Resolution of three distinct populations of nerve endings from rat brain homogenates by zonal isopycnic centrifugation. Conditions have been established for the fractionation of subcellular components of rat forebrain homogenates by zonal isopycnic equilibration in continuous sucrose density gradients using a B-XIV rotor. The fractions were analyzed biochemically and by ultra-structural morphometry. Starting from postnuclear supernates of forebrain homogenates, it has been possible to resolve three distinct populations of nerve endings from one another, as well as from free mitochondria and myelin fragments. The three types of nerve endings differ in their apparent specific gravity, their biochemical properties, and their ability selectively to accumulate exogenous transmitter substances in vitro. These three particle populations are likely to represent, in order of increasing modal equilibrium density, (a) cholinergic nerve endings, characterized by their high content of acetylcholine, (b) gamma-amino butyric acid (GABA)-containing nerve endings with high glutamate decarboxylase activity and the ability to accumulate exogenous GABA, (c) adrenergic nerve endings that accumulate exogenous dopamine and noradrenaline and exhibit high monoamine oxidase activity.


Ultrastructural localization of concanavalin A receptors in somatic cell hybrids between normal mouse cells and simian virus 40-transformed rat cells.


Bulk isolation of mouse hepatocyte gap junctions. Characterization of the principal protein, connexin.


A single extraction thin-layer chromatographic method in current use.


Quantitative spectrodensitometry on morphine and amphetamine on thin layer chromatograms.


Glycosphingolipids from rabbit aorta, plasma, and red blood cells: effects of high cholesterol-high fat diets on fatty acid distribution and quantity of glycosphingolipids. Four glycosphingolipids were isolated from rabbit aorta, plasma, and red blood cells. They were identified, by thin-layer chromatography and by quantitative analysis of hexose and fatty acid, as cerebroside, diglycosyl ceramide, triglycosyl ceramide, and globoside. The rabbits had been maintained on a normal diet or on one of three high cholesterol diets for 180 days. The quantities of the glycosphingolipids and their fatty acid distributions were determined, and comparisons were made between the control and experimental animals. Aorta and plasma glycosphingolipids were more affected by the high cholesterol diets than were those from red blood cells. The effects on aorta and plasma glycosphingolipids were similar. The amount of cerebroside was increased in aorta and plasma in all animals in the experimental groups. The amount was also increased in red blood cells in rabbits from two of the experimental groups. The average fatty acid chain length was greater in the lipids from the experimental animals than in those from the control animals for all measured glycosphingolipids from aorta. The average chain length was also greater in cerebrosides from the experimental animals from all three tissues. Probably the most notable differences in the experimental animals were the increased 24:1/24:0 ratios and the increased concentrations of 24:2. These increases occurred in nearly all samples from plasma and aorta, but not in red blood cells. There was also an increase of total unsaturated fatty acids in aorta cerebrosides from the experimental animals. Except for the increase in 24:2, lard generally caused more deviation from normal than did cottonseed oil when the level of cholesterol in the diet was 1%.


Inhibition of free fatty acid mobilization by colchicine. Segments of epididymal adipose tissue from normal male rats were incubated with micromolar concentrations of colchicine for different periods of time up to 4 hr, and the mobilization of free fatty acids (FFA) was measured during a subsequent reincubation. Although pretreatment with colchicine did not alter basal unstimulated FFA release, mobilization of FFA in the presence of epinephrine or theophylline was reduced. However, neither lipolysis, as judged by glycerol production, nor cyclic AMP accumulation was impaired under the same conditions. To assess the possibility that colchicine might limit production of fatty acids by accelerating the entry and metabolism of glucose into adipocytes, the metabolism of glucose by adipose tissue was studied. Pretreatment with colchicine did not affect uptake of glucose nor its oxidation to CO(2), although colchicine-treated tissues did have slightly more [(14)C]glucose incorporated into the glyceride moiety of triglyceride. When adipose tissues pretreated with colchicine were incubated in an albumin-free medium, no reduction in FFA production by colchicine was observed. Because no FFA release occurs in albumin-free media, this experiment suggests that colchicine-induced inhibition of FFA mobilization results from impaired extrusion of FFA from adipose cells.


3-Hydroxy-3-methylglutaryl CoA reductase and mevalonate kinase of Neurospora crassa. Two enzymes of polyisoprenoid synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (mevalonate:NADP oxidoreductase [acylating CoA], EC 1.1.1.34) and mevalonate kinase (ATP:mevalonate 5-phosphotransferase, EC 2.7.1.36), are present in the microsomal and soluble fractions of Neurospora crassa, respectively. HMG CoA reductase specifically uses NADPH as reductant and has a K(m) for dl-HMG CoA of 30 micro M. The activities of HMG CoA reductase and mevalonate kinase are low in conidia and increase threefold during the first 12 hr of stationary growth. Maximum specific activities of both enzymes occur when aerial hyphae and conidia first appear (2 days), but total activities peak later (3-4 days). Addition to the growth media of ergosterol or beta-carotene, alone or in combination, does not affect the specific or total activity of either enzyme. The mevalonate kinase of N. crassa, purified 200-fold to a specific activity of 5 micro moles/min/mg, is free from HMG CoA reductase, phosphomevalonate kinase, ATPase, adenylate kinase, and NADH oxidase activities. Mevalonate kinase specifically requires ATP as cosubstrate and exhibits a marked preference for Mg(2+) over Mn(2+), especially at high ratios of divalent metal ion to ATP. Kinase activity is inhibited by p-hydroxymercuribenzoate, and this inhibition is partially prevented by mevalonate or MgATP. Optimum activity occurs at pH 8.0-8.5 and at about 55 degrees C. The Neurospora kinase, like that of hog liver, has a sequential mechanism for substrate addition. The Michaelis constants obtained were 2.8 mM for dl-mevalonate and 1.8 mM for MgATP(-2). Geranyl pyrophosphate is an inhibitor competitive with MgATP (K(i) = 0.11 mM).


Structure and composition of sulfatides isolated from livers of patients with metachromatic leukodystrophy: galactosyl sulfatide and lactosyl sulfatide. The livers of four patients with metachromatic leukodystrophy contained galactosyl sulfatide and lactosyl sulfatide, whereas these substances were undetectable in normal human liver. On the basis of methanolysis and permethylation studies, both sulfatides were shown to be substituted with sulfate at the C-3 position of the galactose moiety. Examination of the fatty acid compositions of these sulfatides showed that C(22:0) and higher 2-hydroxy and nonhydroxy fatty acids predominated in both. Both sulfatides contained the same long-chain bases, predominantly sphingosine, dihydrosphingosine, and phytosphingosine. Using as criteria the proportion of lactosyl sulfatide to galactosyl sulfatide, and the fatty acid and long-chain base compositions, the liver sulfatides from subjects with metachromatic leukodystrophy closely resemble those in the kidney and differ from those in brain and peripheral nerve.


High performance liquid chromatography of ceramides: application to analysis in human tissues and demonstration of ceramide excess in Farber's disease. Conditions have been determined for the benzoylation of ceramides containing nonhydroxy and hydroxy fatty acids, and a high performance liquid chromatography system for the separation and measurement of these derivatives has been devised that is capable of good resolution and high sensitivity. These methods have been used to determine quantitatively the levels of ceramides in human tissues, and in serum and urine, and to demonstrate elevated amounts of ceramide in Farber's disease urine and tissues.


Steryl esters and their relationship to normal and diseased human central nervous system. The composition and distribution of steryl esters in human diseased or developing brain tissue has been studied. The abnormal brain conditions included sudanophilic leukodystrophy, multiple sclerosis plaque, subacute sclerosing panencephalitis, and an old cerebral infarction and two types of brain-derived tumors. In addition to the above abnormal tissue, steryl esters were also examined in developing and normal adult human brain. It was found upon subcellular fractionation that the steryl ester was localized mainly in the soluble nonparticulate material. A cholesteryl ester-rich fraction, floating on top of distilled water after centrifugation, was recovered only in the developing brain or in instances where there was myelin damage. The sterol portion of the steryl ester was largely cholesterol. The fatty acid moiety was mainly composed of C(16), C(18), and C(20) fatty acids. The dominant fatty acid was oleic acid, and the proportion of this fatty acid increased in demyelination. Although there were great differences in the quantities of steryl ester found, the fatty acid profiles of normal developing and adult brain were quite similar. As has been noted by others, the fatty acid composition of brain steryl esters most closely resembles that of brain phosphatidylcholine.


Permeability changes induced by peroxidation in liposomes prepared from human erythrocyte lipids. The diffusion of [2-(14)C]glucose out of liposomes prepared from extracted human erythrocyte lipids was examined. Increased glucose efflux was observed when the lipids were treated with hydrogen peroxide and CuCl(2) before liposome formation, and this phenomenon required both peroxide and metal. Peroxidation of these lipids also resulted in the destruction of polyunsaturated fatty acids and the generation of conjugated dienes, but neither of these processes appeared to be the sole cause of increased glucose efflux. Thin-layer chromatography and the effects of aqueous washes suggested that surface-active lysophosphatides or other lipid degradation products were responsible for the increased permeability of the treated liposomes. It is suggested that the behavior of this liposome model system may be relevant to the high permeability and fragility of vitamin E-deficient erythrocytes.


Quantitative determination of lysolecithin and sphingomyelin in phospholipid mixtures by thin-layer chromatography as applied to the thymus of the fmfm mouse. Lysolecithin and sphingomyelin may be readily separated from other phospholipids on thin-layer plates impregnated with silver nitrate using the solvent system chloroform-methanol-concentrated ammonium hydroxide 65:35:8. Quantitation is carried out by determining the phosphorus content of the developed bands. The minimum amount of phospholipid that can be quantitatively determined is that which contains 0.7 micro g of phosphorus. This method has been used for the determination of lysolecithin and sphingomyelin in the tissues of mice having foam-cell reticulosis.


Use of stainless steel wire coil prosthesis in treatment of anastomotic dehiscence after cervical tracheal resection.


Simple assay for monoacylglycerol hydrolase activity of rat adipose tissue. A simple, sensitive, and specific assay for monoacylglycerol hydrolase activity of rat adipose tissue is described. Monoacyl[(3)H]glycerols with different chain lengths (8-18 carbon atoms) and different degrees of unsaturation in mixed micellar solution with different detergents can be used as substrates. The [(3)H]glycerol that is produced is isolated in a one-step liquid-liquid partition procedure. For routine purposes monooleoyl[(3)H]glycerol was found to be the most suitable substrate. A simple method for the chemical synthesis and purification of this substrate in high yield is given. The assay allows rapid serial sampling of enzymatic activity with a high reproducibility.


Mucus gland adenoma of the bronchus.

Mucus gland adenoma of the bronchus.


Arteriographic findings in mediastinal chemodectoma.


Granular-cell tumor. Review of the literature and report of a case.


The effect of systemic disorders on the dental pulp in experimental animals.


Competitive protein-binding assay for corticoids in the peripheral plasma of the immature chicken.


