The inhibition of pig kidney alkaline phosphatase by oxidized or reduced nicotinamide-adenine dinucleotide and related compounds. 1. The inhibition of alkaline phosphatase by NAD(+), NADH, adenosine and nicotinamide was studied. 2. All of these substances except NAD(+) act as uncompetitive inhibitors, i.e. double-reciprocal plots are parallel. NAD(+), however, is a ;mixed' inhibitor of alkaline phosphatase and is less potent than NADH. 3. Inhibition studies with pairs of the inhibitors suggest that, in spite of the difference in type of inhibition, NAD(+) and NADH bind to alkaline phosphatase at a common site. Adenosine and nicotinamide also seem to bind at the NAD site and the binding of adenosine is facilitated by nicotinamide, and vice versa. 4. The facilitation may indicate the occurrence of an induced fit for NAD(+) and NADH. Attempts to desensitize alkaline phosphatase to NAD(+) and NADH inhibition by partial denaturation were unsuccessful. 5. The results are discussed in terms of a two-site model in which separate, but interacting, regions exist on the enzyme to accommodate the adenosine and nicotinamide moieties of NAD, and a single-site model in which the adenosine part of the molecule is bound preferentially and this interacts with the nicotinamide fraction. 6. The activity of alkaline phosphatase can be changed fourfold by alteration of the NAD(+)/NADH ratio. This sensitivity to the redox state of the coenzyme could be a means of controlling phosphatase activity.


Equilibrium binding of nicotinamide nucleotides to lactate dehydrogenases. 1. No discontinuities were observed during the continuous titration with NADH of the lactate dehydrogenases of ox muscle, pig heart, pig muscle, rabbit muscle, dogfish muscle or lobster tail muscle. The binding was monitored by either the enhanced fluorescence of bound NADH or the quenched fluorescence of the protein. A single macroscopic dissociation constant, independent of protein concentration, could be used to describe the binding to each enzyme, and there was no need to postulate the involvement of molecular relaxation effects. 2. The affinity for NADH decreases only threefold between pH6 and 8.5. Above pH9 the affinity decreases more rapidly with increasing pH and is consistent with a group of about pK9.5 facilitating binding. Muscle enzymes bind NADH more weakly than does the pig heart enzyme. 3. Increasing temperature and increasing concentrations of ethanol both weaken NADH binding. 4. NADH binding is weakened by increasing ionic strength. NaCl is more effective than similar ionic strengths derived from sodium phosphate or sodium pyrophosphate. 5. Commercial NAD(+) quenches the protein fluorescence of the heart and muscle isoenzymes. Highly purified NAD(+) does not, and its binding was monitored by competition for the NADH-binding sites. A single macroscopic dissociation constant is sufficient to describe NAD(+) binding at the concentrations tested. The dissociation constant is about 0.3mm and is not sensitive to changed ionic strength and to changed pH in the range pH6-8.5.


Ionic properties of an essential histidine residue in pig heart lactate dehydrogenase. 1. Pig heart lactate dehydrogenase is inhibited by addition of one equivalent of diethyl pyrocarbonate. The inhibition is due to the acylation of a unique histidine residue which is 10-fold more reactive than free histidine. No other amino acid side chains are modified. 2. The carbethoxyhistidine residue slowly decomposes and the enzyme activity reappears. 3. The essential histidine residue is only slightly protected by the presence of NADH but is completely protected when substrate and substrate analogues bind to the enzyme-NADH complex. The protection is interpreted in terms of a model in which substrates can only bind to the enzyme in which the histidine residue is protonated and is thus not available for reaction with the acylating agent. 4. The apparent pK(a) of the histidine residue in the apoenzyme is 6.8+/-0.2. In the enzyme-NADH complex it is 6.7+/-0.2. 5. Acylated enzyme binds NADH with unchanged affinity. The enzyme is inhibited because substrates and substrate analogues cannot bind at the acylated histidine residue in the enzyme-NADH complex.


The use of ternary complexes to study ionizations and isomerizations during catalysis by lactate dehydrogenase. 1. The binding of oxamate to pig heart and pig muscle isoenzymes of lactate dehydrogenase in the presence of NADH was studied by fluorescence titration. The dissociation constant of oxamate from the heart enzyme complex is 3mum and from the muscle isoenzyme 25mum at pH5. These values quantitatively increase with pH as predicted if oxamate can bind only to the enzyme-NADH complex if a group with pK6.9 is protonated. There are four non-interacting oxamate-binding sites per tetramer. 2. o-Nitrophenylpyruvate is a poor substrate for both isoenzymes but has a reasonable affinity to the heart isoenzyme. Initially, it forms an enzyme-NADH-substrate complex, which can be detected either by protein-fluorescence quenching or by NADH-fluorescence quenching. The pH-dependence of the dissociation constant of nitrophenylpyruvate also shows that this ternary complex can only form if a group with pK6.8 is protonated. Taken with the results of chemical-modification experiments, these results allow the pK of 6.8 to be assigned to a system probably involving the imidazole side chain of histidine-195. Formation of a ternary complex from a binary one at pH8 is predicted to result in a proton being taken up from solution. 3. Isotope-effect studies with NADH and its deuterium analogue show that the rapidly formed ternary complex with o-nitrophenylpyruvate slowly isomerizes to give an active ternary complex, which then rapidly decomposes to NAD(+). The isomerization is pH-independent, and it is suggested that histidine-195 is still protonated in the activated ternary complex, which is present before hydride transfer. 4. All four subunits of the enzyme are kinetically equivalent with respect to the oxidation of bound NADH by o-nitrophenylpyruvate. 5. A partial mechanism for the enzyme is described which emphasizes the isomerizations and ionizations involved in forming the reduced ternary complex at pH6 and 8.


A sensitive and accurate gel osmometer.

