Steroid-binding properties and stabilization of cytoplasmic glucocorticoid receptors from rat thymus cells. 1. A competitive binding assay was adapted for determination of the specific binding of glucocorticoids to cytoplasmic receptors from rat thymus cells. The steroid-receptor complexes prepared by incubation of a cytoplasmic fraction from rat thymus cells with [1,2-(3)H(2)]cortisol or with [1,2,4-(3)H(3)]triamcinolone acetonide had rates of dissociation at 37 degrees C similar to those from intact cells. 2. The cytoplasmic receptor was unstable at 3 degrees C, but the rate of inactivation was decreased in the presence of 2.5mm-EDTA. The steroid-receptor complex was stable. 3. Rate constants for association and for dissociation, and association constants, were determined for the interactions of cortisol, cortexolone, dexamethasone and triamcinolone acetonide with the cytoplasmic receptor at 3 degrees C. Differences in the association constants for different steroids could largely be accounted for by the differences in the rate constants for dissociation, but the rate constants for association did not vary greatly; the implications of these findings for the nature of the steroid-binding site are discussed. 4. A cytoplasmic fraction prepared from cells which had been incubated at 37 degrees C under anaerobic conditions bound much less [1,2-(3)H(2)]cortisol than did a fraction from aerobic cells, but the binding capacity was restored after exposure of the anaerobic cells to O(2). 5. The specific binding of [1,2-(3)H(2)]-cortisol to intact thymus cells incubated aerobically was not affected by the presence of 0.1mm-cycloheximide, nor did this concentration of cycloheximide inhibit the recovery of specific binding observed when anaerobic cells were transferred to an aerobic atmosphere. 6. The energy dependence of specific binding of cortisol to the receptor is discussed with reference to possible mechanisms.


Transport of methionine and proline by rat liver slices and the effect of certain hormones. 1. Transport characteristics of l-methionine and l-proline in rat liver slices in vitro were studied. 2. Intracellular concentration gradients for methionine were obtained. 3. Methionine uptake was inhibited by iodoacetate, dinitrophenol, Na(+)-free media and also by glycine, lysine, cysteine and dithiothreitol but not by alpha-aminoisobutyrate. 4. The rate of methionine metabolism in the slice was slow. 5. Puromycin inhibited methionine incorporation into protein, but not methionine uptake. 6. Methionine inhibited the transport of alpha-aminoisobutyrate but not of cystine. 7. Efflux and exchange diffusion of methionine was studied. 8. Amino acid transport in rat liver slices was not affected by thyroidectomy. 9. Addition of insulin, glucagon, adrenaline or cortisol did not affect the transport of methionine. 10. Addition of 6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate increased methionine transport after a 120min incubation period in some experiments. 11. Studies of l-proline transport were invalidated because of the rapid evolution of CO(2) from the substrate.


Rections of aliphatic methanesulfonates.


The phospholipid composition of human serum lipoprotein fractions separated by electrophoresis on agarose gel. Demonstration of a fraction with high lysolecithin content.


Purification and some properties of the enzyme which conjugates sulfobromophthalein to glutathione in rat liver.


Urinary excretion of neutral steroid glucuronides with reference to the menstrual cycle.


Synaptosomes, a possible system for the study of synaptic transmission.


Type 3 hyperlipoproteinaemia.

Type 3 hyperlipoproteinaemia.


The interaction between estradiol and human platelets.


Type V hyperlipoproteinaemia.

Type V hyperlipoproteinaemia.


Lipoproteins and hyperlipoproteinaemia.

Lipoproteins and hyperlipoproteinaemia.


Type IV hyperlipoproteinaemia.

Type IV hyperlipoproteinaemia.


Type I hyperlipoproteinaemia.

Type I hyperlipoproteinaemia.


Characteristics of cyclic 3',5'-nucleotide phosphodiesterase from the brain of the Madagascar cockroach (Gromphadorhina portentosa).


Estradiol receptors in female rat hypothalamus in the developmental stages and during pubescence.


A biochemical basis for differences in maximal diving time in aquatic mammals.


Heterogeneity of thyroid iodine turnover: last come, last served phenomenon.


Effects of prostaglandin E1, ethanol and TSH on the adenylate cyclase activity of beef thyroid plasma membranes and cyclic AMP content of dog thyroid slices.


Specificity of nucleotide-induced insulin secretion.


Estradiol and 20alpha-dihydroprogesterone dehydrogenase activities in human endometrium during the menstrual cycle.


The effects of dibutyryl cyclic AMP, aminophylline and propranolol on PTE-induced bone resorption in vitro.


Physical characteristics of the Ca++ compartments associated with in vitro ACTH release.


Variations in the levels of cytoplasmic glucocorticoid receptors in lungs of various species at different developmental stages.


Effect of dibutyryl cyclic AMP on in vitro rat testis DNA, RNA and protein labeling.


Environmental calcium and the sensitivity of killifish (Fundulus heteroclitus) in bioassays for the hypocalcemic response to Stannius corpuscles from killifish and cod (Gadus morhua).


Development of a radioligand tissue receptor assay for human follicle-stimulating hormone.


Changes in plasma ACTH and corticosteroid of the maternal and fetal sheep during hypoxia.


The binding of tritiated aldosterone in the rat liver cytosol.


Adenylate cyclase activity in bovine adrenal medulla.


An ultrastructural stereologic study of the effects of 3',5'-cyclic nucleotides on the zona glomerulosa of rat adrenal cortex.


Structural studies on the heptose region of Salmonella lipopolysaccharides.


Comparative study of photophosphorylation coupling factor-ligand complex by circular dichroism and chemical isolation.


Ribonuclease activity in Escherichia coli polyribosomes.


Intracellular titration of cyclic AMP bound to receptor proteins and correlation with cyclic-AMP levels in the surviving rat diaphragm.


A new immobilized NAD+ analogue, its application in affinity chromatography and as a functioning coenzyme.


5-Aminolevulinic-acid synthetase of Rhodopseudomonas spheroides Y. Kinetic mechanism and inhibition by ATP.


Fluorescence study of liver-alcohol-dehydrogenase complexes with berberine and other ligands.


Rate-limiting factors in ethanol oxidation by isolated rat-liver parenchymal cells. Effect of ethanol concentration, fructose, pyruvate and pyrazole.


The effects of trypsin on the membrane-bound nicotinic acid oxidase in Pseudomonas ovalis Chester.


Purification of plasma membranes from immature brain.


A correlation between the buoyant density and the sedimentation coefficient of EMC viral polyribosomes.


Updating the sleeping pill.

Updating the sleeping pill.


Problems of gravimetric dust sampling.

Problems of gravimetric dust sampling.


Immunological factors in coalworkers' pneumoconiosis.


Mixed dust fibrosis in mineworkers.

Mixed dust fibrosis in mineworkers.


Respirable dust in bituminous coal mines in the U.S.


Mineralogical characteristics of airborne dust in coal mines of Western Germany and their relations to pulmonary changes of coal hewers.


The determination of the size distribution of mine dusts using the Coulter Counter.


Characteristics of the airborne dust in British coal mines.


The relation between pneumoconiosis and dust-exposure in British coal mines.


The attack rate of progressive massive fibrosis in British coalminers.


A simple dust index applicable to various dust-contaminated occupations--a program of action for silicosis prophylaxis.


Histochemistry of enzyme response to trauma in the neocortex and corpus callosum of developing rat brain. The enzyme response to injury of the brain was well localized and limited. Some enzymes, even in 12 day old brain, increased rapidly, mainly in neocortical glial cells. In the corpus callosum enzymes were not significantly hyperactive before the light myelination stage. Some hyperactivity declined after 21 days. Oxidative processes and phosphate metabolism were most disturbed.


Sensory conduction in peroneal and posterior tibial nerves using averaging techniques. A method of obtaining pure sensory nerve conduction velocities in the lower extremities is described. This involves the use of electronic summation (signal averaging). Potentials were obtained and velocities calculated from all normal subjects examined. In patients with peripheral neuropathies it was often possible to obtain nerve velocities with signal amplitudes as low as 0·1 μV and these were often slower than those obtained from the normal subjects. The advantages and disadvantages of this method are discussed. It is of significant clinical value in that pure sensory nerve conduction velocities can be measured in the legs when this may be the only valuable parameter in the absence of motor involvement. In addition, investigation of neuropathies at an earlier stage of development and recovery may be facilitated. It is hoped that in the future this technique of obtaining low amplitude responses with an analogue averager can be incorporated with the more routine aspects of nerve conduction testing when clinically indicated.


Levo(-) amphetamine and dextro(+) amphetamine in the treatment of narcolepsy. The narcoleptic syndrome is a life-long and sometimes familial disorder in which there is a disturbance of the rapid eye movement phase of sleep. Patients with periodic sleep in the daytime but no other symptoms seldom develop the narcoleptic syndrome and have a separate unrelated disorder. Twelve patients with the narcoleptic syndrome were treated separately with l(-) amphetamine and d(+) amphetamine. Both drugs abolished narcolepsy, d(+) amphetamine being slightly more potent than l(-) amphetamine. In equipotent doses, unwanted effects of nervousness and insomnia were equal in frequency. No tolerance to either preparation developed during a six month period. Cataplexy was not affected by amphetamine treatment, but was abolished in two patients when clomipramine was given together with either amphetamine.


A study of the H-reflex by single fibre EMG. The latency of consecutive H-reflex responses of single human triceps surae motoneurones varies up to 2,500 μs. A large part of this variation was shown to occur at the synaptic transmission. A moderate increase in stimulus strength from the threshold value shortened the mean latency and reduced the latency variation, presumably as a result of spatial summation of excitatory inputs. Further increase to maximum strength lengthened the mean latency, increased the variation, and resulted in a dropping out of some responses which was not produced by collision by antidromic impulses. These effects are believed to be due to an active inhibition. Changes of the latency were also obtained by Jendrassik's manoeuvre and facilitatory and inhibitory conditioning stimuli.


The glomus bodies ("paraganglia") of the human larynx.


Studies on growth hormones.

Studies on growth hormones.


Adsorption and reactions of chitinase and lysozyme on chitin.


Selective binding properties of vitamin D transport protein in chick plasma in vitro.


Awakening latency from sleep for meaningful and non-meaningful stimuli.


Some observations on the reliability of REM variables.


Change in the activity of chemical mutagens during their interaction with seed metabolites.


Nature of the spots produced on the bodies of female Drosophila melanogaster under the influence of methylmethane sulfonate.


The effect of certain amino acids on reproduction of encephalomyocarditis virus. II. Investigation of the inhibiting effect of L-histidine.


Altered cellular responses to interferon induction by poly I-poly C: priming and hyporesponsiveness in cells treated with interferon preparations.


Sendai virus nucleocapsids in the nucleoli of infected cells.


Foot-and-mouth disease: growth of virus after conjunctival inoculation of cattle. Brief report.


Reflections on possible mechanisms of action of anti-inflammatory drugs.


Biochemical properties of a defective hamster C-type oncornavirus.


A proposed regulator for poliovirus: the equestron.


