The heterogeneous distribution of acid hydrolases within a homogeneous population of cultured mammalian cells. 1. Chinese-hamster ovary fibroblasts were cultured to provide a homogeneous cell population. Homogenates obtained from these cells were fractionated by centrifugation techniques and the resulting fractions were analysed for protein and for enzymes representative of certain subcellular particles. 2. Unlike those in rat liver homogenates, the mitochondrial and lysosomal populations proved impossible to separate by differential centrifugation owing to the similarity of their sedimentation properties. Their resolution was possible by using isopycnic centrifugation in a continuous sucrose density gradient. 3. The mitochondrial population equilibrated at a density of 1.17g.cm(-3) as in rat liver homogenates. However, the lysosomal population equilibrated at a lower rather than a higher density position than the mitochondria and the probable reasons for this are discussed. 4. The lysosomal population subdivided into two groups characterized by differences in acid hydrolase content and equilibrium densities. The fraction with a density of 1.15g.cm(-3) contained the majority of arylsulphatases A and B, of cathepsin and of beta-acetylglucosaminidase activities, whereas that with a density of 1.09g.cm(-3) contained the majority of the acid phosphatase and acid ribonuclease activities. The probable division of the lysosomal population of a single cell into a number of distinguishable subgroups is suggested.


The effects of calcium ions on the activities of trehalase, hexokinase, phosphofructokinase, fructose diphosphatase and pyruvate kinase from various muscles. 1. The effects of Ca(2+) on the activities and regulatory properties of trehalase, hexokinase, phosphofructokinase, fructose diphosphatase and pyruvate kinase from vertebrate red and white muscle and insect fibrillar and non-fibrillar muscle have been investigated. These muscles were selected because of the possible difference in the role of glycolysis in energy production in the vertebrate muscles, and the possible difference in the role of Ca(2+) in the control of contraction in the two types of insect muscle. An increase in Ca(2+) concentration from 0.001mum to 10mum did not modify the activities nor did it modify the regulatory properties of these enzymes from these various muscles. 2. Concentrations of Ca(2+) above 0.1mm inhibited the activities of hexokinase and phosphofructokinase from the different muscles. It has been suggested that this inhibition may provide the basis for a theory of regulation of glycolysis (Margreth et al., 1967). If phosphofructokinase is located within the sarcoplasmic reticulum, its activity will be inhibited when the muscle is at rest, but the release of Ca(2+) from the reticulum during contraction will lead to a stimulation of its activity and hence an increase in glycolytic flux. The distribution of hexokinase and phosphofructokinase in the various cell fractions of these muscles was very variable. In particular, both enzymes were present almost exclusively in the 100000g supernatant fraction in the extracts of insect flight muscles. Thus there is no correlation between the properties of the enzymes and their distribution in muscle. 3. It is concluded that Ca(2+) does not control the activities of the important regulatory enzymes of glycolysis in muscle. It is suggested that in some muscles the sensitivity of the control mechanism at the level of phosphofructokinase to changes in the concentration of AMP may be increased by a process known as ;substrate-cycling'.


Changes in enzyme activities and distributions during glucose de-repression and respiratory adaptation of anaerobically grown Saccharomyces carlsbergensis. 1. During anaerobic glucose de-repression the respiration rate of whole cells of Saccharomyces carlsbergensis remained constant and was insensitive to antimycin A but was inhibited by 30% by KCN. Aeration of cells for 1 h led to increased respiration rate which was inhibited by 80% by antimycin A or KCN. 2. Homogenates were prepared from sphaeroplasts of anaerobically grown, glucose de-repressed cells and the distribution of marker enzymes was investigated after zonal centrifugation on sucrose gradients containing MgCl(2). These homogenates contained no detectable cytochrome c oxidase or catalase activity. The complex density distributions of NADH- and NADPH-cytochrome c oxidoreductases and adenosine triphosphatase(s) [ATPase(s)] were very different from those of anaerobically grown, glucose-repressed cells. 3. The specific activity of total ATPase was lowered and sensitivity to oligomycin decreased from 58 to 7% during de-repression. 4. Cytochrome c oxidase and catalase activities were detectable in homogenates of cells after 10min aeration. Zonal centrifugation indicated complex, broad sedimentable distributions of all enzyme activities assayed; the peaks of activity were at 1.27g/ml. 5. Centrifugation of homogenates of cells adapted for 30min and 3 h indicated a shift of density of the major sedimentable peak from 1.25g/ml (30min) to 1.235g/ml (3 h). After 30min adaptation a minor zone of oligomycin-sensitive ATPase and 15% of the total cytochrome c oxidase activities were detected at rho=1.12g/l; these particles together with those of higher density containing cytochrome c oxidase, ATPase and NADH-cytochrome c oxidoreductase activities were all sedimented at 10(5)g-min. 6. Electron microscopy indicated that the mitochondria-like structures of anaerobically grown, glucose-de-repressed cells were similar to those of repressed cells. After 10min of respiratory adaptation highly organized mitochondria were evident which resembled the condensed forms of mitochondria of aerobically grown, glucose-de-repressed cells. High-density zonal fractions of homogenates of cells after adaptation also contained numerous electron-dense vesicles 0.05-0.2mum in diameter. 7. The possibility that the ;promitochondria' of anaerobically grown cells may not be the direct structural precursors of fully functional mitochondria is discussed.


Developmental changes in microheterogeneity of foetal plasma glycoproteins of mice. Changes in microheterogeneity of foetal plasma glycoproteins during development of mouse embryos were investigated. Analysis of foetal plasma by polyacrylamide-gel electrophoresis indicated three major zones of proteins: (1) transferrins, (2) alpha-foetoproteins and (3) albumin. Three transferrins (Tr1, Tr2, Tr3) and five alpha-foetoproteins (Fp1, Fp2, Fp3, Fp4, Fp5) were resolved. Evidence for the presence of transferrins was the binding of (59)Fe to the three electrophoretic variants. By day 15.5 of gestation, there was a marked increase in the more-acidic components (Tr3, Fp4, Fp5) and a decrease in the less-acidic ones (Tr1, Tr2, Fp1, Fp2, Fp3). Treatment of foetal plasma with neuraminidase at this time of development converted the more acidic components into Tr1 and Tr2 and Fp1, Fp2 and Fp3. Furthermore, it was shown that early in development (day 12.5) only the less-acidic components of transferrin and alpha-foetoprotein were synthesized; at the later time in development (day 14.5) new synthesis of the acidic components of both groups occurred. That these more-acidic components of alpha-foetoprotein (Fp4, Fp5) were in fact electrophoretic variants of the less-acidic alpha-foetoproteins was shown by the immunoprecipitation of labelled Fp4 and Fp5 with anti-Fp1, anti-Fp2 and anti-Fp3. From these results it is postulated that the plasma glycoproteins that are synthesized later in development contain increased amounts of sialic acid and that the observed changes in microheterogeneity of these proteins represent regulation of glycoprotein biosynthesis at the level of carbohydrate attachment.


Pencillin amidase production by Bacillus megaterium.


Phosphorylation of high-molecular-weight membrane protein species in Chinese-hamster ovary cells in culture: effect of 6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate plus testosterone. Growth of Chinese-hamster ovary cells in [(32)P]phosphate and [(3)H]leucine and subsequent assay of the plasma membranes reveals phosphorylation in two protein regions corresponding to molecular weights of 280000 and 195000. Culture in the presence of the 6-N,2-O'-dibutyryl derivative of cyclic AMP plus testosterone does not stimulate [(32)P]-phosphate incorporation, but determines a modification in the qualitative pattern of phosphorylation.


Phospholipase-C from Bacillus cereus: production, purification, and properties.


Detection of circulating hepatoma D23 antigen and immune complexes in tumour bearer serum. Serum from rats bearing progressively growing aminoazo dye-induced rat hepatomata has been fractionated by Sephadex G150 gel filtration chromatography and isolated fractions have been examined by indirect membrane immunofluorescence techniques to detect tumour specific antigen and antibody. Hepatoma D23-specific antigenic activity was associated with material (of approximate molecular weight <150,000) isolated in the included volume of the gel at pH 7·3. The fraction excluded from the gel (of approximate molecular weight >150,000) was adjusted to pH 3·0 and further separated by Sephadex G150 gel filtration chromatography at pH 3·0 into gel included and excluded fractions. Hepatoma D23 specific antibody, demonstrable by membrane immunofluorescence staining of hepatoma D23 cells, was found to be eluted in the excluded volume and specific antigenic activity was retarded into the included volume of the gel. These results indicate that hepatoma D23 bearer serum contains free circulating tumour specific antigen in excess, together with specific immune complexes. The presence of these factors in tumour bearer serum is discussed in terms of "blocking" phenomena whereby serum factors may protect tumour cells from sensitized lymphocyte cytotoxic attack.


Mammary tumour and hepatoma suppression by dietary restriction in C3H Avy mice.


A new model for inducing malignant ovarian tumours in rats. After the implantation of ovarian tissue into the spleen of gonadectomized female Sprague-Dawley rats (splenic ovary), luteomata and later benign granulosa or granulosa-theca cell tumours develop. Treatment of these rats with 7,12 dimethylbenz(a)anthracene (DMBA), given intravenously, 2 mg/kg body weight weekly, total dosage 40 mg/kg, immediately and especially 25 weeks after implantation of ovarian tissue into the spleen, led to malignant, partially metastasizing granulosa, and in one case theca cell tumours, 16-46 weeks after beginning the carcinogen treatment. No malignant neoplastic growth was seen when diethylnitrosamine (DEN), 20 mg/kg once weekly for life, was injected subcutaneously immediately or 25 weeks after implanting ovarian tissue.Since the normal, non-implanted rat ovary was not affected by DMBA treatment the malignant transformation of splenic ovaries in the respective experimental groups may be related to the increased stimulation by pituitary gonadotrophins and formation of luteomata or beginning granulosa and theca cell proliferations.


Enzyme activated alkylating agents.

Enzyme activated alkylating agents.


Possible viral aetiology of human breast cancer.


Cyclic AMP and adenyl cyclase in the developing rat brain.


Two types of response patterns from cat retinal ganglion cells to moving stimuli.


Cyclic 3',5'-adenosine monophosphate in Tetrahymena pyriformis.


The effect of semicarbazide pretreatment on the depressant action of barbiturates.


Toxicity of polychlorinated biphenyls increased with simultaneous ingestion of alkylbenzene sulfonic acid salt.


In vitro corticosteroidogenesis by the adrenal gland of the chicken (Gallus domesticus).


A comparison of dream content in laboratory dream reports of schizophrenic and depressive patient groups.


A psychophysiological study of nightmares and night terrors. I. Physiological aspects of the stage 4 night terror.


Five classes of visual interneurons in the optic nerve of the hermit crab.


Restorative effects of cyclic AMP on complex bioelectric activities of cultured fetal rodent CNS tissues after acute CA++ deprivation.


Chemosensitivity of mouse neuroblastoma cells in vitro.


Melanotic medulloblastoma of the cerebellum.


How is the H-reflex modulated during rapid eye movement (REM) sleep?