A sensitive and accurate gel osmometer. 1. A bilayer strip, cut from a thin layer of cross-linked polyacrylamide gel cast on to cellulose tissue, forms an open circular loop whose ends are close together. Shrinkage of the gel, in response to the osmotic pressure of a non-penetrating solution, causes a proportional separation of the ends of the loop. This is measured with a microscope and micrometer eyepiece. 2. The resulting effective sensitivity is about 30 times that of the Sephadex-bead osmometer (Ogston & Wells, 1970), i.e. of the order of 5Pa, comparable with that of a membrane osmometer. Use of gel up to 70% (w/v) allows the measurement of molecular weights, as low as 1500 in favourable cases, with an accuracy of 1-2%. The useful range of osmotic pressure is up to 5kPa. A single measurement requires 0.5ml of solution. Equilibration is completed in 20-30min. 3. The method is illustrated by measurements on human serum albumin, ovalbumin, cytochrome c, samples of dextrans, polyvinyl alcohol, and polyethylene glycols 6000 and 1000.


The characterization of a non-histone protein isolated from histone F1 preparations. A non-histone protein was obtained by extraction of nuclei derived from rat liver or thymus or ascites-hepatoma cells with 5% (w/v) HClO(4). Separation from histone F1 was achieved by chromatography on DEAE-cellulose. The purified component P1 was characterized and the formation of complexes with histone F1 and polylysine was studied.


Relationships between in vivo and in vitro inhibition of acetylcholinesterase (AChE) and impairment of neuromuscular transmission in the rat phrenic-nerve diaphragm by a tertiary anticholinesterase and its quaternary analogue.


Effect of steady illumination on the binding of carbon monoxide by carboxymethylated cytochrome c. The quantum yield, [unk], is reported for the photodissociation of CO from reduced carboxymethylated cytochrome c. The values of [unk] obtained are low relative to that for myoglobin and are pH-independent, being 0.23 at pH6.1 and 0.27 at pH9.7.


Glycolytic mechanisms in Ehrlich ascites tumor cells-effects of disulfide derivatives of pyridine.


Phospholipids and phospholipase D in the true slime mold Physarum polycephalum.


Age differences in the acyl group composition of phosphoglycerides in myelin isolated from the brain of the rhesus monkey.


The retention of arachidonic acid in ethanolamine plasmalogens of rat testes during essential fatty acid deficiency.


Fatty acid amide of glycerylphosphorylethanolamine-a lytic lipid from hog stomach.


Kinetics of lipoprotein lipase activity: effects of the substrate apoprotein on reaction velocity.


Glucose stimulation of fatty acid desaturation in liver of newly-hatched chicks.


Angiography of the primary retroperitoneal tumors.


Haemonchus contortus: enzymes. 3. Glutamate dehydrogenase.


Studies on metabolism of lung fluke genus Paragonimus. VII. Action of bithionol on glycolytic and oxidative metabolism of adult worms.


Reactivity with oxygen of bacterial cytochrome oxidases a1, aa3 and o.


Effect of luteinizing hormone on 3',5'-cyclic AMP and testosterone production in isolated interstitial tissue of rat testis.


Interaction of transfer RNA with the 30 S subunits of ribosomes in the absence of messenger.


Role of split proteins from 30 S subunits in the ribosome-EF-T GTPase reaction.


Continuous directional degradation. A novel method for sequence analysis of polyribonucleotides.


Routine isolation of the 70 S RNA of a murine oncornavirus by use of an unesterified cellulose column.


Studies on the structure of lipoprotein A of human high density lipoprotein HDL3: the spherically averaged electron density distribution.


Protein phosphokinases of bound and free thyroid polyribosomes.


The primary structure of oligonucleotides. Partial apurinization as a method to determine the positions of purine and pyrimidine residues.


The management of bleeding intraductal papilloma of the breast.


Primary malignant tumors of the liver.

Primary malignant tumors of the liver.


The effect of adrenalectomy on blood corticotrophin in the rat.


Corticosteroid release by adrenal tissue from foetal and newborn lambs in response to corticotrophin stimulation in a perifusion system in vitro.


The effect of pyridine nucleotides and cyclic AMP on the synthesis of progestational steroids in subcellular fractions of rabbit ovarian interstitial tissue.


Adrenocortical function in the Australian brush-tailed possum Trichosurus vulpecula (Kerr).


The relationship between cortisol and adrenocorticotrophin levels in human plasma.


The effect of intravenous catecholamines on circulating levels of growth hormone, corticotrophin and cortisol in man.


Characterization of corticotrophin-like intermediate lobe peptides from rat and pig pituitaries, and identification of alpha-melanocyte-stimulating hormone in the rat pituitary.


The effect of increased K+ concentration and serotonin on cyclic AMP and corticosterone output by dispersed adrenal zona glomerulosa cells.


Halotolerant collagenolytic activity of Achromobacter iophagus.


Studies on proteolytic activity of mycoplasmas: gelatinolytic property.


Intersensory interactions in Hermissenda. Hair cells of the Hermissenda statocyst respond to photic stimulation. This response requires the presence of at least one of the two eyes. Two principal hair cell responses to light were observed. The activity of photoreceptors in response to a light step is interrupted during firing of contralateral hair cells. The intersensory interactions between the statocyst and visual pathway underlying these responses were examined with simultaneous intracellular recordings. Evidence is presented that the statocyst of Hermissenda is an important channel for visual information.


The quantal nature of synaptic transmission at the neuromuscular junction of a spider. Spontaneous and evoked release of transmitter at neuromuscular junctions in three different leg muscles of a tarantula (Dugesiella hentzi) was investigated. In most cases the spontaneous miniature potentials were released independently, although bursts from single synaptic junctions occasionally occurred. In contrast to recent findings in other arthropod muscles, focal extracellular recording from junctional areas revealed that the evoked release of transmitter quanta followed Poisson's theorem at low quantal content synaptic junctions in arachnid muscles.


Ultraviolet irradiation of herpes simplex virus: action spectrum for the survival of infectivity in relation to the small-plaque effect.


The polypeptides of three rhinoviruses.

The polypeptides of three rhinoviruses.


Evidence for the lack of glycoprotein in the encephalomyocarditis virus particle.


The subunits of murine sarcoma-leukaemia virus RNA.


Interference as a measure of cross-relationships in the vesicular stomatitis group of rhabdo viruses.


The infectivity of the nucleic acid of aerosol-inactivated poliovirus.


Herpesvirus hominis type I encephalitis treated with cytarabine, an unresolved problem in encephalitis.


Radical artery occlusion by a carpal ganglion. Case report.