The effect of D-thyroxine on the metabolism of cholesterol in familial hyperbetalipoproteinaemia.


Total recovery of infectious virus from noninfectious type 1 poliovirus-antibody complex by heating in salts.


Radioimmunoassay of avian RNA tumor virus group-specific antigen.


The very low density lipoproteins of cholesterol-fed rabbits. A study of their structure and in vivo changes in plasma.


Rapid diagnosis of enterovirus meningitis by immunofluorescent staining of CSF leukocytes.


Clinical and metabolic effects of pentaerythritol tetranicotinate(Perycit)and a comparison with plain nicotinic acid.


Observations on the rescue of simian virus 40 induced by cell fusion from heterokaryon cultures using electron autoradiography.


Multiplicity reactivation in UV-irradiated herpes simplex type 1 virus.


The effect of combined treatment with phenformin and stanazolol on blood lipids and fibrinolytic activity in patients with hypertriglyceridaemia.


Deoxythymidine kinase from rabbit kidney cells infected with herpes simplex virus types 1 and 2.


Thymidine kinase activity of herpes simplex virus temperature-sensitive mutants.


Hodgkin's disease: involvement of viral agents in the etiology.


Effect of various enzymes and chelating agents on SV40 tumor-specific transplantation antigens.


Potentiation of effect of prolactin by adrenocorticotropic and growth hormones upon weight and nucleic acids contents of female rat mammary gland.


Low resolution structure of adenylate kinase.


Nuclear magnetic resonance study of the rate of electron transfer between cytochrome c and iron hexacyanides.


Properties of the genome in experimental hepatomas: variations in the composition of chromatin.


Lipids of cultured hepatoma cells. I. Effect of serum lipid levels on cell and media lipids.


Lipids of cultured hepatoma cells. II. Effect of media lipids on cellular phospholipids.


Alternate pathways of cerebroside catabolism.


Removal of lipid from intact erythrocytes and ghosts by aqueous solutions and its relevance to membrane structure.


Immunochemical quantification of human plasma Lp(a) lipoprotein.


Ultrastructural findings in acrodermatitis enteropathica.


The ultrastructure of a transplantable rat hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene.


Persistence of adenylate kinase and other enzymes in glycerol extracted muscle.


Pyruvate and citrate concentrations in rabbit aqueous humour determined by an enzymatic procedure.


Enzymes of carbohydrate metabolism in rat hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene.


NMR investigations of caffeine-sodium benzoate interactions.


Ultrastructure of sarcoma 180 cells in mice treated with testosterone propionate.


mRNA synthesis in erythropoiesis: specific effect of erythropoietin on the synthesis of DNA-like RNA.


Messenger RNA processing in vertebrate cells.


Reconstitution of 50S ribosomal subunits and the role of 5S RNA.


Studies on HeLa cell nucleoli.

Studies on HeLa cell nucleoli.


Antibiotic action in protein synthesis.

Antibiotic action in protein synthesis.


Modifications of polysome-associated RNA after poliovirus infection.


Electrical activity in dissociated cell cultures from fetal mouse cerebellum.


Synthesis of mitochondrial proteins.

Synthesis of mitochondrial proteins.


The role of norepinephrine in the function of the area postrema. II. In vitro incubation and stimulated release of tritiated norepinephrine.


In vivo studies on the effect of 6-hydroxydopamine on amino acid metabolism in brain.


The effect of mesencephalic reticular stimulation on intracellular potentials of cat lateral geniculate neurons.


Brain stem stimulation and the hypothesis of presynaptic inhibition in cat lateral geniculate nucleus.


The use of counter-current distribution to examine the effect of damaging agents on DNA.


The biosynthesis and secretion of insulin.


Insulin and insulin-like substances in the circulation.


Respiratory function on asthmatic patients using beclomethasone dipropionate administered by pressurised aerosol.


Enzymology of kidney tissue.

Enzymology of kidney tissue.


Enzymes and isoenzymes in urine.

Enzymes and isoenzymes in urine.


Alkaline phosphatase activity in canine renal homografts.


Neurologic examination.

Neurologic examination.


Absorption and secretion of salt and water by the small intestine.


The manganous-adenosine triphosphate system. A reinvestigation of its proton magnetic resonance spectra.


A 99mTc-pyrophosphate kit: a convenient, economical, and high-quality skeletal-imaging agent.


Ultracentrifugal studies with absorption optics and a split-beam photoelectric scanner.


Chromatography of proteins on hydroxyapatite.


Magneto optical rotation spectroscopy.

Magneto optical rotation spectroscopy.


Study on tumour specific cell surface antigen in avian sarcoma virus-induced mammaliam cells with the aid of peroxidase-labelled antibody.


Electrophoretic properties of the product of protein synthesis in mitochondria of rat liver and Zajdela hepatoma.


Fusion of XC rat sarcoma cells induced by murine leukaemia virus-infected mouse mammary tumour cells. Absence of interference by simultaneously synthesized mammary tumour virus.


Herpesviruses from fish to man--a search for pathobiologic unity.


Demyelinating diseases and certain virus infections.


The relation between structure and function in mitochondria. Its relevance in pathology.


Growth kinetics of solid tumors.

Growth kinetics of solid tumors.


Activity of hydrolytic enzymes in a case of subacute multiple sclerosis.


The immunizing effect of commercial pigeon pox vaccines on pigeons.


Herpes simplex encephalitis. A report of three further cases.


Inefficacy of dietary deficiencies of vitamins A, D3 and riboflavin on the reproductive performance of mature cockerels.


Renal transplantation in children.

Renal transplantation in children.


Plasma renin activity (PRA) in 89 patients on regular haemodialysis.


The presence of glycogen synthase in preparations of platelet plasma membranes.


Regulation of aldosterone in anephric man maintained with regular haemodialysis.


Adrenergic and cholinergic innervation of the turtle heart ventricle.


Ultrastructure of the rat posterior pituitary gland and evidence of hormone release by exocytosis as revealed by freeze-fracturing.


The capillaries of the middle ear mucosa in the guinea pig. Ultrastructure and permeability.


Histochemical changes in the digestive gland of Lymnaea truncatula infected with Fasciola hepatica.


The terminal neuromuscular junctions of lower chordates.


Environmental modifications for controlling acute respiratory disease.


Experimental reovirus infection in monkeys. II. Serologic studies.


The distribution of incubation periods of neoplastic diseases.


The genetic structure of a tribal population, the Yanomama Indians. IX. Gene frequencies for 18 serum protein and erythrocyte enzyme systems in the Yanomama and five neighboring tribes: nine new variants.


Probable autosomal recessive inheritance in a family with Albright's hereditary osteodystrophy and an evaluation of the genetics of the disorder.


Epstein-Barr virus (EBV)-induced transformation of human lymphoid cells and immunosurveillance against lymphoma development.


Systemic eosinophilic infiltrative disease (SEIDI).


Comparison of the direct and indirect immunoferritin tagging of Sendai virus antigen.


The comparative approach to physiological psychology.


Optic nerve pit and associated coloboma with serous detachment.


Plasma renin levels in the normal and anephric fetus at birth.


"Primary" pulmonary histiocytosis X.

"Primary" pulmonary histiocytosis X.


Corticotrophin and cortisol concentrations in the plasma of the chronically catheterised sheep fetus.


Prolonged respirator support for the treatment of intractable myasthenia gravis.


2,3-Diphosphoglycerate fluctuations in erythrocytes reflecting pronounced blood glucose variation. In-vivo and in-vitro studies in normal, diabetic and hypoglycaemic subjects.


Immunoadjuvant activity of bacterial fractions on antibody-forming cells during the primary immune response period.


Ascending connections of a midbrain auditory area in a crocodile, Caiman crocodilus.


Ascending connections of a thalamic auditory area in a crocodile, caiman crocodilus.


Uses and abuses of corticosteroids.

Uses and abuses of corticosteroids.


Partial hepatectomy in metastatic Wilms' tumor.


Cancer in children with primary immunodeficiency diseases.


Ulceration of the colon associated with rheumatoid arthritis and steroid treatment: report of a case.


Molecular weight determination of Sendai and Newcastle disease virus RNA. The molecular weights of Sendai and Newcastle disease virus RNA were estimated by sedimentation in sucrose gradients and by length measurements in the electron microscope under both denaturing and nondenaturing conditions. Sedimentation analyses under denaturing conditions yielded molecular weight estimates of 2.3 x 10(6) to 2.6 x 10(6), whereas length measurements yielded estimates of 5.2 x 10(6) to 5.6 x 10(6) for both denatured and nondenatured viral RNA. It would appear that the conditions of denaturation used (99% dimethyl sulfoxide at 26 C, and reaction with 1.1 M formaldehyde for 10 min at 60 C) do not equally denature parainfluenza virus RNA and other RNAs, such as cellular rRNA, 45S rRNA precursor, and R17 RNA.


Interactions of polyoma and mouse DNAs. I. Lytic infection of bromodeoxyuridine-prelabeled mouse embryo cells. On CsCl isopycnic centrifugation of the DNA extracted from secondary mouse embryo (ME) cultures grown in the presence of 5-bromodeoxyuridine (BUdR) and 5-fluorodeoxyuridine (FUdR) for 40 h, 10 to 25% of the DNA was found to be unsubstituted, 70 to 80% was bromouracil-hybrid DNA, and 5 to 10% was heavy DNA. These results together with cell number determinations, autoradiography, and Feulgen microspectrophotometry revealed three types of cells in these cultures: (i) 60 to 80% of the cells replicated their DNA once, divided, and then stopped mitotic activity, (ii) 5 to 10% were going through a second round of DNA replication; whereas (iii) 10 to 30% did not replicate DNA during the BUdR-FUdR exposure. After the transfer of these cultures to normal medium (without BUdR-FUdR), up to 20% of the cells resumed DNA synthesis asynchronously within 60 h, but no increase in cell number was observed. BUdR-FUdR-treated cultures, which were infected with polyoma virus in the absence of the thymidine analogues, supported a lytic infection to the same extent as did untreated ME cultures. This was concluded from the similar number of cells, which were induced to synthesize DNA, from the similar replication rate of the viral DNA, from the similar number of cells containing polyoma capsid proteins, and from the similar yields of progeny virus determined by hemagglutination and plaque formation. Thus, BUdR-prelabeled ME cultures are suitable for the investigation of interactions of the polyoma and mouse genomes during the lytic infection.


Interactions of polyoma and mouse DNA's. II. Polyoma-induced mouse DNA replication and pseudovirion formation. Secondary mouse embryo (ME) cultures which had been grown prior to infection in the presence of 5-bromodeoxyuridine (BUdR) and 5-fluorodeoxy-uridine were found to be permissive for polyoma virus (16). The DNA extracted from the progeny virus yielded two bands on CsCl isopycnic centrifugation. The light band (LL) contained supercoiled circular (polyoma DNA I), open circular (polyoma DNA II), and linear (polyoma DNA III) molecules, as was seen by electron microscopy. The hybrid band (HL) contained exclusively linear molecules. This DNA was pure, density - labeled, pseudovirion DNA, i.e., fragmented HL mouse DNA. The quantitative comparison of HL and LL polyoma DNA III from six different virus preparations always revealed an excess of HL DNA, the ratio of HL/LL being between 1.2 and 2.2. These results led to the conclusion that in BUdR-prelabeled, polyoma-infected ME cells pseudovirion DNA is excised both from unreplicated and newly replicated regions of mouse DNA.