Studies on bovine para-influenza (type-3) virus.


Determination of the frequency response of isometric soleus muscle in the cat using random nerve stimulation. 1. The frequency response of isometric soleus muscle was determined efficiently by analysis of the unfused tension generated during short periods of random stimulation of the divided ventral roots, in anaesthetized cats.2. Despite the complexities of skeletal muscle, the frequency response of soleus, at moderate lengths and stimulation rates in the physiological range, is closely approximated by the frequency response function for a simple, linear, second-order system near critical damping.3. The soleus muscle shows a uniformly high sensitivity to fluctuations in nerve activity over a range of frequencies similar to the range of frequencies of muscular activity observable during behaviour. The nerve-muscle preparation appears to be well suited for smooth and steady motor activity, since it is much less responsive to the higher frequency components contained in individual action potentials or generated in tremor.4. The second-order parameters: low-frequency gain, natural frequency and damping ratio provide useful descriptions of the changes in the muscle's response caused by variations of muscle length, nerve stimulation rate or number of active motor units.5. A reduction in tension incurred, for example, during fatigue can be compensated to some extent either by a lengthening of the loaded muscle or through an increase in neural spike repetition rate. However, both mechanisms produce concomitant increases in the ;sluggishness' (increased damping and lower natural frequency) of the preparation. This sluggishness may arise out of limitations imposed by the mechanism for the re-uptake of calcium into the sarcotubular system.6. One naturally occurring method of increasing tension, by recruitment of more active motoneurones, seems to be desirable because tension can be augmented in this way without an increase in sluggishness. This is presumably because recruitment increases the muscle's response without affecting excitation-contraction coupling in fibres already active.


Superinfection of simian virus 40 transformed human cells with human adenovirus.


Determining the biological age of the preschool child from a hand-wrist radiograph.


Characteristic behaviour of the cocultures of the SV40 transformed rabbit kidney cells and African green monkey kidney cells.


Experimental studies of peribronchography.


Glomerulonephritis associated with immune complex deposits and viral particles in spontaneous murine leukemia. An electron microscopic study with immunofluorescence.


Ultrastructure of parathyroid glands and plasma immunoreactive parathyroid hormone in pregnant cows fed normal and high calcium diets.


Sulfaguanidine protection of mouse liver from carbon tetrachloride-induced necrosis.


The effect of vincristine on the calcium transport and phospholipid composition of rat skeletal muscle microsomes.


Ultrastructural study of cytochrome oxidase in oncocytoma.


Polypeptide specific for cells with adenovirus 2-SV40 hybrid Ad2+ND1.


Altered metabolism and endogenous cyclic AMP in cultured cells deficient in cyclic AMP-binding proteins.


Identification of two distinct species of procollagen synthesized by a clonal line of calf dermatosparactic cells.


Localization of rat liver alpha-foetoprotein by cell affinity labelling with tritiated oestrogens.


Tumor lipids.

Tumor lipids.


Cyclic 3',5'-adenosine monophosphate in the rat gastric mucosa after starvation, feeding, and pentagastrin.


MHPG excretion in depressive disorders: relation to clinical subtypes and desynchronized sleep. The urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was significantly lower in patients with manic-depressive depressions than in patients with chronic characterological depressions. There was an inverse relationship between MHPG excretion and the amount of time spent in desynchronized sleep, particularly in the manic-depressive disorders. Excretion of MHPG was not related to the degree of retardation, agitation, or anxiety in these patients.


Intracellular receptors for 5alpha-dihydrostestosterone in the epididymis of adult rats. Comparison with the androgenic receptors in the ventral prostate and the androgen binding protein (ABP) in the testicular and epididymal fluid.


The metabolism of estriol in rabbits.

The metabolism of estriol in rabbits.


Retro-steroids. I. Metabolism of the progestogen 6-chloro-9 , 10 -pregna-1,4,6-triene-3,20-dione in man.


Progesterone binding in the immature mouse and rat uterus.


Primary brain tumors: tumor immunity and immunocompetence.


Granular cell myoblastomas of the pituitary region.


Serological evidence for CELO virus infection in chickens and turkeys in Denmark.


Study of Japanese encephalitis virus in Chiangmai Valley, Thailand. I. Introduction and study design.


Study of Japanese encephalitis virus in Chiangmai valley, Thailand. II. Human clinical infections.


Study of Japanese encephalitis virus in Chiangmai Valley, Thailand. 3. Human seroepidemiology and inapparent infections.


Epidemiology of sudden infant death syndrome and lower respiratory tract disease in young children: a comparison.


Epidemiology of respiratory syncytial virus infection among infants and children in Chicago.


The therapeutic tumult and the ophthalmologist. 35th De Schweinitz lecture.


The effect of ophthalmic ointments on corneal wound healing.


Cyclomegalovirus retinitis.

Cyclomegalovirus retinitis.


Isolation and characterization of a rough microsomal fraction from rat kidney that is enriched in lysosomal enzymes. 1. A special population of rough microsomal material (microsomes) rich in lysosomal acid hydrolases was separated by isopycnic centrifugation as a discrete fraction (RM(2)) from the bulk of rough microsomal material in rat kidney because of its greater density. 2. The specific activities of five acid hydrolases in the RM(2) fraction were approximately one-half those of a purified lysosomal (L) fraction and 10- to 30-fold greater than those of an ordinary rough microsomal (RM(1)) fraction. 3. These special rough microsomes have a distinctive ultrastructure and electron-cytochemical properties. Their cisternal content resembles the matrix of lysosomes in that it is electron-dense, osmiophilic and plumbophilic and gives a positive reaction for acid phosphatase activity. 4. Polyacrylamide-gel electrophoresis of soluble proteins from the L fraction resolved nine anionic glycoproteins, most of which exhibit acid hydrolase activities (Goldstone & Koenig, 1970, 1973; Goldstone et al., 1971a). The most anionic glycoprotein is the acidic lipoglycoprotein of the lysosomal matrix (Goldstone et al., 1970). 5. Polyacrylamide-gel electrophoresis of soluble proteins from the RM(2) fraction resolved two cationic glycoproteins with acid hydrolase activities (Goldstone & Koenig, 1973) and an anionic glycoprotein with the same electrophoretic mobility as the lysosomal lipoglycoprotein, but without its lipid constituents or capacity to bind the basic fluorochrome Acridine Orange. These constituents are considered to be the precursors of the lysosomal glycoproteins.


Studies of nuclei separated by zonal centrifugation from liver of rats treated with thioacetamide. 1. The effects of the inclusion of thioacetamide in the diet on the properties of rat liver nuclei were studied both in adolescent rats, in which the parenchymal cells contain diploid nuclei, and in young adult rats, with a high proportion of tetraploid nuclei. 2. These investigations included a survey of the sedimentation properties of the nuclei, the nuclear volumes, content of DNA, RNA and protein, the incorporation in vivo of [(3)H]thymidine into DNA and [(14)C]orotate into RNA, and measurements of the activity of RNA polymerase and ribonuclease. These studies were conducted on nuclei fractionated by zonal centrifugation. 3. In both groups of animals, exposure to thioacetamide produced large numbers of nuclei that were abnormal in their chemical composition and enzymic activity. The changes were complex as regards both the types of nuclei that were affected and in their variation with time. 4. In adolescent rats two waves of synthesis of DNA and RNA were observed, one at 3 days and the other after 2 weeks of treatment. The first decline in the incorporations into both DNA and RNA coincided with a decrease in the pool sizes of some of the precursors. The activity of RNA polymerase was not substantially altered. A marked increase in the content of protein was observed before the first wave of synthesis. The normal progressive increase in tetraploid nuclei was prevented. 5. In young adult rats two waves of DNA synthesis were detected. Each was preceded by a large increase in the amount of protein per nucleus but was not accompanied by increased RNA synthesis. After 4 weeks of treatment, the diploid stromal nuclei appeared mainly unaffected and large numbers of tetraploid nuclei with a greatly increased quantity of protein were observed.


Adrenal microsomal C19-steroid 5alpha-reductase activity in the Snell transplantable rat adrenocortical tumour 494 and the effect of oestradiol, testosterone propionate and adrenocorticotrophin in intact and gonadectomized rats. The C(19)-steroid 5alpha-reductase activity in the microsomal fraction of rat adrenal tissue under various hormonal treatments was examined. In intact control rats the activity is similar in both males and females, and after gonadectomy it is markedly increased. Treatment with oestradiol (150mug/day per animal for 7 days) or testosterone propionate (2mg/day per animal for 7 days) lowered the activity of 5alpha-reductase in castrated animals to approximately the values for intact animals in both sexes, and in intact animals the activity was also decreased by these treatments. The enzyme activity was also decreased by adrenocorticotrophin treatment but to a lesser extent than by the steroid hormones. The activity of the 5alpha-reductase enzyme in the Snell adrenocortical tumour 494 is very low when incubated as a whole homogenate, but the activity in microsomal material of the tumour was measured and unexpectedly found to be similar to that in intact controls.


Control of ovarian cholesterol ester biosynthesis. 1. Experimental evidence is presented for a role of progesterone and 20alpha-hydroxypregn-4-en-3-one as inhibitors of cholesterol ester synthetase in the acute depletion of ovarian cholesterol ester after trophic stimulation. 2. Luteinizing hormone in vitro decreased by 84% the rate of esterification of cholesterol with added [(14)C]oleate by slices of rabbit ovarian interstitial tissue; this effect was mimicked by cyclic AMP (adenosine 3':5'-cyclic monophosphate) in vitro, and occurred without large changes in precursor pool sizes or membrane permeability. 3. Cyclic AMP was shown to have no direct effect on cholesterol ester synthetase or cholesterol esterase in cell-free extracts of rabbit ovarian interstitial tissue, but decreased the activity of cholesterol ester synthetase (not that of cholesterol esterase) in extracts prepared from slices previously incubated with it. 4. The inhibitory effect of cyclic AMP on esterification of cholesterol with added [(14)C]-oleate was prevented by both cycloheximide and aminoglutethimide phosphate (which also inhibited steroid synthesis in response to cyclic AMP). 5. Cyclic AMP raised the intracellular concentrations of progesterone and 20alpha-hydroxypregn-4-en-3-one in incubated slices by factors of 2.8 and 3.9 respectively. 6. Cycloheximide and aminoglutethimide phosphate administered in vivo blocked cholesterol ester depletion in response to luteinizing hormone in rats; in these ovaries cycloheximide and aminoglutethimide phosphate decreased the concentrations of progesterone and 20alpha-hydroxypregn-4-en-3-one and luteinizing hormone raised them. 7. Progesterone and 20alpha-hydroxypregn-4-en-3-one added to cell-free extracts of rabbit ovarian interstitial tissue in vitro (at concentrations comparable with those found in incubated slices) inhibited cholesterol ester synthetase by up to 85%. 8. The results are discussed with reference to the acute control of cholesterol ester concentrations in the ovary and adrenal cortex.