Isolation and purification of turkey heme proteins.


Steroid metabolism by human breast and rat mammary carcinomata.


Dual role of calcium in steroidogenesis in the isolated adrenal cell of rat.


A novel form of covalently bound flavin from thiamine dehydrogenase.


Comparative study on the binding of estrogens by human and rat serum proteins in development.


The role of tryptophan in neutral fructose diphosphatase.


A different pattern of insulin release in the perifused islets of the rabbits.


Activity of protein-deficient 30S ribosomal subunits in elongation factor G-dependent GTPAse.


Antibiotic mucidin, a new antimycin A-like inhibitor of electron transport in rat liver mitochondria.


Sialic acid residues exposed on mammalian cell surface: the effect of adsorption of denatured virus particles.


A recognition marker required for uptake of a lysosomal enzyme by cultured fibroblasts.


Linoleic- and linolenic acid dependency of some brain membrane-bound enzymes after lipid deprivation in rats.


Insulin and non-suppressible insulin-like activity (NSILA-s): evidence for separate plasma membrane receptor sites.


A fluorescent spot test for the detection of galactokinase deficiency.


Immunity to cancer: naturally occurring tumours in domestic animals as models for research. 2. Part 1 of this Memorandum appeared in Vol. 49, pages 81-91. Part 2 covers neoplasia of the bovine urinary bladder; tumours of unknown cause (including melanomas, osteosarcomas, mammary tumours, lymphosarcomas, mastocytomas, transmissible venereal tumours, and histiocytomas); and the applications of animal models in studies of neoplasia. A summary of animal models is included as an annex.


Case report No. 16942.

Case report No. 16942.


Phospholipids of adrenal cortex mitochondria and the steroid hydroxylases: the lipid-environment of cytochrome P-450.


Protein kinase in adipose tissue: effect of hypophysectomy.


Renal handling of cortisol in dogs. II. Effect of ACTH on stop flow pattern.


The cyclic AMP-mediated action of epinephrine on the activity of carbonic anhydrase in avian erythrocytes.


Repair of soft tissue injuries of the face.


What is CWIM?

What is CWIM?


Kidney function during anesthesia and hemorrhage.


Explanation for the apparent inefficiency of reduced nicotinamide adenine dinucleotide in energizing amino acid transport in membrane vesicles. Lineweaver-Burk plots of reduced nicotinamide adenine dinucleotide (NADH) oxidation by membrane preparations from Bacillus subtilis are biphasic, with two K(m) values for NADH. The higher K(m) corresponds to the only K(m) observed for NADH oxidation by whole cells, whereas the lower K(m) corresponds to that observed with open cell envelopes. Membrane preparations apparently contain a small fraction of open or inverted vesicles which is responsible for the low K(m) reaction, whereas entry of NADH into the larger portion of closed, normally oriented vesicles is rate limiting and responsible for the high K(m) reaction. In contrast, the oxidation of l-alpha-glycerol-phosphate (glycerol-P) by membrane preparations shows only one K(m) that corresponds to that of glycerol-P oxidation by whole cells or lysates. Since glycerol-P dehydrogenase (NAD independent) has the same K(m), this enzyme reaction rather than entry of glycerol-P into vesicles represents the rate-limiting step for glycerol-phosphate oxidation. The K(m) for amino acid uptake by vesicles in the presence of NADH corresponds to the high K(m) for NADH oxidation, indicating that NADH energizes transport only if it enters closed, normally oriented vesicles. Studies with rotenone and proteolytic enzymes support this interpretation. The apparent efficiency of NADH in energizing uptake seems to be lower than that of glycerol-P because, under the experimental conditions usually employed, open or inverted vesicles that do not participate in amino acid uptake are responsible for the major portion of NADH oxidation. When the results are corrected for this effect, the efficiency of NADH is essentially the same as that of l-alpha-glycerol-P.


Osmiophilic structure in pigment-producing Flavobacterium mutants. A highly osmiophilic structure observed in all pigment-producing mutants of Flavobacterium examined is described. Several factors favor the possibility that this structure might be related to pigment synthesis or pigment accumulation.


Homoserine kinase from Escherichia coli K-12: properties, inhibition by L-threonine, and regulation of biosynthesis. We have partially purified homoserine kinase from a genetically derepressed strain of Escherichia coli K-12. The optimum pH of the enzyme-substrate reaction was 7.8 and the K(m) values for l-homoserine and adenosine 5'-triphosphate were both 3 x 10(-4) M. K(+) (or NH(4) (+)) as well as Mg(2+) were required for its activity. The sedimentation coefficient determined by ultracentrifugation in a sucrose density gradient was 5.0 +/- 0.25S. l-Homoserine was an excellent protector against heat inactivation of homoserine kinase. l-Threonine was a competitive inhibitor of homoserine kinase, suggesting that end-product inhibition of this enzyme plays a role in vivo in the overall regulation of threonine biosynthesis. The specific activity of aspartokinase I-homoserine dehydrogenase I and of homoserine kinase showed a strong positive correlation in extracts from strains under widely varying conditions of genetic or physiological derepression; it was concluded that these two enzymes are coordinately regulated in E. coli K-12.


Intracellular and extracellular nucleotides and related compounds during the development of Myxococcus xanthus. Changes in nucleotide pools and extracellular nucleotides during the developmental cycle of the myxobacterium Myxococcus xanthus were determined using a high-pressure liquid chromatography nucleotide analyzer. A general increase in all nucleotide pools occurred during the morphological phase of glycerol conversion of vegetative cells to myxospores. The levels of the nucleoside triphosphate pools remained high as the myxospore matured and throughout subsequent germination. Oxidized nicotinamide adenine dinucleotide levels were elevated in the dormant myxospore and then declined during germination. The adenylate energy charge value was 0.85 +/- 0.02 for vegetative cells, germinating myxospores, and 6-h-old myxospores. It was interesting that the value for the so-called dormant myxospore was the same as that characteristic of physiologically active cells. The germinating myxospores excreted large quantities of uracil along with lesser quantities of purine nucleoside monophosphates. Although the source of the extracellular uracil cannot be determined from these experiments, it may have been derived from a shift in base ratios accompanying an assumed ribonucleic acid turnover during germination.


Lung collagen composition and synthesis. Characterization and changes with age.


Electron spin resonance studies with dioldehydrase. II. The hyperfine structure of proposed radical intermediates derived from isotopic substitution in 2-chloroacetaldehyde.


Electron paramagnetic resonance, 1-H, and 13C nuclear magnetic resonance studies of the interaction of manganese and bicarbonate with ribulose 1, 5-diphosphate carboxylase.


Effect of uridine on de novo pyrimidine biosynthesis in rat hepatoma cells in culture.


Adenylate cyclase. A new kinetic analysis of the effects of hormones and fluoride ion.


Purification and properties of electron-transferring flavoprotein from Peptostreptococcus elsdenii.


Phosphorylation of acid-soluble nucleolar proteins of Novikoff hepatoma ascites cells in vivo.


Properties of gonadotropin receptors in the cell membranes of bovine corpus luteum.


Oxidation and reduction of soluble cytochrome c by membrane-bound oxidase and reductase systems.


Regulation of the L-arabinose operon BAD in vitro.


Averaged encephalic response of aphasics to linguistic and nonlinguistic auditory stimuli.


Influence of stimulus level and sleep stage on the early components of the averaged electroencephalic response to clicks during all-night sleep.


Surveillance of viral infections at the National Taiwan University Hospital.


Cyclic nucleotide phosphodiesterase activity in rat adrenal gland zones.


Stimulation of brain aromatic alkylamine N-methyltransferase activity by FAD and methylcobalamin.


Composition of myelin. Enzymes.

Composition of myelin. Enzymes.


Effects of hormone treatment and age on the stimulation of rat anterior pituitary adenylate cyclase and cyclic adenosine 3',5' monophosphate by hypothalamic extract.


Proceedings: The immunizing potency of foot-and-mouth disease virus vaccines for swines.


Proceedings: Quantitative assay of the immunizing dose of monovalent vaccines against foot-and-mouth disease prepared from the virus propagated on cattle tongue mucosa and in culture after Frenkel.


Proceedings: Isolation of various types of enteroviruses from ill children from a nursery school.


Proceedings: The role of vegetables in spread of enteroviruses. I. The presence of poliovirus in overground parts of the plants cultivated on infected soil.


Proceedings: Cow teat inflammation due to a poxvirus.


Action of two hypothalamic factors (TRH, MIF) and of angiotensin II on the behavioral effects of L-DOPA and 5-hydroxytryptophan in mice.


A tissue culture system for studies of the regulation of ether-linked and ester-linked aliphatic moieties in glycerolipids.


Inhibition of subtilisin by boronic acids, potential analogs of tetrahedral reaction intermediates.


The occurrence of beta-glucocerebrosidase activity in the glucocerebroside-rich deposits of Gaucher's disease.


Studies on the in vitro transcription and translation of the lac operon.


Increased response to catecholamines of the cyclic AMP system of rat pineal gland induced by decreased sympathetic activity.


Characterization of the threonine-sensitive aspartokinase--homoserine dehydrogenase of Escherichia coli K12 by transient electric birefringence.


Rapid purification of lactate dehydrogenase from rat liver and hepatoma: a new approach.


Pseudomonas putida cytochrome P-450. Binding of a spin-labeled analog of the inhibitor metyrapone.


Prolyl hydroxylase and an immunologically related protein in mammalian tissues.


Subcellular location of rat liver calciferol-25-hydroxylase.


Changes in membrane lipid structure of illuminated chloroplasts: studies with spin-labeled and freeze-fractured membranes.


Apocrine hidrocystoma (cystademnoma).

Apocrine hidrocystoma (cystademnoma).


Effect of the sodium salt and ethyl ester of alpha-p-chlorophenoxyisobutyric acid (clofibrate) on a fat-mobilizing factor in serum.


Vesicle ultrastructure and RNA synthesis during male meiosis of Glossina austeni (Diptera, Glossinidae).


The activity of 2',3'-cyclic adenosine monophosphate 3'-phosphoesterhydrolase in elasmobranch and teleost brain.


Lysosomal and mitochondrial enzymes in avian muscle.


Subcellular distributions of catalase in rat skeletal muscle.


The fatty acid composition of cholesteryl esters, phospholipids and triglycerides of the baboon, Papio ursinus.


Lipid deposits in ageing human arteries, tendons and fascia.


Gas phase analytical methods for the study of human metabolites. Metabolic profiles obtained by open tubular capillary chromatography.


Clinical and metabolic effects of pentaerythritol tetranicotinate in combination with cholesolvin or clofibrate.


Effect of increased aortic perfusion pressure on fluorescent emission of the isolated rat heart.


The after care project: a viable alternative to home care.


Inhibition of central pressor effects of agiotensin I and II.


Infectious bursal disease virus: growth and characterization in cell cultures.


Arrhenoblastoma in a chukar partridge.

Arrhenoblastoma in a chukar partridge.


