum lesions on hippocampus theta rhythm during paradoxical sleep in the rat]. Electrolytic lesions of the dorsolateral pontine tegmentum aimed at the locus coeruleus (LC) were performed bilaterally in 13 chronically implanted Rats. Following lesions, transient alterations of characteristic components of theta rhythm appeared. No shortening of duration of paradoxical sleep (PS) was observed. These results do not support the hypothesis that neurons of LC are directly involved in the production of theta rhythm during PS; moreover they seem not to be necessary to the normal appearance of this state of sleep.


[Self-association of 5'-GMP: nucelation by potassium ions]. 23Na and 39K nuclear magnetic resonance are used to follow the self-assocation of 5'-GMP in aqueous solutions. For a 0,1 M concentration in 5'-GMP, large aggregates are formed only in presence of the potassium ion, at greater than 0.2 M concentrations. They do not appear with the other alkali metal cations. A plausible explantation is inclusion of the cation in the central cavity of 5'-GMP tetramers, with a marked selectivity in favor of potassium.


[Receptors for vasoactic intestinal peptide (VIP) in human colonic adenocarcinoma membranes: specific binding and stimulation of adenylate cyclase]. Human colonic adenocarcinoma plasma membranes exhibit specific receptors for VIP. Adenylate cyclase activity is stimulated by a VIP concentration as low as 10(-10) mol/1.


[Immunofluorescent localization of beta-lipotropin (beta-LPH) and beta-endorphins in normal and anencephalic human fetal pituitary gland]. The use of antibodies to alpha-(17-39) ACTH, beta-LPH, alpha- and beta-endorphins has enabled the detection of immunoreactive cells in human fetal pituitary glands as early as the eight week of gestation. The same cells reacted with the different antibodies. Immunoreactive cells were also observed in the pituitary of 6 human anencephalic fetuses.


Recurrent nocturnal asthma due to tolylene di-isocyanate: a case report. In a carpenter with a history of nocturnal dyspnoea, a bronchial provocation test with a tolylene di-isocyanate (TDI) activator elicited a non-immediate asthmatic reaction, followed by recurrent nocturnal asthma for five subsequent nights. Subsequently, the study of the circadian rhythm of airflow, registered during work, confirmed the presence of recurrent nocturnal asthma of occupational origin.


Two-point determination of plasma ammonia with the centrifugal analyzer. A simple, convenient, and rapid method for determining ammonia in plasma by the glutamate dehydrogenase reaction is described for the centrifugal analyzer. The measuring principle is fixed-time, with NADH as the coenzyme. ADP is added to stabilize glutamate dehydrogenase and prevent interference from endogenous plasma ADP. The reaction is linear to 400 mumol of ammonia per liter. The plasma sample volume is 100 microliter and the whole procedure takes only 25 min, including the 15-min preincubation. The normal range for venous plasma was 44 +/- 13.5 (SD) mumol of ammonia per liter.


N-Ethylmaleimide prevents destruction of corticotropin (ACTH) in plasma. Addition of N-ethylmaleimide, an inhibitor of proteolytic enzymes, to samples for plasma corticotropin determinations prevents destruction of the hormone at room temperature for at least 72 h. A concentration of 125 mg per liter of blood is effective. N-Ethylmaleimide is not so effective in preventing corticotropin degradation in whole blood. Use of the inhibitor should make plasma corticotropin determinations more practical and reliable.


Cholinesterase in serum and low density lipoprotein of hyperlipidemic patients. Cholinesterase activity in the low density lipoprotein fraction of serum is increased in types IIa, IIb and IV hyperlipoproteinemic patients, whereas only types IIb and IV show increases in serum cholinesterase activity. In obese patients, cholinesterase activity is increased both in the serum and low density lipoprotein fraction only when hyperlipidemia is present. Cholinesterase activity is also found to increase in proportion with increases in low density lipoprotein, cholesterol, and triglycerides both in the serum and low density lipoprotein fraction. We suggest on the basis of these findings that cholinesterase has a function in lipid and lipoprotein metabolism.


Ultrastructural and steroidogenic characteristics of an androgen-producing adrenocortical tumour. A 16-year-old female patient with an adrenal tumour was studied. Clinically she had progressive hirsutism, showed high urinary 17-oxosteroid excretion with normal plasma cortisol. Plasma C19-steroids, both unconjugated (including testosterone) and sulphate-conjugated, were greatly elevated. On surgical exploration an adrenal tumour was histologically an adenoma. On ultrastructural analysis the cells in all zones of the adjoining adrenal were considered normal. Although the tumour cells had the general appearance of a steroid-secreting cell their structure diverged from the cells of every subzone of the cortex. This was the case particularly with mitochondria and lipid inclusions. The  only endogenous unconjugated steroids detected in the adjoining cortex were corticosterone and cortisol while in tumour tissue these were present in lesser amounts. The tumour tissue contained large amounts of C19-steroids, 11beta-hydroxy-androstenedione being quantitatively most significant. On the basis of the steroid profile an impaired defect of 21-hydroxylation in tumour cells leading steroid synthesis from corticosteroidogenesis to the C19 pathway is proposed.


Growth retardation, skeletal maturation and thyroid function in children with homozygous beta-thalassaemia. Growth rate, skeletal maturation and thyroid function were measured in fifty thalassaemic children (age 2-13 years) and in fifty controls (matched for sex and age who were not anaemic. Growth retardation was present in several patients during the first years of life and affected almost all subjects examined when they were approaching puberty. Discrepancy between bone and height age in patients was not significantly different from controls. The finding of low T4 and T3 with a high TSH indicated thyroid hypofunction. This finding, already present early in life, did not worsen with increasing age. In beta-thalassaemia hypothyroidism cannot be the cause of retarded growth since there is no relationship between the impairment in thyroid function and severity of growth retardation. In addition, height age was not different from bone age, while a discrepancy is a constant feature of low stature due to hypothyroidism.


Swan mice: autoimmune mice without xenotropic type C virus production. Swan mice are characterized by various autoimmune disorders and the Swan disease resembles that of (NZB X NZW)F1 hybrids. A virological study of these animals shows that: (a) they do not produce xenotropic type C viruses at a detectable level; (b) old Swan mice can produce ecotropic type C virus but at a low level; and (c) this virus production and the appearance of antinuclear antibodies are dissociated in some mice. These results do not support the role of xenotropic type C viruses in murine autoimmune pathology. A possible role of ecotropic type C viruses cannot be definitely excluded, but appears unlikely.