Hepatic lipid droplets. Isolation, morphology and composition. The floating lipid layer isolated centrifugation of rat liver was examined for composition and ultrastructure. It was chiefly composed of triglycerides and cholesterol esters plus much smaller amounts of free cholesterol, diglycerides, phospholipid and protein. No free fatty acids were detected. The triglyceride and cholesterol ester fractions consisted mostly of esters of linoleic acid, oleic acid and palmitic acid. Electron micrographs of the floating lipid layer revealed numerous spherical osmiophilic droplets having a mean diameter of 0.5-2mum with a very-thin dense outer coat. Similar structures were observed as organelles in electron micrographs of the intact liver cell. The amount of triglyceride in the layer decreased in rats starved for 72h, but pellet triglyceride (homogenate minus the floating lipid layer) was unchanged. These results suggest that the floating lipid layer is the representative in vitro of lipid-rich organelles which probably function as a depot form of hepatic-cell neutral lipid.


The effects of selective interruption and deprivation of sleep in the human newborn.


Hypothyroidism and the maturation of the hypothalamo-hypophyseal-adrenal axis.


The effect of phentolamine on adenylate cyclase and on isoproterenol stimulation in leukocytes from asthmatic and nonasthmatic subjects.


An epizootic of malignant catarrhal fever in feedlot cattle.


Evidence of bovine C-type (leukemia) virus in dairy cattle.


Incidence of Clostridium perfringens in dehydrated soup, gravy, and spaghetti mixes.


Renal hamartomas and nephroblastomatosis with fetal gigantism: a familial syndrome.


Varicella reactivation in nephrotic syndrome treated with cyclophosphamide and adrenal corticosteroids.


Complete analysis of levodopa capsules and tablets by GLC.


Peripheral neuropathy secondary to isoniazid-induced pyridoxine deficiency.


Some clinical aspects of non traumatic mechanical lesions of peripheral nerves. Analysis of 3465 personal cases.


Attempts to propagate human tumor explants in mice inoculated with human thymus antiserum.


An examination of two bovine respiratory disease vaccines.


Carbohydrate metabolism in the rat uterus during early pregnancy.


Modification of metabolic effects of ethanol by fructose.


Spectroscopic methods in biology, with application to neurophysiology.


Metabolism of fructose in liver.

Metabolism of fructose in liver.


Compressive behaviour of a physiological tissue.


Filamentous forms of enveloped A particles in cell cultures from chemically induced rat hepatomas.


The effects of protein on lipid organization in a model membrane system: a spin probe and x-ray study.


3-(Tetraacetyl glucopyranos-2-yl)-1-(2-chloroethyl)-1-nitrosourea, an antitumor agent with modified bone marrow toxicity.


Enzymatic and immunological studies on pyruvate carboxylase in livers and liver tumors.


Studies on certain cytoplasmic enzymes and specific estrogen receptors in human breast cancer and in nonmalignant diseases of the breast.


Inhibition by N6, O2'-dibutyryl 3',5'-cyclic adenosine monophosphate of phosphate transport and metabolism in BHK21C13 and BHK21Py cells.


The isolation and characterization of gallium-binding granules from soft tissue tumors.


Folate deficiency in rats bearing the Walker tumor 256 and the Novikoff hepatoma.


A method for measuring DNA damage and repair in the liver in vivo.


Patterns of damage and repair of liver DNA induced by carcinogenic methylating agents in vivo.


A comparative study of the interaction between concanavalin A and mitochondria from normal and malignant cells.


The estimation of citrate in serum and urine using a citrate lyase technique.


Effect of hydrocortisone on cell viability, Epstein-Barr virus genome expression, and interferon synthesis in human lymphoblastoid cell lines.


Radioimmunoassay of oestriol in pregnancy plasma.


The response to plant mitogens of two subpopulations of lymphocytes in a case of chronic lymphocytic leukaemia.


Reversible blockage of specific synaptic transmission by localized and moderate cooling with a vacuum insulated probe connected to a closed circuit apparatus.


Virus-specific immunoglobulins in multiple sclerosis.


Coordination: the key to rehabilitation.


Returning long-term patients to the community.


A network of volunteers for community programs.


A support group for maintaining chronic patients outside the hospital.


Separation of cocaine, some of its metabolites and congeners on glass fibre sheets.


Agricultural fungicides. I. Identification of systemic fungicides using thin-layer chromatography.


Rapid determination of some plasma oxypurines using high-pressure liquid chromatography.


The effect of proteolytic enzymes on the induction of heterotopic bone formation by demineralized dentin in guinea pigs.


Influence of gene 55 on the regulation of synthesis of some early enzymes in bacteriophage T4-infected escherichia coli. In Escherichia coli B infected with phage T4 with mutations in gene 55 the shut-off of synthesis of two early enzymes was found to be delayed 10 to 15 min as compared to wild-type T4 infection. The kinetics of early enzyme formation was very similar to that obtained after DNA-negative mutant infection. The transcription of gene 1 (one of the genes coded for early enzymes) ceased at 9 to 12 min after infection whether the gene 55 product was active or not, as determined by the time dependence of fluorouracil rescuability of DNA synthesis in cells infected with a gene 1 amber mutant. The synthesis of the major part of the early RNA species, determined by pulse-labeling with uracil-5-(3)H, was furthermore found to be regulated independently of gene 55. An explanation for the extended early enzyme synthesis in DNA-negative and gene 55 mutant infection is offered: translation of early messengers is restricted after about 12 min in wild-type infection, whereas in cells infected with DNA-negative or gene 55 mutants, i.e., the absence of late protein synthesis, early messengers direct the formation of early enzymes for a longer time.


Characterization of two simian virus 40-specific RNA molecules from infected BS-C-1 cells. Two discrete simian virus 40 (SV40) RNA species sedimenting at 19 and 16S, respectively, that are present in infected BS-C-1 cells were characterized with respect to the base composition and the ribonuclease T1 fingerprints. The base composition of the 19S SV40 RNA was found to be cytidylic acid (C), 23.0; adenylic acid (A), 28.3; guanylic acid (G), 23.9; and uridylic acid (U), 24.8; that of the 16S SV40 RNA was C, 19.3; A, 34.0; G, 22.0; and U, 24.7 mol%. Analysis of the ribonuclease T1 fingerprints indicated a difference in the base sequence of the 19 and 16S SV40 RNA. The presence of long sequences of adenylic acid residues (poly A) in these viral RNAs was confirmed.


Adaptation of plaque assay methods to the in vitro quantitation of the radiation leukemia virus. A modification of the XC cell procedure for murine leukemia virus assay which yields quantitative data over a wide range of virus concentrations is described. By using serial passage of infected cell cultures and reversal of the plating sequence in the XC procedure, titers of radiation leukemia virus (RadLV) were obtained which were about 10-fold higher than those found by using the conventional assay. By using the modified procedure, it was observed that, even at high multiplicities of infection, less than 10% of the cells function as infective centers, although the proportion increases with serial passage. It was also observed that exposure of infected cells to UV light, which is commonly used to make plaques more visible in the conventional XC cell test, inhibits plaque formation in the RadLV system. Substitution of X irradiation for UV exposure improved plaque visibility without loss of sensitivity.


Variants of simian virus 40-transformed 3T3 cells that are resistant to concanavalin A. By treating populations of simian virus 40 (SV40)-transformed 3T3 cells with concanavalin A, variants have been isolated which are resistant to the killing action of the lectin. The variants (i) resemble 3T3 cells morphologically and in some of their growth characteristics; (ii) are not agglutinated by high concentrations of concanavalin A or wheat germ agglutinin, but can be rendered agglutinable by treatment with low concentrations of trypsin; (iii) bind the same number of concanavalin A molecules as 3T3 or SV3T3 cells; (iv) cannot be transformed by SV40 and are resistant to focus formation after infection with murine sarcoma virus; (v) contain SV40-specific T antigen and RNA and; (vi) yield wild-type SV40 virus after heterokaryon formation with BS-C-1 cells.


Transcription of simian virus 40. II. Hybridization of RNA extracted from different lines of transformed cells to the separated strands of simian virus 40 DNA. The amount of simian virus 40 (SV40) DNA present in various SV40-transformed mouse cell lines and "revertants" isolated from them was determined. The number of viral DNA copies in the different cell lines ranged from 1.35 to 8.75 copies per diploid quantity of mouse cell DNA and from 2.2 to 14 copies per cell. The revertants had the same number of viral DNA copies per diploid quantity of mouse cell DNA as their parental cell lines. (However, they showed an increased number of viral DNA copies per cell due to their increased amount of DNA.) By using separated strands of SV40 DNA, the extent of each DNA strand transcribed into stable RNA species was determined for the transformed and "revertant" cell lines. From 30 to 80% of the "early" strand and from 0 to 20% of the "late" strand was present as stable RNA species in the cell lines tested. There was no alteration in the pattern of the stable viral RNA species present in three concanavalin A-selected revertants, whereas in a fluorodeoxyuridine-selected revertant there appeared to be less viral-specific RNA present in the cells.


Relationship between replication of simian virus 40 DNA and specific events of the host cell cycle. The relationship between replication of simian virus 40 (SV40) DNA and the various periods of the host-cell cycle was investigated in synchronized CV(1) cells. Cells synchronized through a double excess thymidine procedure were infected with SV40 at the beginning or the middle of S, or in G(2). The first viral progeny DNA molecules were in all instances detected approximately 20 h after release from the thymidine block, independent of the time of infection. The length of the early, prereplicative phase of the virus growth cycle therefore depended upon the period of the cell cycle at which the cells were infected. Infection with SV40 was also performed on cells obtained in early G(1) through selective detachment of cells in metaphase. As long as the cells were in G(1) at the time of infection, the first viral progeny DNA molecules were detected during the S period immediately following, whereas if infection took place once the cells had entered S, no progeny DNA molecule could be detected until the S period of the next cell cycle. These results suggest that the infected cell has to pass through a critical stage situated in late G(1) or early S before SV40 DNA replication can eventually be initiated.


Simultaneous sudden death in infancy in identical twins.


Adrenocortical function and skin pigmentation in idiopathic haemochromatosis.


Experience with the Entamoeba histolytica fluorescent antibody test in Western Australia.


Gas gangrene.

Gas gangrene.


Histochemistry of nucleic acids and proteins in cells of neuroectodermal tumours of different grades of malignancy.


Increase of EB virus positive cells in cultured Burkitt lymphoma cells after short-time exposure to heat.


Pleomorphic adenoma of the nasal septum.


Dye staining of neural end-feed for light microscopy after glutaraldehyde fixation.


Effects of adrenocorticotropic hormone and gonadotropins on urinary 17-ketosteroid production in the male pseudohermaphrodite rat.


Properties of mouse leukemia viruses. IV. Hemagglutination assay and characterization of hemagglutinating surface components.


Properties of mouse leukemia viruses. V. Hemagglutination-inhibition and indirect hemagglutination tests.


The membrane protein of influenza virus: extraction from virus and infected cell with acidic chloroform-methanol.


The evolution of new species of viral DNA during serial passage of simian virus 40 at high multiplicity.


Mapping of base sequence heterologies between genomes from different adenovirus serotypes.


Two types of target cells for transformation with avian myelocytomatosis virus.


Picornavirus receptors and picornavirus multiplication in human-mouse hybrid cell lines.