Composition and concentration of apolipoproteins in very-low-and low-density lipoproteins of normal human plasma.


Norepinephrine--an antagonist of dibutyryl cyclic AMP in the regulation of narcosis in the rat.


Cytomegalovirus antibody in uremic patients prior to renal transplantation.


Serum lipoproteins in pigs on high-cholesterol-high-triglyceride diets.


The influence of angiotensin II and of adrenaline on the critical opening pressure of vessels in forearm skin. Evidence for a qualitatively different response to angiotensin II in vessels of forearm skin from that in some digital vessels.


A contrast in vascular reactivity between two kinds of experimental hypertension studied by measurements of the critical opening pressure of tail vessels in the conscious rat.


Heat treatment of rat liver denosine 3':5'-monophosphate phosphodiesterase. Kinetic characterization of the low affinity enzyme.


Fructose-1,6-diphosphatase from rat liver. Purification and properties.


Specificities of rat alkaline ribonucleases and cytochemical localization of pancreatic-like ribonucleases.


Dihydroxyacetone sulfate as substrate analogue for alpha-glycerol phosphate dehydrogenase.


Nucleotide and divalent cation interactions with the (Na+ plus K+)-dependent ATPase.


The inhibition by saccharin and cyclamate of phosphotransferase and phosphohydrolase activities of glucose-6-phosphatase.


Inorganic pyrophosphate-phosphohydrolytic activity associated with human placental alkaline orthophosphatase. Nature of the substrate and role of magnesium.


Stereochemistry of hydrogen transfer between pyridine nucleotide and some intermediates of cholesterol catabolism catalyzed by liver alcohol and aldehyde dehydrogenase.


Studies on cyclic nucleotides in the adrenal gland. 3. Properties of cyclic AMP- and GMP-dependent protein kinases in the adrenal gland.


Inhibitors of glucagon inactivation. Effect on glucagon--receptor interactions and glucagon-stimulated adenylate cyclase activity in liver cell membranes.


Rabbit muscle L-glycerol-3-phosphate dehydrogenase. Substrate activity of 3,4-dihydroxybutyl 1-phosphonate and 4-hydroxy-3-oxobutyl 1-phosphonate.


Adenosine 3',5'-cyclic monophosphate in higher plants: assay, distribution and age-dependency.


Analogs of alpha-tocopherol as inhibitors of cyclic-AMP and cyclic-GMP phosphodiesterases and effects of alpha-tocopherol deficiency on cyclic AMP-controlled metabolism.


Formation, accumulation and release of adenosine 3',5'-monophosphate induced by histamine in the superior cervical ganglion of the rat in vitro.


Protein-bound carbohydrate content of normal and tumorous human lung tissue.


Regulation of fructose metabolism in the perfused rat liver. Interrelation with inorganic phosphate, glucose, ketone body and ethanol metabolism.


Alterations in adenylate cyclase activity of the rat prostate gland.


Effects of glucagon on cyclic AMP and carbohydrate metabolism in livers from diabetic rats.


Insulin receptors in murine mammary cells: comparison in pregnant and nonpregnant animals.


Studies of the metabolism of asialotransferrins: potentiation of the catabolism of human asialotransferrin in the rabbit.


Changes in the adenyl cyclase system of skeletal muscle of cold-acclimated rats.


Studies on corticosterone-receptor complexes from mouse placenta.


Biosynthesis of the diguanosine nucleotides. II. Mechanism of action of GTP:GTP guanylyltransferase on nucleotide metabolism in brine shrimp embryos.


Inhibition of lipogenesis by cylic AMP without altered lipolysis.


Effects of actinomycin D on purine ribonucleotide metabolism in Ehrlich ascites tumor cells in vitro.


Pyrimidine metabolism in Pseudomonas acidovorans.


Characteristics of a reserve alpha-glucan from Clostridium pasteurianum.


Sequential action of cell wall hydrolases in the germination and outgrowth of Microsporum gypseum macroconidia.


Morphologic and functional studies in lymph nodes regional to cancer.


A comparison of the properties of FSH from several species as determined by a rat testis tubule receptor assay.


The mechanism of frog skin lightening by acetylcholine.


Adhesion of red cells to foreign surfaces in the presence of flow.


Extracellular lipids of Pseudomonas aeruginosa NCTC2000 obtained by n-butanol extraction of stationary liquid cultures.


Studies on the degradation of poliovirus by heat.


Demonstration of myositis ossificans by 99mTc pyrophosphate bone scanning.


Aldehyde-osmium fixation of the rat olfactory bulb: correlation between synaptic patterns and nature of the transmission.


Neurosurgical aspects of leprosy.

Neurosurgical aspects of leprosy.


Phosphorylation in vitro of adrenal subcellular proteins by adenosine-3',5'-monophosphate-dependent protein kinase: effect of ACTH in vivo.


Accentuation by angiotensin II of the antidiuretic and dipsogenic responses to intracarotid infusions of NaCl and fructose.


Hypercorticism in rabbits immunized against corticosteroids.


Action of cyclic adenosine 3',5' monophosphate on protein synthesis in a thyroidal cell-free system. Relation to ATP and GTP.


Gastric localization of endodermal sinus tumour.


The fine structure of possible carcinoma-in-situ in the seminiferous tubules in the testis of four infertile men.


Ultrastructural study of heterokaryons from rous rat sarcoma cells and normal chickens cells.


Intracranial tumours induced in guinea pigs with Rous sarcoma virus.


Ultrastructural changes of rat blastocysts induced by estrogen during delayed implantation.


Competition between p-aminophenol, p-nitrophenol, and bilirubin for glucuronidation in cultures of rat hepatoma cells and homogenates of the same cells.


Inhibition of vesicular stomatitis virus replication by 9-beta-D-arabinofuranosyladenine. 9-beta-d-Arabinofuranosyladenine (Ara-A) effectively inhibited the production of infectious vesicular stomatitis virus (VSV) in MDBK cells. Furthermore, inhibition was shown to begin as early as the first 3 hr of infection. Studies employing (3)H-l-leucine indicated that Ara-A did not affect protein synthesis in uninfected cells, although it did cause a marked stimulation of protein synthesis in VSV-infected cells during the log phase of the growth cycle. Puromycin, an inhibitor of protein synthesis, was a more effective viral inhibitor than Ara-A. However, the combination of Ara-A and puromycin was less effective than puromycin alone except when present for long time periods. Short-term labeling experiments with (3)H-uridine demonstrated that Ara-A depressed ribonucleic acid (RNA) synthesis in uninfected cells, whereas periods of stimulation and depression of radioisotope incorporation occurred in infected cells. The results support the notion that Ara-A is incorporated into RNA early during viral replication.


Spectrophotometric method for the estimation of 6-aminopenicillanic acid. A simple, rapid, and sensitive method is described whereby 6-aminopenicillanic acid can be spectrophotometrically determined in the presence of penicillins and their degradation products without prior separation. d-(+)-Glucosamine is used as reagent. The effect of such parameters as pH, temperature, and time of heating on the formation of the chromophore is described. The recommended range is from 25 to 250 mug of 6-aminopenicillanic acid.


Metabolism of penicillins to penicilloic acids and 6-aminopenicillanic acid in man and its significance in assessing penicillin absorption. Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation.


Reversible inhibition of herpes simplex virus replication by hydroxyurea. Hydroxyurea, at a concentration of 5 x 10(-2) M, inhibits the replication of herpes simplex deoxyribonucleic acid (DNA) in the nuclei of infected cells. As a result, the synthesis of infectious virus progeny was prevented. The presence of parental viral DNA genomes in inhibited cells led to the synthesis of the viral structural peptides. The inhibitory effect of hydroxyurea was reversible; after washing the cells free from hydroxyurea, virus progeny appeared after a lag of 3 h. Upon resumption of viral DNA replication, the content of radioactive viral structural peptides gradually increased in parallel with the increase in mature virions. It is concluded that the information for the synthesis of viral structural peptides is transcribed from the parental DNA genomes.


Antiviral activity of tobacco smoke condensate on encephalomyocarditis infection in mice. A water-soluble nontumorigenic acidic fraction of tobacco smoke condensate of cigarettes has been found to have antiviral activity against encephalomyocarditis (EMC) virus infection in mice. The portion of lower molecular weight was inhibitory to the growth of EMC virus, vesicular stomatitis virus, reovirus type 2, vaccinia virus, and poliovirus type 2, but not against adenovirus type 12, in KB cell cultures. The cigarette smoke agent did not induce serum interferon although it protected mice from EMC disease by pretreatment.


Trial of the antiviral action of isoprinosine against rhinovirus infection of volunteers. Isoprinosine (NPT-10381) was given orally to a group of 22 volunteers at a daily dose of 6 g for 7 days; a control group of 23 volunteers received placebo. Volunteers were inoculated intranasally with both rhinovirus type 9 and rhinovirus type 31, and the clinical picture, extent of virus shedding, and serological responses were assessed. There was no evidence that the compound had useful antiviral activity under the conditions of this trial.


N,N-dioctadecyl-N',N'-bis(2-hydroxyethyl) propanediamine: antiviral activity and interferon stimulation in mice. CP-20,961, N,N-dioctadecyl-N', N'-bis(2-hydroxyethyl)propanediamine, is an antiviral drug with low acute toxicity in mice. Parenteral injection of this compound protected mice against lethal infections with encephalomyocarditis and Semliki Forest viruses and effectively suppressed pox formation by vaccinia infection. Maximal antiviral effects were observed when CP-20,961 was administered 6 to 12 h before infection. An interferon detected in plasma 12 to 20 h after the drug was given appeared to mediate these effects. Comparison of the minimal effective and lethal doses in mice established a therapeutic index of 300.


Synergism of polymyxin and sulfonamides in L-forms of Staphylococcus aureus and Proteus mirabilis. Earlier workers suggested that synergism of polymyxin and sulfonamides occurred because sulfonamides produced changes in the cell wall which permitted the more ready access of polymyxin. We tested this hypothesis by using L-forms, which lack cell wall. The demonstration that synergism of polymyxin and sulfonamides occurs in L-forms of Proteus mirabilis and Staphylococcus aureus suggested that the synergism is a result of some mechanism other than alterations of the cell wall.


Interaction of poliovirus-specific RNAs with HeLa cells and E. coli.


Double-stranded ribonucleic acid from Mengo virus: production, characterization, and interferon-inducing and antiviral activities in comparison with polyriboinosinic-polyribocytidylic acid. Mengo virus double-stranded ribonucleic acid (dsRNA) was obtained on a semi-industrial scale from infected cultures of BHK-21 cells grown in suspension. Yield of the extraction and purification operations was small (about 22 mg from 10(11) cells in a 100-liter culture). Physicochemical characterization of this dsRNA gave an estimated molecular weight close to 4 x 10(6), a density of 1.59 (similar to that of the poliovirus dsRNA), and a thermal transition midpoint of 94 C. This product was a little more toxic for the mouse, by the intravenous route, than polyriboinosinic . polyribocytidylic acid (poly I:C) and strictly comparable in this respect to poliovirus dsRNA. The interferon-inducing capacity in the mouse and the antiviral activities in the mouse (infected with encephalomyocarditis, Semliki Forest, influenza, foot-and-mouth disease, and murine hepatitis viruses) and in the rabbit (Shope fibroma virus) of the ultraviolet light-inactivated product were practically identical, on a quantitative basis, with those of poly I:C. In vitro and in vivo experiments showed the dsRNA from Mengo virus to be slightly but significantly more resistant than poly I:C to the inactivating effect of human serum.