Herpes simplex virus as a source of thymidine kinase for thymidine kinase-deficient mouse cells: suppression and reactivation of the viral enzyme. Thymidine kinase (EC 2.7.1.21)-deficient mouse cells were infected with inactivated herpes simplex virus, after which "transformed" cells that produce viral thymidine kinase were isolated. Shortly after transformation, the expression of the viral enzyme could be suppressed and reactivated with high efficiency. On continued multiplication in nonselective medium, the proportion of cells producing the viral enzyme decayed exponentially. This decay seemed to represent a change in the expression of the viral gene for thymidine kinase rather than the loss of the gene from the cells, since the viral enzyme could be apparently reactivated in every cell, albeit at a very low frequency.


Evaluation of a program of aftercare for patients discharged from the hospital.


Relationship of replication and transcription of Simian Virus 40 DNA. RNA produced by the Simian Virus 40 (SV40) mutant tsA30 during lytic infection of kidney cells of African green monkeys was examined by RNA-DNA competition-hybridization. This mutant is temperature-sensitive in a function (gene A) that regulates synthesis of viral DNA. No detectable difference between mutant RNA synthesized at the permissive temperature (33 degrees ) and wild-type viral RNA was found. During continuous infection with the mutant at the restrictive temperature (41 degrees ) only early viral RNA was produced. When mutant DNA and late RNA synthesis were initiated at the permissive temperature, a shift to the restrictive temperature rapidly terminated synthesis of viral DNA but not that of late viral RNA. The data indicate that the function of gene A is required before synthesis of late viral RNA and that after initiation, the production of late RNA continues without further expression of gene A or concomittant viral DNA synthesis.


Interferon: evidence for its glycoprotein nature. In an attempt to understand the structure of rabbit interferon, the possibility of carbohydrate being part of the molecule was tested. Interferon incubated with neuraminidase from Vibrio cholera is homogeneous in charge as revealed by isoelectric focusing. Treatment of "asialointerferon" with galactose oxidase (EC 1.1.3.9) from Dactylium dendroides and subsequent reduction with tritiated sodium borohydride yields labeled material with unimpaired antiviral activity. Enzymic incorporation of N-[(14)C]acetylneuraminic acid into tritiated asialointerferon restores the original charge heterogeneity. The newly generated sialointerferon contains both (3)H and (14)C activity. Asialointerferon is retained by an affinity column containing phytohemagglutinin from Phaseolus vulgaris and can be displaced from the adsorbent by a glycoprotein of known structure. It is concluded that rabbit interferon is a glycoprotein containing the terminal oligosaccharide sequence sialic acid --> galactose.


Primary dysbetalipoproteinemia: predominance of a specific apoprotein species in triglyceride-rich lipoproteins. Lipoproteins of very low density that are unusually rich in cholesteryl esters accumulate in blood plasma in a characteristic primary form of human hyperlipoproteinemia. These lipoproteins, which are thought to be products of the initial catabolic step in the metabolism of normal triglyceride-rich lipoproteins, have beta rather than pre-beta mobility on electrophoresis, presumably because they have lost certain protein components from their surface. In this study, we have used polyacrylamide gel electrophoresis of apoprotein components that are soluble in tetramethylurea to show that the very low-density lipoprotein fraction of blood serum from seven patients with hyperlipoproteinemia contains unusually large amounts of an arginine-rich protein. Pre-beta migrating, very low-density lipoproteins separated from serum of post-absorptive patients and chylomicrons obtained after a fat-rich meal contain normal amounts of this arginine-rich protein, but beta-migrating, very low-density lipoproteins and chylomicron-like particles separated from serum of post-absorptive patients contain more than twice as much. These apparently partially degraded lipoproteins also contain more tetramethylurea-insoluble protein and smaller amounts of the other soluble protein components than their normal counterparts.


Collagen and procollagen production by a clonal line of Schwann cells. A well-characterized line of rat Schwann cells has been examined for its ability to produce collagen. About 14% of the [(3)H]proline in the proteins that were secreted into the culture medium by the cells was hydroxylated, while only 1% of the labeled proteins in the cell layer contained [(3)H]hydroxyproline. Three sizes of procollagen polypeptides, of molecular weights about 105,000, 120,000, and 155,000, were present in the medium, as well as tropocollagen molecules that contained the usual alpha1 and alpha2 chains. Subsequently, the Schwann cells ceased producing the smaller collagenous polypeptides, although the total [(3)H]hydroxyproline content of the medium was unchanged. The [(3)H]hydroxyproline was almost entirely accounted for by the polypeptide of 155,000 daltons; this peptide was rapidly digested by collagenase or pepsin or chymotrypsin. The destruction by pepsin and chymotrypsin indicates that the large polypeptide, in contrast to procollagen and tropocollagen, is not in the collagenous (helical) conformation. Possibly, this substance is a very early form of procollagen that does not fold into the collagen conformation. The data show that cells of neuroectodermal origin can synthesize collagen, and also suggest that Schwann cells may be responsible for a large proportion of the collagen seen in peripheral neurinomas in vivo.


A tumor-associated antigen in human nephroblastomas. Antisera prepared against extracts of human nephroblastomas (Wilms' tumors) allowed the characterization in these extracts, and in a few extracts of tumors of other organs, of a tumor-associated antigen. This antigen is different from all previously described antigens, and was named W antigen (W for Wilms). It does not seem to be a carcinoembryonic antigen, and hence it could be of viral origin.


Virus-specific messenger RNA and nascent polypeptides in polyribosomes of cells replicating murine sarcoma-leukemia viruses. We present evidence that virus-specific RNA is present in polyribosomes of transformed cells replicating the murine sarcoma-leukemia virus complex and that it serves as messenger RNA for the synthesis of viral-coded proteins. Both virus-specific RNA (detected by hybridization with the [(3)H]DNA product of the viral RNA-directed DNA polymerase) and nascent viral polypeptides (measured by precipitation with antiserum to purified virus) were found in membrane-bound and free polyribosomes. Membrane-bound polyribosomes contained a higher content of both virus-specific RNA and nascent viral polypeptides. From 60 to 70% of viral RNA sequences were released from polyribosomes with EDTA, consistent with a function as messenger RNA. Maximum amounts of both virus-specific RNA and nascent viral polypeptides were found in the polyribosome region sedimenting at about 350 S.