Preferential integration of simian virus 40 deoxyribonucleic acid into a particular size class of CV-1 cell deoxyribonucleic acid.


Nonproducer clones of murine sarcoma virus transformed guinea pig embryo cells.


Symmetrical in vivo transcription of polyoma DNA and the separation of self-complementary viral and cell RNA.


Liquid scintillation counting of 14C- and 3H-labeled samples on solid supports: a general solution of the problem.


A quantitative estimation of degree of purity of preparations of subcellular structures.


Detection of methanesulfonic acid in ethyl methanesulfonate.


Isolation of intact spinach chloroplasts in the CF-6 continuous-flow zonal rotor; implications for membrane-bound organelles.


A sensitive and specific method for the measurement of monophosphoinositide at a microregional level in brain.


An automated fluorescence method for determination of K+-dependent phosphatase.


Fatty acid composition of neutral lipids and phospholipids of enamel and dentine from rat incisors and molars.


The alveolar macrophage and its role in toxicology.


The response of the multiple forms of lactate dehydrogenase to drugs.


Some developmental observations on the effects of prolonged deprivation of low-voltage fast-wave sleep in the deermouse, Peromyscus maniculatus bairdi.


Neutralizing antibody response in bovine serum and nasal and salivary secretions after immunization with live or inactivated food-and-mouth disease virus. Calves develop nasal and salivary neutralizing antibodies against foot-and-mouth disease virus after nasal inoculation with live virus. Nasal and salivary antibody was not detected after exposure to inactive virus. Serum antibodies were induced by live and inactive virus given subcutaneously. Passively acquired antibodies were detected as long as 7 months after birth.


Further studies on the influence of steroids on viral infection in mice. Certain steroids have been reported to enhance experimental viral infections, whereas others have little or no effect. Interference with the interferon system has been suggested as a possible mechanism for the viral infection-enhancing (VIE) activity of hormones. In the present study, steroids (prednisolone, progesterone, testosterone) which had no effect on MM virus infection demonstrated VIE activity against Mayaro virus infection. It is suggested that the VIE activity of a hormone may be dependent on the viral agent used for challenge. Data are also presented which suggest that, in addition to interference with the interferon system, the VIE activity of steroid hormones may be the result of at least two other actions: (i) alteration of cell membranes; (ii) stimulation of initial viral replication.


Studies of the antigenic relationships of the new human papovaviruses by electron microscopy agglutination. Virus-antibody interactions observed by electron microscopy show that new human papovavirus isolates are antigenically distinct, but share common antigens.


Analytical isotachophoresis in capillary tubes. Transformation of pyruvate to succinate by calf heart mitochondrial enzymes.


Inferior venacavograms and renal venograms in the management of renal tumors.


Polymorphonuclear leukocyte collagenase: localization in granules subjected to zonal centrifugation.


Availability of magnesium: balance studies in rats with various inorganic magnesium salts.


Increasing sensitivity rates of urinary gram-negative bacilli to antimicrobials.


Arteriography of Wilms tumor.

Arteriography of Wilms tumor.


Regulation of levels of guanosine cyclic 3',5'-monophosphate in the central nervous system: effects of depolarizing agents.


Fatty acid profiles of cells from the insect cell line IPRL-21 (Spodoptera frugiperda) and of the tissue culture medium after repeated use.


Thyrotoxic periodic paralysis. Function of sarcoplasmic reticulum and muscle glycogen.


Effect of Mg++ on neuromuscular transmission in the Eaton-Lambert syndrome.


Neurologic manifestations in tropical sprue. A clinical and electrodiagnostic study.


Correlative insulin and glucagon secretion of the perfused rat pancreas following pituitary peptides.


Early effects of testosterone on phospholipid metabolism in the seminal vesicles of immature rats.


Differences in the age-dependent development and sexual differentiation of soluble and membrane-bound activities of 3alpha- and 3beta-hydroxysteroid-dehydrogenase in rat liver.


Cyclic AMP and gastrointestinal hormones. Studies in isolated pancreatic islets.


Long-term ADH-treatment of rats with genetic diabetes insipidus.


In vivo "radioimmunoassay" of aldosterone in rats.


A simple and sensitive radioimmunoassay for plasma angiotensin II.


Response of plasma aldosterone to various stimuli in the angiotensin II-immune rabbit.


Relationships between weight changes and renin, aldosterone, estrogens and progesterone in cyclical edema.


PTH-infusion and estimation of urinary cAMP in hyperparathyroidism.


Suppression and stimulation of plasma testosterone and DHT in hirsute women.


Lipolytically active peptides from hog pituitary glands.


Differential diagnosis of female hirsutism, Cushing's and Conn's syndrome. Quantitative sequential scintigraphy of the adrenals with 131-J-19-iodocholesterol.


Fine structure of corticotrophic cells and of pituitary adenomas in Cushing's syndrome.


Isolated pituitary cells: ACTH secretion and synthesis.


Contribution on regulation of corticotrophic partial function. Reference to an active negative regulation.


Human pharmacological studies with a new synthetic corticotrophic peptide consisting of 18 amino acids.


ACTH determinations before and after selective removal of pituitary adenomas in Nelson's syndrome.


Cortisol, cortisone, and corticosterone in plasma following ACTH-stimulation during the first 6 hours of life.


Studies on cyclic adenosine 3':5' monophosphate concentrations in human cervical mucus.


Species differences in luteinizing hormone as infered from slope variations in a radioligand receptor assay.


Dihydrotestosterone receptor in human mammary cancer.


Radioligand receptor assay for the determination of LH and HCG activities utilizing rat ovarian receptors.


Interrelationship of two microsomal estrogen receptor molecules.


In-vitro corticosteroid synthesis in rat adrenals. I. Results indicating (an) alternative pathway(s) of synthesis without the intermediates cholesterol, pregnenolone and progesterone.


The influence of ACTH and HCG on the steroidogenesis of fetal adrenals in vitro.


Oscillatory glycolysis in yeast: the pattern of phase resetting by oxygen.


Pathways of carbohydrate metabolism in Tetrahymena. Subcellular distribution and properties of hexokinase, aldolase and alpha-glycerophosphate dehydrogenase.


Bull semen nicotinamide adenine dinucleotide nucleosidase. IV. Nonpolar interactions of inhibitors with the substrate binding site.


ESR probing of macromolecules: spin-labeling of the active sites of the proteolytic serine enzymes.


ESR probing of macromolecules: spin label study of the conformational integrity and transitions in modified alpha-chymotrypsin.


Mechanism of action of a respiratory inhibitor from the gill tissue of the sporulating common mushroom, Agaricus bisporus.


A study of postoperative cytostatic medication in patients with operable carcinoma of the lung.


Comparison of the effects of two phosphodiesterase inhibitors, theophylline and papaverine, on blood glucose, plasma FFA and glycerol in the rat.


Ocular pathology of GM2 gangliosidosis--Type 2 (Sandhoff's disease).


Cyclic AMP inhibition of cytotoxin ("lymphotoxin") elaboration by stimulated lymphocytes.


Electron microscopy of endothelial and epithelial components of the lungs: correlations of structure and function.


Calcium metabolism at the cellular level.


Mechanism of action of cytochrome c oxidase and its implications for energy conservation.


Electron transfer across membranes and energy coupling.


Nucleic acids. 14. Synthesis and antiviral activity of some 5'-esters of 9-beta-D-arabinofuranosyladenine (ara-A).


Factors that influence the antagonistic properties of angiotensin II antagonists.


Uptake of androgen analogs by prostate tissue.


A synthesis of noformycin.

A synthesis of noformycin.


Seromucoid and albumin levels in maternal and cord serum in relation to obstetric stress.


Cattle and Culicoides biting midges as possible overwintering hosts of bluetongue virus.


Cytomegalovirus: conversion of nonpermissive cells to a permissive state for virus replication. Human embryonic kidney cells are epithelioid cells which are normally nonpermissive for in vitro replication of human cytomegalovirus. These cells were converted to a permissive state for the virus by prior treatment with 5-iodo-2'-deoxyuridine. When this method was used, a nonpermissive cell was made permissive to an infecting virus.


Utilization of somatic cell hybrids for genetic studies in man.


I-cell disease, mucolipidosis II. Pathological, histochemical, ultrastructural and biochemical observations in four cases.


Technetium-99m labelled pyrophosphate: a simple and reproducible bone scanning agent.


Virological studies in Reiter's disease.


Sexual transmission of intestinal parasites.


Characterization of genital strains of Herpesvirus hominis.


Progress in myasthenia gravis.

Progress in myasthenia gravis.


Hypothesis: breast cancer regression under oestrogen therapy. Recent reports have thrown doubt on both of the major mechanisms which have been suggested for the regression of breast cancer under high-dosage oestrogen therapy-a direct effect on binding sites and an indirect inhibition of prolactin release. A searching review on the clinical response of 407 patients with advanced breast cancer treated by oestrogen therapy under my direction showed certain anomalies, including age determined tumour inhibition and stimulation, dose dependence of tumour inhibition and stimulation, differential site sensitivity, and tumour regression with oestrogen withdrawal. The hypothesis usually postulated to explain these anomalies is that the tumour may in the same individual be composed of multiple genetically distinct clones of cells. It is suggested instead that the effect of high-dosage oestrogen therapy in breast cancer may depend critically on the absolute and relative concentrations of prolactin and oestrogen actively available at the tumour. On this basis the clinical manifestation of tumour stimulation in response to oestrogen administration suggests that the oestrogen concentration at the target is inadequate. Differences in site sensitivity in the same patient may depend on tumoral factors such as the level of oestradiol and prolactin binding receptors in the tissue.


Ultrastructure of cysts of E. histolytica.


Ultrastructure of E. histolytica--strain NIH 200.


Specific binding of (3H) lysine-vasopressin to pig kidney plasma membranes. Relationship of receptor occupancy to adenylate cyclase activation.


Studies on the mechanism of action of the gal repressor.


Mechanism of activation of a cyclic adenosine 3':5'-monophosphate phosphodiesterase from bovine heart by calcium ions. Identification of the protein activator as a Ca2+ binding protein.


Studies on calciferol metabolism. 8. Evidence for a cytoplasmic receptor for 1,25-dihydroxy-vitamin D3 in the intestinal mucosa.


Succinic semialdehyde dehydrogenase from a Pseudomonas species. I. Purification and chemical properties.


Succinic semialdehyde dehydrogenase from a Pseudomonas species. II. Physical and immunochemical properties of the enzyme.


The oxidation of catechols by reduced flavins and dehydrogenases. An electron spin resonance study of the kinetics and initial products of oxidation.


The kinetics and mechanism of reduction of electron transfer proteins and other compounds of biological interest by dithionite.


Kinetic studies on the substrate reduction of xanthine oxidase.


Steroid structure and androgenic activity. Specificities involved in the receptor binding and nuclear retention of various androgens.


Receptors for thyrotropin-releasing hormone in prolactin producing rat pituitary cells in culture.


Stimulatory and inhibitory effects of guanyl nucleotides on fat cell adenylate cyclase.