The SV40 "S" antigen and other papovavirus-induced surface antigens.


Alterations in bovine endothelial histidine decarboxylase activity following exposure to shearing stresses.


Alcoholic steatonecrosis. II. Prospective study of prevalence of Mallory bodies in biopsy speciemens and comparison of severity of hepatic disease in patients with and without this histological feature.


Endoscopic localization of a duodenal wall tumor in Zollinger-Ellison syndrome.


Implications of portal hepatotrophic factors in hepatology.


Possible involvement of cyclic AMP in regulation of masculine sexual behaviour by testosterone.


Proceedings: Effect of synthetic corticotrophin analogues on plasma delta4-androstenedione, testosterone and gonadotrophins in normal men.


Proceedings: Cytoplasmic steroid hormone 'receptors' in reproductive organs.


Plasma testosterone, androstenedione and urinary 17-oxosteroids in hirsutism.


Proceedings: Effects of prostaglandin E1 and an endogenous inhibitor of vasopressin action on the cyclic AMP system in toad bladders.


Proceedings: The influence of the oestrous cycle upon the energy supply for angiotensin-induced contractions of rat uterus and colon.


Proceedings: Corticosterone in the control of corticotrophin secretion in the rat.


Proceedings: Pituitary-adrenocortical function in the reserpine-treated rat.


Inhibition of formation of birefringent crystals by high humidity in citrus red mites infected with virus.


The development of spindle inclusions of Choristoneura fumiferana (Lepidoptera: Tortricidae) infected with entomopox virus.


67Ga-citrate imaging in untreated primary lung cancer: preliminary report of Cooperative Group.


Tumor uptake of 99mTc-polyphosphate: its similarity with 87mSr-citrate and dissimilarity with 67Ga-citrate.


Modification of intestinal stimulatory effects of 5-hydroxytryptamine by adrenergic amines, prostaglandin E1 and theophylline.


Effects of verapamil on the short-circuit current of an epithelial membrane: the toad urinary bladder.


Lipid composition of rat superior cervical ganglion.


In vitro desaturation of 1-14C linoleic acid in Novikoff hepatoma.


Fluorocarbon emulsion as a blood substitute: cerebral microcirculation and related parameters.


Immunologic competence of the immature human fetus. Morphologic evidence from intrauterine Cytomegalovirus infection.


Recurrent herpes genitalis. Treatment with Mycobacterium bovis (BCG).


The nature of pressor responsiveness to angiotensin II in human pregnancy.


Adenoid cystic carcinoma of the uterine cervix.


Relation of type 2 Herpesvirus antibodies to cervical neoplasia. Barbados, West Indies, 1971.


Hypercalcemia associated with chronic renal failure: a unifying hypothesis.


Influence of anti-inflammatory drugs on the electroencephalographic effect of morphine in rabbits.


Influence of citrate ions on the dissolution of silica from asbestos.


Interrelation between silicosis and lung cancer. Preliminary report.


Development of the capillitium in Perichaena vermicularis, a plasmodial slime mold.


A possible virus infection in the brown alga Pylaiella littoralis.


Clinical and polygraphic study of the cataplectic attacks.


ACTH therapy in some nonhypsarrhythmic forms of epilepsy.


Measurement of a progestational and antiandrogenic compound by a competitive protein binding assay.


Histochemical data on the parotid glands of the marmosets, Callithrix jacchus and Callithrix penicillata.


Ulastructural modifications in the keratinization process of the intermediate-layer cells in the epidermis of Natrix natrix (L.).


Histochemical observations on the seminiferous epithelium of the snake testis.


Crystalloid material in marrow macrophages of specific pathogen-free mice.


Cytoplasmic microfilaments in the anterior lobe of the human pituitary gland.


Canine mycoplasmas II: biochemical characterization and serological identification.


Effect of some chemical mutagens on proteolytic activity in Lactobacilli.


Rapid diagnosis by immunofluorescence of viral infections associated with the croup syndrome in children.


Letter: Cyclic GMP and gastric acid secretion.


Are cyclic AMP effects related to real physiological phenomena?


Abnormally high rate of cyclic AMP excretion from an Escherichia coli mutant deficient in cyclic AMP receptor protein.


Content of 3',5' cyclic AMP and cyclic AMP phosphodiesterase in dormant and activated tissues of Jerusalem artichoke tubers.


Adenosine 3',5'-monophosphate-dependent protein kinase and amylase secretion from rat parotid gland.


Regulation of prostaglandin metabolism: inhibition of 15-hydroxyprostaglandin dehydrogenase by thyroid hormones.


Venom exonuclease (phosphodiesterase) immobilized on concanavalin-A-sepharose.


Glucocorticoid tight binding in rat liver and thymus particles.


On the relationship between Lp(a) lipoprotein, "sinking pre-beta-lipoprotein" and inherited hyper-beta-lipoproteinaemia.


Antimicrobial therapy in experimental pseudomonas infection. II.


Enzyme and enzyme fragments purification by specific immunoadsorbents. Application to structural studies of aspartokinase I-homoserine dehydrogenase I of Escherichia coli.


Thyrotropin-binding properties of isolated thyroid cells and their purified plasma membranes. Relation of thyrotropin-specific binding to adenylate-cyclase activation.


A study of the density pattern of ATPase and respiratory enzymes during mitochondrial biogenesis of Saccharomyces cerevisiae.


Isolation and properties of hydroxycinnamate: CoA ligase from lignifying tissue of Forsythia.


Properties of soluble and bound protein kinases isolated from swine kidney.


Metabolism of isolated kidney tubules. Regulation of pyruvate dehydrogenase by metabolic substrates.


Template specificity of eucaryotic DNA-dependent RNA polymerases. Effect of DNA structure and integrity.


Multilayering of the capillary basal lamina in the granular cell tumor. A marker of cellular injury.


Herpetic esophagitis. A common cause of esophageal ulceration.


Testing for drugs. II. Techniques and issues.


Some international differences in histology and survival in breast cancer.


Relationship between the sensitivity of EBV-carrying lymphoblastoid lines to superinfection and the inducibility of the resident viral genome.


Histologic characteristics of breast cancer in Boston and Tokyo.


Oncogenic activity of N-nitrosododecamethyleneimine in liver, glandular stomach and other tissues of NZO-B1 mice.


Temperature-dependent alterations in 2-deoxyglucose uptake in rat cells transformed by a cold-sensitive murine sarcoma virus mutant.


Fractionation of plasma membrane-associated tumor-specific antigen from an aminoazo dye-induced rat hepatoma.


Immunological studies on a case of recurrent Burkitt's lymphoma during immune stimulant treatment.


Distribution of basic azo-dye-binding protein in normal rat tissues and carcinogen-induced liver tumors.


Isolation and characterization of a primate sarcoma virus: mechanism of rescue.


Reversion in hybrids between SV40-transformed hamster and mouse cells.


Aggregation of feline lymphoma cells by hyaluronic acid.


Cell-mediated immunity and blocking factors in patients with tumours of the central nervous system.


The horizontal development of cell-mediated tumor-specific immunity in Rous sarcoma virus tumorigenesis in rats.


Cell-mediated immunity to human oral leukoplakia demonstrated by the leukocyte migration test.


Congenital non-progressive peripheral neuropathy with arthrogryposis multiplex. A family is described in which a hereditary peripheral neuropathy occurs, inherited as an autosomal dominant character. The syndrome is present at birth and does not show any significant progression thereafter. Three of the cases have suffered from arthrogryposis multiplex congenita. A secondary myopathy is also present. The condition appears to be intermediary between peroneal muscular atrophy and Friedreich's ataxia. Appearance at birth, presence of arthrogryposis multiplex congenita, and the non-progressive nature separate it sharply from the other heredofamilial ataxias and peripheral neuropathies.


Acidophilic adenoma of the pituitary with polyneuropathy. An acromegalic man aged 70 developed progressive polyneuropathy affecting mainly the extremities. The peripheral nerves showed hypertrophic neuropathy and accumulation of acid mucopolysaccharides in the nerve without `onion bulb' formation. The myelin showed a lamellar disintegration and vesicular formation. It is suggested that the association of these findings represents a pathological entity, acromegalic polyneuropathy.


In vivo lipogenesis and enzyme levels in adipose and liver tissues from pair-fed genetically obese and lean rats.


Electrophysiological studies of peripheral nerves in patients with organic mercury poisoning. Nineteen patients with organic mercury poisoning were examined clinically and electrophysiological studies were carried out on their peripheral nerves. Four severely affected patients were disorientated, restless, and unable to speak. Vision was abnormal in nearly half the patients, usually consisting of gross constriction of visual fields with preservation of central acuity. Severe cerebellar abnormalities were present in most. Paraesthesiae were common. On sensory examination, all except three patients had one or more of the following abnormalities: reduced appreciation of pin prick peripherally, defective position sensation, abnormal two-point discrimination, astereognosis. Vibration sensation was normal in all. Despite these sensory findings no electrophysiological abnormality was demonstrated in the peripheral nerves. It is suggested that the sensory disturbances are predominantly or entirely due to damage to the central nervous system.


The inhibition of L-3-hydroxyacyl-CoA dehydrogenase by acetoacetyl-CoA and the possible effect of this inhibitor on fatty acid oxidation.


The influence of caffeine on d-amphetamine- and apomorphine-induced stereotyped behavior.


Metabolism of prostaglandin A. I. The kidney cortex as a major site of PGA2 degradation.


Rate of inactivation of adenyl cyclase and phosphodiesterase: determinants of brain cyclic AMP.


Effects of hypothyroidism and hyperthyroidism on dipyrone metabolism in man.


Letter: Adenovirus type 19 keratoconjunctivitis.


BCG and cancer (first of two parts).

BCG and cancer (first of two parts).


Lipid biosynthesis.

Lipid biosynthesis.


Functional parameters in the study of metabolic regulation.


Effect of beta receptor blockade on liver injury induced by carbon tetrachloride.


Letter: Femoral neuropathy.

Letter: Femoral neuropathy.


Sleep-waking patterns and brain biogenic amine levels in cats after administration of 6-hydroxydopamine into the dorsolateral pontine tegmentum.


Roentgenography of the ear and eye in Pyle disease.


Letter: Bile duct adenomatosis of the liver.


Elicitation of water ingestion in the Mongolian gerbil (Meriones unguiculatus) by intracranial injections of angiotensin II and 1-norepinephrine.


Idiopathic hypoglycemia in infancy. Surgical management.