Independent segregation of loci for activation of biologically distinguishable RNA C-type viruses in mouse cells. Two genetic loci for induction of RNA C-type virus in BALB/c mouse embryo cells segregate independently in backcross embryo cell lines. The viruses at these loci are shown to be biologically distinguishable. The first, described previously, codes for activation of a virus that grows preferentially in NIH Swiss embryo cells. The newly detected locus codes for activation of a virus that grows poorly, if at all, in NIH Swiss or BALB/c cells, but replicates well in a rat cell line. Its serologic properties are different from those of viruses of the two major serologic subgroups of murine leukemia virus. The present findings provide support for the hypothesis that the loci for virus induction in BALB/c cells represent genetic information for C-type viruses and that the endogenous viruses are subject to different cellular genetic controls.


Activation of a covalent enzyme-substrate bond by noncovalent interaction with an effector. The absorption spectrum of an activesite specific chromophoric acyl enzyme, sturgeon beta-(2-furyl)-acryloyl-glyceraldehyde-3-phosphate dehydrogenase, is reported. This acyl enzyme undergoes all of the catalyzed reactions characteristic of the intermediate of the physiological acyl enzyme, 3-phospho-D-glyceroyl-glyceraldehyde-3-phosphate dehydrogenease. The rates of reactions of both these acyl enzymes depend strongly on the extent of interaction of the acyl enzyme with the oxidized coenzyme, NAD(+), even where the "redox" properties of the coenzyme are not required. Likewise, the spectral properties of chromophoric acyl enzyme are affected by the extent of bound NAD. Under the pseudophysiological conditions reported herein, there is a stoichiometric limitation of two furylacryloyl-acyl groups per enzyme molecule containing four covalently-equivalent subunits. The binding of NAD both to the apoenzyme and to the diacyl enzyme is heterogeneous: at low extents of NAD occupancy, NAD binding is stronger. The binding to acyl enzyme can be quantitatively described by an enzyme model involving a tetramer with 2-fold symmetry, and consequently containing equal numbers of two classes of sites. NAD binding to difurylacryloyl-enzyme occurs virtually discretely, first to the two unmodified (tight-binding) sites, followed by looser binding to the two acyl-sites. NAD occupancy at these latter sites transforms the chromophoric acyl spectrum from that characteristic of a model furylacryloyl-thiol ester in H(2)O to a highly perturbed furylacryloyl spectrum characteristic of monomeric native "active-thiol" furylacryloyl-enzymes. Likewise the acyl reactivity towards arsenolysis depends on the extent of NAD bound to the loose sites. Elimination of the tight binding of NAD to the difurylacryloyl enzyme tetramer by alkylation of the remaining two free SH groups with iodoacetate has no apparent influence on the NAD-dependent furylacryloyl-spectral perturbation at the "two equivalent acyl sites," even though it eliminates the apparent "negative cooperativity" in NAD binding.


Relationship between post-transcriptional adenylation of herpes virus RNA and messenger RNA abundance. Analysis of the hybridization kinetics of labeled DNA of herpes simplex virus with unlabeled excess RNA from infected cells showed that viral RNA sequences form two classes differing in molar concentration. The abundant class constituted 93.5-99.3% of total virus-specific RNA and was complementary to 14-16% of the early DNA (2 hr after infection) and to 19-22% of the late DNA (8 hr after infection) in the reproductive cycle of the virus. The early RNA sequences were found to be a subset of the late sequences. The scarce sequences constituted 0.7-6.5% of total virus-specific RNA and were complementary to 28-30% of DNA both early and late in the reproductive cycle. In this study, abundant and scarce sequences were quantitatively separated on the basis of the finding that abundant species are adenylated, i.e., contain post-transcriptionally added poly(A), whereas the scarce RNA is not. Thus, nuclear and polyribosomal adenylated RNA were complementary to 24 and 22%, respectively, of viral DNA and, in abundance competition tests, were found to compete with each other and with abundant RNA from infected cells after 8 hr. The nonadenylated polyribosomal RNA was complementary to 27% of total viral DNA of which 6% was also complementary to adenylated polyribosomal RNA. Hybridization kinetics indicated that each of the fractionated adenylated RNA formed two classes complementary to 6 and 21% of viral DNA.


Prophylaxis and immunization in mice by use of virus-free defective T particles to protect against intracerebral infection by vesicular stomatitis virus. Defective interfering T particles of vesicular stomatitis virus provide remarkable protection against viral disease and death when introduced intracerebrally in large numbers along with an otherwise rapidly fatal low dose of standard infectious virus. This profound prophylactic effect of defective T particles is due to homologous autointerference since it is serotype-specific and interferon is not induced. This protective effect can be demonstrated only with preparations of T particles that have been purified completely free of infectious virions. When pure T particles are injected intracerebrally along with large doses of infectious virus, they convert an otherwise rapidly fatal disease process to a slowly progressing virus infection that generally terminates in death after many days of wasting disease and paralysis. Intracerebral injection of virus-free T particles alone is apparently innocuous to mice and stimulates immunity to massive doses of homologous infectious virus. In vitro, virus-free T particles at extremely high multiplicities depress cellular RNA and protein synthesis and kill BHK21 cells in culture, but do not exhibit such effects at moderately high multiplicities.


Discrimination between messenger ribonucleic acids by a mammalian translation initiation factor. A factor from rabbit-reticulocyte ribosome, which stimulates by 5-fold initiation of hemoglobin mRNA translation in Krebs ascites cell extracts, was purified to homogeneity. The factor, a protein of about 65,000 molecular weight in sodium dodecyl sulfate, discriminates between various mRNAs: it stimulates translation of alpha globin mRNA and of tobacco mosaic virus RNA, but has only a small effect on beta globin mRNA and no effect at all on Mengo virus RNA translation.