Estrogen receptor in a human cell line (MCF-7) from breast carcinoma.


Inhibition of cellular differentiation by phospholipase C. I. Effects of the enzyme on myogenesis and chondrogenesis in vitro. In cell culture, a partially purified commercial preparation of phospholipase C (PLC) from Clostridium welchii inhibited fusion of myoblasts at concentrations of 12-50 microg per ml. At lower concentrations, PLC-treated cultures were indistinguishable from controls, and at concentrations above 100 microg per ml, PLC-treated cells detached from their substrates. The effect was reversible and fusion resumed approximately one cell cycle time after removal of the enzyme. Neither the percent of cells in the mitotic cycle nor the duration of the different phases of the cycle were altered by PLC at concentrations which inhibited fusion. Cell motility was not reduced by the enzyme. Unfused, PLC-treated myoblasts were virtually indistinguishable in ultrastructure from untreated cells just before fusion. In the presence of PLC, mononucleated myogenic cells did not synthesize thick (150 A) filaments. Treatment of culture medium with insolubilized commercial PLC did not abolish the capacity of the medium to support myogenesis. Chondrocytes treated with PLC divided repeatedly but failed to synthesize metachromatic matrix and failed to incorporate labeled sulfate into chondroitin sulfate. PLC was further purified by chromatography on Sephadex G-100. The resulting preparation was free of detectable protease, yielded one band on SDS-acrylamide gel electrophoresis, and displayed all of the biological activities of the less pure material.


A radioimmunoassay for beta-melanocyte-stimulating hormone in human plasma.


Establishment and characterization of ethidium bromide resistance in simian virus 40-transformed hamster cells. Effects on mitochondria in vivo. This study describes the isolation and subsequent characterization of four mammalian cell lines resistant to ethidium bromide (EB). Treatment of the simian virus 40- (SV40) transformed hamster cell line F5-1 first led to the establishment of the F2 cell line, which is resistant to 2 microg EB/ml. At this concentration cytochromes c and b are present in almost normal or only slightly diminished amounts, whereas cytochromes a + a(3) show an obvious decrease. The mitochondria of the F2 cell show a normal ultrastructure, not distinct from the parental cell line F5-1, and contain closed circular DNA. The sensitive parental F5-1 cells, however, when exposed to the same dye concentration exhibit the typical EB-induced ultrastructural changes in the mitochondria, and no more component I mitochondrial DNA can be demonstrated. 1 yr after establishment we derived from the F2 cell three more cell lines, resistant against 4, 8, and 16 microg of EB/ml. These cell lines, termed F4, F8, and F16, respectively, also revealed relatively intact-appearing mitochondria, although distinguishable from F5-1 and F2 mitochondria by a more condensed or unorthodox cristae conformation. F4, F8, and F16 cell lines contained closed circular mitochondrial DNA in the same position as that of the parental F5-1 cells, when analyzed in an isopycnic CsCl-EB gradient. A small shoulder at the lower density side of the DNA I peaks was observed. The newly acquired drug resistance of the F cells is hereditarily transmitted to the progeny cells and retained even after a period of growth in EB-free medium.


Distribution of fructose, citric acid, sialic acid and lipids in male accessory glands of the hamster, Mesocricetus auratus.


Incorporation of 32P into phospholipids of the hypothalamo-neuro-hypophysial system and subcellular distribution of labelled phospholipids in the rat neural lobe.


Embryonic chick intestine in organ culture. A unique system for the study of the intestinal calcium absorptive mechanism. Duodena from 20-day-old chick embryos can be maintained in large scale organ culture on specially designed stainless-steel grids in contact with serum-free medium for 48 h with excellent preservation of mucosal structure at both the light and electron microscope levels. Although mitotic rate was subnormal, several other factors attest to the essential viability of the cultured intestine: L-leucine incorporation into protein, as well as the synthesis of a specific vitamin D(3)-induced calcium-binding protein (CaBP), increased over a 48-h culture period, and the electropotential gradient across the intestine was maintained throughout the culture period as was a concentration gradient for calcium. The tissue responded to vitamin D(3) in the medium by synthesizing the calcium-binding protein within 6 h and by exhibiting enhanced (45)Ca uptake within 12-24 h. Concentrations of vitamin D(3), or its 25-hydroxylated derivative, higher than necessary for CaBP induction, also increased the activity of alkaline phosphatase. The 1,25-dihydroxylated derivative of vitamin D(3), at a level extremely potent in CaBP induction, did not stimulate alkaline phosphatase. Mucosal to serosal transport of (45)Ca could also be measured in everted duodenal sacs, subsequent to culture under similar conditions, and was also increased by vitamin D(3) in the medium. Other embryonic organs, esophagus, stomach, liver, pancreas, lung, skin, and muscle, did not produce CaBP in response to vitamin D(3) in the culture medium. However, CaBP-synthesizing capacity was present in the entire intestinal tract, exclusive of the rectum. (59)Fe and (32)P uptake by cultured duodenum were also stimulated by vitamin D(3). The system has proven quite useful in the study of the vitamin D-mediated calcium absorptive mechanism but should be applicable to the study of the absorption of other nutrients, drugs, hormones, etc., as well as other studies of intestinal function.


The influence of carbon dioxide on the growth of obligate and facultative anaerobes on solid media.


Resistotyping of Shigella sonnei.

Resistotyping of Shigella sonnei.


Intracellular growth and type variation of Neisseria gonorrhoeae in tissue cell-cultures.


Estimation of the concentration of low density lipoprotein cholesterol and very low density lipoprotein cholesterol by selective adsorption from serum with magnesium compounds.


Effect of thyrotropin and of LATS on mouse thyroid cyclic AMP.


Monolayer culture of a human pancreatic beta-cell adenoma.


Mutations affecting growth of the Escherichia coli cell under a condition of DNA polymerase I-deficiency.


Subfornical organ: site of drinking elicitation by angiotensin II. Angiotensin II applied directly to the subfornical organ in a dose as small as 0.1 nanogram elicited short-latency drinking behavior in water-sated rats. Lesions in the body of this structure blocked drinking induced by angiotensin II applied to the basal telencephalon (including preoptic area). These results call attention to the subfornical organ as an important central nervous structure involved in the conrol of drinking behavior.


Familial gouty malignant uric acid lithiasis due to mutant phosphoribosylpyrophosphate synthetase.


Nitrogen transformations in soils. I. In sandy soil under barley and peanut in a two years' rotation.


Nitrogen transformation in soils. II. In sandy soil under horse-bean and sesame in a two years' rotation.


Centrally induced drinking: comparison of angiotensin II- and carbachol-sensitive sites in rats.


pH dependence of reversal potential for acetylcholine-induced currents in neurons.


Spontaneous cytomegalovirus mononucleosis. Clinical and laboratory observations in nine cases.


Cytomegalovirus infection in previously healthy adults.


Adrenal ablation by venous catheter.

Adrenal ablation by venous catheter.


Effect of ionophorous antibiotics (nigericin, gramicidin and valinomycin) on cyclic AMP synthesis in rat adipose tissue.


Effect of highly specific inhibitors of oxidative phosphorylation, dicyclohexylcarbodiimide, antimycin A and piercidin A, on cyclic AMP accumulation induced by noradrenaline and theophylline in rat adipose tissue.


Inhibition of hypoxanthine transport by chlorpromazine and SKF 525-A in cell culture.


Formation of nucleotides of (6-14C)allopurinol and (6-14C)oxipurinol in rat tissues and effects on uridine nucleotide pools.


Effect of ethoxyquin on the carbon tetrachloride-induced changes in rat hepatic microsomal enzymes.


Bilateral patellar metastases from carcinoma of the male breast.


Interactions of acetaldehyde, ethyl alcohol and oxybarbiturates affecting mitochondrial functions.


Equine coital exanthema in the United Kingdom.


Diagnosing the state of the diagnostic function: an analysis of the literature.


Psychiatric aftercare clinic effectiveness as a function of patient demographic characteristics.


Identification of a critical period during the S phase for activation of the Epstein-Barr virus by 5-iododeoxyuridine.


Spare gonadotrophin receptors in rat testis.


EB viral genomes in epithelial nasopharyngeal carcinoma cells.


Motor nerve conduction velocity and electromyogram in chronic lead poisoning.


Congenital hemihypertrophy with oligophrenia. Genetic and Dermatoglyphic data, muscle structural and ultrastructural aspects. (Report of a case).


Improved hemagglutination inhibition assay for mammary tumor virus antigen. It is our experience that the use of sheep red blood cells pretreated with formaldehyde and pyruvaldehyde before sensitizing with viral antigen yields results that are comparable to that obtained by using the tannic acid method. The double aldehyde method provides the added advantage of being useful for assaying the viral antigen content in substances which contain high levels of interfering substances which would preclude the use of other assay methods.


Assay methods for Clostridium perfringens type A enterotoxin. Enterotoxin produced by a sporulating culture of Clostridium perfringens type A NCTC 8798 was purified to a level of 3,500 mouse mean lethal doses per mg of nitrogen. High-titer sera were obtained from rabbits injected with enterotoxin and used to compare the sensitivity of serological tests and bioassays for C. perfringens enterotoxin. Reversed passive hemagglutination was by far the most sensitive test, followed by microslide diffusion, single gel diffusion and electroimmunodiffusion, guinea pig skin test, mouse test, and rabbit ileal loop test.


Studies on the postnatal development of responses of hepatic histidase to endocrine control.


The role of phospholipids in TSH stimulation of adenylate cyclase in thyroid plasma membranes.


Evidence for a peptidic factor in spermatozoa inhibiting the ovarian maturation.


The chemotactic effect of 5'-amido analogues of adenosine cycle 3',5'-monophosphate in the cellular slime moulds.


The role of the anion-binding site of transferrin in its interaction with the reticulocyte.


The physical chemistry of hemes and hemopeptides. I. Physiochemical properties and reduction of chlorodeuterohemin in organic solvent.


Distribution of glutamine hexosephosphate aminotransferase in rat tissues; changes with state of differentiation.


Phosphatidyldiglucosyl diglyceride from Streptococci and its relationship to other polar lipids.


Phospholipids of a moderately halophilic halotolerant bacterium. Isolation and identification of glucosylphosphatidylglycerol.


Synthesis in vivo of phospholipids of liver mitochondria and endoplasmic reticulum from glycerol and fatty acids.


The response of diphosphoinositide and triphosphoinostitide to perturbations of the adenylate energy charge in cells of Saccharomyces cerevisiae.


The exchange of phospholipids between plasma lipoproteins and rapidly dividing human cells grown in tissue culture.


A method for the determination of the initial rate of reaction of lecithin: cholesterol acyltransferase in human plasma.


Uncoiling and protein cleavage of paramyxovirus nucleocapsid after incubation with ribosomes in vitro.


Studies on bovine pancreatic deoxyribonuclease A. II. The effect of different bivalent metals on the specificity of degradation of DNA.


Gaucher-like cells and congenital dyserythropoietic anaemia, type II (HEMPAS).


Effect of isopropyl methane sulphonate (IMS) on haemopoietic colony-forming cells.