Theoretical view of REM sleep function: maintenance of catecholamine systems in the central nervous system.


Sleep and serotonin in two strains of Mus musculus.


The action of D-amphetamine on spontaneous activity in the caudate nucleus and reticular formation of the rat.


Family treatment within the milieu of a residential treatment center.


Audiological comparison of cochlear and eighth nerve disorders.


Proceedings: Experimental herpes arthritis--chronicity and species specificity.


An Israeli experimental group with primary school dropouts outside the school setting.


Association of nerve fibers and plasma cells in abnormal human nasal respiratory mucosa.


Effect of phenobarbitone treatment on vitamin D metabolism in mammals.


Melatonin and the endocrine role of the pineal organ.


Investigation of serum lipoproteins and apoproteins in abetalipoproteinaemia.


Luteinizing hormone and human chorionic gonadotropin: structure and activity.


The effect of corticotrophine and cortisone on arylsulphatase activity in stomach mucosa of rats.


Cochlear and neural diseases: classification and oto-audiologic correlations.


Effects of BCG on various facets of the immune response against polyoma tumors in rats.


EBV infections in Brazil. I. Occurrence in normal persons, in lymphomas and in leukemias.


Antibody to Epstein-Barr virus and cellular immunity in Hodgkin's disease and chronic lymphatic leukemia.


Comparison of blood platelet and erythrocyte lipids in man in three age groups from three regions: Milan, Cincinnati and Sicily.


Cell locomotion and contact inhibition of normal and neoplastic rat cells.


Platelet lipid modifications induced by fatty acids. Experimental studies and correlations with human neuropathology.


Growth and antigenic properties of a biopsy-derived Burkitt's lymphoma in thymus-less (nude) mice.


Synthesis of murine leukemia virus in cell culture.


Growth regulation and tumour formation of normal and neoplastic rat cells.


Cold-sensitive mutant of Salmonella typhimurium defective in nucleosidediphosphokinase. A cold-sensitive mutant of Salmonella typhimurium defective in nucleosidediphosphokinase (ATP:nucleosidediphosphate phosphotransferase, EC 2.7.4.6) has been isolated and characterized. The mutant contains only 2% of the enzyme activity found in the parent, and the heat lability of this activity is 10 times that from the parent at 33 C. Mutant extracts lack the ability to convert any of 11 nucleoside diphosphates tested to the corresponding nucleoside triphosphates, but the nucleosidemonophosphatase activities are normal. Although the nucleoside triphosphate pools of the mutant are depressed significantly at the restrictive temperature (20 C), they are slightly elevated at the permissive temperature (37 C). The levels of guanosine pentaphosphate and guanosine tetraphosphate are dramatically increased. Two representative enzymes of pyrimidine de novo synthesis, aspartic transcarbamylase and dihydroorotate dehydrogenase, are fully repressed at both 37 and 20 C. Intracellular pools of uridine diphosphate are depressed at both permissive and restrictive temperature.


Effect of lipids and hypolipaemic drugs on platelet aggregation and thrombosis.


Ribonucleic acid regulation in premeabilized cells of Escherichia coli capable of ribonucleic acid and protein synthesis. A cell permeabilization procedure is described that reduces viability less than 10% and does not significantly reduce the rates of ribonucleic acid and protein synthesis when appropriately supplemented. Permeabilization abolishes the normal stringent coupling of protein and ribonucleic acid synthesis.


Inhibition of transformation by sodium metaperiodate in Streptococcus sanguis (Wicky): demonstration that deoxyribonucleic acid binding sites contain amino acids. Addition of sodium metaperiodate to competent Streptococcus sanguis (Wicky) cells at 0 or 37 C revealed that the deoxyribonucleic acid binding sites consist of amino acids.


Properties of a thermosensitive asporogenous filamentous mutant of Bacillus megaterium. Mutant TH14 of Bacillus megaterium ATCC 19213 is thermosensitive and defective in cell-division septation and spore formation at the restrictive temperature (39 C). As a consequence, the mutant forms multinucleate aseptate filaments and is asporogenic. The mutation does not result in any qualitative compositional changes in extractable membrane proteins. At the restrictive temperature, the mutant membrane has a reduced content of a small molecular weight protein(s). A membrane protein(s) with a molecular weight of nearly 80,000 appears to be partially derepressed in the mutant grown at the restrictive temperature. In addition, numerous unidentified spherical inclusions of fairly uniform size (diameter approximately 100 nm) are present in the cytoplasm at the restrictive temperature. They are especially concentrated at only one pole of each filament. Filamentous growth of the mutant is less sensitive to penicillin than growth in the rod form. Growth in either form is equally sensitive to d-cycloserine at the concentrations used for selection of the mutant. Temperature shift-up experiments suggest that one to two rounds of deoxyribonucleic acid (DNA) replication occur before the phenotypic expression of the mutation occurs. The septations after these replication events can be either two-division septations or a single-division septation plus a subsequent sporulation septation. This conclusion, coupled with previously reported work, supports the hypothesis that the early stages of sporulation represent a modified cell division.


Characteristics and relationships of mercury-resistant mutants and methionine auxotrophs of yeast. Approximately one-half of the mutants of Saccharomyces cerevisiae that are selected as resistant to methyl mercury are also found to require methionine. Eighty-four percent of these met mutations occur at the met15 locus, and the remaining 16% occur at the met2 locus. Surprisingly, the methionine-requiring mutants are recovered at a much higher frequency on methionineless media than on media supplemented with methionine. Growth patterns of the met mutants on media having a continuous concentration gradient of methionine and mercury compounds indicate that, at a critical concentration of the mercury compounds, the methionine requirement of certain met mutants is partially or completely alleviated. This was found for met2, met15, and to a lesser extent for met6, but not for any other methionine mutants. This loss of methionine requirement is produced with methyl mercury, phenyl mercury, and mercuric chloride although met2 and met15 strains can be shown to be resistant only to methyl mercury. Other methionine auxotrophs are not resistant to any of the three mercury compounds. The met2 and met15 mutants, but not the other methionine auxotrophs, develop a sheen of an unidentified product when grown on media with mercuric chloride but not with methyl mercury or phenyl mercury. It is suggested that met2 and met15 mutants produce a simple diffusible substance, which detoxifies methyl mercury, which reacts with mercuric chloride to produce a sheen, and which is the cause of the methionine requirement.


Threonine locus of Escherichia coli K-12: genetic structure and evidence for an operon. Three genes, thrA, thrB, and thrC, were previously defined and localized in the threonine locus of Escherichia coli K-12. thrA, thrB, and thrC specify the enzymes aspartokinase I-homoserine dehydrogenase I, homoserine kinase, and threonine synthetase, respectively. A complementation analysis of the threonine cluster using derivatives of a lambda phage carrying the threonine genes (lambdadthr(c)) demonstrates that: (i) thrB and thrC each consist of a single cistron; and (ii) thrA is composed of two cistrons, thrA(1) and thrA(2), although it specifies a single polypeptide chain. thrA(1) and thrA(2) correspond to aspartokinase I and homoserine dehydrogenase I, respectively. Their relative order is established. The demonstration of polar effects of mutations (nonsense or induced by phage Mu) in thrA and thrB is taken as evidence for the existence of a thrA thrB thrC operon, transcribed in this order.


Autogenous immunity to endogenous RNA tumor virus. Identification of antibody reactivity to select viral antigens. The viral antigenic determinants recognized in an autogenous immune response in mice against their endogenous C-type virus have been identified by SDS-polyacrylamide gel electrophoresis of immune precipitates between various sera and H(3)-labeled intact or disrupted AKR leukemia virus. Normal B6C3F(1) [(C57BL/6 x C3H/Anf)F(1)] serum reacts with viral envelope antigens having mol wt of approximately 68,000, 43,000, and 17,000. In addition, minor reactions with viral antigens having mol wts of approximately 19,000 and 15,000 are demonstrable. The 68,000 and 43,000 mol wt antigens can be labeled with [(3)H]glucosamine and may correspond to the major viral envelope antigens M(2) and M(1), respectively. The antigens recognized by autogenous immune sera do not differ with respect to age of the animal, nor are they significantly different in sera from various strains of mice (BALB/c, C57BL/6, and C3H/Anf). These results suggest that the age-asociated and strain variations in the autogenous immune response, as determined by radioimmune precipitation assays against intact virus, are due to quantitative and qualitative alterations of antibody levels against common antigens.


Hormonal control of lysosomal enzyme release from human neutrophils. Effects of autonomic agents on enzyme release, phagocytosis, and cylic nucleotide levels. The purpose of this investigation was to examine the effects of autonomic neurohormones, cyclic nucleotides, and related agents on the immunologic discharge of lysosomal enzymes from, and phagocytosis by, purified human neutrophils. In order to discern the possible intracellular mechanisms by which certain neurohormones influence neutrophil function, the concentrations of cyclic AMP and cyclic GMP in neutrophils were assessed during cell contact with phagocytizable particles and autonomic agents. The model system employed for study was the interaction of purified human neutrophils with rheumatoid arthritic (RA) serum-treated zymosan particles at 37 degrees C in a neutral, balanced salt solution containing glucose. Neutrophils ingested the particles and discharged beta-glucuronidase but not lactate dehydrogenase activity during 30 min of incubation. Treatment of zymosan particles with RA serum was more effective than treatment with normal serum with regard to the extent of both particle uptake and lysosomal enzyme release. During contact of neutrophils with RA serum-treated zymosan particles epinephrine, isoproterenol, and cyclic AMP inhibited both particle ingestion and beta-glucuronidase discharge. These actions of epinephrine were associated with a concomitant elevation of cyclic AMP levels. In contrast to the actions of catecholamines and cyclic AMP, acetylcholine and cyclic GMP accelerated lysosomal enzyme release without affecting particle uptake. The actions of acetylcholine were associated with a concomitant elevation of cyclic GMP levels. Increases in neutrophil levels of cyclic GMP but not of cyclic AMP were associated also with the discharge of beta-glucuronidase provoked by particles in the absence of added cholinergic agents. The data suggest that the immunologic release of lysosomal enzymes from human neutrophils can be regulated by autonomic neurohormones, perhaps via the selective formation of appropriate nucleotides.


3-Substituted 5,7-dimethylpyrazolo(1,5-a)pyrimidines, 3',5'-cyclic-AMP phosphodiesterase inhibitors. 1.


Enzymatic isotopic assay for and presence of beta-phenylethylamine in brain.


Isolation and partial characterization of rat brain synaptic plasma membranes.


The lipid composition of axons from bovine brain.


Mechanisms activating glycolysis in the brain in arterial hypoxia.


The effect of porta-caval anastomosis upon the energy state and upon acid-base parameters of the rat brain.


Effect of neurotransmitters on phospholipid metabolism in rat cerebral-cortex slices: cellular and subcellular distribution.


Changes in brain alcohol dehydrogenase activity during chronic ethanol ingestion and withdrawal.


Effects of neonatal hyperthyroidism on activity of cyclic AMP-dependent microsomal protein kinase.