Chemical synthesis and biochemical properties of peptide fragments of apolipoprotein-alanine. Apolipoprotein-alanine is an apolipoprotein isolated from very-low-density lipoproteins of human plasma. This protein contains 79 amino acids and binds phosphatidyl choline. Four fragments of this molecule corresponding to sequence positions 41-79 (I), 48-79 (II), 55-79 (III), and 61-79 (IV) have been synthesized by standard solid-phase methods. The resulting peptides were cleaved from the resin and deblocked with liquid HF, then purified by chromatography on Sephadex G-50 and DEAE-cellulose. Each purified peptide eluted as a single, symmetrical peak, exhibited a single band on polyacrylamide gel electrophoresis, and gave an amino-acid analysis in good agreement with the theoretical value. Circular dichroism studies indicated that only fragments I and II became more helical in the presence of phosphatidyl choline and significantly inhibited the reactivation of delipidated beta-hydroxybutyrate dehydrogenase (EC 1.1.1.30), an enzyme that requires phosphatidyl choline for activity. When subjected to ultracentrifugation at density 1.064 g/ml in the presence of phosphatidyl choline, fragments I, II, III, and IV floated to the top of the tube to the extent of 85, 50, 13, and 9%, respectively. These results indicate that residues 55-79 do not contain the minimum determinants required for the binding of phospholipid. However, extension of the peptide's N-terminus by seven residues produces a molecule that does bind phosphatidyl choline.


Measurements of rates of adenosine 3':5'-cyclic monophosphate synthesis in intact Escherichia coli B. A method for labeling adenosine 3':5'-cyclic monophosphate in vivo from precursor adenosine followed by quantitative analysis of the labeled nucleotide is described. When the labeling period is short and the specific activity of the ATP pool is determined, the rate of incorporation of radioactivity corresponds to a determination of adenylate cyclase activity in vivo. In E. coli B the specific activity of adenylate cyclase in vivo varies under different growth conditions. Under all conditions tested, the adenylate cyclase activity in vivo is great enough to account for the pattern of accumulation of cyclic AMP. This is in contrast to previous adenylate cyclase assays in vitro, where the measured enzyme activities were insufficient to account for the amounts of cyclic AMP accumulated.


Variation of type-B DNA x-ray fiber diagrams with base composition. Eight natural DNAs of widely differing base composition have been studied by x-ray diffraction in fibers at high relative humidity. The resulting type B diffraction diagrams showed that all of the DNAs had a 34-A pitch and 3.4-A interbase pair separation. However, the intensity distribution on the inner three layer lines was a strong function of the base content. In diffraction diagrams of very AT-rich DNA, the intensity of the first and third layer line was 2- or 3-times stronger than in the patterns of GC-rich DNA. These high humidity diffraction patterns agree with x-ray scattering from solutions of DNA. The results are interpreted to imply that each AT base pair may have a different cross section than a GC pair. If this is so, it would appreciably alter the currently held ideas concerning DNA recognition.


Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts by lipoproteins. The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), the rate-limiting enzyme of hepatic cholesterol biosynthesis, is suppressed in human fibroblasts cultured in the presence of serum. This enzyme activity increases by more than 10-fold after the removal of serum from the medium. The rise in enzyme activity requires de novo protein synthesis and is not accompanied by changes in the activities of several other cellular enzymes. The factor responsible for the suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured fibroblasts is present in the sera of at least four mammalian species, and in human serum it is found in the low-density lipoproteins. Human high-density lipoproteins, very low-density lipoproteins from chicken egg yolk, and the fraction of human serum containing no lipoproteins do not suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase.


Electron spin resonance studies of electron irradiated peptides. A single crystal of N-acetylglycine at 77 K.


ESR and INDO-MO studies of radicals and radical reactions in irradiated single crystals of 5-nitro-6-methyluracil.


Microlymphangiography of human gastric musosa for the interpretation of early spread of gastric cancer.


Dreams and the social environment.

Dreams and the social environment.


Lipid metabolism in uremia and the effects of dialysate glucose and oral androgen therapy.


Considerations of the middle molecular hypothesis. II. Neuropathy in nehprectomized patients.


An approach to "middle molecules" identification in artificial kidney dialysate, with reference to neuropathy prevention.


Nerve excitability in chronic renal disease.


Role of pyrophosphate in renal osteodystrophy.


Viraemia and antibody development in chicks following the administration of turkey herpesvirus.


Development of a pharmacy care plan.

Development of a pharmacy care plan.


Adenovirus in the sinuses of an asthmatic patient with apparent selective antibody deficiencies.


Acute ulcerative colitis associated with cytomegalic inclusion virus.


Bone collagen metabolism in vitamin D deficiency. Radioisotope studies have shown that collagen synthesized in the shafts of bones from rachitic rats and chicks is similar in chain composition to that normally synthesized. However, the extent of lysine hydroxylation in both alpha1- and alpha2-chains is increased, by approx. 15-30% in the rat and by 50% in the chick.


Hepatic redox state and gluconeogenesis from lactate in vivo in the rat. 1. To examine the role of the hepatic redox state on the rate of gluconeogenesis the effects of sodium crotonate injection (6mmol/kg body wt.) on rat liver metabolite concentrations and gluconeogenesis from lactate were studied in vivo. 2. Crotonate caused a marked oxidation of cytoplasmic and mitochondrial redox couples; decreases were observed in the ratios of [lactate]/[pyruvate], [glycerol 3-phosphate]/[dihydroxyacetone phosphate], [hydroxybutyrate]/[acetoacetate] and measured [NAD(+)]/[NADH]. 3. Increases occurred in the liver concentrations of all gluconeogenic intermediates from pyruvate through to glucose 6-phosphate, but there was no change in lactate concentration. 4. To determine whether gluconeogenesis from lactate was altered by the more-oxidized hepatic redox state l-[2-(14)C]lactic acid was infused into the inferior vena cava (50mumol/min per kg body wt.) and the incorporation of radioactivity into blood glucose was measured. 5. Administration of crotonate transiently decreased the rate of lactate incorporation into glucose but within a few minutes the rate of incorporation returned to that of the controls. 6. The results indicate that in these experiments alteration of the NAD(+)-NADH systems of cytoplasm and mitochondria to a more-oxidized state did not change the rate of gluconeogenesis.


The absence of an integrated copy of mitochondrial DNA in the nuclear genome of Tetrahymena pyriformis.