Effect of glucocorticoids and ACTH on antipyrine clearance in children. Administration of dexamethasone and infusion of adrenocorticotropic hormone (ACTH) to children for periods up to 4 days did not alter the half-life, apparent volume of distribution, or metabolic clearance rate of antipyrine, a drug principally metabolized by the mixed-function oxidase system of the liver. We conclude that the short-term administration of glucocorticoids and ACTH with ensuing stimulation of endogenous glucocorticoid production is unlikely to produce clinically significant changes in the rate of drug metabolism.


Assignment of the gene for adenosine kinase to chromosome 14 in Mus musculus by somatic cell hybridization. Evidence is presented for the assignment of the gene for adenosine kinase to Mus musculus chromosome 14 by synteny testing and karyotypic analysis of mouse X Chinese hamster somatic cell hybrid clones. ADOK and two enzymes previously mapped to mouse chromosome 14, NP and ES-10, were expressed concordantly in 29 hybrid clones. Chromosome analysis confirmed this assignment. Syntenic evidence is also presented using several clones of a gene transfer system in which the gene for human HPRT had integrated into modified mouse chromosome 14's.


Inflammatory fibrous histiocytoma of the bronchus. A 33 year-old woman underwent lobectomy of the middle and lower lobes of the right lung because of inflammatory fibrous histiocytoma of the bronchus. To our knowledge, this is the first description of such a tumor originating in the bronchus.


Inflammatory changes related to active tuberculosis: confusion with oat cell carcinoma of the lung on cytology specimens. One case of small cell lung carcinoma diagnosed on cytology specimens could not be confirmed histologically. We feel this likely represents cytopathologic changes induced in response to the patient's active tuberculosis. To avoid aggressive systemic therapy in such cases, patients with localized lesions should have further diagnostic procedures to confirm the cytologic diagnosis histologically.


[Differential diagnosis of hypothalamic-hypophyseal Cushing's syndrome and ectopic ACTH syndrome (author's transl)]. Endocrinological symptoms of, on the one hand, hypothalamic-hypophyseal Cushing's syndrome and, on the other, ectopic ACTH syndrome (usually caused by bronchial carcinoma) can often not be distinguished. Reliable differentiation of these two forms of secondary hypercortisolism is necessary, because in hypothalamic-hypophyseal Cushing's syndrome therapy is more and more frequently directed at the anterior pituitary and hypothalamus rather than attempted by bilateral adrenalectomy. The following method was used for distinguishing between the two in six patients: blood was withdrawn by catheter from the jugular vein and the inferior petrosal sinus and the ACTH concentrations measured. Compared with ACTH concentration in a peripheral vein (e.g. cubital vein) that in the jugular vein was higher in five patients by a factor of 1.47 +/- 0.1 and in the inferior petrosal sinus by 2.39 +/- 0.64. A positive diagnosis of hypothalamic-hypophyseal Cushing's syndrome can thus be made. In one patient the diagnosis of ectopic ACTH syndrome could be made from the gradient of ACTH concentration between the cardiac right ventricle and the bronchial artery (1 : 3.75), before there was radiological demonstration of the bronchial carcinoma.


Metabolic effects of some antibilharzial drugs: inhibition of NAD-linked substrate oxidation in rat liver by bilharcid. BILHARCID inhibited malate and pyruvate oxidation. The degree of inhibition reached 50% when the concentration of Bilharcid was 10(-3) M. The mechanisms of the inhibitory action of the drug are discussed with reference to the effects of both adenine and pyridine nucleotides on the activity of the oxidoreductase enzymes.


Carcinogenicity studies on halogenated hydrocarbons. A series of halogenated compounds was tested by oral intubation in 200 Osborne-Mendel rats and 200 B6C3F1 mice of both sexes. Carbon tetrachloride, used as a positive control, induced liver and adrenal tumors in mice and neoplastic nodules in the livers of rats. 1,2-Dibromoethane and 1,2-dibromo-3-chloropropane caused stomach tumors with many metastases in both rats and mice. Chloroform, known to cause hepatocellular carcinomas in mice, led in addition to kidney tumors in male rats. 1,2-Dichloroethane was much weaker than the analog, 1,2-dibromoethane, and induced only a few stomach tumors in rats. It increased liver and lung tumors in mice. Most of the compounds, namely, trichloroethylene, 1,1-dichloroethane, 1,1,2-trichloroethane, hexachloroethane, and tetrachloroethylene, increased hepatocellular carcinomas in mice but had little or no action in rats. Iodoform tended to increase thyroid tumors in male rats and hepatocellular carcinomas in male mice. The action of 3-chloropropene was questionable. No tumors could be attributed to 1,1,1-trichloroethane (methyl-chloroform).


Synthesis of an oligonucleotide inhibitor of protein synthesis in rabbit reticulocyte lysates analogous to that formed in extracts from interferon-treated cells. A heat-stable, low-molecular-weight inhibitor of protein synthesis is formed on incubation of haemin-supplemented rabbit reticulocyte lysates with ATP and double-stranded RNA (dsRNA). It inhibits the translation of both added encephalomyocarditis virus RNA (EMC RNA) and endogeneous messenger RNA in reticulocyte lysates and mouse L-cell extracts. The enzyme responsible for the synthesis of the inhibitor binds to dsRNA and can be purified on a column of poly(I).poly (C) bound to an inert support. The highly purified enzyme in its stable column-bound state can be conveniently employed to synthesise the inhibitor and to label it with [3H]ATP, or [alpha-32P]ATP or [gamma-32P]ATP as substrate. The radioactive inhibitor synthesised in this way with material from rabbit reticulocyte lysates shows the same spectrum of resistance and sensitivity to alkali and a variety of enzymes as corresponding material similarly synthesised with extracts from interferon-treated mouse L-cells. The inhibitors from the two systems have comparable absorbance spectra, are chromatographically and electrophoretically indistinguishable and are apparently identical in specific activity in the inhibition of protein synthesis in the cell-free system. The inhibitor is also formed on inhibition of protein synthesis by dsRNA in reticulocyte lysates. On comparison of the spectrum of polypeptide products synthesised in response to EMC RNA in the reticulocyte lysate, the effects of the inhibitor or dsRNA were similar: a distinctly different effect was obtained with the haemin-controlled repressor, a known inhibitor of initiation. The significance of these results with respect to the mechanism of action of the inhibitor and its role in the inhibition observed in response to dsRNA is discussed.