Control of simian virus 40 gene expression in adenovirus-simian virus 40 hybrid viruses. Synthesis of hybrid adenovirus 2-simian virus 40 RNA molecules in cells infected with a nondefective adenovirus 2-simian virus 40 hybrid virus. The effect of interferon on simian virus 40 (SV40) and adenovirus 2 (Ad2) T antigen synthesis has been examined in cells infected with SV40, with Ad2, and with a nondefective Ad2-SV40 hybrid virus, Ad2(+)ND(4). The induction of SV40 T antigen by SV40 was highly sensitive to interferon, whereas the induction of Ad2 T-antigen by Ad2 was resistant. This difference in interferon sensitivity was also noted in cells simultaneously infected with both viruses. However, the induction of SV40 T antigen by Ad2(+)ND(4), which contains covalently linked SV40 and Ad2 DNAs, was as resistant to interferon as the induction of Ad2 T antigen. This change in the interferon sensitivity of SV40 T antigen synthesis suggests that the expression of at least this portion of the SV40 genetic information in Ad2(+)ND(4) is under Ad2 genetic control. When RNA extracted from Ad2(+)ND(4)-infected cells was examined by means of sequential hybridization with Ad2 DNA, elution, and rehybridization with SV40 DNA, 27% of the SV40-specific RNA was found to be linked to Ad2 RNA. No such linkage was detected in control mixtures of Ad2 and SV40 RNAs. The presence of Ad2 and SV40 nucleotide sequences in the same RNA molecule implies that, in Ad2(+)ND(4) infection, transcription is initiated in the DNA of one virus (Ad2 or SV40) and continues without interruption across the point of junction into the DNA of the other virus. Furthermore, the interferon resistance of Ad2(+)ND(4)-induced SV40 T antigen synthesis suggests that transcription of the genetic information for SV40 T antigen is initiated in a region of Ad2 DNA.


Isolation and characterization of Sendai virus temperature-sensitive mutants. Ten temperature-sensitive mutants of Sendai virus, a paramyxovirus, were isolated and partially characterized. The mutants replicated in chicken embryo lung cells at 30 C, but not at 38 C; wild-type virus grew equally well at both temperatures. Complementation tests divided the mutants into seven groups. Six groups synthesized neither infectious virus nor RNA when incubated at 38 C from the beginning of infection. Temperature shift-up experiments demonstrated that three of these complementation groups were blocked in early steps required for RNA synthesis, but these gene functions were not needed throughout the replicative cycle. In contrast, the other three RNA-negative complementation groups were defective throughout the replicative cycle in functions required for virus-specific RNA synthesis. Only one mutant, which complemented all of the above, synthesized RNA but not infectious virus when placed at 38 C; the hemagglutinin of this mutant functioned only at the permissive temperature.


Virus replication in enucleate cells: vesicular stomatitis virus and influenza virus. The requirement of the presence of a nucleus for the replication of vesicular stomatitis virus and influenza virus has been examined by following the growth and development of these viruses in enucleate BS-C-1 cells. Vesicular stomatitis virus replicates normally in enucleate cells with the rate of production of infectious virus, the amount of virus-specific protein synthesis, and the type of proteins produced being essentially the same in nucleate and enucleate cells. Influenza virus does not replicate in enucleate cells, no virus gene products can be detected, and there is no inhibition of cellular protein synthesis.


Phosphorylation of vesicular stomatitis virus in vivo and in vitro. The structural protein, NS, of purified vesicular stomatitis virus (VSV) is a phosphoprotein. In infected cells phosphorylated NS is found both free in the cytoplasm and as part of the viral ribonucleoprotein (RNP) complex containing both the 42S RNA and the structural proteins L, N, and NS, indicating that phosphorylation occurs as an early event in viral maturation. VSV contains an endogenous protein kinase activity, probably of host region, which catalyzes the in vitro phosphorylation of the viral proteins NS, M, and L, but not of N or G. The phosphorylated sites on NS appear to be different in the in vivo and in vitro reactions, and are differentially sensitive to alkaline phosphatase. After removal of the membrane components of purified VSV with a dextran-polyethylene glycol two-phase separation, the kinase activity remains tightly associated with the viral RNP. However, viral RNP isolated from infected cells shows only a small amount of kinase activity. The protein kinase enzyme appears to be a cellular contaminant of purified VSV because an activity from the uninfected cell extract can phosphorylate in vitro the dissociated viral proteins NS and M. The virion-associated activity may be derived either from the cytoplasm or the plasma membrane of the host cell since both of these cellular components contain protein kinase activity similar to that found in purified VSV.


Primate and murine type-C viral nucleic acid association kinetics: analysis of model systems and natural tissues. Hybridization studies employing single-stranded (3)H-DNA transcripts of type-C viruses isolated from a woolly monkey or gibbon ape failed to detect nucleic acid sequences homologous to these viruses in the DNA from a variety of uninfected primate species. The possible significance of these results for the epidemiology of type-C viruses in primates is discussed.


Structure of the mouse mammary tumor virus: polypeptides and glycoproteins. The polypeptide and glycoprotein compositions of the mouse mammary tumor virus virion from primary monolayer cultures of BALB/cfC3H mouse mammary tumor cells were studied by polyacrylamide gel electrophoresis by using internal and external labeling and Coomassie blue and periodic acid Schiff (PAS) staining. Twelve polypeptides were reproducibly resolved by the combined methods. Five major polypeptides were demonstrable with estimated molecular weights of 52,000, 36,000, 28,000, 14,000, and 10,000. Seven minor polypeptides were also consistently detected and had estimated molecular weights of 70,000, 60,000, 46,000, 38,000, 30,000, 22,000, and 17,000. Carbohydrate was associated with five of these polypeptides as measured by PAS stain or [(3)H] glucosamine labeling, or both. These glycoproteins had estimated molecular weights of 70,000, 60,000, 52,000, 36,000 and 10,000. The majority of the PAS stain and glucosamine was found in the 52,000 and 36,000 dalton peaks.


Preliminary observations pertaining to polyadenylation of rhinovirus RNA. Human rhinovirus type 14 contained polyadenylated RNA. Virus growth in HeLa cells was inhibited by cordycepin or polyuridilic acid and stimulated by polyadenylic acid. Polyadenylic acid also reversed cordycepin inhibition of virus-induced cytopathology of infected HeLa cells.


Proposal for numbering mutants of avian leukosis and sarcoma viruses. A system for the numbering of mutants of avian sarcoma and leukosis viruses is proposed.


Protein kinase associated with Sendai virions. A protein kinase activity has been found associated with purified Sendai virions. Most of the virion proteins and exogenous protamine served as substrates for this enzyme.


Diagnosis of adrenal hypertensions.

Diagnosis of adrenal hypertensions.


Change in baroreceptor sensitivity by angiotensin.


Augmentation of pressor response to exogenous renin in rats with acute mercuric chloride intoxication: failure to demonstrate renin activating princile (s) in plasma.


Murine virus-induced proteins synthesized by hamster tumor cells transformed by, but not producing, murine sarcoma virus. The 8303 hamster tumor cells transformed by Moloney strain of murine sarcoma virus (M-MSV), but which do not produce virus, do contain murine virus-induced proteins. The virus-induced proteins within the cell were identified either as free proteins or in association with membranous material, including the plasma membrane. In addition, some were excreted by the 8303 hamster tumor cells into the growth medium. Most virus-induced proteins were larger than 68,000 daltons, and they did not dissociate into components of smaller size in the presence of detergent and a reducing agent. A small amount of virus-induced protein with a molecular weight of less than 20,000 was also found in the hamster tumor cells. No virus-specific proteins with the identical antigenic specificity or size of the major internal group specific antigen (molecular weight about 30,000) of the murine leukemia viruses were present in these cells. There is a common cell surface antigen present in three other tumor cell lines, both virus-producing and non-virus-producing, identical in reactivity to that of the murine virus-induced antigen of the 8303 hamster tumor cell. This antigen is not present on the cell surface of normal mouse embryo cells.


Effects of cyclic AMP and dibutyryl cyclic AMP on renin release in vivo and in vitro.


Lysosomal enzyme activities in rat kidney treated with DOCA, especially with reference to renin, cathepsin and beta-glucuronidase.


Metabolism of vasoactive substances in the lung.


Granular cell tumour in a male breast.

Granular cell tumour in a male breast.


Formation of steroid conjugates in the human. I. Biosynthesis of uridine diphosphate glucuronic acid.


Research still holds the answer.

Research still holds the answer.


Mechanism of action of glucocorticoids.

Mechanism of action of glucocorticoids.


Editorial: Cat leukemia: a threat to man?


Extended observations on the secretion of an influenza virus inhibitor in the colostrum of a Caucasian donor.


Effect of distilled water, hypertonic saline, freezing and freeze-drying on the haemagglutinin and haemolytic properties of Sendai virus.


Case reports. Benign renal tumor in a 16-month-old boy treated with pre-operative radiotherapy.


Restoration of the conversion of desmosterol to cholesterol in L-cells after hybridization with human fibroblasts. Hybrids between different human cells (which synthesize cholesterol) and mouse cells (whose end-product of sterol synthesis is desmosterol) were analyzed for the ability to convert desmosterol to cholesterol. Conversion of [(14)C]desmosterol to cholesterol and incorporation of [(14)C]acetate into the end-product sterol were studied in the parental and hybrid cells. Concordant segregation of the conversion of desmosterol to cholesterol and the human chromosome F-20 was observed.


Interferon induction by synthetic polynucleotides: importance of purine N-7 and strandwise rearrangement. The antiviral activity and interferon-inducing ability of single-, double-, and triple-stranded polynucleotides, modified at pyrimidine C-5 or purine N-7, were evaluated in primary rabbit kidney cells challenged with vesicular stomatitis virus. (1) There is a parallel increase in antiviral activity and the temperature at which double-stranded polynucleotides rearrange to inactive triple-stranded complexes. (2) When the purine N-7 of (A)(n) is replaced by CH, all resulting double-stranded complexes fail to provide antiviral protection or to induce interferon, even though such complexes meet all requirements previously recognized for interferon induction. (3) Competition experiments between inactive and active polynucleotides indicate that single-stranded polynucleotides apparently do not bind to the cellular receptor sites for interferon induction, whereas triple-stranded complexes and inactive double-stranded complexes bind to such receptor sites but, probably for conformational reasons, fail to trigger the necessary message for interferon induction.


Transformation of cultured mammalian cells by viable herpes simplex virus subtypes 1 and 2. A continuous line of rodent cells carrying the genome of the Rous sarcoma virus was stably transformed by exposure to viable herpes simplex virus of either subtype 1 or 2. Transformation was accompanied by alteration of morphology, growth characteristics, acquisition of a thymidine kinase activity (EC 2.7.1.21) resembling the corresponding specific activity of the enzyme in the herpes simplex virus, and capacity to express continuously some antigens specific for herpes simplex virus.