The effect of glucose, insulin and noradrenaline on lipolysis, and on the concentrations of adenosine 3':5'-cyclic monophosphate and adenosine 5'-triphosphate in adipose tissue. Glycerol release and tissue concentrations of ATP and cyclic AMP were followed during the incubation of adipose tissue with or without glucose, insulin and noradrenaline. Glucose plus insulin or, to a lesser extent, glucose alone increased the accumulation of glycerol during incubations both with and without noradrenaline by slowing the decline in the rate of glycerol release with time. Insulin alone decreased the accumulation by accelerating the fall in glycerol release. In the absence of noradrenaline, ATP and cyclic AMP concentrations were not significantly affected by insulin or glucose. With noradrenaline or noradrenaline plus insulin the ATP concentration gradually fell. With noradrenaline plus glucose the ATP concentration fell rapidly and then stabilized, or, if insulin was also present, returned to the control value. In the presence of noradrenaline, the concentration of cyclic AMP rose during the first 20min and then fell. Insulin lowered the peak concentration of cyclic AMP, but glucose had no effect either on the peak value or the fall in the concentration of the nucleotide. The increase and fall in the concentration of cyclic AMP with noradrenaline or noradrenaline plus insulin bore similarities to the increase and decline in the lipolytic rate in incubations without glucose. It is proposed that glucose stimulates ATP production by furnishing glycerol 1-phosphate and thus removing free fatty acids, but that it can influence lipolysis by a mechanism which is distinct from any which is mediated by free fatty acids, possibly by inhibiting the inactivation of the lipase.


The analysis of polydeoxyribonucleotides by digestion with phosphatase and phosphodiesterases.


Ribosomal RNA cistron topography in Escherichia coli.


A clinicopathologic analysis of adriamycin cardiotoxicity.


Radiologic evaluation of soft tissue tumors. A retrospective study.


Perineural invasion and anaplastic transformation of verrucous carcinoma.


Cirrhosis and hepatoma occurring at Boston City Hospital (1917-1968).


Sinus histiocytosis with massive lymphadenopathy. Report of a case associated with elevated EBV antibody titers.


Benign liver cell tumors. Classification and ultrastructural pathology.


Malignant mixed tumor of the gallbladder.


Benign lipoblastomatosis. An analysis of 35 cases.


Pituitary insufficiency, inappropriate antidiuretic hormone (ADH) secretion, and carcinoma of the bronchus.


Studies on the relationship between the catecholamine distribution in the atrium and the specific granules present in atrial muscle cells. 1. Isolation of a purified specific granule subfraction.


Techniques for studying adrenergic transmitter release in an isolated perfused artery.


New approaches to treatment of osteogenesis imperfecta.


Thermal activation of the cyclic AMP stimulated sodium transport across isolated toad bladder and Na+-K+ ATPase in toad bladder homogenates.


Synaptic frequency demodulation.

Synaptic frequency demodulation.


Sleep in parabiosis.

Sleep in parabiosis.


Crayfish neuromuscular junction: facilitation with constant nerve terminal potential.


Sleep in the giant South American armadillo Priodontes giganteus (Edentata, Mammalia).


Vesicle hypothesis: effect of nerve stimulation on the synaptic vesicles of motor endplates.


Induction of ingestive responses by cAMP applied into the rat hypothalamus.


The influence of some biogenic amines and cyclic N-2-O-dibutyryl-adenosine-3',5'-monophosphate on glycogen content in rat brain slices.


Milk microsomes, viruses, and the milk fat globule membrane.


The influence of propranolol and dibenzyline on glycogenolytic effects of some biogenic amines in rat brain slices.


Pea phytohemagglutinin selective agglutination of tumour cells.


Radioimmunological determination of plasma cortisol.


Behaviour of a guanidine-dependent strain of poliovirus 1 in sucrose density and pH gradients.


Thiopyrimidines: specific inhibitors of poliovirus induced early cell damages.


Gas-liquid and thin-layer chromatography of some 3- and 3,x-substituted pyrenes.


Circular thin-layer chromatography for diagnosis and follow-up of neural crest tumours.


Layer pre-loading in partition thin-layer chromatography of amino acids.


Generation of ATP during cytochrome-linked anaerobic electron transport in propionic acid bacteria.


Acquisition of parainfluenza 3 virus infection by hospitalized children. I. Frequencies, rates, and temporal data.


Viral interference with exoerythrocytic forms of malaria (Plasmodium gallinaceum) in ovo.


An outbreak of a febrile disease (Izumi fever) associated with high anti-eb virus antibody titers.


Interference mediated by a variant of Sindbis virus. II. Actinomycin D-sensitive interference in the absence of interferon.


The establishment of cultured cell lines from the patients with Izumi fever and infectious mononucleosis like diseases.


Some biochemical studies on the nonspecific acid phosphomonoesterases of Dirofilaria immitis.


Alterations in lipoprotein pattern in liver plasma membranes from rats of different ages.


Basic mechanisms of aging in the neuromuscular system.


Biosynthesis of collagen (14C)hydroxyproline and (14C)hydroxylysine during maturation of chick embryos.


Some properties of seryl-tRNA synthetase from rat liver.


Rearing experience, stress and adrenocorticosteroids in the rhesus monkey.


Influence of environmental temperature on the sleep-wakefulness cycle in the rat.


Does the desert black snake venom inhibit release of acetylcholine from motor nerve endings?


The mechanisms of testosterone action of the sebaceous glands of the Syrian hamster.


Complications of antimicrobial therapy.

Complications of antimicrobial therapy.


Three sites for hormonal control of the pigment cell.


Microbiologic studies on young infants with lower respiratory tract disease.


Amebic liver abscess in childhood. A case study of a 21-month-old Thai child and a literature review.


Cytologic detection of minute ovarian, endometrial and breast carcinomas, with emphasis on clinical-pathological approaches.


Pneumonia and massive pleural effusion associated with adenovirus type 7.


False positive roentgenologic diagnosis of small intracanalicular acoustic neurinomas.


Radiation therapy of the glomus jugulare tumor.


Cytologic diagnosis of salivary gland tumors by aspiration biopsy.


An 18-month longitudinal lymphographic study of filarial diseases in dogs infected with Brugia pahangi (Buckley and Edeson, 1956).