The linear electric field effect in stellacyanin, azurin and in some simple model compounds. All mononuclear Cu(II) sites in frozen solution are non-centrosymmetric and, unless physically constrained, will have a tetrahedral distortion away from the usual square planar structure often presented for Cu(II) complexes. Blue copper sites such as are found in azurin and stellacyanin have a greater distortion towards a tetrahedral geometry than do simple Cu(II) complexes. The distortion is comparable to that which is observed for Cu(II)-o-phenanthroline dichloride, a known tetrahedral complex. Blue copper sites possess an axis of asymmetry directed away from g parallel which could arise from a metal-sulfur interaction.


Electron transport in the cni-1 mutant of Neurospora crassa. 1. Mitochondria from the nuclear mutant cni-1 have no optically detectable cytochrome aa3 in early log phase growth. These mitochondria have a high level of respiration that is not inhibited by cyanide but is inhibited by salicylhydroxamic acid. They also show a substantial amount of cyanide-sensitive respiration. 2. As cultures of mutant cni-1 age, flux through the hydroxamate-sensitive pathway decreases markedly while flux through the cytochrome chain remains constant. 3. Growth studies with mutant cni-1 indicate that the cytochrome chain in this mutant is more important in supporting growth than the hydroxamate-sensitive pathway. 4. Measurements of the steady-state level of reduction of cytochrome c in mutant cni-1 indicate that the rate-limiting step in the cytochrome chain is at the position occupied by cytochrome oxidase. 5. Electron spin resonance studies with cni-1 mitochondria show normal cytochrome oxidase signals in the g approximately 6 region although there is little or no optically detectable cytochrome aa3.


Thermal regulation of the fatty acid composition of lipopolysaccharides and phospholipids of Proteus mirabilis. The fatty acid composition of the lipid A moiety of the lipopolysaccharide and phospholipid fractions of Proteus mirabilis changed significantly on varying the growth temperature. A decrease in the growth temperature from 43 degrees C to 15 degrees C resulted in a decrease in the palmitic acid content of the lipopolysaccharide from 19.4% of total fatty acids at 43 degrees C to 1.4% at 15 degrees C, and by the appearance of an unsaturated fatty acid residue, hexadecenoic acid. Changes in the 3-hydroxy-myristic acid content of the lipid A were minimal. The decrease in the growth temperature also resulted in a decrease in the saturated fatty acid content of the phospholipid fraction, which was accompanied by an increase in their fluidity, as measured by the freedom of motion of spin-labeled fatty acids incorporated into dispersions made of the phospholipids. Nevertheless, the fluidity obtained with membrane phospholipids extracted from the cells grown at various temperatures were essentially the same when fluidity was determined at the growth temperature, supporting the hypothesis that variations in the fatty acid composition of membrane phospholipids serve to produce membranes having a constant fluidity at different temperatures of growth.


Translation of encephalomyocarditis virus RNA in vitro yields an active proteolytic processing enzyme. In contrast to other cell-free translation systems, the mRNA-dependent reticulocyte lysate can translate encephalomyocarditis virus RNA efficiently and completely when supplemented with heterologous tRNA. Cleavage of the nascent polypeptide chain occurs, and one of the translation products appears to be a specific proteolytic enzyme which correctly processes the primary products. The identity of the proteins made in vitro was verified by comparison with infected cell proteins on dodecylsulphate/polyacrylamide gels, and by mapping their coding sequences on the viral genome.


Purification and characterization of DNA polymerases from the plasmacytoma MOPC 104E and Abelson murine leukemia viruses. RNA-dependent DNA polymerases of intracisternal A particles from the mouse plasma cell tumor MOPC 104E and of Abelson murine leukemia virus (A-MuLV) were isolated from particle preparations by Nonidet P40 and ultrasonic treatment and purified by column chromatography on DEAE-cellulose and phosphocellulose, followed by centrifugation in linear sucrose gradients. Both DNA polymerases were very similar in their elution patterns from phospho and DEAE-cellulose, template specificities, requirements for optimum activity and inactivation by anti-(reverse transcriptase) antiserum. They are associated with ribonuclease H activity. For molecular weight determinations, antibody-precipitated enzymes were bound to staphylococcal-protein-A-Sepharose, solubilized and run on dodecylsulfate/polyacrylamide gels. Their apparent molecular weight was estimated to be 80000.


Endotoxin stimulated nitroblue-tetrazolium (NBT)-test in patients with hypoparathyroidism, pseudohypoparathyroidism and other forms of hypocalcemia. Endotoxin-stimulated NBT-tests were carried out in 15 patients with hypocalcemia of varying etiology and in 14 normocalcemic children free of infection. In the control group the formazan cell percentage (FCP) was 73.8 +/- 1.6% (range 63% to 83%). In 5 patients with hypoparathyroidism or pseudohypoparathyroidism the FCP before treatment was lower than normal. Vitamin D3 therapy produced a rapid increase of serum calcium but normalisation of NBT-test was only achieved after a latent period of one or more months. Patients with hypocalcemic rickets and children with an acute relapse of the nephrotic syndrome also showed abnormal results. The clinical significance of the NBT-test in hypocalcemic conditions is discussed.


Wilms' tumor and adrenocortical carcinoma with hemihypertrophy and hamartomas. A girl with hemihypertrophy and hamartomas, now 14 years old, had Wilms' tumor and subsequently developed adrenocortical carcinoma. The occurrence of the two tumors with the signs of an inborn defect of growth control supports the hypothesis that both tumors can be caused by the same etiologic factors, which are also teratogenic. An alternative explanation of induction of the second tumor by previous radio- and chemotherapy is discussed. Possible relationships between our case and the syndrome of Wiedemann and Beckwith are pointed out.


Hepatic collagen proline hydroxylase activity in primary biliary cirrhosis. The enzyme collagen proline hydroxylase has been measured in liver biopsies from fourteen patients with primary biliary cirrhosis. The activity was elevated in ten of the patients, but not to the degree previously found in patients with active cirrhosis. There was no correlation between the enzyme activity and the liver copper concentration, which was elevated in all except one of those measured. This suggests that excessive collagen synthesis in PBC is not directly related to the high liver copper concentrations.