2',3'-Cyclic AMP 3'-phosphohydrolase activity during Wallerian degeneration.


The biosynthesis and concentration of galactosyl diglyceride in glial and neuronal enriched fractions of actively myelinating rat brain.


Detergent-like action of tetraphenylborate on phospholipid labelling in guinea pig cortex subfractions.


Neuronal cell body enriched and glial cell enriched fractions from young and adult rat brains: preparation and morphological and biochemical properties.


Elevation of cyclic GMP levels in central nervous system by excitatory and inhibitory amino acids.


In vivo changes of cerebral cyclic adenosine 3',5'-monophosphate induced by biogenic amines: association with phosphorylase activation.


Enzymatic acylation of histidine to mengovirus RNA.


Influence of cephalin and egg lecithin on pig heart malate dehydrogenase activity.


Structure of inositol hexaphosphate--human deoxyhaemoglobin complex.


Prostaglandins and the regulation of uterine blood flow in pregnancy.


Expression of polyoma-induced antigens in low malignant hybrids derived from fusion of a polyoma-induced tumour with a fibroblast line.


Presence of HCN in chlorella vulgaris and its possible role in controlling the reduction of nitrate.


Solubilisation of angiotensin II receptors in rabbit aortae membranes.


Class of promotor sites for Escherichia coli DNA-dependent RNA polymerase.


Cytochrome c oxidase: some current biochemical and biophysical problems.


Alpha-hydrazino-ornithine blocks net synthesis of putrescine but not of RNA and DNA.


Blocking antibodies and enhancement.

Blocking antibodies and enhancement.


Thyroid hormone action: in vitro demonstration of putative receptors in isolated nuclei and soluble nuclear extracts. Saturable binding activities for triiodothyronine were demonstrated in vitro with isolated nuclei and soluble nuclear extracts of rat liver, kidney, and cultured GH(1) cells. The binding activity can be extracted from nuclei in soluble form with no significant change in hormone affinity and has properties of a nonhistone protein.


Latent ganglionic infection with herpes simplex virus types 1 and 2: viral reactivation in vivo after neurectomy. Inoculation of the cornea, lip, or footpad of mice with herpes simplex virus type 1 resulted in a latent infection of the local sensory ganglia. Inoculation of the vagina and cervix with herpes simplex virus type 2, as well as type 1, also induced a latent ganglionic infection. With the use of sciatic nerve section as a stimulus, a reproducible model of viral reactivation in vivo was established.


Invasive mole, gestational choriocarcinoma and transplantation antigens.


Phospholipid requirements in thrombin formation.


A new in vitro method for assay of the biological activity of growth hormone.


Effects of hypophysectomy with or without ACTH maintenance therapy on the final steps of aldosterone biosynthesis in the rat.


Serum pre-beta-1 lipoprotein fraction in coronary atherosclerosis.


Pre-beta-1 lipoprotein and early detection of risk factors for coronary heart disease.


Ribonuclease T1, Structure and function.


Effect of bicarbonate and phosphate on the adrenergic receptor response in human adipose tissue in vitro.


Serum and liver triglycerides in malnourished Jamaican children with fatty liver.


Normal and abnormal sexual maturation.

Normal and abnormal sexual maturation.


Papillary adenofibroma of the uterus: a benign mesodermal mixed tumor of Müllerian orgin.


Studies on amikhellin. I. Intercalative binding to double-stranded DNA.


Effect of cyclic 3'-5' GMP on in vitro protein synthesis.


Properties of 3-aldoxime pyridine adenine dinucleotide, an NAD+ analogue.


Editorial: Guidelines on the analysis of tumour rates and death rates in experimental animals.


Fibrosis as in indication of time in infiltrating breast cancer and its importance in prognosis. The histological grading of tumours according to their intrinsic malignancy is very important in the prognosis of breast cancer but within each grade the ultimate prognosis depends mainly on the age of the tumours.We have shown that tumour fibrosis is an indication of this time factor, increasing with the age of the tumour. Within each grade the metastatic ratio is higher and the 5 year and 10 year survival less with the scirrhous than with the non-scirrhous tumours. The establishment of axillary metastases is closely connected with both the degree of malignancy and the time available, the unfavourable effect upon survival being greater in the scirrhous than in the non-scirrhous tumours.Another consequence of the passage of time, as indicated by fibrosis, is the gradual diminution of lymphoid infiltration (LI) which is mostly present in young tumours, especially those of high grades. The favourable effect of LI upon survival is demonstrated in the non-scirrhous tumours of grade III, possibly because of its great intensity, but this influence upon survival is lost as fibrosis increases and the intensity of the reaction diminishes.


Pulmonary blastoma.

Pulmonary blastoma.


Survival rates of lung cancer according to histological type. The post-operative survival in 554 lung carcinomata, classified according to the histological type, was calculated by the actuarial method. On the whole, squamous cell carcinoma was the most favourable and anaplastic small cell carcinoma the least favourable lesion. However, in tumours smaller than 4 cm, confined to the lung and with negative lymph nodes (stage I), small cell carcinoma had the highest percentage of 5 year survivors, followed by large cell carcinoma, squamous cell carcinoma and adenocarcinoma. When tumours had attained a larger size and/or spread to neighbouring structures and regional lymph nodes (stage II and III), the histological type was a much more determining factor in survival, squamous cell carcinoma being a significantly more favourable lesion. On the other hand, no difference in survival in relation to the histological type was found when distant metastases were probably present (stage IV). It was concluded that in assessing the role of histopathology in the prognosis of lung cancer, the mutual relationship to other pathological factors must be taken into account.


The effects of the inhalation of asbestos in rats. Two experiments in which SPF Wistar rats were exposed by inhalation to dust clouds of the UICC standard reference samples for periods of between one day and 2 years are described. All the samples of asbestos produced asbestosis which continued to progress after removal from exposure but only a little fibrosis was observed in control rats. Lung tumours, ranging in severity from adenomata to squamous carcinomata, were produced by all samples but in the controls there were only a few adenomata and none of the more serious tumours. Of the 20 tumours which metastasized, 16 occurred after exposure to one or other of the 2 chrysotile samples. In addition, a total of 11 mesotheliomata occurred, 4 of which were with crocidolite and 4 with Canadian chrysotile. Two of the mesotheliomata occurred with only one day's exposure to asbestos. There was a positive association between asbestosis and lung tumours.


Management of an infected simple renal cyst by percutaneous aspiration.


Characterization of the periodate oxidation of glycerol and related compounds, and application toward determination of serum triglyceride concentrations.


Plasma corticotropin radioimmunoassay, with use of fuller's earth for extraction.


Diabetic neuropathic cachexia.

Diabetic neuropathic cachexia.


A linear steady-state treatment of enzymatic chains. A mathematical model of glycolysis of human erythrocytes.


RNA ligase activity in phage-infected bacteria and animal cells.


Kinetics of the interaction between pig-plasma benzylamine oxidase and hydrazine derivatives.


Autoradiographic studies on the influence of ACTH and ovarian hormones on proliferation of epithelial cells of the mammary gland in white mice.


Alteration of ribosomal proteins and functions by 2-methoxy-5-nitrotropone.


Affinity chromatography on immobilised adenosine 5'-monophosphate. Some kinetic parameters involved in the binding of group-specific enzymes.


Prostaglandin induction of mitochondrial respiration and adaptive changes of enzymes in the perfused rat liver.


Studies on the quaternary structure of the threonine-sensitive aspartokinase-homoserine dehydrogenase of Escherichia coli. A proposed subunit-interaction model.


Effect of bacterial enterotoxins on the gastrointestinal tract.


Lipolysis in genetically obese and diabetes-prone mice.


Electron microscopic studies on the existence of the so called "acinar-islet cells" in the regenerating pancreas of the rat.


Circadian rhythmicity of hypothalamic CRH and its central nervous regulation.


Cushing's syndrome following ectopic neoplastic production of corticotropin. (Report of 4 cases studied by clinical and biochemical methods, and by microscopic and macroscopic anatomy).


Diabetes mellitus--a disorder of cellular information transmission?


Potentiation by antidiuretic hormone (vasopressin) of the ability of parathyroid hormone to stimulate the proliferation of rat thymic lymphocytes.


Immunochemical localization of parathyroid hormone in cancer tissue from patients with ectopic hyperparathyroidism. Immunoreactive parathyroid hormone (PTH) in nonparathyroid malignant tumors associated with hypercalcemia and hypophosphatemia in the absence of demonstrable bone metastases was determined by radioimmunoassay and immunofluorescent techniques. Six of seven tumors contained material with immunological cross-reactivity to bovine PTH by radioimmunoassay and immunofluorescence. The intensity of the immunofluorescent stain varied considerably in the different tumors. From 15 to 90% of neoplastic cells were stained specifically with fluorescein-labeled anti-PTH. In contrast, normal parathyroid glands and parathyroid adenomas showed uniform distribution of immunofluorescence in all parenchymal cells. In one malignant tumor, PTH was localized also by immunoautoradiography. In every case PTH was detected only in the cytoplasm of parenchymal cells. One patient lacked detectable PTH in his tumor, yet showed regression of the hypercalcemia to normal values after removal of large masses of neoplastic tissue and recurrence of hypercalcemia when new growth occurred.Dilutional radioimmunoassay curves of nonparathyroid malignant tumors were in most cases different from those obtained with extracts of normal parathyroid glands and parathyroid adenomas. Although both nonparathyroid neoplasmas and parathyroid extracts demonstrated immunoheterogeneity by gel filtration, greater heterogeneity was found in nonparathyroid malignant tumors. In those tumors in which immunological cross-reactivity to PTH was detected, the capability of secreting PTH may be restricted to derepressed cell clones amidst other neoplastic cells, whereas the greater heterogeneity of ectopic PTH may reflect hormone cleavage by proteolytic enzymes in the tumor that is less specific than the Pro-PTH cleaving enzyme in the parathyroids.


The effect of ethidium bromide on the membrane glycopeptides in control and virus-transformed cells.


The effect of parathyroid hormone and thyrocalcitonin on the accumulation of cyclic adenosine 3':5'-monophosphate in freshly isolated bone cells.