Interruption of the sequential release of small and large molecules from tumor cells by low temperature during cytolysis mediated by immune T-cells or complement. Specific lysis of tumor cells by thymus-derived lymphocytes from alloimmunized mice (T-effector specific lysis) was studied with target cells labeled with isotopes attached to both small ((14)C-labeled nicotinamide) and large ((51)Cr-labeled) molecules. The results confirm and extend previous reports that target cells release small molecules considerably earlier than large molecules during T-effector specific lysis. After interruption of T-effector specific lysis by specific antibody and complement directed against the killer cells, or by ethylenediaminetetraacetic acid, release of both isotopes continued, eventually reaching identical levels of specific release, the value of which represents the fraction of the target cell population which had been committed to die at the time these treatments were applied. On the other hand, release of both isotopes during T-effector specific lysis stops immediately when the cultures are cooled to 0 degrees . Thus, while ethylenediaminetetraacetic acid or specific complement-mediated lysis of the killer cells merely prevents the initiation of any new damage to target cells, cooling to 0 degrees also stops the lytic process in already-damaged target cells. The colloid osmotic phase of target cell lysis induced by specific antibody and complement was similarly stopped at 0 degrees in tumor cells, but not in erythrocytes. Thus, in tumor target cells, both T-effector specific lysis and complement cause a sequential release of progressively larger molecules which can be immediately stopped at any point by cooling to 0 degrees .


Evidence that the AKR murine-leukemia-virus genome is complete in DNA of the high-virus AKR mouse and incomplete in the DNA of the "virus-negative" NIH mouse. The AKR mouse has a high titer of murine leukemia virus early in life, and virus-negative cells derived from embryos of this mouse strain can be activated to yield murine leukemia virus by treatment with 5-iododeoxyuridine. In contrast to this high-virus strain, the NIH Swiss mouse has a low incidence of leukemia and no murine leukemia virus has been isolated from it (virus-negative). We have investigated this difference between AKR and NIH mice by examining the sequences specific for murine leukemia virus in nucleic acids of these mice. A single-stranded viral-DNA probe synthesized in vitro using murine-leukemia-virus from the AKR mouse contains at least 87% of the sequences present in the 70S viral RNA; most of these sequences are in proportions similar to their content in the 70S RNA. Using this probe in nucleic acid hybridization experiments, we have shown that NIH-mouse-cell DNA and AKR-mouse-cell DNA differ with respect to sequences specific for AKR murine-leukemia-virus: NIH-mouse-cell DNA lacks some of the virus-specific sequences present in AKR-mouse-cell DNA, and there are two distinct sets of virus-specific sequences in AKR-mouse-cell DNA, whereas there is only one set in NIH-mouse-cell DNA.RNA from virus-negative AKR-mouse cells grown in tissue culture contains some, but not all, virus-specific RNA sequences; however, within 48 hr after initiating treatment of these cells with 5-iododeoxyuridine, the complete viral genome is represented in cellular RNA.


Collagen biosynthesis in nonfibroblastic cell lines. Prolyl hydroxylase and other enzymes of collagen synthesis have been found in cloned cells, including epithelium, melanoma, liver, HeLa, pituitary, kidney, and neuroblastoma. The significance of collagen biosynthesis in nonfibroblastic cells lines is discussed.


Penetration of mouse fibroblasts by the 5'-phosphate of 9-beta-D-arabinofuranosyladenine and incorporation of the nucleotide into DNA. 9-beta-D-Arabinofuranosyladenine 5'-monophosphate (araAMP) is more lethal to mouse fibroblasts (L cells) than the identical exogenous concentration of 9-beta-D-arabinofuranosyladenine (araA) (Cancer Res. 32, 1512, 1972). [(3)H,(32)P]AraAMP (0.1 mM) was taken into L cells for 4 hr in the presence of a large excess of (32)P(i). The radioactivity was subsequently found mainly in the adenine nucleotides in the acid-soluble fraction and in the cell DNA. The cellular concentration of 9-beta-D-arabinofuranosyladenine 5'-triphosphate (araATP) exceeded 2 muM. More than 90% of the (3)H was associated with araA in the nucleotides. After degradation of the adenine-containing triphosphates with apyrase, the adenine mononucleotides were separated by thin-layer electrophoresis and chromatography. All of the (32)P and 97% of the (3)H were associated with araAMP. The small amounts of (3)H and (32)P in the acid-insoluble material were similar during a 4 hr incubation. The DNA fraction was degraded enzymatically to 5'-mononucleotides. Both (32)P and (3)H were associated predominantly with 5'-dAMP. Most of the (3)H was in araA, detected after dephosphorylation. Enzymatic degradation of the DNA fraction to 3'-mononucleotides and fractionation revealed (3)H primarily in the 3'-adenine nucleotide and (32)P in each of the deoxynucleoside 3'-monophosphates. After dephosphorylation of the 3'-mononucleotides, 93% of the (3)H was found in araA. These results suggest that small amounts of araAMP penetrated the cell as an intact nucleotide, were further phosphorylated to the triphosphate, and subsequently incorporated in internucleotide linkage into DNA.


Effects of guanosine tetraphosphate, guanosine pentaphosphate, and beta-gamma methylenyl-guanosine pentaphosphate on gene expression of Escherichia coli in vitro. The effects of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), both produced by E. coli, were measured on the activities of several genes in a cell-free system. Gene activity is measured as gene-directed synthesis of biochemically competent protein or transfer RNA. Both ppGpp and pppGpp stimulated the activities of the ara, lac, and trp operons and inhibited the arg operon. Production of transfer-RNA(Tyr) was unaffected by moderate levels of either ppGpp or pppGpp and only slightly inhibited at higher levels of ppGpp. Since the cell-free reaction mixtures hydrolyze pppGpp to ppGpp, we performed similar studies with a hydrolysis-resistant analog of pppGpp, the beta-gamma methylenyl derivative (pcppGpp). In general, pcppGpp shows the same inhibitory potency as pppGpp for the arg operon, but lacks the stimulatory effects on the ara, lac, and trp operons. This result suggests that the stimulation of these gene activities is specific for ppGpp.Under similar conditions, pppGpp and ppGpp show a slight inhibitory effect on the messenger-directed synthesis of beta-galactosidase and no effect on the messenger-directed synthesis of MS2 viral-coat protein. These observations, together with the fact that in the same system these nucleotides affect coupled transcription and translation, lead us to surmise that the activities of pppGpp and ppGpp are exerted at the level of RNA polymerase activity.


ACTH antagonists.

ACTH antagonists. Structural modifications within the active site of the ACTH molecule have produced analogs that inhibit the hormone sensitive adenylate cyclase system of bovine adrenal cortical plasma membranes. It is demonstrated that the tryptophan residue of the ACTH molecule is essential for stimulation of the enzyme. Substitution of tryptophan by phenylalanine or by N(alpha)-methyltryptophan as in [Gln(5), Phe(9)]corticotropin(1-20) amide or [N(alpha)-Metrp(9)]corticotropin(1-24) provides ACTH analogs that exhibit high affinity for the ACTH receptor(s) but fail to activate the adenylate cyclase system. It is concluded that affinity for the receptors alone is not sufficient for expression of hormonal activity. The observation that adrenal cortical adenylate cyclase activated by fluoride ion is not inhibited by the antagonists indicates that hormonal and fluoride activation proceed via different mechanisms.


Kinetics of early changes in phosphate and uridine transport and cyclic AMP levels stimulated by serum in density-inhibited 3T3 cells. A kinetic study of the early changes in uridine- and phosphate-transport rates and 3':5'-cyclic AMP levels induced by the addition of serum to quiescent 3T3 cells revealed that the increase in phosphate uptake and the decrease in the intracellular concentration of 3':5'-cyclic AMP immediately follow the addition of serum. In contrast, the increase in uridine transport occurred after a lag of several minutes and was clearly preceded by the other changes. The activation of phosphate transport involved an increase in V(max), while a more complex pattern was observed for uridine transport. A possible role of phosphate in connection with the other early events was also studied. The addition of phosphate to quiescent cells produced a time-dependent decrease in 3':5'-cyclic AMP levels and this ion was required for full activation of uridine transport by serum. The results show that the increase in phosphate transport is a primary event in the reinitiation of growth and suggest that the increase in phosphate transport may be connected with subsequent metabolic steps.


Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Chronic (5-16 hr) exposure of cultured human lymphocytes to 10(-8) M insulin at 37 degrees in vitro produced a decrease in insulin receptor concentrations unaccounted for by simple occupancy of sites; acute exposure (0-2 hr) was without effect. These results reproduced observations in vivo where chronic hyperinsulinemia (e.g., 10(-8) M insulin in the circulation of obese insulinresistant hyperglycemic mice) is associated with a substantial reduction in the concentration of insulin receptors per cell, while acute hyperinsulinemia in vivo has no effect on receptor concentration. These data suggest a reciprocal relationship between insulin in the extracellular fluid and the concentration of insulin receptors per cell, which is mediated at the target cell itself by intracellular insulin-sensitive regulatory processes and directly affects target-cell sensitivity to hormone.


Granulocytes containing cytoplasmic inclusions in human tuberculous pleuritis.


Nonhistone chromosomal proteins and gene regulation. Evidence from several model systems suggests that nonhistone chromosomal proteins may regulate gene expression in eukaryotic cells. The data indicate that the synthesis of new species of nonhistone chromosomal proteins as well as modifications of preexisting nonhistone chromosomal proteins are involved in the control of transcription. However, from the vast number of proteins included in this class, it is apparent that, in addition to regulating the transcription of defined genome loci, the nonhistone chromosomal proteins include enzymes that have a general function, proteins that are involved in determining the structure of chromatin, as well as proteins that serve as recognition sites for binding of regulatory macromolecules. The presence of a nucleoplasmic pool of nonhistone chromosomal proteins which may exchange with the chromatin has also been reported (89). While it is clear that the nonhistone chromosomal proteins play a key role in the regulation of gene expression, the exact manner in which they interact with the genome to initiate, modify, or augment the transcription of specific RNA molecules remains to be resolved.


Amorphous semiconductor switching in melanins. Melanins produced synthetically and isolated from biological systems act as an amorphous semiconductor threshold switch. Switching occurs reversibly at potential gradients two to three orders of magnitude lower than reported for inorganic thin films, and comparable to gradients existing in some biological systems. Of a number of other biological materials tested, only cytochrome c acted similarly, but at the high potential gradients reported for thin film amorphous semiconductors.


Hormonal control of neutrophil lysosomal enzyme release: effect of epinephrine on adenosine 3',5'-monophosphate. Human neutrophilic leukocytes release neutral protease and beta-glucuronidase during cell contact with, and phagocytosis of, zymosan particles treated with rheumatoid arthritic serum. Release of lysosomal enzymes is inhibited by epinephrine and adenosine 3',5'-monophosphate (cyclic AMP), but not by phenylephrine or adenosine 5'-monophosphate. Inhibition of enzyme release by epinephrine may be mediated by cyclic AMP because the cyclic AMP in the neutrophils is increased by epinephrine treatment at the time when enzyme release is reduced.