Responses of the canine hepatic arterial and portal venous vascular beds to dopamine. Dopamine was injected in graded doses into the hepatic artery of the anaesthetized dog: the typical response was an initial vasoconstriction followed by a more protracted vasodilatation. The vasodilatation was unaffected by propranolol, but was antagonized by haloperidol. The initial hepatic arterial vasoconstriction was inhibited both by haloperidol and by phentolamine. The experiments suggest that the initial vasoconstriction was due to alpha-adrenoceptor stimulation and that the secondary vasodilatation was the result of the stimulation of dopamine receptors. In separate experiments, dopamine was injected into the hepatic portal vein of the dog. The only response seen was a dose-dependent portal vasoconstriction which was antagonized both by haloperidol and by phentolamine. Since both of these antagonists attenuated the portal vasoconstrictor effects of intraportal phenylephrine, it is probable that the portal vasoconstriction effect of dopamine is due to alpha-adrenoceptor stimulation.


Isoproterenol-stimulated taurine influx in the perfused rat heart. Taurine influx in the perfused rat heart was characterized and the effect of isoproterenol on this process determined. Hearts were perfused by the Langendorff technique with [3H]-taurine in a non-recirculating system. The rate of taurine influx was constant for at least 20 min and the process was saturable. A Km of 45 micron indicated that taurine influx is mediated by a high affinity transport system. Competition between taurine and beta-alanine, but not alpha-amino acids, for influx indicated that the transport sites are specific for beta-amino acids. Isoproterenol (4 X 10(-7) M) stimulated the rate of taurine influx, but propranolol (1 X 10(-8) M) blocked this stimulation. The enhancement of influx by isoproterenol was specific for beta-amino acids in that alpha-amino acid influx was not affected. Dibutyryl cyclic AMP (1 X 10(-3) M) and theophylline (1 X 10(-3) M) also stimulated taurine influx, whereas alterations in heart rate had no effect on the rate of taurine influx. The results are suggestive of a beta-adrenergically activated, cyclic AMP-mediated mechanism controlling isoproterenol-stimulated taurine influx.


FMRFamide increases the adenylate cyclase activity and cylic AMP level of molluscan heart. FMRFamide (phenylalanyl-methionyl-arginyl-phenylalanine amide) is a cardioexcitatory peptide recently isolated and identified in molluscan ganglia. Both FMRFamide and 5-hydroxytryptamine (5HT), the cardioexcitatory neurotransmitter in molluscs, were tested on the ventricle of the bivalve Mercenaria mercenaria. Both agents increased myocardial contractility, the intracellular cyclic AMP concentration of intact hearts and the adenylate cyclase activity of a myocardial membrane fraction. FMRFamide was 5--10 times more potent than 5HT. All of the effects of 5HT, and none of those of FMRFamide, were blocked by methysergide, a specific 5HT antagonist.


SEM observations on Sendai virus-induced fusion of embryonic mouse erythroblasts. The events of fusion of 11- and 16-day embryonic mouse liver erythroblasts induced by Sendai virus (SV) were followed with the scanning electron microscope (SEM). Erythroid precursors incubated with the virus showed numerous 'pores' on the cell membrane. The cell fusion began with the appearance of a fine 'meshwork' structure between the adjacent cells, followed by a gradual formation of a common cell membrane and terminated with the appearance of polykaryons, in which the nuclei were easily recognized when located in the vicinity of the polykaryon membrane. There was no difference in the process of fusion between erythroblasts at identical and those at different stages of maturation.


Athymic nude mice: induction of tumors containing Epstein-Barr virus using Burkitt's-related cell lines. We studied tumor induction in athymic nude mice by D98/HR-1 cells, an epithelial somatic cell hybrid containing the Epstein-Barr virus (EBV) genome, and by the parental D98 and HR-1 cells. Groups of animals were inoculated with cells grown in culture, with cells from tumors induced by the cell lines, or with cells from lines derived from tumors. The tumors induced by D98/HR-1 cells were undifferentiated carcinomas; those induced by D98 cells were carcinomas and those induced by HR-1 cells were poorly differentiated lymphomas. Preliminary data suggest that the number of EBV genome equivalents was sharply reduced in cells from both D98/HR-1 and HR-1 tumors. Subsequent passage of tumor cells in vitro resulted in a partial recovery in the number of EBV genome equivalents in HR-1 cells and a complete recovery in D98/HR-1 cells. The reduction in the number of EBV genomes in the tumor cells suggests that in vitro passage can influence the number of EBV genomes in these cells.


Plasma membrane involvement in brown fat thermogenesis. Recent experiments indicate that plasma membranes of brown adipocytes contain distinct alpha- and beta-adrenergic receptors able to recognize norepinephrine. Although activation of either receptor leads to brown fat thermogenesis via pathways that have some, but not all, events in common, the beta-induced calorigenesis appears quantitatively greater than that elicited by the alpha-pathway. The sensitivity of the adrenergic-evoked respiration to Na+/K+ pump blockade as well as to atractyloside supports the view that a significant portion of brown fat thermogenesis reflects increased ATP turnover and enhanced mitochondrial ATP synthesis.


Cytochrome c oxidase is not a proton pump. We conclude that the reduction of O2 to 2 H2O by cytochrome c oxidase of rat liver mitochondria involves the translocation of 4-from cytochrome c at the outer surface of the cristae membrane per O2 reduced and protonated by 4 H+ ions that enter the reaction domain from the inner aqueous phase. This net electron-translocating function of cytochrome c oxidase plugged through the mitochondrial cristae membrane is not linked to a proton-pumping function, such as that proposed by Wikström [7,8].


Effect of prolactin on tetracycline binding to human spermatozoa. The effect of different concentrations of prolactin (0 to 60 ng) on the release of tetracycline from human spermatozoa labeled with 7-3H-tetracycline hydrochloride was studied. Prolactin significantly enhanced the release of bound tetracycline, indicating that prolactin may influence the processes associated with sperm capacitation.


Calcium ion requirement for rabbit spermatozoal capacitation and enhancement of fertilizing ability by ionophore A23187 and cyclic adenosine 3':5'-monophosphate. The presence of extracellular calcium is required for the in vitro occurrence of rabbit spermatozoal capacitation. However, calcium itself was found to be an inefficient agent for capacitating rabbit spermatozoa (following insemination with spermatozoa incubated for 10 hours in the presence of 2.5 X 10(-3) M calcium, only 9% of the ova cleaved). The addition of the divalent ionophore A23187 induced the early occurrence of capacitation and increased the percentage of full capacitated spermatozoa in a concentration-dependent manner (i.e, following insemination with spermatozoa incubated for 4 hours in the presence of 2.5 X 10(-3) M calcium and 2 X 10(-5) M A23187, 44% of the ova cleaved). Physiologic levels of capacitation were attained as estimated by the high proportion of ova that cleaved following in vitro insemination, when dibutyryl cyclic adenosine 3':5'-monophosphate (10(-6) m) was added in the presence of calcium (2.5 X 10(-3) M) and A23187 (2 X 10(-5) M) for treatment of spermatozoa.