Considerations in the radiation therapy of Wilms' tumor.


Treatment of Wilms' tumor and factors affecting prognosis.


Wilms' tumor--an interdisciplinary treatment program with and without dactinomycin.


Serial catecholamines in the radiation management of children with neuroblastoma.


Some nonspecific morphological changes in neuromuscular diseases.


Type 3 hyperlipoproteinaemia and sinking prebeta lipoprotein.


Release factor regulating termination of complete protein in a eukaryotic organism.


Self-annealing of 4 S strands from replicating simian virus 40 DNA.


Association of polyadenylic acid with messenger RNA of vesicular stomatitis virus.


The storage and release of transmitter substances from Helix neurones.


Renal vasodilation and the antinatriuretic effect of angiotensin in the rat.


Effects of various secretagogues upon 42K and 22NA uptake during in vitro hormone release from the rat adenohypophysis. 1. The in vitro uptake of (22)Na and (42)K was measured simultaneously in rat adenohypophyses during hormone release produced by several secretagogues and during inhibition of hormone release in Ca-free media.2. Intracellular adenohypophysial [Na(+)] and [K(+)] changed only slightly when the uptake changed. This would indicate that relative permeability changes were the primary effect of the treatments.3. The uptake of (42)K was increased by elevated external [K(+)], but was unaffected by the presence or absence of Ca(2+). Acid extracts of hypothalamus-stalk-median eminence or cerebellum also increased the (42)K uptake.4. The uptake of (22)Na or (24)Na was decreased by elevated [K(+)]. Uptake was increased in Ca-free Krebs-Ringer bicarbonate; but was unaltered when [K(+)] was concurrently increased.5. Neither purified growth hormone releasing hormone, synthetic lysine-vasopressin, dibutyryl cyclic AMP nor theophylline had an effect on the uptake of either K(+) or Na(+).6. The rapid uptake of (22)Na and its smaller volume of distribution compared to absolute measurements of intracellular [Na(+)] suggest that the plasma membrane of adenohypophysial cells is relatively impermeable to Na(+).7. We conclude that changes in the uptake of Na(+) and K(+) associated with hormone release are incidental to the release process.8. Hormone release produced by elevated external [K(+)] is most likely due to a non-specific increase in permeability of the cell membranes, facilitating Ca(2+) entry into the cytoplasm.9. The results suggest that the low resting transmembrane potentials of adenohypophysial cells may be due to their conjoint relatively high permeability to both K(+) and Ca(2+), rather than K(+) and Na(+).


Individualization of angiotensin receptors in smooth muscle cell membranes.


The effect of divalent cations on angiotensin stimulation of fluid transport by rat colon.


Evidence for two corticosteroid receptor mechanisms in the feedback control of corticotrophin secretion.


Mechanism of excitation of uterine smooth muscle. Changes in ionic fluxes induced by angiotensin.


The physiological role of prostaglandins in parturition.


Effects of intrafollicular injection of hormones and drugs.


Nature, role and control of the gonadotrophins.


-Autoradiography of 10B compound distribution in tissue by use of superimposition technique.


Hepatitis B antigenemia. Clinical implications.


Pituitary and gonadal function in hypogonadotrophic hypogonadism.


The effect of dihydroergotamine on ACTH-stimulated lipolysis in rat adipocytes.


Hypothalamic-pituitary-adrenal function in patients with pituitary tumours.


Evidence for the internal feedback phenomenon in human subjects: effects of ACTH on plasma CRF.


Oestriol conjugates in amniotic fluid. Qualitative and quantitative aspects, including preliminary studies in Rh isoimmunization.


Differential action of parathyroid and thyroid hormones on effective intestinal absorption of calcium. In vivo studies with 47calcium in rats.


Review of treatment of Méniére's syndrome.


The effect of betahistine hydrochloride in Méniére's disease.


The effect of Serc (betahistine hydrochloride) on the circulation of the inner ear in experimental animals.


A study of the efficacy of betahistine in Méniére's syndrome.


Méniére's disease: subjective and objective evaluation of medical treatment with betahistine HCl.


Factors influencing the cure rate in nephroblastoma. A review of 335 cases.


Formation of the native structure of proteins: inferences from the kinetics of denaturation and renaturation.


Mechanisms in the chemical syntheses of polypeptides and polynucleotides.


The kinetics of transmitter release in myasthenia gravis. II. An electrophysiological analysis of the replenishment of transmitter stores.


Inhibition of the noradrenaline-induced adenyl cyclase stimulation by augmented alpha-adrenergic response in subcutaneous adipose tissue from hypothyroid subjects.


Metabolic abnormalities in asthma--decreased urinary cycle AMP.


Adjuvant induced formation of lysophosphatides and their role in the immune response.


The effects of adjuvants and stress on the production of IgE antibody in rats.


Studies on surface antigens of mammalian cells.


The relationship between the viruses causing hepatitis and autoimmunity in liver disease.


Studies on the mechanism of T lymphocyte-mediated cytolysis.


The mechanism of action of macrophage migration inhibitory factor (MIF).


Cerebrocortical adenyl cyclase activity following neonatal thyroid hormone deficiency.


Immunological properties of carbohydrate and protein fractions of Timothy grass pollens.


Enhanced effects of prostaglandin E1 and dibutyryl cyclic AMP upon human lymphocytes in the presence of cortisol. The combined effects of cortisol and agents acting through a cyclic AMP-mediated mechanism have been studied in cultures of highly purified human peripheral lymphocytes. Incubation with prostaglandin E(1) (PGE(1)), dibutyryl cyclic AMP, or cortisol results in a concentration-dependent inhibition of [(3)H]-thymidine incorporation by both unstimulated and phytohemagglutinin (PHA)-stimulated lymphocytes, and PHA-induced morphologic transformation is prevented. When cortisol and PGE(1) (or dibutyryl cyclic AMP) are added together to lymphocyte cultures, enhanced inhibitory effects are observed. Incubation of unstimulated or PHA-stimulated lymphocytes with PGE(1) results in an elevation of intracellular cyclic AMP levels within 20 min. The concentration of cyclic AMP gradually returns to base-line levels over a 1-6 h period of time. Cortisol alone does not significantly alter cyclic AMP concentrations. However, incubation with PGE(1) in the presence of cortisol results in a greater stimulation of intracellular cyclic AMP levels than that observed with PGE(1) alone. These findings suggest that cortisol may act synergistically with PGE(1) to elevate lymphocyte cyclic AMP levels and to regulate [(3)H]thymidine incorporation and transformation.


Mechanism of the hypolipemic effect of clofibrate in postabsorptive man. Splanchnic metabolism of triglycerides and other major substrates was studied in the postabsorptive state in normotriglyceridemic and hypertriglyceridemic human subjects who received (1/2) g of clofibrate four times daily for 3 wk. Transport in blood plasma of triglycerides produced in the splanchnic region was quantified by three methods: (a) measurement of the transsplanchnic gradient of (14)C-labeled triglycerides during constant intravenous infusion of [1- (14)C] palmitate (b) chemical measurement of the transplanchnic gradient in concentration of triglycerides of very low density lipoproteins; and (c) determination of clearance of (14)C-labeled triglycerides in extrasplanchnic tissues. The first method measures only triglycerides derived from free fatty acids and the last two measure total splanchnic production. In hypertriglyceridemic subjects treated with clofibrate, average rates of total splanchnic production of triglycerides and production from free fatty acids were the same as those of comparable untreated subjects despite a consistent fall in plasma triglyceride levels. The hypotriglyceridemic effect of the drug was therefore accompanied by improved disposal of triglycerides in extrasplanchnic tissues. In treated normotriglyceridemic subjects, unlike their untreated counterparts, total splanchnic production was significantly higher than production from free fatty acids. Failure of clofibrate to reduce triglyceride levels in normotriglyceridemic subjects may have been related to increased total splanchnic production, coupled with improved extrasplanchnic disposal. Systemic transport and net splanchnic uptake of free fatty acids were similar in treated and control subjects but the fraction of [1-(14)C]palmitate converted to acetoacetate in splanchnic tissues was significantly higher in treated subjects. Net splanchnic extraction of plasma amino acids that enter the glucogenic pathway via pyruvate was increased in treated subjects and their arterial concentrations were reduced.


Hypoxanthine-guanine phosphoribosyltransferase variant associated with accelerated purine synthesis. We have previously described a 14-yr-old boy with hyperuricemia, renal failure, and accelerated purine production resistant in vivo and in vitro to purine analogs. This patient demonstrated normal red cell hypoxanthine-guanine phosphoribosyltransferase (HPRT) heat stability, electrophoresis at high pH, and activity at standard substrate levels. In the present report an abnormal HPRT enzyme was demonstrated by enzyme kinetic study with phosphoribosylpyrophosphate (PRPP) as the variable substrate and inhibitory studies with sodium fluoride. Apparently normal HPRT activity in a patient with hyperuricemia and gout does not exclude a functionally significant HPRT mutation.


Cyclic AMP and sodium transport. Quantitative and temporal relationships in toad urinary bladder. The effects of oxytocin upon tissue cAMP content and short-circuit current (SCC) were measured in the urinary bladder of the toad, Bufo marinus. Tissue cAMP levels doubled before any increment in SCC was observed, the two hormone responses were quantitatively related, and a threshold level for an effect of cAMP upon sodium transport was demonstrated. The period of time over which cAMP levels continued to rise after the threshold level had been attained seemed invariant with hormone concentration. The rate at which cAMP levels rose increased with hormone concentration yielding hormone concentration-dependent maximal levels. The decay of cAMP levels was delayed when sodium influx was curtailed, suggesting a sodium-regulatory effect upon tissue cAMP levels.


Maturation of responsiveness to cardioactive drugs. Differential effects of acetylcholine, norepinephrine, theophylline, tyramine, glucagon, and dibutyryl cyclic AMP on atrial rate in hearts of fetal mice. Freshly isolated hearts of fetal mice of gestational ages ranging between 12 and 22 days (term) were exposed to several concentrations of a variety of chronotropic agents. Acetylcholine (10(-4)-10(-2) M) caused marked bradycardia in all hearts, even after only 12-14 days' gestation (i.e., even before cardiac innervation had occurred), and the intensity of the response increased steadily with advancing age throughout gestation. Responsiveness to norepinephrine was present but minimal at 12-14 days, so that mean atrial rate rose by < 10% with a maximal concentration of the drug (10(-5) M); responsiveness became more marked by 15-16 days (just after the time atrial innervation is thought to begin) and still greater effects appeared just before term. Glucagon had no effect in hearts of < 17 days' gestational age, but caused tachycardia thereafter, indicating that cardiac responsiveness to glucagon differentiates later than does responsiveness to norepinephrine. Responses to theophyl-line in 12-14 day hearts exceeded those to norepinephrine, indicating that the drug can affect heart rate independently of its ability to cause release of endogenous catecholamines. In contrast, tyramine caused no response until 21-22 days, well after the time the beta-receptor has differentiated and after innervation is fairly well developed, suggesting that the drug's primary sympathomimetic effect is indirect rather than direct. Dibutyryl cyclic AMP did not cause tachycardia at any fetal age. It is concluded that maturation of responsiveness of the mouse heart to cardioactive drugs develops in specific patterns for different agents. The identification of differential patterns of maturation for various drugs may provide valuable means for characterizing the differentiation of specific receptors and for investigating possible mechanisms of action of the drugs.