Hydrocortisone influences developing collaterals. 2. A cytochemical study.


A new sensor for pneumatic tonometry. Construction and working principle.


Clinical evaluation of the luteinizing hormone-releasing hormone (LH-RH) test in cases with anatomically verified disorders of the hypothalamo-pituitary region.


Trabeculotomy ab externo.

Trabeculotomy ab externo.


The heredity of glaucoma.

The heredity of glaucoma.


Trabeculotomy, trabeculectomy and sinusotomy--some clinical results.


Adrenalin therapy in glaucoma.

Adrenalin therapy in glaucoma.


Experience with keratoprostheses.

Experience with keratoprostheses.


Ophthalmological involvements in diabetes. An introduction.


Clinical and histological findings in crystalline corneal dystrophy.


Peripheral versus central mechanisms accounting for antianxiety effects of propranolol.


Pigment granules in iris pigment epithelium of diabetics.


Pregnancy and diabetic retinopathy.

Pregnancy and diabetic retinopathy.


Follow-up of initially nonglaucomatous patients with fibrillopathia epitheliocapsularis (so-called senile exfoliation of the anterior lens capsule).


Importance of callosal transfer in the extramacular inhibition phenomenon along the hemiopic border.


The intraocular pressure. An introduction.


Experiences in surgical treatment of haemorrhagic glaucoma. A follow-up study.


Newer respiratory viruses: their role in respiratory illness of children.


Reflex organization and contraction properties of facial muscles. An experimental study in the cat.


Human memory and the cholinergic system. A relationship to aging?


Amyotrophic lateral sclerosis. Abnormal cellular inflammatory response.


Hepatoma in Papua New Guinea.

Hepatoma in Papua New Guinea.


Assembly of tobacco mosaic virus rods in vitro. Elongation of partially assembled rods.


Cutaneous amoebiasis.

Cutaneous amoebiasis.


Selenium as a catalyst for the reduction of cytochrome c by glutathione.


Instability of the uterine estrogen receptor under in vitro conditions.


Estrophilic binding sites of the uterus. Relation to uptake and retention of estradiol in vitro.


Interaction of ovarian receptors with human luteinizing hormone and human chorionic gonadotropin.


Excited states and reactivity of 5-deazaflavine. Comparative studies with flavine.


Estimate of minimal distance between rapidly exchanging zinc and nucleotide binding sites in liver alcohol dehydrogenase.


The function of the descending root of the fifth nerve.


Deuterium isotope effects on initial rates of the liver alcohol dehydrogenase reaction.


Cytoplasmic inclusions in the vermiform appendix and skeletal muscle in two types of so-called neuronal ceroid-lipofuscinosis.


Evolutionary perspectives on the function of the optic tectum.


Mouse leukemia virus growth in mouse cells contaminated with Mycoplasma.


Isolation and chemical characterization of mucopolysaccharides from rat tumors.


Effects of hexosamines and their acetyl derivatives on aggregation of rat hepatoma cells in rotation culture.


Studies of initiation factors in protein synthesis of host liver and transplantable hepatoma.


Two-dimensional gel electrophoresis of acid-extractable nuclear proteins of regenerating and thioacetamide-treated rat liver, Morris 9618a hepatoma, and Walker 256 carcinosarcoma.


Recent studies on the formation of cerebrospinal fluid.


Symmetrical epileptogenic foci in cerebral cortex of immature rat.


Phenylalanyl-tRNA synthetase from Escherichia coli K10. Synergistic coupling between the sites for binding of L-phenylalanine and ATP.


The wall peptidoglycans of Neisseria perflava, Moraxella glucidolytica, Pseudomonas alcaligenes and Proteus vulgaris strain P18.


Products of mitochondrial protein synthesis in Neurospora crassa. Determination of equimolar amounts of three products in cytochrome oxidase on the basis of amino-acid analysis.


The covalent structure of collagen. 1. The chymotrypsin, trypsin, and thermolysin-derived peptides of alpha1-CB7 from calf-skin collagen.


The covalent structure of collagen. 2. The amino-acid sequence of alpha1-CB7 from calf-skin collagen.


Cirrhosis and heterozygous FZ alpha1-antitrypsin deficiency in an adult. Case report and review of the literature.


Mechanisms and control of secretion of bile water and electrolytes.


Progressive enzyme studies on spontaneous hepatocarcinogenesis in reciprocal F1 crosses of C3H (JAX) and ICRC strains.


Carcinoma of the lung--a correlative cytological and histopathological study.


Melanoameloblastoma--report of a case and review of literature.


Mixed salivary tumours.

Mixed salivary tumours.


The application of ultrasound tomography in radiation therapy.


A case report on calcified mucinous adenocarcinoma of the stomach.


Genetic influences affecting the occurrence of a diabetes mellitus-like disease in mice infected with the encephalomyocarditis virus. The M variant of encephalomyocarditis virus produces a diabetes mellitus-like disease in DBA/2 mice but not in animals of the C3H strain. Fewer than one-third of infected F(1) (DBA/2 x C3H) progeny exhibit the disease, whereas the prevalence in backcrosses (F(1) x DBA/2, F(1) x C3H) is comparable to the parental inbred strain. Thus, the mode of inheritance of the diabetic predisposition appears to be polygenic. DBA/2 animals develop striking inflammatory and necrotizing lesions of the islets of Langerhans; in contrast, alterations of the insular tissue in the C3H mice are minimal. Although metabolic abnormalities appear to be consequent to lesions of beta cells, the factors influencing the severity of these insular changes are incompletely understood.


Renal hypertension in rats immunized against angiotensin I and angiotensin II. Rats, actively immunized against angiotensin I (AI) and angiotensin II (AII), were subjected to unilateral renal artery constriction to determine whether the resulting hypertension, which may still ensue in the animal immunized against AII, could be prevented by such combined immunity. Sustained immunity to both AI and AII neither changed preoperative blood pressures of the rats from those of control mock-immunized rats nor altered the incidence or severity of renal dip hypertension. Vascular hyperresponsiveness to small quantities of free angiotensin could not be invoked to explain the hypertension, for there was no significant difference between mock-immunized hypertensive animals, and those remaining normotensive, regarding pressor sensitivity to intravenous AI, AII, renin, and norepinephrine. (AI + AII)-immunized hypertensive rats required AI doses averaging 260 times greater than nonimmune hypertensives to elicit equipressor responses, and were refractory to renin, but not to norepinephrine. Thus, while previous studies have not excluded direct participation of endogenous AI in renal clip hypertension in rats, evidence from our experiments makes it extremely difficult to sustain any pressor function therein for circulating AI or AII. Our results also preclude involvement of AII produced from circulating AI by conversion within arteriolar walls, close to receptor sites, since AI immunity would block this mechanism of action.


Cell transformation by viruses and the role of viruses in cancer. The eleventh Marjory Stephenson Memorial Lecture.


Cell-mediated immunity to herpes simplex virus in man.


Guinea pig model for cutaneous herpes simplex virus infection.


Viral studies in pemphigus.

Viral studies in pemphigus.


The mechanism of drug-induced erythrocyte vacuole formation.


The influence of dietary potassium on the renin and aldosterone response to diuretic-induced volume depletion.


Glomerular glycoprotein: galactosyl transferase activity in rat kidney.


Biologically active components from mycobacterial cell walls. II. Suppression and regression of strain-2 guinea pig hepatoma.


Lack of effect of erythropoietin on cyclic adenosine-3',5'-monophosphate levels in rat fetal liver cells.


Autogenous immunity to endogenous RNA tumor virus: chronic humoral immune response to virus envelope antigens in B6C3F1 mice.


Neoplastic transformation in vivo and in vitro of regenerating hamster hepatic cells by oncogenic DNA Simian virus 40.


Rat alpha1 fetoprotein. IV. Effect of growth and surgical removal of Morris hepatoma 7777 on the serum alpha1F concentration of Buffalo rats.


Differential inhibition by fucoses of aggregation of rat hepatoma cells in rotation-mediated cell cultures.


Familial medullary thyroid carcinoma and pheochromocytoma: epidemiologic investigations.


Associations between tumor types in a large-scale carcinogenesis study of CF-1 mice.


Development of leukemia in rats with tumors induced by chicken sarcoma virus.


Coexistence of particles resembling herpesvirus and type-C virus in feather follicle epithelium of chickens.


Sendai virion transcriptase complex: polyeptide composition and inhibition by virion envelope proteins. Sendai virions, disrupted in 2% Triton X-100 in 1 M KCl, were separated into nucleocapsids and envelope proteins by centrifugation. The nucleocapsids, representing 46% of the virion proteins, had a buoyant density of 1.29 gm/cm(3) in D(2)O sucrose. RNA-dependent transcriptase activity associated with them had a ninefold greater specific activity than transcriptase assayed in unfractionated detergent-disrupted virions. These enzyme-active nucleocapsids contained only two polypeptides, the largest virion polypeptide (molecular weight 75,000) and the nucleocapsid structure unit (molecular weight 60,000). Virion envelope proteins, either glycoproteins or nonglycosylated matrix protein, inhibited nucleocapsid-associated polymerase activity; brief heat denaturation abolished their inhibitory activity. Yeast RNA stimulated nucleocapsid-associated enzyme, suggesting that stimulatory polyanions act at the enzyme-template level.


In vitro polyoma DNA synthesis: characterization of a system from infected 3T3 cells. A lysate from hypotonically swollen polyoma-infected BALB/3T3 cells incorporated labeled deoxynucleotide triphosphates into both viral and cellular DNAs. The incorporation was stimulated by the presence of ATP, deoxynucleotide triphosphates, thiols, and magnesium ions. Strong inhibition of incorporation was observed with thiol reagents and arabinosyl nucleotide triphosphates. The rate of in vitro synthesis increased with the temperature of incubation as expected. Incorporation into cellular DNA for up to 2 h was observed in lysates from virus-infected and serum-stimulated cells but not from resting cells. Synthesis in the system, therefore, appeared to reflect the physiological state of the cells before preparation of the lysate. Incorporation into viral DNA stopped far sooner than that into cellular DNA. During the initial phase of the in vitro incubation, incorporation occurred into viral replicative intermediates (RI). These RIs had identical properties to those isolated after in vivo pulse labeling and a substantial proportion of them was matured to form I DNA at later times in the incubation through all the stages known to occur in vivo. Density labeling of the in vitro product showed that practically all of the RIs pre-existing in the infected cell took part in the in vitro reaction. Analysis of DNA labeled in vitro in the presence of 5-bromodeoxyuridine triphosphate showed that synthesis occurred on RIs at all stages of replication and that the progeny strands were elongated by up to 80% of unit viral DNA length. Pre-existing RIs, pulse labeled in vivo, showed evidence of a pool at a late stage of replication which required elongation of their progeny strands by approximately 25% during conversion to form I molecules. From density-labeling experiments, we were also able to show that viral DNA synthesis in vitro was semiconservative. The major reason for cessation of viral DNA synthesis in vitro was the very limited ability of the lysate to initiate new rounds of viral DNA synthesis.