[Effect of isadrine and propranolol on the membrane potential of mammary secretory cells]. 1.10(-7)--1.10(-5) g/ml of isadrine induced a 2-phase hyperpolarization changes of MP of the secretory cell. Propranolol (1.10(-6) g/ml) decreased the amplitude of hyperpolarization response of the MP to oxytocin by 36%; 1.10(-9)--1.10(-8) g/ml of isadrine induced a 42% and 53% decrease respectively, and 1.10(-7)--1.10(-5) g/ml blocked the response of secretory cells to oxytocin. The data obtained suggest that catecholamines can effect the MP by means of interaction with beta-adrenoreceptors of mammary secretory cells.


[Glucocorticoid-induced hypertiglyceridemia: effects of cortisone acetate on triglyceride secretion rates and post-heparin lipolytic activity in rabbits (author's transl)]. In order to elucidate the mechanisms of glucocorticoid-induced hypertriglyceridemia, 3mg or 10mg/kg of cortisone acetate were administered daily intramuscularly for 8 days to male albino rabbits which were fed 150g/day of a complete commercial diet. Plasma triglyceride (TG), cholesterol (Chol), free fatty acid (FFA), glucose, IRI, very low density lipoprotein (VLDL)-TG, and post-heparin lipolytic activity (PHLA) were determined. PHLA was measured 10 minutes after a heparin (Novo Co., Denmark; 10 units/kg) injection, and then 30, 60, 120 and 180 minutes after pulse injections of heparin (100 units/kg) at 30 minute intervals up to 120 minutes. In another experiment, following 1 week of daily intramuscular injections of 3mg/kg of cortisone acetate, triglyceride secretion rates (TGSR) were estimated, using intravenous injections of Triton WR-1339 (750mg/kg). Also, plasma glucose, IRI, and FFA responses were measured after an intravenous glucose administration test (1.Og/kg) which was performed before and after cortisone acetate treatment. The results were the following: (1) Significant increase (p less than 0.001) in plasma TG and VLDL-TG without any rise of plasma Chol. (2) Increased plasma IRI, glucose and FFA levels at fasting and after intravenous glucose load. (3) No change in PHLA. (4) Highly significant increments (p less than 0.001) in TGSR. Plasma TG and VLDL-TG showed a significant correlation with fasting plasma IRI and sigma glucose (summation of each time glucose level in intravenous glucose load). These findings suggest that glucocorticoid-induced hypertiglyceridemia is primarily a consequence of increased hepatic TG production rates, through elevated plasma FFA, IRI and glucose levels.


Crystalloid bodies in Euglena.

Crystalloid bodies in Euglena. A study has been made of the formation of crystalloid bodies (CB) in the cytoplasm of Euglena gracilis. CB have been found in strains of three bleached mutants as well as in the green wild type where they have been hitherto unknown. These bodies accumulate in the lag-phase of growth in media rich in organic carbon source (ethanol, acetate or sugars). The formation of CB is light-independent and reversible. The ultrastructure of CB reveals that they consist of aggregates of thin plates which are often associated with an osmiophilic substance. Several properties of CB indicate that they do not represent paramylon but are mostly lipid in nature and consist primarily of crystalline wax esters. The formation and role of CB is discussed.


Epinephrine enhancement of potassium-stimulated immunoreactive insulin secretion. Role of beta-adrenergic receptors. Although epinephrine stimulates insulin release by activation of beta-adrenergic receptors, its dominant effect (mediated by stimulation of alpha-adrenergic receptors) is an inhibition of insulin secretion that is powerful enough to suppress the secretory activity of insulin's most potent stimulants. The insulin-secretory response to potassium chloride (KCl) infusion, however, is not suppressed; in fact, in ureter-ligated dogs simultaneously infused with 360 microgram. epinephrine per hour and 2 mEq. KCl per kilogram per hour, insulin release is actually increased about threefold (over controls). Propranolol blockade of beta-adrenergic receptors essentially abolishes the insulin response to KCl infusion, with and without epinephrine. It is unlikely that KCl, like epinephrine, provokes insulin release by direct stimulation of the beta-adrenergic receptors of the beta cells of the pancreatic islets. However, potassium in some way enhances the beta adrenergic (secretory) activity of epinephrine and blunts its usually dominant alpha-adrenergic (inhibitory) effect.


[125I] Glucagon binding by liver membranes from young and adult rats. We have previously shown that adipocytes from adult (between four and five months old) rats have reduced glucagon binding and glucagon-stimulated lipolytic activity when compared with cells from young (1.5 months old) animals. In the present study we measured specific [125I] glucagon binding by purified liver plasma membranes isolated from young and adult rats. When expressed on the basis of membrane protein content, 5'-nucleotidse activity, or specific [125I] insulin binding, the extend of [125I] glucagon binding by liver membranes was not influenced by aging. Furthermore, the degree of [125I] glucagon degradation was the same in both membrane preparations. These data describe a unique condition in which glucagon binding and hormone sensitivity diminish in one tissue but remain unaltered in another.


Cholinergic inhibition of adrenergic neurotransmission in the canine gastric artery. Experiments were performed to examine the possible interaction between the cholinergic transmitter and the reactivity of gastric arteries to adrenergic activation. Helical strips of dogs' gastric arteries were mounted for isometric tension recording. The strips contracted on exposure to norepinephrine; these contractions were inhibited by phenoxybenzamine. Electrical stimulation caused an increase in tension, which was abolished by tetrodotoxin and phenoxybenzamine, indicating that electrical stimulation causes contraction by liberation of norepinephrine. Acetylcholine did not alter basal tension; it caused relaxation during responses to electrical simulation, but not during those to norepinephrine. The relaxation caused by acetylcholine was abolished by atropine. This indicates that acetylcholine inhibits adrenergic neurotransmission in the dog's gastric artery. When added during electrical stimulation, atropine caused an increase in tension. The same concentrations of atropine did not affect basal tension or the response to norephrine. Physostigmine depressed the response to electrical stimulation, but not that to norepinephrine. In the blood-perfused stomach of the intact dog, vagal stimulation depressed vasoconstrictions caused by sympathetic nerve stimulation more than comparable constrictor responses obtained with the infusion of norepinephrine. These experiments suggest that liberated acetylcholine can modulate adrenergic neurotransmission in the gastric blood vessels. The removal of cholinergic inhibition on the release of norepinephrine may help explain why vagotomy has a beneficial effect on gastric bleeding.