A study of some enzymes of glycerolipid biosynthesis in rat liver after subtotal hepatectomy. 1. The accumulation of triglyceride in the liver remnant after subtotal hepatectomy (removal of 82% of the liver) exceeded that described for partial hepatectomy (removal of 70% of the liver). 2. Palmitoyl-CoA synthetase, glycerol phosphate acyltransferase and diglyceride acyltransferase activities were measured in the microsomal fraction, and phosphatidate phosphohydrolase activity was measured in the particle-free supernatant fraction, prepared from the liver remnant at various times after subtotal hepatectomy. 3. The only enzyme showing a significant change in specific activity was phosphatidate phosphohydrolase. The specific activity was approximately fivefold that of the control value at 6h after operation and threefold that of the control at 10, 16 and 24h after operation. A smaller increase in the specific activity of the enzyme in sham-operated animals occurred only at 6h after operation. 4. However, at this time the total phosphohydrolase activity of the remaining liver in the sham-operated rats was approximately threefold that in hepatectomized rats. 5. Injection of actinomycin D prevented the increase in activity of phosphatidate phosphohydrolase but did not prevent the accumulation of triglyceride.


The use of deoxyribonucleic acid-cellulose chromatography and isoelectric focusing for the characterization and partial purification of steroid-receptor complexes. 1. Two characteristic properties of the specific high-affinity steroid-binding proteins or receptors, their ability to bind to DNA-cellulose and their relatively acidic isoelectric point, have been exploited as a means of purification. These two fundamental properties distinguish the receptors from the steroid-binding proteins in serum and the non-specific low-affinity steroid-binding proteins in hormone-responsive cells. 2. A significant degree of purification of both cytoplasmic and nuclear steroid-receptor complexes can be achieved with practical facility by these procedures. The purity of the receptor complexes is sufficient to enable studies on their possible control of metabolic processes to be investigated in the future. 3. After extensive purification the physicochemical properties of the cytoplasmic androgen-receptor complex, such as sedimentation coefficient, were unchanged. Further, the purified complex fully retained at least one of its fundamental physiological properties, namely the ability to transfer 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) into chromatin in vitro. 4. The methods may also be employed for studying the changes in the structure and properties of the receptor complexes that are an essential prerequisite for the transfer of cytoplasmic receptor complexes into nuclear chromatin. The temperature-dependence of the binding of androgen-receptor complexes into chromatin is essentially due to a major change in cytoplasmic receptor complex before its attachment to nuclear chromatin. 5. The resolution of these analytical procedures was sufficient to enable a critical comparison of the receptor proteins from different male accessory glands to be undertaken. From these studies, no substantial evidence in support of the tissue specificity of androgen receptors could be established; rather the receptors from different androgen-dependent glands were remarkably similar in physicochemical properties. 6. Although the methods were initially developed for the partial purification of androgen-receptor complexes, they are equally suitable for the prompt and extensive purification of oestrogen-receptor and progesterone-receptor complexes.


Adenosine 3':5'-cyclic monophosphate concentrations and phosphodiesterase activities during axenic growth and differentiation of cells of the cellular slime mould Dictyostelium discoideum. During growth of myxamoebae of Dictyostelium discoideum (strain Ax-2) in axenic medium, the myxamoebae secrete cyclic AMP. As the cells leave the exponential phase of growth and enter the stationary phase, there is an approximate doubling of the intracellular cyclic AMP content, but the amount of extracellular cyclic AMP remains proportional, at all times, to the number of myxamoebae present. During development of axenically grown myxamoebae, there is first a rise in the intracellular concentration of cyclic AMP, followed by a rise in the amount of extracellular cyclic AMP, which reaches a peak at the time of aggregation and then declines. There is a second peak in the amount of extracellular cyclic AMP found at the time of fruiting-body formation, but this second peak is not associated with a rise in the intracellular cyclic AMP concentration. Controls thus exist over the synthesis and secretion of cyclic AMP. Evidence is presented for the belief that the activity of the adenylate cyclase enzyme controls the amount of cyclic AMP synthesized rather than the activity or amount of cyclic AMP phosphodiesterase present. Similar changes occur in extracellular cyclic AMP and phosphodiesterase concentrations during incubation of myxamoebae in buffered suspensions to those occuring during the first few hours of development of such cells on solid media, but the timing of these changes is different.


Regulation of renal gluconeogenesis by calcium ions, hormones and adenosine 3':5'-cyclic monophosphate. 1. The effect of Ca(2+), glucagon, adrenaline and adenosine 3':5'-cyclic monophosphate on gluconeogenesis by rat kidney-cortex slices was studied. 2. Glucose formation from a range of substrates, with the exception of glycerol, was increased by an increase in extracellular Ca(2+) concentration. 3. Hormones and adenosine 3':5'-cyclic monophosphate, at low Ca(2+) concentrations, stimulated glucose production from several substrates, but not from glycerol, fructose, malate or fumarate. 4. Hormonal stimulation was not detected in the absence of Ca(2+) or at 2.5mm-Ca(2+). 5. Ca(2+), hormones and adenosine 3':5'-cyclic monophosphate had no effect on phosphoenolpyruvate carboxylase activity. 6. It is proposed that Ca(2+) and adenosine 3':5'-cyclic monophosphate-mediated hormone action activate the same rate-limiting step in gluconeogenesis: this step is tentatively identified as the rate of transfer of substrates across the mitochondrial membrane.