Protein kinase and phosphoproteins of vesicular stomatitis virus. Protein kinases of similar but not identical activity were found associated with vesicular stomatitis (VS) virions grown in mouse L cells, primary chicken embryo (CE) cells, and BHK-21 cells, as well as being present in VS virions grown in HeLa and Aedes albopictus cells. The virion kinase preferentially phosphorylated the nucleocapsid NS protein in vitro and to a lesser extent the envelope M protein. Other virion proteins were phosphorylated in vitro only after drastic detergent treatment. Partial evidence that the virion kinase is of cellular origin was obtained by finding reduced enzyme activity in virions released from cells pretreated with actinomycin D and cycloheximide. Selective detergent and detergent-salt fractionation of VS virions revealed that the kinase activity was present in the envelope but not the spikes. The virion kinase activity in a Triton-salt-solubilized envelope fraction could be separated from M and G proteins and partially purified by phosphocellulose column chromatography. Virions released from L, CE, and BHK-21 cells infected in the presence of [(32)P]orthophosphate were labeled almost exclusively in the NS protein. Both soluble and nucleocapsid-associated NS phosphoprotein were present in cytoplasmic extracts of VS viral-infected L cells. The origin and function of the NS phosphoprotein remain to be elucidated.


Virus type-specific thymidine kinase in cells biochemically transformed by herpes simplex virus types 1 and 2. Transformation of mouse cells (Ltk(-)) and human cells (HeLa Bu) from a thymidine kinase (TK)-minus to a TK(+) phenotype (herpes simplex virus [HSV]-transformed cells) has been induced by infection with ultraviolet-irradiated HSV type 2 (HSV-2), as well as by HSV type 1 (HSV-1). Medium containing methotrexate, thymidine, adenine, guanosine, and glycine was used to select for cells able to utilize exogenous thymidine. We have determined the kinetics of thermal inactivation of TK from cells lytically infected with HSV-1 or HSV-2 and from HSV-1- and HSV-2-transformed cells. Three hours of incubation at 41 C produces a 20-fold decrease in the TK activity of cell extracts from HSV-2-transformed cells and Ltk(-) cells lytically infected with HSV-2. The same conditions produce only a twofold decrease in the TK activities from HSV-1-transformed cells and cells lytically infected with HSV-1. This finding supports the hypothesis that an HSV structural gene coding for TK has been incorporated in the HSV-transformed cells.


Endogenous C-type viruses of BALB-c cells: frequencies of spontaneous and chemical induction. A sensitive biological assay has been developed for studying the frequency of virus induction from mouse cells containing poorly infectious endogenous C-type viruses. A low spontaneous frequency of virus activation of one but not a second endogenous virus of BALB/c cells has been demonstrated. The resistance of BALB/c cells to superinfection by the more inducible virus appears to be absolute, whereas resistance to the other virus is only relative. Thus, the evidence indicates that the BALB/c cell exerts differential effects at two levels of regulation on the expression of its biologically distinguishable endogenous C-type viruses.


Protein kinase stimulated by cyclic GMP in uninfected and simian virus 40-infected monkey kidney cells. Uninfected African green monkey kidney cells contain a cyclic GMP-stimulated protein kinase. The level or specific activity of the enzyme was not significantly increased after infection of the cells with simian virus 40. This enzyme probably catalyzes the phosphorylation of the structural proteins of the virus.


Biochemical studies on the chi mutation of bacteriophage T4: differential inhibition of chi+ and chi DNA synthesis by mitomycin C. Biochemical studies were carried out to determine the effect of chi mutation on T4 DNA synthesis. The rate and final extent of DNA synthesis are almost the same with T4D- and T4chi-infected cells, although the burst size of T4chi is about one-sixth that of the wild type. The DNA synthesis of T4chi-infected cells is more readily inhibited by mitomycin C than is that of T4 wild type. When mitomycin C was added during active phage growth, DNA synthesis of T4chi halted almost immediately. T4 DNA polymerases isolated from chi(+)- and chi-infected cells, however, exhibit no difference with regard to their sensitivities to mitomycin C, priming activities with alkylated or ultraviolet light-irradiated templates and other enzymatic properties.


In vitro polyoma DNA synthesis: studies on an early temperature-sensitive mutant. The polyoma ts-a function was investigated by using an in vitro DNA-synthesizing system. A comparison of systems derived from ts25 (a ts-a group mutant)-and ts1260 (a late group mutant)-infected cells showed that the activation energies for DNA chain elongation and the mechanisms of discontinous growth were identical for both mutants.


Viruses of Entamoeba histolytica. V. Ultrastructure of the polyhedral virus V301. The polyhedral amoebal virus V(301) presents sectioned profiles consistent with its having icosahedral (532) symmetry. The DNA appears to be packed in an orderly, folded arrangement of lesser symmetry.


Detection of homologous RNA sequences among six rhabdovirus genomes. Complete transcripts of the genome of vesicular stomatitis virus Indiana strain have been used to hybridize to virion RNA to determine if there is RNA sequence homology among these viruses. Cellular RNA from cells infected by each of these viruses has also been used for hybridization with the homologous or heterologous virion RNA. The results indicate that there is little exact sequence homology among these viruses.


Location of the transcription defect in group I temperature-sensitive mutants of vesicular stomatitis virus. The ribonucleoprotein-dependent RNA transcriptase in vesicular stomatitis B virions of four temperature-sensitive (ts) mutants belonging to complementation group I was analyzed in vitro at permissive (31 C) and restrictive (39 C) temperatures. The RNA-synthesizing activity of all four ts mutants was more labile at 39 C than was the transcriptive activity of wild-type (wt) virions. In order to locate the temperature-sensitive transcription defect in the mutants, wt and ts mutant virions were fractionated by Triton X-100-high salt solubilizer into a sedimentable ribonucleoprotein template and a nonsedimentable enzyme fraction, each of which alone had little or no transcriptive activity. The template- and enzyme-containing fractions of wt virions were then tested for their capacity to restore transcriptive activity at 39 C to corresponding template and enzyme preparations of ts mutant virions. Recombination of wt template and ts enzymes resulted in no significant restoration of capacity to synthesize RNA at restrictive temperature. In contrast, transcriptive function at 39 C was reconstituted by recombining the wt enzyme with the template component of ts mutants. It appears, therefore, that the enzyme, rather than the template, is the temperature-sensitive component of the transcription complex of group I vesicular stomatitis virus mutants.


Analysis of minimal functions of simian virus 40. 3. Evidence for "host cell repair" of oncogenicity and infectivity of UV-irradiated simian virus 40. The in vitro transforming capacity of simian virus 40 (SV40) for Syrian hamster cells is highly resistant to inactivation by UV light in comparison to infectivity. In the same cell system, we demonstrated a "host cell repair mechanism" sensitive to caffeine which is, to a large extent, responsible for the high resistance to UV inactivation of the transforming capacity of SV40. The survival of infectivity of UV-irradiated SV40 in CV-1 cells was also sensitive to caffeine, again indicating host cell repair. On the other hand, depression of normal cell DNA synthesis by hydroxyurea during the first 24 h postinfection only modestly reduced, and to a similar extent, the transforming capacity of UV-irradiated and nonirradiated SV40.


Enzymatic radioiodination of the envelope proteins of avian myeloblastosis virus. Purified avian myeloblastosis virus was iodinated by the lactoperoxidase method. Disruption of the labeled virions and chromatography of the viral proteins showed that radioiodine was associated only with the glycoproteins of the viral envelope. Reaction of the radiolabeled virus with antiviral antibody followed by mild detergent treatment and subsequent recovery of immune complexes showed this technique to be useful for the isolation of viral envelope antigens.


Translation of vesicular stomatitis messenger RNA by extracts from mammalian and plant cells. RNA was isolated from polyribosomes of vesicular stomatitis virus (VSV)-infected cells and tested for its ability to direct protein synthesis in extracts of animal and plant cells. In cell-free, non-preincubated extracts of rabbit reticulocytes, the 28S VSV RNA stimulated synthesis of a protein the size of the vesicular stomatitis virus L protein whereas the 13 to 15S RNA directed synthesis of the VSV M, N, NS, and possibly G proteins. In wheat germ extracts, 13 to 15S RNA also directed synthesis of the N, NS, M, and possibly G proteins. Analysis of extracts labeled with formyl [(35)S]methionine showed that the 28S RNA directed the initiation of synthesis of one protein, whereas the 13 to 15S RNA directed initiation of at least four proteins. It is concluded that the 28S RNA encodes only the L protein, whereas the 13 to 15S RNA is a mixture of species, presumably monocistronic, which code for the four other known vesicular stomatitis virus proteins.


Physiopathology of portal hypertension. Circulatory neophysiology after portacaval shunt.


Regulation of expression of late genes of bacteriophage T5. Amber mutants of bacteriophage T5 defective in gene C2 have been characterized. The product of this gene is required for the normal turn-on of synthesis of late RNA's and proteins, and, apparently, for the normal continued synthesis of early RNA's and proteins during late stages of infection. The inability of nonpermissive cells to synthesize any proteins, either late or early, during the late period after infection with a C2-mutant is not due to premature lysis of the infected cells, to a depletion of the cellular energy supply, or to degradation of phage DNA at late times. A possible role for the product of gene C2 in early and late transcription of the viral genome is suggested.


Biochemical studies on the regulation of myocardial contractility.


Periodic acid-Schiff positive myeloblasts in chronic myelogenous leukaemia: relation to karyotype evolution.


Platelet function in hyperlipoproteinemia.


Pathology of gout.

Pathology of gout.


Pseudogout.

Pseudogout.


Determinants for the establishment of permanent tissue culture lines from human gliomas.


Comparative study of proteins, non-specific esterases and acid phosphatases in testicular fluids of different vertebrate species.


Hemangiopericytoma.

Hemangiopericytoma.


Spontaneous rupture of hepatoma: a misdiagnosed surgical emergency.


Comparative studies of synaptic membrane protein solubilization by chlorpromazine and sodium dodecylsulfate.


The control of renal cortical perfusion by the renin angiotensin system.


The effect of gold salts on the purine:pyrophosphate phosphoribosyltransferase enzymes of human blood cells.


The effect of gold salts on the biosynthesis of uridine nucleotides in human granulocytes.


Effect of bioamines on the cellular differentiation of Hartmannella culbertsoni.


Levels of nucleoside and nucleotide kinases in rhesus monkey tissues.


Aspartate transcarbamylase from Streptococcus faecalis. Steady-state kinetic analysis.


Allosteric and nonallosteric interactions with reduced nicotinamide adenine dinucleotide in two forms of cytoplasmic malic dehydrogenase.


Nasopharyngeal carcinoma (NPC). VI. Presence of an EBV nuclear antigen in fresh tumour biopsies. Preliminary results.


Parsley plastocyanin. The possible presence of sulfhydryl and tyrosine in the copper environment.


Arterial hypertension in retrospect.

Arterial hypertension in retrospect.