Effect of exchange exocrine pancreatic insufficiency on small intestine in the mouse. A genetically conditioned mouse model of exocrine pancreatic insufficiency (epi) has been used to study the effect of the absence of lumenal proteases on small intestinal mucosal proteins. The small bowel was divided into eight equal segments. Enzyme activity was increased only in the first three segments in the case of maltase, sucrase, and lactase (all mol wt above 200,000). Alkaline phosphatase (mol wt 145,000), trehalase (mol wt 95,000), and peptidase (mol wt 175,000) activities were unaffected in proximal segments from epi mice. Proximal brush border proteins were identified and measured quantitatively by sodium dodecyl sulfate acrylamide gel electrophoresis. Those enzymes with increased activity were associated with increased amounts of protein in epi mice. Double labeled studies of protein turnover revealed a longer half-life for large brush border proteins (mol wt above 175,000) in epi mice than in normal mice. Enterokinase activity (a marker for duodenal mucosa) was nearly absent from the duodenum of epi mice. Receptors for the intrinsic factor-vitamin B12 complex (markers for ileal mucosal) were present in the ileum equally in normal and in epi mice. Enterokinase activity can be induced in epi mice by feeding its substrate trypsinogen, but not by trypsin or chymotrypsinogen. Epi mice thus retain the ability to synthesize enterokinase. Pancreatic proteases play an important role in the turnover of certain large mucosal proteins and in the induction of enterokinase.


A chromosomal translocation causing overproduction of iso-2-cytochrome c in yeast. The CYC7-1 mutation in the yeast Saccharomyces cerevisiae causes the production of approximately 30 times the normal amount of iso-2-cytochrome c. Genetic analysis established that the CYC7-1 mutation is a reciprocal translocation involving the left arm of chromosome V and the right arm of chromosome XVI. The chromosome V arm was broken adjacent to the gene CYC7, which determines the primary structure of iso-2-cytochrome c, and this fragment containing the CYC7 gene was joined to the segment of chromosome XVI. It appears as though the elevation of iso-2-cytochrome c is caused by an abnormal controlling region adjacent to the structural region of the CYC7 gene.


[Inheritance characteristics of syndactylia]. On the basis of the analysis of 39 pedigrees with syndactylies it is concluded an autosomal dominant mode of the inheritance with incomplete penetrance. The variability of penetrance is more pronounced in females who are frequently healthy carriers of the gene transmitting it to both sexes. The significant prevalence of males in syndactylies can be explained by deathes of female embryos in utero, the sex ratio in healthy sibses being normal.


Abnormal vitamin D metabolism in cirrhosis. Vitamin D metabolism was investigated in 10 patients with cirrhosis. Mean plasma 25 hydroxycholecalciferol (25 OHD) centration in alcoholic cirrhosis was lower than in controls but the difference was not significant. In three patients restudied after the summer, plasma 25 OHD had risen. In contrast to the finding in normal subjects, the half-life of intravenously administered 3H cholecalciferol was short in cirrhotics and showed no correlation with plasma 25 OHD. Furthermore, the appearance of 3H 25 OHD from 3H cholecalciferol was reduced compared to the control group four hours after injection. Increased rate of metabolism of cholecalciferol and deficient production of 25 ohd contribute to vitamin D deficiency in liver disease.


[The diagnosis and therapy of bilateral Wilm's tumour (author's transl)]. The diagnosis and successful treatment in two patients with bilateral Wilms' tumour are described. In one patient the kidneys were affected simultaneously, the left kidney being duplex; in the second patient, the tumours occurred sequentially.


[Organic complications of alcoholism].

[Organic complications of alcoholism]. With the enormous increase of alcohol consumption after a period of latency of many years an increase of organic damage is associated, the knowledge of which leads to correct diagnosis. Most often the liver, the central organ of alcohol decomposition, is affected. Many other organs are involved in a specific way. Symptomatology and diagnosis are dealt with in detail.


Effect of somatostatin in the Syrian hamster bearing a transplantable islet-cell tumor. The influence of somatostatin (SRIF) on blood glucose, plasma insulin and plasma glucagon was studied in hamsters bearing a transplantable islet-cell tumor secreting insulin and glucagon as well as in normal controls. Fed anesthetized animals were infused intraperitoneally either at a dose of 10 microgram in 15 min or of 150 microgram in 30 min, and intravenously at a dose of 250 microgram in 30 min. Blood was withdrawn from the jugular vein before and after infusion. Before the infusions, tumor bearing animals (TB) had lower blood glucose, markedly elevated plasma glucagon and slightly lower plasma insulin by comparison with normal hamsters (N). Both doses of somatostatin infused by the intraperitoneal route produced a slight but significant hypoglycemia in TB hamsters but not in normals. Ten microgram SRIF did not affect insulin and plasma glucagon levels whereas 150 microgram SRIF significantly depressed plasma insulin in both types of hamsters (N and TB). This latter dose of SRIF decreased plasma glucagon in normal but not in tumor-bearing hamsters. Intravenous infusion of 250 microgram SRIF did not reduce the hyperglucagonemia of TB hamsters either. These results indicate that somatostatin does not reduce the hyperglucagonemia due to the transplantable islet-cell tumor but nevertheless decreases blood glucose and plasma insulin.


Calcium antagonists and lipolysis in isolated rat epididymal adipocytes: effects of tetracaine, manganese, cobaltous and lanthanum ions and D600. The present study reports the effects on lipolysis occurring in isolated rat epididymal adipocytes of several agents which have each been found to interfere with membrane calcium transport in a variety of tissues. As reported by other workers, the local tetracaine was a strong inhibitor of hormone accelerated but not of basal lipolysis. The bivalent cations Mn2+ and Co2+ were similarly found to inhibit lipolysis stimulated with either epinephrine, ACTH, theophylline or dibutyryl cyclic AMP, whereas basal lipolysis was not markedly altered. This effect of Mn2+ and Co2+ was not mimicked by either Sr2+, Ba2+, Mg2+ or Ca2+. Cyclic AMP levels in adipocytes stimulated with epinephrine or ACTH tended to be higher in the presence of Mn2+ and Co2+. It is concluded, therefore, that Mn2+ and Co2+ inhibit lipolysis by uncoupling cyclic AMP accumulation from activation of triglyceride lipase. In contrast to Mn2+ and Co2+, the calcium antagonists La3+ and D600 were without effect on lipolysis. The antilipolytic effect of tetracaine, Mn2+ and Co2+ was found to persist in the absence of extracellular calcium, suggesting therefore that the antilipolytic effect of these drugs is unrelated to inhibition of calcium influx into adipocytes. The possibility is discussed that lipolytic agents cause an intracellular redistribution of calcium ion and that local anesthetics, Mn2+ and Co2+ interfere with lipolysis by preventing this intracellular redistribution of calcium.