Biological defense mechanisms. The effect of bacteria and serum on superoxide production by granulocytes. We previously reported that granulocytes are able to produce superoxide (O(2) (-)), a highly reactive compound formed by the one-electron reduction of oxygen. The demonstration of O(2) (-) production was based on the observation that the reduction of extra-cellular cytochrome c by granulocytes was greatly diminished by superoxide dismutase, an enzyme catalyzing the conversion of O(2) (-) to hydrogen peroxide and oxygen. In the present report, studies concerning the effect of bacteria and serum on O(2) (-)-dependent cytochrome c reduction by granulocytes are described.In the absence of bacteria, the O(2) (-)-dependent reduction of extracellular cytochrome c by granulocytes under optimal assay conditions amounted to 9.2+/-2.8 SD nmol/3 x 10(6) cells/20 min. When bacteria (100 organisms/cell) were present, the O(2) (-)-dependent cytochrome c reduction under otherwise similar conditions increased by a factor of nearly four (34.5+/-9.4). There was no effect of albumin or catalase on cytochrome c reduction, and boiled dismutase had only a small effect. Omission of granulocytes or substitution of live cells by cells by cells killed by heat abolished O(2) (-)-dependent cytochrome c reduction. Bacteria killed by autoclaving were almost as effective as live bacteria in stimulating granulocyte O(2) (-) production. Measurements of particle uptake and O(2) uptake by granulocytes indicated that superoxide dismutase did not affect granulocyte metabolism nonspecifically, supporting the conclusion that the diminution of cytochrome c reduction in the presence of dismutase was due to the destruction of O(2) (-) by this enzyme. Stimulation of O(2) (-) production by bacteria was strongly dependent on the presence of serum in the incubation mixture. Serum heated to 56 degrees C for 45 min was as effective as unheated serum in stimulating O(2) (-) production in the presence of bacteria, but boiled serum had no effect. Other experiments suggested that incubation of bacteria with serum resulted in the release of a nonparticulate heat-labile substance capable of stimulating O(2) (-) production in the absence of bacteria. Certain characteristics of the O(2) (-)-dependent cytochrome c reduction by granulocytes were studied, including the dependence of this process on granulocyte, cytochrome c, and bacterial concentrations. In addition, O(2) (-)-dependent cytochrome c reduction was followed as a function of time. A constant rate was found with resting granulocytes. With bacteria the time course was more complex. A well-defined lag was followed by a fairly brief period of extremely vigorous cytochrome c reduction. During this period, the maximum rate of cytochrome c reduction exceeded the rate observed in the absence of bacteria by a factor of 12. The rate then decreased until by 40 min, it had slowed to the rate observed in the absence of bacteria. From the above results, it was concluded that the exposure of the granulocyte to bacteria plus serum initiates a process in which a defined quantity of O(2) (-) is formed in a rapid burst lasting 20-30 min. It is conceivable that the O(2) (-) generated by this process may be involved in the killing of bacteria by the granulocytes.


Receptor-binding affinities and biological activities of analogs of thyrotropin-releasing hormone in prolactin-producing pituitary cells in culture.


Human platelet collagenase.

Human platelet collagenase. The presence of proteolytic enzymes such as cathepsin and elastase in platelets and the important role of collagen in platelet aggregation suggested that collagenase might be present in platelets. Epinephrine, ADP, and collagen liberate collagenase from platelets in plasma as measured by the hydrolysis of [(14)C]glycine-labeled collagen fibrils. The collagenase activity appeared in an early phase of platelet aggregation and was not a part of the release reaction. However, only 50% of the total collagenase could be liberated by the aggregating agents used. Sucrose density gradient analysis of platelet homogenates using appropriate sub-cellular markers indicated that collagenase appeared in both the granule and membrane fractions. Gel-filtered platelets failed to show collagenase activity before exposure to aggregating agents but released more collagenolytic activity than was found in platelet-rich plasma. This observation was explained by the finding that collagenolytic activity was inhibited by normal human plasma. One of the inhibitors is alpha(1)-antitrypsin as demonstrated by decreased inhibition in plasma from a patient with homozygous alpha(1)-antitrypsin deficiency. Platelet collagenase activity could also be demonstrated by its ability to decrease the viscosity of collagen solutions and to produce collagen fragments similar to those produced by other mammalian collagenases on disk gel electrophoresis. The observation that partially purified platelet collagenase could destroy the platelet-aggregating activity of collagen suggests that the enzyme might function in a negative feedback mechanism limiting thrombus formation.


The effects of epinephrine and prostaglandin E-1 on cyclic adenosine 3':5'-monophosphate levels in WI-38 fibroblasts.


Electron paramagnetic resonance studies of cobalt-copper bovine superoxide dismutase.


Purification and kinetic characterization of a monovalent cation-activated glycerol dehydrogenase from Aerobacter aerogenes.


Iron, an essential component of lipoxygenase.


Magnetic resonance and kinetic studies of the mechanism of sodium and potassium ion-activated adenosine triphosphatase.


The subcellular localization of glutaminase isoenzymes in rat kidney cortex.


Regulation of renal ammoniagenesis. Subcellular localization of rat kidney glutaminase isoenzymes.


Two nucleid acid-dependent nucleoside triphosphate phosphohydrolases from vaccinia virus. Purification and characterization.


Two nucleic acid-dependent nucleoside triphosphate phosphohydrolases from vaccinia virus. Nucleotide substrate and polynucleotide cofactor specificities.


Single-stranded deoxyribonucleic acid-specific nuclease from vaccinia virus. Endonucleolytic and exonucleolytic activities.


Nonessentiality of the active sulfhydryl group of rabbit muscle creatine kinase.


Conformational transition in polypeptide elongation factor Tu as revealed by electron spin resonance.


Photoaffinity labeling with cyclic nucleotides.


The kidney as an endocrine organ involved in calcium homeostasis.


Disordered divalent ion metabolism in kidney disease: comments on pathogenesis and treatment.


Treatment of renal osteodystrophy with calciferol (vitamin D) and related steroids.


Fucosylglycolipids in cells transformed by a temperature-sensitive mutant of murine sarcoma virus.


Presence of a large poly(rC) tract within the RNA of encephalomyocarditis virus.


Parathormone, cyclic AMP and neonatal kidneys.


Carbohydrate groups in the major glycoprotein of Rous sarcoma virus.


Regulation of cell growth by cyclic AMP.


Cytomegalovirus infections in New York State.


Positive control of transformed phenotype in hybrids between SV40-transformed and normal human cells. Somatic cell hybrids have been obtained between SV40-transformed Lesch-Nyhan fibroblasts, which are deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and display glucose-6-phosphate dehydrogenase A (G6PD-A) activity, and late-passage HGPRT-positive W138 human embryo fibroblasts, which display G6PD-B activity. The human-human hybrid clones, which display G6PD-A and G6PD-B and heteropolymers of the two enzyme forms, have the same growth characteristic as the SV40-transformed parental cells and behave as continuous cell lines. The SV40 tumor antigen, the gene for which has been assigned to human chromosome 7, is present in all clones examined.


Ultrastructural and functional relationships of some human endocrine tumors.


On the mechanism of the enhancement by smooth muscle stimulants of the motor responses of the guinea-pig vas deferens to nerve stimulation.


Conversion of angiotensin I in pulmonary and systemic vascular beds of children.


Differences in recruitment order and discharge pattern of motor units in the early and late flexion reflex components in man.


Carcinogenic response of brood sows fed aflatoxin for 28 to 30 months.


The effect of dopa on the spinal cord. 8. Presynaptic and "remote" inhibition of transmission from Ia afferents to alpha motoneurones.


Infectivity of bovine C- type (leukemia) virus for sheep and goats.


Stimulation of adenosine 3,5-monophosphate formation in mast cells by 5-hydroxytryptamine and guanethidine.


Genital disease in dogs caused by canine herpesvirus.


Activities of rat muscle enzymes after acute exercise.


Lesions in nervous tissue of owl monkeys experimentally infected with herpesvirus-T.


Study of the use of evoked cortical activity for clinical evaluation of spinal cord sensory transmission.


Antigenic comparisons and serologic survey of equine adenoviruses.


Phagocytosis of Babesia canis by neutrophils in peripheral circulation.


Reduction of mercury to the elemental state by a yeast. A yeast of the genus Cryptococcus has been isolated from a stream and was shown to be capable of reducing mercury to the elemental state. The organism grows in Wickerham broth supplemented with high concentrations of mercury (II) chloride (180 mg of mercury per liter) and will metabolize [(14)C]glucose in this medium as do cells in the absence of mercury. Mercury was associated with the cell wall and membrane, and in vacuoles within the cytoplasm.


The plaque-antiserum method: an assay of virus infectivity and an experimental model of virus infection. Areas of cytopathic effect can be circumscribed in cell monolayers by adding antiserum to the liquid nutrient medium after adsorption of virus. This procedure represents a simple and reliable tool for the titration of virus infectivity and provides an experimental model for studying some aspects of virus infection.


Environmental factors influencing isolation of enteroviruses from polluted surface waters. The influence of water quality upon the concentration of virus on location was assessed in field studies conducted in the Houston ship channel, Galveston Bay, and Houston waste treatment plants. Clarification of polluted surface waters was accomplished with minimal loss of virus. Virus from clarified sewage effluents and saline waters was then adsorbed and concentrated on textile and membrane filter surfaces. Direct measurements of virus from large volumes of polluted surface waters under existing field conditions were then made using the virus concentrator equipment.


Concentration of oncogenic herpesviruses by methyl alcohol precipitation. Oncogenic herpesviruses, like many other viruses, can be concentrated effectively from large volumes of culture fluids by precipitation with methanol with good recovery of infectivity.


Electrophoretic characterization of human phosphoribosylpyrophosphate synthetase.


Hepatitis B (Australia) antigen--current clinical and epidemiological concepts.


Metabolite levels reflecting changes in liver energy metabolism during the neonatal period.


Influence of asphyxia and of dexamethasone on ATP concentrations in the immature rat brain.


Pyruvate carboxylase in human liver. Apparent loss of a component of catalytic activity in a form of lactic acidosis with hypoglycemia.


Acetylcholine sensitivity of the chick fast muscle after cross-union with the slow muscle nerve.


Modulation of synaptic transmission in cat's superior colliculus by saccadic eye movements.


Cytoplasmic solvent structure of single barnacle muscle cells studied by electron spin resonance. A free radical probe was introduced into single barnacle muscle cells, and its freedom of motion inferred from the spin resonance spectra. The probe reported an average local viscosity of 5-10 cp compared with 1 cp for pure water. From a comparison of the temperature dependence of the probe's tumbling rate in model aqueous systems and in the muscle we concluded that in the muscle the probe was undergoing fast exchange between sites of different mobility. Thus 10 cp must be taken as an upper limit for the viscosity of most cell water.


Stimulation- and calcium-dependence of vesicle attachment sites in the presynaptic membrane: a freeze-cleave study on the lamprey spinal cord.


Common synaptic effects of pentylenetetrazol and penicillin.


Ascending monoamine-containing fiber pathways related to intracranial self-stimulation: histochemical fluorescence study.


The action of norepinephrine in the rat hippocampus. II. Activation of the input pathway.


The action of norepinephrine in the rat hippocampus. I. Iontophoretic studies.


Histochemical studies on the effect of sodium fluoride on metabolism in Purkinje's cells.


The effect of oxytocin on the oxidoreductive activity and spermatogenesis in the rabbit testicle.