Identification of a distinction between cytoplasmic histone synthesis and subsequent histone deposition within the nucleus.


Poly(adenosine diphosphoribose) polymerase in mammalian nuclei. Characterization of the activity in mouse fibroblasts (LS cells).


Properties of arginine kinase from Drosophila melanogaster.


Immunochemical studies on rat-liver microsomal NAD glycohydrolase.


Fine structure of epithelial cell of secretory endometrium in unexplained primary infertility.


Sperm transport through vas deferens: review of hypotheses and suggestions for a quantitative model.


Interaction of bilayers with basic polypeptides. II. Interaction of phospholipid bilayers with copolymer L-lysine-L-phenylalanine.


Studies on plasma membranes. XX. Sialidase in hepatic plasma membranes.


Hierarchy levels in the control of blood flow to the hind limb of the dog. A new approach to the analysis of integrative neural cardiovascular control.


Event train decoders with many inputs, pulse density versus momentaneous frequency.


Considerations on models of movement detection.


Equine infectious anemia.

Equine infectious anemia.


Breathing before birth in animals and man. An essay in developmental medicine.


Drug therapy. Antacid therapy.

Drug therapy. Antacid therapy.


Choline acetyltransferase level in cyclic AMP and x-ray induced morphologically differentiated neuroblastoma cells in culture.


The central effects of thiopental and morphine in rats with renal hypertension.


Characterization of a feedback-resistant phosphoribosylpyrophosphate synthetase from cultured, mutagenized hepatoma cells that overproduce purines. A clone of cells in which the regulation of purine metabolism is genetically altered was selected and isolated from chemically mutagenized HTC cells (a line of rat hepatoma cells in continuous culture). The clone, designated MAU V, was selected for increased ability to salvage exogenous purines by isolating it in medium containing methylmercaptopurine ribonucleoside, adenine, and uridine, in which medium wild-type cells cannot divide. We have characterized these cells as having an increased rate of de novo purine biosynthesis, apparently as the result of an altered phosphoribosylpyrophosphate (PRPP) synthetase. The altered enzyme has normal catalytic properties but an altered sensitivity to feedback inhibition by purine and pyrimidine nucleotides. The types of inhibitions (competitive and uncompetitive) exerted by AMP, ADP, and TDP on the wild-type enzyme have been maintained in the altered enzyme, but values for K(i) have been increased by factors of 10, 17.5, and 5, respectively. The specific catalytic activities of AMP: pyrophosphate phosphoribosyltransferase and IMP:pyrophosphate phosphoribosyltransferase are normal. The mutant cell may serve as a model for a specific human disease, one type of dominantly inherited overproduction hyperuricemia.


Studies on the orientation of cyclic AMP-dependent protein kinase in human erythrocyte membranes. The topographic location of cyclic AMP-dependent protein kinase has been studied in preparations of permeable and sealed membranes derived from human erythrocytes. Both the catalytic and cyclic AMP-binding components of protein kinase are localized on the inner, cytoplasmic, surface of the plasma membrane.


Temperature-dependent formation of dimers and oligomers of mitochondrial DNA in cells transformed by a thermosensitive mutant of Rous sarcoma virus. In chick-embryo fibroblasts infected by T5, a temperature-sensitive mutant of Schmidt-Ruppin Rous sarcoma virus, the level of catenated dimeric and oligomeric mitochondrial DNA is temperature-dependent and correlates with the phenotypic manifestation of transformation. At the permissive temperature (36 degrees ), where transformation is expressed, the 2- to 3-fold elevated level characteristic of cells transformed by the wild-type Rous sarcoma virus was observed, but at the nonpermissive temperature (41 degrees ), at which cells appear normal and behave normally, the oligomer level was characteristic of uninfected cells. Temperature shifts from 41 to 36 degrees and vice versa resulted in phenotypic reversion and reversals of the respective levels of multiple-length DNA. Cellular growth rates were not altered. Treatment of control cells with cycloheximide resulted in a 5-fold increase of oligomeric DNA, whereas exposure to 9-beta-D-arabinofuranosyladenine had little effect. With both inhibitors, nuclear but not mitochondrial DNA synthesis was inhibited. The possible relation of formation of oligomeric mitochondrial DNA to alterations in the mitochondrial membranes of transformed cells and to inhibition of protein synthesis in the cytoplasm is discussed.


Size and base composition of RNA in supercoiled plasmid DNA. The average size and base composition of the covalently integrated RNA segment in supercoiled ColE(1) DNA synthesized in Escherichia coli in the presence of chloramphenicol (CM-ColE(1) DNA) have been determined by two independent methods. The two approaches yielded similar results, indicating that the RNA segment in CM-ColE(1) DNA contains GMP at the 5' end and comprises on the average 25 to 26 ribonucleotides with a base composition of 10-11 G, 3 A, 5-6 C, and 6-7 U.


Interrelationship between adenylate cyclase activity, adenosine 3':5' cyclic monophosphate phosphodiesterase activity, adenosine 3':5' cyclic monophosphate levels, and growth of cells in culture. To investigate how cell population density influences the intracellular concentration of cyclic AMP we have measured adenylate cyclase and cyclic AMP phosphodiesterase activities and cyclic AMP levels at various stages of cell density in normal rat-kidney (NRK) cells, which exhibit contact-inhibition of growth, and in normal chick-embryo fibroblasts (CEF), which do not show contact inhibition of growth under our conditions. Until NRK cells reach confluency, both activities increase with increasing cell population and cyclic AMP levels are low. As NRK cells reach confluency, cyclic AMP phosphodiesterase activity decreases somewhat whereas adenylate cyclase activity continues to rise. This increase in synthetic ability is accompanied by the increase in cyclic AMP levels which occurs in these cells at confluency. In CEF grown in 5% serum where density-dependent inhibition of growth is not observed, both adenylate cyclase and cyclic AMP phosphodiesterase activities increase proportionately with increasing cell population density. No significant alteration occurs in the ratio between these two enzyme activities and no change is observed in cyclic AMP levels. The NaF-stimulated activity in NRK cells increases with increasing cell density until the cells reach confluency; thereafter the NaF-stimulated activity remains constant. In contrast, the NaF-stimulated activity observed in CEF does not vary appreciably between light and heavy density. The observed changes in the enzymes of cyclic AMP metabolism accurately reflect the changes in cyclic AMP concentration as a function of cell population density. The data indicate that these two enzyme activities respond to increasing cell density to elicit a rise in intracellular cyclic AMP levels. The elevated cyclic AMP levels are thought to be involved in the regulation of cellular growth rate and the mediation of contact inhibition of growth.


Regulation of cyclic nucleotide concentrations in photoreceptors: an ATP-dependent stimulation of cyclic nucleotide phosphodiesterase by light. Regulation of cyclic nucleotide concentrations in rod outer segments (Rana pipiens) has been further examined. The present studies show that illumination markedly diminishes the concentration of cyclic nucleotides in suspensions of photoreceptor membranes, but the locus of regulation is cyclic nucleotide phosphodiesterase (EC 3.1.4.c) (light-stimulated) and not adenylate cyclase. There is a marked disproportionality between bleaching of rhodopsin and stimulation of phosphodiesterase. Bleaching only 0.6% of the rhodopsin produces half the stimulation produced by bleaching 100% of the rhodopsin. The process of activation of phosphodiesterase by light is in two steps, a light-dependent step followed by an ATP-dependent step. Illumination (in the absence of ATP) produces a trypsin-resistant, heat-labile, macromolecular stimulator. In the presence of 0.75 mM ATP (GTP or ITP) this stimulator produces a greater than 5-fold increases in the V(max) of photoreceptor phosphodiesterase without changing the K(m). At physiological substrate concentrations (10(-7) M) the rate of hydrolysis of cyclic GMP is 23 times greater than that of cyclic AMP. The light-produced stimulator appears unique to the photoreceptor membranes and does not activate phosphodiesterase in other tissues.


Phosphorylation of 5-bromodeoxycytidine in cells infected with herpes simplex virus. 5-Bromodeoxycytidine is phosphorylated to 5-bromodeoxycytidine 5'-monophosphate in extracts of cells infected with herpes simplex virus but not in extracts of uninfected cells. The conversion of 5-bromodeoxycytidine to nucleotides and its utilization for DNA synthesis in uninfected cells occurs by deamination of 5-bromodeoxycytidine to 5-bromodeoxyuridine followed by phosphorylation of 5-bromodeoxyuridine to 5-bromodeoxyuridine 5'-monophosphate. In contrast, in cells infected with herpes simplex virus, 5-bromodeoxycytidine is phosphorylated directly to 5-bromodeoxycytidine 5'-monophosphate, which can then be deaminated to 5-bromodeoxyuridine 5'-monophosphate and incorporated into DNA. These results indicate a difference in the substrate specificity of nucleoside kinases induced by herpes simplex virus and the enzymes present in uninfected cells. It is suggested that this difference in substrate specificity between virus-induced and host-cell enzymes may allow selective chemotherapy of herpes simplex infections with 5-bromo- or 5-iododeoxycytidine.


Effects of bradykinin and indomethacin on cyclic GMP and cyclic AMP in lung slices. Bradykinin, 1-100 mug/ml, produced a rapid rise in the concentration of 3':5'-guanosine monophosphate (cyclic GMP) and 3':5'-adenosine monophosphate (cyclic AMP) in slices of guinea pig lung. Concentrations of both nucleotides reached a maximum in about 2 min, then declined to a basal levels in 6-12 min. The transient nature of the effect was presumbaly due to the rapid destruction of bradykinin as evidenced by (1) reaccumulation of nucleotides when bradykinin was added a second time, and (2) potentiation of the bradykinin effects by pyroGlu-Lys-Trp-Ala-Pro, a peptide that inhibits inactivation of bradykinin by kininase. It has been reported elsewhere that histamine, prostaglandins E(1) and E(2), and beta-adrenergic stimulation can cause accumulation of cyclic AMP in lung slices without affecting cyclic GMP concentration, whereas acetylcholine increases the concentrations of both cyclic GMP and cyclic AMP. Thus it was possible that the effects of bradykinin were indirect, i.e., secondary to release of one or more of these compounds. Promethazine (an antihistamine), propranolol (a beta-adrenergic blocking agent) and atropine (an anticholinergic agent) did not alter basal cyclic nucleotide concentrations or the effects of bradykinin. Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, which alone were without effect, in the presence of bradykinin completely prevented the rise in cyclic AMP but did not interfere with cyclic GMP accumulation. Similarly, the effect of acetylcholine on cyclic AMP was abolished by indomethacin while that on cyclic GMP was unaltered. We suggest that in lung and probably in other tissues, bradykinin, acetylcholine, and perhaps other stimuli enhance the synthesis and release of prostaglandins as one of the consequences of their effects on cyclic GMP metabolism.