Regulation of pyruvate dehydrogenase by Ca2+, 3'5' cyclic AMP and adrenalin in isolated rat kidney tubules. Renal pyruvate dehydrogenasea activity was measured in suspensions of kidney cortex tubules from fed rats after incubation with various concentrations of Ca2+, 3'5' cyclic AMP or adrenalin. At certain concentrations these agents all decreased pyruvate dehydrogenasea activity and increased glucose formation from pyruvate. There appeared to be some interdependence between the effects of Ca2+ and 3,5, cyclic AMP on pyruvate dehydrogenasea activity. Effects of adrenalin on pyruvate dehydrogenasea activity were no longer observed when palmitate was included in incubations. The possibility that regulation of pyruvate dehydrogenasea may indirectly contribute to the control of gluconeogenesis by influencing pyruvate metabolism is briefly discussed.


Postmaturity in the rat: phosphorylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the fetal liver. Liver glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were increased in the postmature rat fetus (23.5 day old) when compared to term rat fetus (21.5 day old). Postmaturity was without effect on liver phosphorylase activity. The three liver enzyme activities were also determined in normal 2 day old neonates. These results are correlated with the mobilisation of fetal liver glycogen occuring during postmaturity in the rat and are discussed in relation to the secretory pattern of the pancreatic hormones.


Dynamics of hormone release from the perfused canine thyroid during cyclic AMP infusion. In order to try to characterize the sequence of processes leading to hormone secretion from the stimulated thyroid, the effect of cyclic 3'5' adenosine monophosphate (cAMP) and related compounds were examined in 15 two-sided perfusions of canine thyroids isolated in situ. T4 and T3 concentrations in the effluent were measured radioimmunologically. cAMP 5 mM and TSH 100 muU per ml induced the same pattern of hormone release from the thyroid. After a latency period of 15--25 minutes a steep increase occurred in both T4 and T3 release. During the initial part of the stimulation the rise in T4 relase was somewhat slower than that of T3 release. The prolonged latency period before response earlier recorded in the same preparation during infusions of low concentrations of TSH was not observed during infusions of decreasing concentrations of cAMP (1, 0.8, 0.5 and 0.2 mM) or theophylline (5 and 1 mM). Either there was no response or the latency period was of the same length as that observed after a strong stimulus. These findings suggest that the latency period can be divided in two parts: () a variable, dose dependent satency period confined to the early part of the process sequence leading to secretion--i.e. before cAMP exerts its effect, and 2) an obligatory latency period related to the processes taking place after the formation of pseudopods. The duration of these late processes seems to be independent of the degree of stimulation.


Effect of parathyroid extract on renal cyclic AMP excretion in patients with normocalciuric nephrolithiasis. It is uncertain whether normocalcemic, normocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) INFUSION (1.4 U/kg body weight) on the urinary cyclic AMP excretion in 16 such patients. For comparison, we investigated groups of normal individuals and patients with primary hyperparathyroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 +/- 0.3 mumol/h (mean +/- SEM), versus 2.5 +/- 0.5 mumol/h in normal subjects (p less than 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (increase, 0.3 +/- 0.06 mumol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but sub-normal stimulation by PTE (increase, 0.46 +/- 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 +/- 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in normocalcemic stone formers suggested by others.


An estimation of the parathyroid hormone secretion rate in vitamin D deficient rats. In an attempt to define the rate of endogenous secretion of parathyroid hormone in vitamin D deficiency, graded amounts of hormone were infused constantly into vitamin D deficient and vitamin D fed acutely thyroparathyroidectomized rats in a perfusion balance study. The dose of hormone needed to compensate for acute thyroparathyroidectomy was estimated. Serum levels of calcium and phosphorus, renal clearances of phosphorus and urinary excretion of cyclic AMP, each determined 16 hr after the surgery, were employed as parameters of the hormone effect. It was concluded that, in the condition of the perfusion balance study, the secretion rate of parathyroid hormone was 5.1-8.6 USP u/hr in the vitamin D deficient animals compared with 0.81-0.84 USP u/hr in the control.


Improving continuity of care through a state hospital-CMHC liaison program. After several abortive attempts, a state hospital and a community mental health center located in the same county made a more successful attempt to improve continuity of care. A study of 78 discharged hospital patients identified several problems in the continuity-of-care system. A liaison team made up of a social worker from the hospital and a psychiatric nurse from the center was set up to carry out such tasks as contacting county residents admitted to the hospital, participating in treatment and discharge planning, and contacting patients who did not keep aftercare appointments. The program had several positive results; the authors believe they were related to such factors as an objective definition of the problems, administrative cooperation, and strong linkage, through a middle-management team, between the liaison team and top-level management and between the hospital and the center.


No association of red cell adenylate kinase phenotypes with affective disorders. Red cell adenylate kinase (AK) phenotypes were studies in 195 patients with affective disorders (41 with the bipolar and 81 with the unipolar form of the disease) and 418 controls. No significant differences were found between patients and controls and between patients with different types of affective disorders. Thus the previous observation by Rundle et al. (1977) showing an increased frequency of the AK2 allele in the unipolar group was not confirmed.


Hereditary sensory neuropathy, a new type. Two brothers with a new type of hereditary sensory neuropathy are described. The main clinical feature is late onset sensory ataxia without ulcerating acropathy or other autonomic abnormality. The older patient also has oculomotor dysfunction and extensor plantar responses.


Regional mapping on human genes for phosphoglucomutase-1 on chromosome 1 and beta-glucuronidase on chromosome 7 using mouse x human hybrids. Two independent mouse-human somatic cell hybrid clones contained different, de novo chromosome rearrangements involving the short arm of human chromosome 1. One hybrid clone contained a translocation between human chromosomes 1 and 7; the other clone contained a rearrangement product between human chromosomes 1 and 14. Analysis of these clones for expression of genes previously assigned to chromosome 7 and to the short arm of chromosome 1 provided evidence for localization of PGM--1 in segment 1p22.1 leads to 1p31.1, AK--2, ENO--1 and UMPK in region 1pter leads to 1p31.1, and GUS in region 7 pter leads to 7q22. The results have been used to examine the relationship between cytologic and genetic map distances on the short arm of chromosome 1.