Circadian rhythm of plasma aldosterone concentration in patients with primary aldosteronism. Plasma aldosterone, cortisol, and renin activity were measured in nine recumbent patients with hyperaldosteronism, including seven with adenomas, one with idiopathic hyperplasia, and one with glucocorticoid suppressible hyperplasia. All had peak values of plasma aldosterone concentration from 3 a.m. to noon and lowest values at 6 p.m. or midnight. This rhythm was similar to the circadian pattern of plasma cortisol in the same patients. When these data were normalized to eliminate the wide variation in ranges of plasma aldosterone and cortisol between individuals, there was an excellent correlation (r = + 0.87, P < 0.005) between the two hormones. In contrast, plasma aldosterone concentrations did not correlate with plasma renin activity before or after normalization of data. Short term suppression of ACTH by administration of dexamethasone eliminated the circadian variation of plasma aldosterone in both patients with hyperplasia and in four of five patients with adenomas, while it markedly altered the rhythm in the fifth. Similar doses of dexamethasone were administered to four normal subjects and did not flatten the circadian rhythm of plasma aldosterone. These data suggest that patients with primary aldosteronism have a circadian rhythm of plasma aldosterone mediated by changes in ACTH.


Infection with herpes-simplex viruses 1 and 2. II. Herpes-simplex virus 1 (HSV1) and 2 can cause recurrent infection in man and in nonhuman species localized on a specific area of the body, such as face, cornea, or genitals.  The origin of the virus responsible for a recurrent infection is not usually apparent.  Some possible sources of virus can be exogenous infection, endogenous infection from another site of the body, chronic, continuous viral multiplication around the site of involvement, and persistence of the virus at the site of the recurrent infection.  No definite information is yet available regarding the mechanism by which HSV1 or HSV2 persists and it is triggered to multiply, or regarding the cells that harbor the virus.  It is possible that frequent or constant antigenic stimulation occurs in at least some cases of recurrent herpetic infections.  The role of antibodies and of interferon in host resistance to HSV remains to be elucidated.  Several recent studies have shown the association of more than a dozen herpes viruses with cancer in man and various animals; for example with limphoma, and with squamous cell carcinoma of the lip and cancer of the cervix.  Genital HSV infections and cervical cancer were first linked when it was noted that women with genital herpes had a high frequency of cervical dysplasia and cancer.  The results of new seroepidemiologic studies on this subject are still difficult to evaluate.  Inocculation of HSV2 in laboratory animals has resulted in sarcomas, but it has never been possible to prove that the virus caused the tumors, since no HSV antigens could be detected in the tumors.  However, herpesvirus antigens have been demonstrated by immunofluorescent technics in exfoliated cervical cells obtained from women with dysplasia, carcinoma in situ, and invasive carcinoma.  In the absence of other kinds of data, it is difficult to rule out the possibility that the presence of HSV2 or of antigens is not an independent event unrelated to the cancer.


Potassium, angiotensin and the dual control of aldosterone secretion.


The chemotherapy of viral infections.

The chemotherapy of viral infections.


Endocrine complications of malignancy.

Endocrine complications of malignancy.


Clinical and epidemiologic clues to the diagnosis of respiratory infections.


Herpes viruses and cancer.

Herpes viruses and cancer. Type 2 herpes simplex virus belongs to the herpes virus group, members of which have been shown to cause cancer in animals -- kidney cancer in frogs, lymphoid cancer in chickens and rabbits, and lung cancer in sheep.  A herpes virus causes Burkett's lymphoma in humans;  another causes nasopharyngeal cancer in humans.  Herpes simplex viruses are common in humans in cervical and vaginal sores in women and in the genital tract in men (an estimated 15% of men older than 15).  It is transmitted venereally.  Type 2 herpes simplex virus has been epidemiologically associated with cervical cancer.  It has been found in prostate cancer cells.  In a hybridization experiment with DNA from cervical cancer cells, DNA from type 2 herpes simplex virus was found, but 60% of the viral DNA molecule was missing.  In the chicken lymphoid cancer caused by a herpes virus, live virus vaccine eradicated the disease.  This suggests that, if type 2 herpes simplex virus is found to cause cervical cancer, a vaccination cure can be developed.


Immunohistological, microscopical and neurochemical studies on encephalitides. 7. Subacute sclerosing panencephalitis. Susceptibility of dogs to the virus, and characterization of host response.


Differential sensitivity of virulent and attenuated strains of type 1 poliovirus to polyethylene glycol as a possible new genetic marker.


Haemadsorption-negative assay of rubella virus in baby hamster kidney cells.


Differential growth of MHV (PRI) and MHV (C3H) in genetically resistant C3H mice rendered susceptible by eperythrozoon infection.


The isolation and partial characterization of a herpesvirus from a case of bovine metritis.


Ultrastructural examination of phytohemagglutinin stimulated lymphocytes infected with vesicular stomatitis virus.


Genetic studies of respiratory syncytial virus temperature-sensitive mutants.


Electron microscopic studies of respiratory syncytial temperature-sensitive mutants.


Multiplication of the virus of epizootic haemorrhagic disease of deer in culicoides species (Diptera, Ceratopogonidae).


Elevation of the intracellular levels of cyclic adenosine monophosphate during in vitro infection of transmissible gastroenteritis virus. Brief report.


Location of Rous sarcoma viral structural polypeptides on the virion surface. Brief report.


Effects of hycanthone on rapidly proliferating cells.


Effects of quinidine on some reactions and ion translocations catalyzed by the Na+, K+ -ATPase complex.


Preservation of structural integrity of liver lysosomes and membrane-stabilizing action of anti-inflammatory drugs, catecholamines and cyclic adenosine monophosphate in isotonic salt media.


Leukokinin-forming system in the ascitic fluid of a murine mastocytoma.


Carbohydrate metabolism in the plasmodium of the myxomycete Physarum flavicomum.


Isolation and some characteristics of liver plasma membranes from rainbow trout.


Plasma enzyme levels and erythrocyte G6P-DH activity in ducks and chicken.


Intermediary metabolism in Dicrocoelium dendriticum (Trematoda).


Metabolism in porifera. I. Some studies on the biosynthesis of fatty acids, sterols and bromo-compounds by the sponge Verongia aerophoba.


Characterization of ubiquinone from vegetative amoebae and mature sorocarps of the cellular slime mold, Dictyostelium discoideum.


Identification of astaxanthin in Scottish salmon.


The management of oral ulceration.

The management of oral ulceration.


Growth hormone regulation and hypothalamic-pituitary-adrenal function in anorexia nervosa.


Characterization of an avian reovirus isolated in Queensland.


Cytostatic elimination of syngeneic rat tumor cells in vitro by nonspecifically activated macrophages. Syngeneic tumor cell lines induced in inbred DA rats by polyoma virus, dimethylbenzanthracene, or methylcholanthrene were interacted in vitro with syngeneic effector cells. Glycogen-induced peritoneal exudate cells, predominantly polymorphonuclear leukocytes, and proteose peptone-induced peritoneal cells, principally macrophages, were the effector cells employed. Activated, nonimmune macrophages or exudative polymorphonuclear leukocytes produced pronounced morphological changes in syngeneic tumor cells as evidenced by a substantial reduction in tumor cell numbers and appearance of shrunken cells, even though there was no increase in cell debris. Polymorphonuclear leukocytes exerted a generally similar but quantitatively much diminished effect. These effector cells constantly produced a decrease in the incorporation by tumor cells of DNA precursors such as [(3)H]thymidine and of RNA precursors such as [(3)H]uridine. In this regard, the effector cells were quite refractory to high doses of X-irradiation. Interaction of target cells with activated, nonimmune macrophages yielded low but consistent signs of cytotoxicity, whereas polymorphonuclear leukocytes gave no such effects. Elimination of functional macrophages by silica, an agent specifically toxic for macrophages, resulted in unrestricted tumor cell proliferation despite continued generation of cytotoxicity. Accordingly, cytostatic mechanisms appear to play a predominant role in the elimination of tumor cells by nonimmune phagocytes. Evidence from a variety of experimental approaches suggest that the cytostatic effect is dependent on cell-to-cell contact.


Stimulation of glucose-6-phosphatase activity in the mucosal cells of the mouse intestine.


Latent herpes simplex virus in the central nervous system of rabbits and mice. Herpes simplex virus (HSV) type 1 induces a long-standing latent infection in the central nervous system of mice and rabbits. The infection was extablished in the brain stems of rabbits after corneal inoculation of the virus, and in the spinal cords of mice after rear footpad infection. In these animals, infectious virus could not be recovered by direct isolation from tissues; it was detected only after the tissues were maintained as organ cultures in vitro.


Ultrastructural comparison of transformed human cells and their normal counterparts at various passage levels.


A characterization of nucleoside diphosphatase in the onion root tip.


Infection with herpes-simplex viruses 1 and 2. 1.


Technical problems with agarose-hormone linkage.


The male as a reservoir of infection with cytomegalovirus, herpes and mycoplasma.


Sleep learning and progressive blurring of perception during sleep.


Primary visual experience and secondary cognitive elaboration in stage REM: a modest confirmation and an extension.


Actions of glucagon and dibutyryl cyclic 3',5'-AMP on chronotropic responses to vagal stimulation and acetylcholine.


Localization of the cyclic AMP system in the arterial wall.


The morphological consequences and the significance of cytomegalovirus infection in renal transplant patients.


A method for inducing unilateral silicosis in rabbits by an injection technique with some observations on lung clearance and quantitative evaluation of experimental silicosis.


Early effects of quartz and titanium dioxide dust on pulmonary function and tissue. An experimental study on rabbits.


The isolation and transmission of the virus of infectious bovine rhinotracheitis-infectious pustular vulvo-vaginitis.


Benign mixed mesodermal tumors of the uterus: a histogenetic study.


Diagnosis of mixed infections with myxovirus influenzae A equi 2 and herpes virus equi 1 among Danish stud horses.


The role of the platelet membrane in platelet function. I. Blood coagulation.


Antacids before obstetric anaesthesia. A clinical evaluation of the effectiveness of mist. magnesium trisilicate BPC.


Agar plate dilution method for routine antibiotic susceptibility testing in a hospital laboratory.


The locus of pathogenicity of asbestos dust: a theory.


Terminal innervation ratio in neuromuscular disease. II. Disorders of lower motor neuron, peripheral nerve, and muscle.


Terminal innervation ratio in neuromuscular disease. I. Methods and controls.


Herpesvirus hominis encephalitis. Virus isolation from brain biopsy in seven patients and results of therapy.


Glomus jugulare tumors: effect of irradiation.


Enhanced release of insulin by prostaglandins in isolated pancreatic islets.


Neuromuscular junction defect in diabetes.


Protein synthesis in the rat anterior pituitary. 3. The fate of total protein, prolactin and growth hormone labeled in an in vitro incubation.