The importance of calcium ions for the regulation of guanosine 3':5'-cyclic monophosphage levels. Guanosine 3':5'-cyclic monosphosphate (cyclic GMP) levels in the ductus deferens of the rat were increased 2- to 3-fold by acetylcholine (10-1000 muM) or by 125 mM KCl, while adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were not changed. After incubation for 30 min in the absence of Ca(++), cyclic GMP control levels were decreased by 85% and were not affected by acetylcholine or KCl. The readdition of Ca(++) (1.8 mM) for 3 min to Ca(++)-deprived tissue partially restored basal cyclic GMP levels and the effects of acetylcholine and KCl. The addition of Sr(++) (3.6 mM) or of Ba(++) (1.8 or 10 mM) also caused an increase in basal cyclic GMP in Ca(++)-deprived tissue. Cyclic AMP levels were not significantly changed under any of these conditions. The addition of the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (0.1 mM), to ductus deferentes increased the amount of cyclic AMP about 50% and that of cyclic GMP about 2-fold. The later effect also depended on the presence of Ca(++). 1-Methyl-3-isobutylxanthine (0.1 mM) increased cyclic GMP and cyclic AMP levels in slices of rat submaxillary glands. Methacholine increased cyclic GMP if added in the presence of methyl isobutylxanthine. Cyclic GMP control levels and the effect of methyl isobutylxanthine were unchanged by Ca(++) omission, but the effect of methacholine was abolished.These findings indicate that calcium ions are important for the control of cyclic GMP levels in these tissues.


Properties of the beta nerve growth factor receptor of avian dorsal root ganglia. Iodination of the beta nerve growth factor protein up to 4.1 iodines per mole of nerve growth factor was achieved with no loss of biological activity. At this level of incorporation no native or monoiodo nerve growth factor remained, the major species being the tri- and tetraiodo derivatives. An (125)I-labeled beta nerve growth factor of high specific activity containing 0.5 iodine per mole of beta nerve growth factor was used to determine the specific binding of nerve growth factor to dorsal root ganglion cells of 8-day-old embryonic chicks. The specific binding of (125)I-labeled nerve growth factor reached saturation at 30-50 ng/ml and half-saturation at 7-8 ng/ml (0.26 nM). The number of receptors per responsive medio-dorsal cell was calculated to be about 2 x 10(4). The pattern of displacement of bound (125)I-labeled beta nerve growth factor by native beta nerve growth factor showed that the two proteins had identical affinities for the receptor. The specificity of the binding for beta nerve growth factor was demonstrated by the fact that only native beta nerve growth factor displaced the bound (125)I-labeled form. Partially inactivated derivatives of beta nerve growth factor retained the same fraction of their specific-binding capacity as of their biological activity. The specificity of the binding for cell type was shown by the lack of any specific component of (125)I-labeled beta nerve growth factor binding to liver or brain cells. The rate constant for association of beta nerve growth factor with its receptor, k(1), was 1.0 x 10(7) mol(-1) sec(-1) and the rate constant for dissociation, k(-1), 1.2 x 10(-8) sec(-1).


Ultrastructure of herpes simplex virus infection of the nervous system of mice.


Recurrent control from motor axon collaterals of Ia inhibitory pathways to ventral spinocerebellar tract neurones.


Nerve biopsy findings in two cases of Tangier disease.


Parallelism between mechanical and metabolic responses to cholecystokinin and prostaglandin E2 in extrahepatic biliary tract.


An introductory note to ginseng.

An introductory note to ginseng.


Experimental and clinical oncology in People's Republic of China.


Endocrine dysfunction and anencephaly and spina bifida: an epidemiologic hypothesis.


Anticancer Chinese herbal medicines.

Anticancer Chinese herbal medicines.


Effect of angiotensin II and its nonpressor derivatives on renin secretion.


Rhinovirus infections in an industrial population. V. Change in distribution of serotypes.


Effect of prostaglandins on renin reactivity.


Angiotensin interaction with thirst mechanisms.


Reticuloendotheliosis in a duck.

Reticuloendotheliosis in a duck.


Sympathetic cardiac stimulation in Bufo marinus under MS-222 anesthesia.


Mechanism of action of a microsomal inhibitor of protein synthesis potentiated by oxidized glutathione. Extracts of microsomal fractions cause an inhibition of protein synthesis that is most pronounced in the presence of 0.1mm-GSSG and 0.01mm-GTP, and is abolished by thiol or 0.4mm-GTP (Scornik et al., 1967). Fractionation of microsomal extracts showed that this inhibition of protein synthesis was caused by an enzyme, nucleoside diphosphate phosphohydrolase. Direct inhibition of protein synthesis on detergent-treated polyribosomes by 0.1mm-GSSG was observed under conditions of GTP limitation induced by omission of a GTP-regenerating system, or addition of a nucleoside triphosphate diphosphohydrolase. Thus GSSG potentiated the inhibition of protein synthesis caused by an enzyme that promoted removal of GTP. The inhibition was abolished by adding 4mm-2-mercaptoethanol or 0.4mm-GTP. Nucleoside diphosphate phosphohydrolase was thought also to act by promoting removal of GTP, thus causing an inhibition of protein synthesis that was potentiated by GSSG.


Cross sensitivity to mono- and bifunctional alkylating agents of three radiation-sensitive Saccharomyces mutants.


The effects of cytoplasmic extracts on DNA synthesis in vitro.


Effects of storage conditons on survival and free radical populations in dried irradiated spores of Osmunda regalis.


Activation of volatile fatty acids in bovine liver and rumen epithelium. Evidence for control by autoregulation. 1. The total capacities of homogenates of bovine liver and rumen epithelium to activate acetate, propionate and butyrate were determined. 2. Activating capacities were assayed by measuring the rate of formation of the corresponding CoA esters. The methods used for determining the concentrations of the CoA esters allowed the CoA esters of acetate, propionate and butyrate to be distinguished. It was thus possible to investigate the effect of the presence of a second volatile fatty acid on the rate at which a given volatile fatty acid was activated. 3. The propionate-activating capacity in rumen epithelium was decreased by about 87% in the presence of butyrate, the acetate-activating capacity in liver was decreased by about 55% in the presence of either propionate or butyrate, and the butyrate-activating capacity in liver was decreased by about 40-50% in the presence of propionate. 4. All three activating capacities in liver appeared to be located in the mitochondrial matrix and membrane. The three activating capacities had similar locations to each other in rumen epithelium as well, although in this case activity was more evenly divided between the mitochondria and the cytoplasm. 5. The relative activating capacities towards the volatile fatty acids in the two tissues, together with the ability of one volatile fatty acid to inhibit the activation of another volatile fatty acid, appear to ensure that butyrate is mainly metabolized in the rumen epithelium and that propionate is metabolized in the liver.


The metabolism of biological alkylating agents.


Isolation of temperature sensitive mammalian cells by selective detachment.


A temperature-sensitive function in a Chinese hamster line affecting DNA synthesis.


Newer knowledge of chemotherapy in the treatment of tuberculosis of bones and joints.


The importance of the techniques employed during the enzymatic preparation of isolated liver parenchymal cells.


Changes in membrane transport function in G0 and G1 cells.


Origin of esterified cholesterol transported in the very low density lipoproteins of human plasma. In two subjects the specific activity of esterified cholesterol in plasma lipoprotein subfractions was measured for up to 9 hr after an intravenous injection of [(3)H]mevalonic acid. It was found to be consistently higher in larger (S(f) > 100) than in smaller (S(f) 20-100) very low density lipoproteins (VLDL). Four subjects were given an intravenous injection of heparin so that the VLDL could be studied as its concentration fell and subsequently rose again. During the first hour the relative reduction was greatest for triglyceride, intermediate for free cholesterol, and least for esterified cholesterol. Between 1 and 7 hr postheparin, the VLDL pool was restored, but the pattern of increase of individual lipids was not parallel. The triglyceride increment was much greater during the 1-4-hr period than during the 4-7-hr period; in three of the subjects the free cholesterol increment was also greater during the earlier period. The increase in esterified cholesterol, however, was consistently greater during the 4-7-hr period. In six other subjects the specific activity of VLDL esterified cholesterol was related to that of its possible plasma precursors in samples collected at 1-hr intervals for 8 hr after the injection of [(3)H]mevalonic acid. Free cholesterol emerged as the most likely immediate precursor with the possibility of a hepatic as well as an intraplasma origin. The results did not support a major in vivo transfer of esterified cholesterol from high density lipoproteins to VLDL.


Deoxyglucose transport of uninfected, murine sarcoma virus-transformed, and murine leukemia virus-infected mouse cells.


Application of electron spin resonance in research on mineralized tissues.


Metabolism of sulfoquinovosyl diglyceride in Chlorella pyrenoidosa by sulfoquinovosyl monoglyceride: fatty acyl CoA acyltransferase and sulfoquinovosyl glyceride: fatty acyl ester hydrolase pathways. Cell-free preparations of Chlorella pyrenoidosa catalyze the transfer of the fatty acyl moiety of fatty acyl CoA derivatives to sulfoquinovosyl monoglyceride to form sulfoquinovosyl diglyceride. This reaction is stimulated by Triton X-100 concentrations of up to 0.6 mg/ml and has a pH optimum of 7.7. Similar Chlorella preparations catalyze the stepwise removal of both fatty acyl groups from sulfoquinovosyl diglyceride to form sulfoquinovosyl monoglyceride and then sulfoquinovosyl glycerol. This reaction is inhibited by both calcium and magnesium. The nonionic surfactant Triton X-100 inhibits the enzymatic deacylation at concentrations of less than 0.5 mg/ml but stimulates it at higher concentrations. The pH optimum for the deacylation of sulfoquinovosyl glycerides is 8.2, with little activity observed below pH 8. The enzymatic activities for both the transacylation and deacylation reactions are associated with a 30,000 g particulate fraction of Chlorella. Sulfoquinovosyl glycerol was found not to be an acceptor of the fatty acyl moiety of fatty acyl CoA derivatives. Methods are described for the preparation of sulfoquinovosyl monoglyceride, sulfoquinovose, and 3-sulfo-1,2-propanediol.


Studies of glucagon resistance in large rat adipocytes: 125I-labeled glucagon binding and lipolytic capacity. This study is concerned with potential modifications of large fat cells from adult rats (400-450 g) that make them resistant to stimulation by glucagon. The lipolytic capacity and (125)I-labeled glucagon-binding capability of these cells were compared with these properties of small glucagon-sensitive cells from young rats (130-160 g). As determined by maximal stimulation with theophylline, dibutyryl cAMP, or epinephrine, the lipolytic capacity of large cells was not markedly different from small cells, which suggests that an alteration contributing to glucagon insensitivity is not present in the enzymes involved with hormone-mediated lipolysis. Glucagon-binding studies did indicate a difference between the two cell types. Both large cells and particulate fractions from large cells bound less (125)I-labeled glucagon than small cells or small-cell particles. That diminished binding is not a consequence of glucagon degradation is indicated by the similar amounts of (125)I-labeled glucagon degraded by both cell types. The decrease in (125)I-labeled glucagon binding was not as marked as the decrease in lipolytic response to glucagon stimulation. This lack of correlation and the relationship between elevated phosphodiesterase levels and glucagon insensitivity described in the accompanying report suggest that diminished binding explains only in part the marked resistance to glucagon found in large cells.