The seroepidemiological pattern of acute viral hepatitis. An epidemiological study on viral hepatitis in the Hannover region. The natural incidence of the etiologically distinct types of viral hepatitis was determined by investigating acute phase sera of symptomatic hepatitis cases occuring in the Hannover area in 1975 for the presence of hepatitis B surface antigen, antibodies to hepatitis A, hepatitis B core and surface antigens, and by measuring the IgM serum levels. Fourteen different seroepidemiologic patterns were recognized. Although there was a high prevalence of hepatitis A antibody in the population, the frequency of hepatitis A was low (n = 56) suggesting that the hepatitis A virus does not play a major role in symptomatic hepatitis in the Hannover area at present. Spread of the hepatitis A virus was mostly associated with person-to-person contact or tourist travel in southern Europe. Hepatitis B was the predominant type of hepatitis (n = 211). Hepatitis non-A, non-B was observed infrequently (n = 62). A high percentage of patients with hepatitis B and hepatitis non-A, non-B reported parenteral exposure to potentially contaminated materials. No other findings, however, suggested an infectious etiology of hepatitis non-A, non-B.


Diarrhea in newborn cynomologus monkeys infected with human rotavirus. Of six newborn cynomolgus monkeys (Macaca fascicularis) naturally delivered and normally nursed five developed diarrhea after oral administration of human rotavirus. Virus excretion was observed in the stool of four animals. This virus was transmitted to four out of six other monkeys causing diarrhea in only one animal.


Specificity studies of leukocytic catecholamine receptors. Using tritium-labeled dl(+/-)epinephrine, we have extended previous studies demonstrating binding of epinephrine to human leukocytes. We have now further assessed the biological significance of this catecholamine binding by comparing the specificity of binding by human leukocytes with the ability of these compounds to inhibit epinephrine-stimulated adenyl cyclase. Binding is specific for catechols, but does not distinguish between physiologically active and inactive stereo isomers, nor between alpha- and beta-adrenergic agonists. Although 2.5 X 10(-4) M 1(-)DOPA, dopamine, d(+)epinephrine and serotonin failed to stimulate leukocytic adenyl cyclase and prevented adenyl cyclase stimulation by 2.5 X 10(-4) M 1(-)epinephrine, the inhibition of adenyl cyclase by d(+)epinephrine is noncompetitive. This catechol-binding site is clearly not the beta-adrenergic receptor. Its physiological significance, if any, remains to be elucidated.


Adenyl cyclase.

Adenyl cyclase. Certain hormones regulate the activity of their target cells by stimulating adenyl cyclase, which is an enzyme located within the target cell's plasma membrane. Adenyl cyclase catalyzes the formation of cyclic AMP, which is released into the cell and modulates cell functions. In this communication the characteristics of adenyl cyclase are reviewed. The coupling between hormone receptors and this enzyme is discussed as is the ability of agents such as hormones, ATP, magnesium, calcium, guanine nucleotides and prostaglandins to alter cyclase activity. Several diseases that result from derangements of the adenyl cyclase system are known and the molecular bases for these diseases are discussed in this review.


Cyclic AMP.

Cyclic AMP. Cyclic AMP mediates the effects of many hormones on their target cells. Some of the mechanisms by which this occurs are discussed in this review. The role of cyclic AMP in regulating glycogen metabolism in liver and skeletal muscle is firmly established. Data suggesting that cyclic AMP mediates hormonally stimulated salivary gland amylase secretion, cardiac muscle contractility, smooth muscle relaxation, and platelet aggregation are summarized.


Chains of alternating sulfur and pi-bonded atoms in eight small proteins. This paper demonstrates the existence of regions in eight small globular proteins in which the side chains of sulfur-containing amino acids (cysteine and methionine) alternate in space with side chains of aromatic amino acids (histidine, phenylalanine, tryptophan and tyrosine). The proteins are: rubredoxin, high potential iron protein, cytochrome c, flavodoxin, deoxyhemoglobin, trypsin inhibitor, ribonuclease-S, and lysozyme. The sulfur-pi-bonded 'chains' involve a minimum of five and a maximum of 10 amino acids, and contain the most polarizable atoms within proteins. S-pi-chains give extra stability to the folding of proteins; they may also afford paths for the step-wise movement of electrons.


The characteristics of adsorption of pyrophosphate and citrate onto whewellite. The adsorption of pyrophosphate and citrate to whewellite was measured by solution depletion. At pH 6.5, the concentration for one-half surface coverage CE(1/2) by pyrophosphate is 15 micrometer. The estimated maximum coverage is 37.5 mumoles per m2. The CE (1/2) for citrate is 4 micrometer, and the estimated maximum coverage is 6.42 mumoles per m2.


Ultrastructural findings on lipoproteins in vitro and in xanthomatous tissue. The application of OSO4 plus K3 [Fe(CN)6] as a secondary fixative following aldehyde fixation, permitted demonstration of the presence of 30-300 nm 'membrane-bound' particles in xanthomatous tissue. With the same fixation method, isolated low density lipoprotein particles in a fibrin matrix could be observed in the transmission electron microscope in a way permitting comparison with similarly fixed tissue. However, isolated particles of very low density lipoproteins treated in the same way as low density particles had an irregular appearance and a diameter varying between 30 and 80 nm.


Two kinds of mutants defective in multiple carbohydrate utilization isolated from in vitro fosfomycin-resistant strains of Escherichia coli K--12. Two types of in vitro fosfomycin-resistant mutants defective in multiple carbohydrate utilization were selected from Escherichia coli strain K--12. One mutant, FR182, was defective in phosphoenolpyruvate: sugar phosphotransferase system and the ability to form adenosine 3',5'-cyclic monophosphate (cAMP) was lowered. Another mutant, FR190, was defective in cAMP formation. Restoration by cAMP of fosfomycin (FOM) sensitivity coupled with recovery of utilization of many carbohydrates including sn-glycerol-3-phosphate (G-3-P) was observed in both of the resistant mutants. FOM was not taken up by these resistant strains but, in the cells cultured in the presence of cAMP, accumulation of FOM was equivalent to that of the sensitive parent strain. Decreased uptake of G-3-P was also restored in both of the resistant strains cultured in the presence of cAMP. These results indicate that the resistance to FOM in these mutants is due to impairment of G-3-P transport system, one of the pathways for uptake of FOM. They were sensitized to FOM by D-glucose-6-phosphate because of the induction of hexose phosphate transport system, another uptake pathway.