Action of Escherichia coli enterotoxin: adenylate cyclase behavior of intestinal epithelial cells in culture. Heat-labile enterotoxin preparations obtained from two enteropathogenic strains of Escherichia coli of porcine and human origin were shown to stimulate adenylate cyclase activity of human embryonic intestinal epithelial cells in culture. Comparable results were also obtained when cholera toxin was used. The degree of enzyme stimulation was proportional to the concentration of enterotoxin. Similar preparations from two strains of non-enterotoxigenic E. coli had no effect on adenylate cyclase activity. Cells exposed to enterotoxin could be washed after 1 min of contact time without altering the subsequent course of maximum adenylate cyclase activity, which was maintained for at least 18 h at 37 C. During long periods (18 h) of tissue culture incubation, the determination of adenylate cyclase activity was 200- to 300-fold more sensitive than quantitating fluid accumulation in the adult rabbit ileal loop model. Decreasing the incubation time appreciably reduced the sensitivity of the epithelial cells to enterotoxin. E. coli enterotoxin is an effective activator of nonintestinal adenylate cyclase systems. Treatment of KB and HEp-2 cell lines with enterotoxin also resulted in significant enzyme stimulation. The intestinal epithelial cell tissue culture model provides a sensitive homogenous biological system for studying the response of intestinal adenylate cyclase to enterotoxin while eliminating the numerous cellular and tissue components present in the ligated ileal loop model.


Replication of Marek's disease virus in cell cultures derived from genetically resistant chickens. Various parameters of replication of Marek's disease virus (MDV) were studied in cells derived from genetically resistant (line 6) and susceptible (line 7) chickens. Cell-free and cell-associated preparations of three strains of pathogenic MDV (JM, GA, and Id-1) replicated equally well in cells of resistant and susceptible chickens. There were no demonstrable differences between the two genetic sources of cells for the chronological appearance and type of cytopathic effects and for the type of virus-induced antigens detectable by immunofluorescent and agar-gel precipitin tests. MDV propagated for about 4 weeks in cells of resistant line 6 chickens remained nonvirulent for line 6 and fully virulent for line 7 chickens. The lack of expression of genetic resistance to Marek's disease at cellular level contrasts the infection mechanisms of MDV from those of viruses associated with lymphoid leukosis in chickens.


Synthesis and biological activity of some 8-substituted seleno cyclic nucleotides and related compounds.


Synthesis of analogs of (8-isoleucine)angiotensin II with variations in position 1.


Synthesis of some trinucleoside monophosphates of biological interest.


The pathology of the human muscle spindle: effect of denervation.


A thin-layer chromatographic procedure for the separation of aspirin, cocaine, caffeine, codeine, heroin, 6-monoacetyl morphine, and morphine.


Oligonucleotide photoproducts formed by photolysis of polyribobromouridylic acid.


The phosphorescent triplet state of some hydroxycoumarins.


Photochemistry of biological molecules. IV. Gaseous products from the photolysis of alanine peptides in the solid state.


The egg yolk very low density lipoproteins of fresh and stored shell eggs.


Synthesis of simian virus 40 DNA in isolated nuclei. Nuclei isolated from African green monkey kidney cells infected with simian virus 40 at different times after infection maintain in vitro the same temporal sequence of host and viral DNA synthesis as that seen in intact cells. The viral DNA synthesized by the nuclei of cells previously infected for 32-35 hr was characterized by centrifugation through neutral and alkaline sucrose gradients, and by isopycnic banding in a propidium iodide-cesium chloride gradient. DNA synthesis in this system is maintained for only 4-5 min. Neutral sucrose gradient analysis showed that most of the radioactivity is associated with the replicative intermediate of simian virus 40 DNA and the rest sediments at 5-7 S. Alkaline gradient analysis showed that 50-60% of the radioactivity sediments as 3-7S fragments, and the rest between 7 and 16 S. Pulsechase experiments showed that in this system 3-7S fragments do not mature into long chains. A model is presented to explain the failure of these fragments to join into long chains in this in vitro nuclear system.


Genetic control of melanization: isolation and analysis of amelanotic variants from cultured melanotic melanoma cells. MELANOMA CELLS EXPRESS A PHENOTYPE THAT IS EASY TO RECOGNIZE: the synthesis of melanin. We used this marker to isolate clones of amelanotic variants from large populations of wild-type melanotic clones. Cloudman mouse melanoma (S91, clone M-3, CCL 53.1) was chosen as the parental line because the cells are highly pigmented, grow well as clones in soft agar, and fuse readily with Sendai virus. Subclones (10(7)) of this line were screened without prior mutagenesis, and nine amelanotic variants were isolated. The mutagen ethylmethanesulfonate increased the frequency of variants by three to four orders of magnitude. Wild-type cells had both basal and melanocyte stimulating hormone-inducible tyrosinase activities. The four amelanotic variants that we have examined to date all behaved similarly: they lost basal tyrosinase (EC 1.14.18.1; monophenol monooxygenase) activity but retained melanocyte stimulating hormone-inducible activity; they contained Stage-II melanosomes but no melanized melanosomes; they exhibited growth characteristics similar to those of wild-type cells in culture but produced fewer tumors in mice.


Octopamine- and serotonin-stimulated phosphorylation of specific protein in the abdominal ganglion of Aplysia californica. Phosphorylation of a protein (or proteins) of molecular weight 120,000 in the Aplysia abdominal ganglion, as measured by incorporation of [(32)P] or [(33)P]sodium phosphate in vitro followed by separation of the phosphoproteins on sodium dodecyl sulfate-polyacrylamide gels, was specifically stimulated by incubation in the presence of the putative neurotransmitters octopamine or serotonin. The stimulatory effect of octopamine and serotonin was inhibited by phentolamine and methysergide, respectively, and was mimicked by incubation in the presence of dibutyryl cyclic AMP. Label-chase experiments indicated that the difference between control and octopamine-treated ganglia persists for several hours after removal of the drug from the incubation medium. This result suggests that neurotransmitters may produce relatively long-lasting changes in a phosphoprotein in the ganglion, perhaps in postsynaptic cells.


Relationship of a proton gradient to the active transport of proline with membrane vesicles from Mycobacterium phlei. Electron transport particles prepared from Mycobacterium phlei were depleted of bound coupling factors by washing with water in the absence of inorganic ions. The depleted electron transport particles were void of latent ATPase activity and were capable of oxidation, but were unable to support coupled phosphorylation. Nevertheless, the depleted electron transport particles were capable of substrate-induced active transport of proline. Changes in pH in response to substrate oxidation were measured in normal and depleted electron particles with bromthymol blue. A bromthymol blue response upon substrate oxidation was not observed with depleted electron transport particles. The level of oxidative phosphorylation with succinate or NADH oxidation was not reduced in the presence of proline, and proline did not have an effect upon the proton gradients formed by the oxidation of either succinate or NADH.


Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA. Explanted mouse blastocysts were microinjected in the blastocoel cavity with simian virus 40 (SV40) viral DNA. After surgical transfer to the uteri of pseudopregnant surrogate mothers, approximately 40% of the blastocysts developed to term and became healthy adults without apparent tumors at 1 year of age. Molecular hybridization tests for the presence of SV40-specific DNA sequences were conducted on DNA extracted from various organs of these animals. Between 0.5 and 13 SV40 genome equivalents per diploid mouse DNA value were found in some organs of approximately 40% of the adult survivors; this represents a substantial augmentation of the amount administered per embryo. The results are consistent with the working hypothesis that the SV40 DNA may have been integrated into the host genome; alternatively, the viral DNA may have replicated as an extrachromosomal entity or by lytic infection in a few permissive cells. Persistence of the viral DNA from preimplantation stages to adult life may thus provide a new tool for experimental investigation of vertical transmission and expression of tumor viruses.


Cell-free transcription of mammalian chromatin: transcription of globin messenger RNA sequences from bone-marrow chromatin with mammalian RNA polymerase. A mammalian cell-free transcriptional system was developed in which mammalian RNA polymerase synthesizes globin messenger RNA sequences from bone-marrow chromatin. The messenger RNA sequences are detected by measurement of the ability of the transcribed RNA to hybridize with globin complementary DNA. The globin complementary DNA is synthesized by the enzyme from avian myeloblastosis virus, RNA-directed DNA polymerase, with purified globin messenger RNA as template. The specificity of the globin complementary DNA in annealing reactions was verified by preparing DNA complementary to liver messenger RNA and showing that the globin and liver complementary DNAs are specific for their own messenger RNAs. Both DNA-dependent RNA polymerase II from sheep liver and RNA polymerase from Escherichia coli can transcribe globin messenger RNA sequences from rabbit bone-marrow chromatin; however, the mammalian enzyme appears to be more specific in that globin gene sequences represent a higher proportion of the RNA synthesized. Neither polymerase can transcribe globin messenger RNA sequences from rabbit-liver chromatin. This cell-free assay system should be useful in searching for mammalian transcriptional regulatory factors.


Regulation of a plant 5'(3')-ribonucleotide phosphohydrolase by cyclic nucleotides and pyrimidine, purine, and cytokinin ribosides. A highly specific 5'(3')-ribonucleotide phosphohydrolase has been purified extensively from wheat seedling leaves. While catalyzing the hydrolysis of a wide variety of phosphomonoesters, the enzyme has K(m) values for adenosine 5'-monophosphate and adenosine 3'-monophosphate in the micromolar range and appears highly specific for 5'- and 3'-ribonucleoside monophosphates as substrates at pH 5.0. The cyclic nucleotides adenosine 3':5'-cyclic monophosphate, guanosine 3':5'-cyclic monophosphate, and 8-bromoadenosine 3':5'-cyclic monophosphate, as well as 8-bromoadenosine 5'-monophosphate, are powerful competitive inhibitors of the enzyme; the apparent K(i) values for these nucleotides are 3.4 muM, 1.6 muM, 26 muM, and 9.1 muM, respectively. The enzyme is inhibited noncompetitively by a variety of pyrimidine and purine (including cytokinin) ribosides and 2'-deoxyribosides. Since the cyclic nucleotide competitive inhibitors are also active growth promoters of higher plants, and, furthermore, since elevation of cyclic AMP levels appears to be a consequence of some phytohormone treatments that promote plant growth, it is suggested that negative control of this 5'(3')-ribonucleotide phosphohydrolase may be a significant component of growth regulation through the maximizing of the levels of nucleotide precursors for RNA and DNA synthesis.


Rapid loss of translatable messenger RNA of phosphoenolpyruvate carboxykinase during glucose repression in liver. The rate of synthesis of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in rat liver decreased with a half-life of 30 min after fasted rats were refed either a chow diet or glucose. A requirement for both glucose and insulin to bring about this rapid deinduction was shown, as well as the ability of dibutyryl adenosine 3':5'-cyclic monophosphate to block the decrease in enzyme synthesis. Estimates of the stability of messenger RNA of phosphoenolpyruvate carboxykinase were made by using the inhibitors actinomycin D and cordycepin to block further messenger RNA synthesis, and then measuring the decrease in specific enzyme synthesis. It is suggested that the use of actinomycin D yields an overestimation of the template stability. The results with cordycepin imply that the enzyme messenger RNA has a short half-life of approximately 1 hr. Thus, it is possible that deinduction may proceed by way of a decrease in messenger RNA production, leading to a rapid fall in the synthesis of phosphoenolpyruvate carboxykinase.