Estrogen receptor in a prolactin secreting pituitary tumor (MtTW5).


Electrically stimulated ACTH release in pharmacologically blocked rats.


An increase of thyroid hormone secretion in response to excess iodide in rats treated with thyroxine.


Role of microtubules in basal and stimulated release of growth hormone and prolactin in rat adenohypophysis in vitro.


Corticosteroidogenesis and its relation to ACTH dependence of mitochondrial components.


Influence of alpha- and beta-subunits on the kinetics of formation and activity of native and hybrid molecules of LH and human chorionic gonadotropin.


The toxicology of dieldrin (HEOD). I. Long-term oral toxicity studies in mice.


Metabolism of Aflatoxin B1 by the guinea-pig.


Pulmonary adenomatosis in guinea pigs exposed to coal dust inhalation.


Hepatoblastoma in children.

Hepatoblastoma in children.


An experimental Wilms' tumor suitable for therapeutic and biologic studies. II. The inhibition of renal compensatory hypertrophy by a transplantable tumor.


The use of chronic catheterization techniques in foetal sheep.


The effects of gamma irradiation on the structure and reactivity of native and cross-linked collagen fibres.


Characterization of invertase activity from cariogenic Streptococcus mutans. Invertase activity from Streptococcus mutans GS-5 has been partially purified and shown to possess beta-fructofuranosidase specificity. The enzyme has a broad pH optimum between pH 5.5 and 7.5 and exhibits maximal activity at 37 C. Fructose, but not the glucose analogue alpha-methyl-d-glucoside, acts as a competitive inhibitor of the enzyme. None of the common glycolytic intermediates or adenine nucleotides had any significant effect on enzyme activity. A molecular weight of approximately 47,000 was estimated for the enzyme. The enzyme does not appear to be catabolically repressed by glucose nor inducible by sucrose. Higher specific activities of the enzyme are observed in fructose or glucose-grown cells compared to sucrose-grown cells. These results are discussed in terms of the regulation of invertase activity in vivo.


Physiological effects of menaquinone deficiency in Bacillus subtilis. Several aspects of the respiratory physiology of a mutant of Bacillus subtilis deficient in menaquinone-7 (MK-7) and in cytochromes were investigated. The mutant, an aromatic amino acid auxotroph blocked at dehydroshikimate reductase, is unable to synthesize MK-7 unless grown in the presence of the common aromatic amino acid intermediate, shikimate. The inability to synthesize MK-7 prevents the mutant from expressing the normal postexponentialphase cytochrome phenotype. When grown in the presence of shikimate, normal levels of these electron transport components are formed. It was found that the intracellular concentration of MK-7 could be predictably regulated by growing the cells with known concentrations of exogenous shikimate. When the mutant was grown under conditions where MK-7 biosynthesis was severely limited, there was a decrease in oxygen uptake and in membrane-associated reduced nicotinamide adenine dinucleotide (NADH) oxidase and succinate oxidase activity. NADH oxidase, but not succinoxidase, could be restored in membrane preparations by the addition of menadione to the reaction mixture. Reduced-minus-oxidized cytochrome difference spectra indicate that an MK-7 deficiency limits electron flow through the cytochrome chain. Furthermore, oxidation-reduction patterns suggest that MK-7 functions between the primary dehydrogenases and the cytochromes. Although the mutant is asporogenous when grown under conditions where MK-7 biosynthesis is limited, the inability to sporulate does not appear to result from lesions in the electron transport system.


Isolation of a mutant of Escherichia coli defective in cytosine-specific deoxyribonucleic acid methylase activity and in partial protection of bacteriophage lambda against restriction by cells containing the N-3 drug-resistance factor. A mutant (designated mec(-)) of Escherichia coli F(+) 100 endo I(-)su(+) r(K) (-)m(K) (+) has been isolated which is defective in cytosine-specific deoxyribonucleic acid (DNA) methylase activity. The DNA of this mutant, as well as the DNA of phages lambda and fd propagated in it, is virtually devoid of 5-methyl-cytosine (MeC); in contrast, the mutation has no significant effect on the level of N(6)-methyladenine in DNA. Phage lambda grown on the mec(-) mutant is more strongly restricted by N-3-containing cells than is lambda grown on the mec(+) parent. These results suggest that methylation of certain cytosine residues by the E. coli K-12 enzyme partially protects lambda DNA from either the N-3 restriction nuclease or against secondary degradation subsequent to N-3-specific degradation. Analysis of the MeC level in viral and cellular DNA obtained from mec(+), mec(+) (m(N3) (+)), and mec(-) (m(N3) (+)) strains has led to the conclusion that the R-factor controlled DNA-cytosine methylase may be capable of methylating a sequence(s) which is a substrate for the K-12 enzyme.


Studies on mitochondria membrane proteins in Saccharomyces cerevisiae under different degrees of glucose repression. Mitochondrial membrane proteins synthesized in vivo in the presence of cycloheximide were analyzed on electrofocusing polyacrylamide gels. Five of the six protein bands observed have their isoelectric points below pH 7. The six proteins are not synthesized when both cycloheximide and chloramphenicol are present, and they are absent in a petite mutant lacking mitochondrial deoxyribonucleic acid (DNA), leading to the conclusion that the proteins are synthesized on mitochondrial ribosomes. By labeling cells of Saccharomyces cerevisiae cultivated in a chemostat under different degrees of glucose limitation, the effect of glucose repression on the synthesis of the mitochondrial membrane proteins was determined. Two of the protein bands showed a relatively reduced synthesis under the strongest glucose repression tested. The specific activity of the cytochrome oxidase and the percentage of mitochondrial DNA in the total DNA were found to be influenced at a lower level of glucose repression.


Effects of ethylenediaminetetraacetate and chloramphenicol on mitochondrial activity and morphogenesis in Mucor rouxii. The present study demonstrates the importance of mitochondrial activities in controlling Mucor rouxii morphogenesis. The respiratory capacity of the spores of this facultatively anaerobic, dimorphic fungus becomes repressed if germination and growth take place in the absence of oxygen. The level of activity of mitochondrial enzymes such as cytochrome oxidase and malate dehydrogenase is lower in the anaerobic yeastlike cells than it is in ungerminated spores and in aerobic hyphae, but the reverse is true for glycolytic enzymes such as pyruvate kinase and alcohol dehydrogenase. Following exposure to air, yeastlike cells convert into hyphae after a lag period corresponding to aerobic adaptation. Anaerobic cultures grown in the presence of ethylenediaminetetraacetate (EDTA) at a concentration of 10(-4) M exhibit hyphal morphology. These cells, which are fully adapted to anaerobic fermentation, nevertheless have potentially active mitochondria with the same levels of respiratory enzymes as ungerminated spores. These cells are able to grow immediately after aeration, without an adaptation lag. Evidence is presented which indicates that the morphogenetic effect of EDTA is not the result of elimination of free metals. Additional evidence proving mitochondrial control of morphogenesis in M. rouxii is that chloramphenicol (4 mg/ml) induced the formation of respiratory-deficient, yeastlike cells in aerobic cultures.


Cross-feeding of Escherichia coli mutants defective in the biosynthesis of nicotinamide adenine dinucleotide. Mutants of Escherichia coli defective in the biosynthesis of nicotinamide adenine dinucleotide (NAD) are able to grow in a Casamino Acids medium lacking NAD and its immediate precursors, nicotinic acid and nicotinamide. This property has allowed the development of a system to measure cross-feeding between a nadA and a nadB mutant. This system provides a means of isolating the intermediate, prequinolinic acid, as well as a biological assay for the compound. The nadB mutant feeds the nadA mutant, indicating that the nadA enzyme occurs first in the pathway and the nadB enzyme second. No cross-feeding was detected between nadA and nadC or between nadB and nadC.


Regulation of aspartokinase activity in Clostridium perfringens. Cells of Clostridium perfringens type D apparently possess only a single species of aspartokinase. This enzyme has been partially purified and shown to be feedback inhibited by meso-diaminopimelate in an allosteric manner. The inhibitor exerts its action noncompetitively with respect to both substrates. The kinetic analysis further indicates that no homotropic cooperative interactions occur between either multiple substrate or inhibitor sites. Like aspartokinases from other bacteria, the clostridial enzyme is stimulated by the presence of either potassium or ammonium cations. A molecular weight of 102,000 was estimated for the enzyme following gel-filtration chromatography. Enzyme activity remains relatively constant throughout the growth cycle of the organism even well into the stationary growth phase. These results are discussed in terms of the role of the enzyme in the growth of the organism.


Factors in the identification of human skeletal remains.


The gua operon of Escherichia coli K-12: evidence for polarity from guaB to guaA. Guanine auxotrophs of Escherichia coli K-12 were isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methane sulfonate, or the acridine mustard ICR 372. guaA (xanthosine 5'-monophosphate [XMP] aminase-less) mutants were distinguished from guaB (inosine 5'-monophosphate [IMP] dehydrogenase-less) mutants by their growth response to xanthine and by enzyme assay. Mutations were classified as base substitutions or frameshift on the basis of mutagen-induced reversion patterns. All guaA strains, including three frameshift mutants, produced derepressed levels of IMP dehydrogenase when cultured with a growth-limiting concentration of guanine. The guaB strains were of two types: (i) those producing derepressed levels of XMP aminase, and (ii) those producing basal levels of XMP aminase when grown under conditions of guanine starvation. In the guaB strains of the second type, the expression of the adjacent guaA gene is reduced. It is proposed that this pleiotropic effect of some guaB mutations is a result of polarity. The orientation of polarity suggests the gene order "operator"-guaB-guaA. Gel diffusion studies with IMP dehydrogenase antiserum showed that strains carrying polar guaB mutations do not produce cross-reacting material (CRM). The remaining guaB mutants were either CRM(+) or CRM(-). Mapping the mutations by three-factor crosses showed that polar and nonpolar guaB sites are clustered in a small genetic region cotransducible with guaA. The relative positions of the guaB mutational sites established that the polar mutations lie within the structural gene for IMP dehydrogenase.


The effect of synthetic peptide on chronic renal hypertension in the rat.


Elevated circulating renin activity in rats following doses of cadmium known to induce hypertension.


Cord-blood low-density lipoprotein cholesterol: estimation versus measurement with the preparative ultracentrifuge.


The nature of the granules within sulcular epithelial cells.


A dual precipitation method for quantitative plasma lipoprotein measurement without ultracentrifugation.


Hycanthone-induced hepatic changes in mice infected with Schistosoma mansoni.


Comparative study of the action of phenothiazine and para-fluorobutyrophenone derivatives on rat brain membranes using the spin label technique.


Adrenergic-adenosine 3',5'-monophosphate regulation of serotonin N-acetyltransferase activity and the temporal relationship of serotonin N-acetyltransferase activity synthesis of 3H-N-acetylserotonin and 3H-melatonin in the cultured rat pineal gland.


Renin-angiotensin system in human hypertension due to segmental renal ischemia.


Enhancement of the inotropic action of glucagon by small concentration of angiotensin.


Bursa-dependent and thymus-dependent "surveillance" of a virus-induced tumour in the chicken.