A reappraisal of the effects of adenosine 3':5'-cyclic monophosphate on the function and morphology of the rat prostate gland. 1. A comparison was made of the binding of 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and cyclic AMP in the rat prostate gland. Distinct binding mechanisms exist for these compounds, and cyclic AMP cannot serve as a competitor for the 5alpha-dihydrotestosterone-binding sites and vice versa. In contrast with the results obtained with 5alpha-dihydrotestosterone, very small amounts of cyclic AMP are retained in nuclear chromatin and the overall binding of this cyclic nucleotide is not markedly affected by castration. 2. Androgenic stimulation does not lead to major increases in the adenylate cyclase activities associated with any subcellular fraction of the prostate gland. Accordingly, changes in the concentration of cyclic AMP in the prostate gland after hormonal treatment are likely to be small, but these were not measured directly. 3. When administered to whole animals in vivo, small amounts of non-degraded cyclic AMP are found in the prostate gland but sufficient to promote an activation of certain carbohydrate-metabolizing enzymes in the cell supernatant fraction. The stimulatory effects of cyclic AMP were not evident with cytoplasmic enzymes engaged in polyamine synthesis or nuclear RNA polymerases. These latter enzymes were stimulated solely by the administration of testosterone. 4. By making use of antiandrogens, a distinction can be drawn between the biochemical responses attributable to the binding of 5alpha-dihydrotestosterone but not of cyclic AMP. Evidence is presented to suggest that the stimulation of RNA polymerase, ornithine decarboxylase and S-adenosyl-l-methionine decarboxylase is a consequence of the selective binding of 5alpha-dihydrotestosterone. Only the stimulation of glucose 6-phosphate dehydrogenase can be attributed to cyclic AMP or other metabolites of testosterone. 5. Overall, this study indicates that the formation of cyclic AMP is not a major feature of the androgenic response and affects only a restricted number of biochemical processes. Certainly, cyclic AMP cannot be considered as interchangeable with testosterone and its metabolites in the control of the function of the prostate gland. This difference is additionally emphasized by the failure of cyclic AMP to restore the morphology of the prostate gland in castrated animals; morphological restoration only follows the administration of androgens.


Induction and suppression of the key enzymes of glycolysis and gluconeogenesis in isolated perfused rat liver in response to glucose, fructose and lactate. 1. Measurements were made of the activities of the four key enzymes involved in gluconeogenesis, pyruvate carboxylase (EC 6.4.1.1), phosphoenolpyruvate carboxylase (EC 4.1.1.32), fructose 1,6-diphosphatase (EC 3.1.3.11) and glucose 6-phosphatase (EC 3.1.3.9), of serine dehydratase (EC 4.2.1.13) and of the four enzymes unique to glycolysis, glucokinase (EC 2.7.1.2), hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40), in livers from starved rats perfused with glucose, fructose or lactate. Changes in perfusate concentrations of glucose, fructose, lactate, pyruvate, urea and amino acid were monitored for each perfusion. 2. Addition of 15mm-glucose at the start of perfusion decreased the activity of pyruvate carboxylase. Constant infusion of glucose to maintain the concentration also decreased the activities of phosphoenolpyruvate carboxylase, fructose 1,6-diphosphatase and serine dehydratase. Addition of 2.2mm-glucose initially to give a perfusate sugar concentration similar to the blood sugar concentration of starved animals had no effect on the activities of the enzymes compared with zero-time controls. 3. Addition of 15mm-fructose initially decreased glucokinase activity. Constant infusion of fructose decreased activities of glucokinase, phosphofructokinase, pyruvate carboxylase, phosphoenolpyruvate carboxylase, glucose 6-phosphatase and serine dehydratase. 4. Addition of 7mm-lactate initially elevated the activity of pyruvate carboxylase, as also did constant infusion; maintenance of a perfusate lactate concentration of 18mm induced both pyruvate carboxylase and phosphoenolpyruvate carboxylase activities. 5. Addition of cycloheximide had no effect on the activities of the enzymes after 4h of perfusion at either low or high concentrations of glucose or at high lactate concentration. Cycloheximide also prevented the loss or induction of pyruvate carboxylase and phosphoenolpyruvate carboxylase activities with high substrate concentrations. 6. Significant amounts of glycogen were deposited in all perfusions, except for those containing cycloheximide at the lowest glucose concentration. Lipid was found to increase only in the experiments with high fructose concentrations. 7. Perfusion with either fructose or glucose decreased the rates of ureogenesis; addition of cycloheximide increased urea efflux from the liver.


The mode of action of adenosine 3':5'-cyclic monophosphate in mammalian islets of Langerhans. Effects of insulin secretagogues on islet-cell protein kinase activity. 1. Protein kinase activity was measured in islets of Langerhans that had been incubated in the presence of agents known to affect insulin release. 2. Glucagon, theophylline, caffeine and 3-isobutyl-1-methylxanthine, agents that raise cyclic AMP concentrations in islet cells and stimulate insulin release, increased protein kinase activity. Adrenaline and diazoxide, agents that decrease cyclic AMP concentrations and inhibit insulin secretion, decreased the activity. 3. The increase in protein kinase activity produced by different concentrations of 3-isobutyl-1-methylxanthine was apparently related to the increase in intracellular concentrations of cyclic AMP. 4. The sulphonylureas, tolbutamide and glibenclamide, agents that increase insulin release, also increased the protein kinase activity; however, leucine, arginine and xylitol, which also stimulate insulin release, were without effect on the kinase activity. 5. Increasing the glucose concentration of the incubation medium from 2 to 20mm had no effect on protein kinase activity. Further, the ability of 3-isobutyl-1-methylxanthine to increase the protein kinase activity was not affected by the glucose concentration of the incubation medium. 6. These results suggest that agents which affect insulin secretion by altering cyclic AMP concentrations may exert their effects on hormone release by altering the activity of a cyclic AMP-dependent protein kinase in islet cells.


Comparative studies on the carbohydrate-containing membrane components of normal and adenosine 3':5'-cyclic monophosphate-treated Chinese hamster ovary cells. 1. We investigated some of the changes in plasma-membrane composition that accompany the alteration in cell growth and morphology induced by treating Chinese-hamster ovary cells with dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP). 2. A double-labelling technique was employed in which normal cells were given (14)C-labelled precursor, and those treated with dibutyryl cyclic AMP were given (3)H label. l-Leucine, d-glucosamine, and l-fucose were used to label the membranes. 3. After 3 days growth, the two populations of cells were harvested by trypsin treatment, the cells were pooled, and plasma membranes isolated. Proteins and glycoproteins of the membranes were separated by electrophoresis on sodium dodecyl sulphate-polyacrylamide gels, and the radioactive profiles for (14)C and (3)H and the staining patterns with Amido Black were compared. 4. Although certain components of the membrane from treated cells showed marked quantitative changes, there was neither major addition nor major deletions of components. 5. Complete proteolysis of the mixed membranes, of the material released from the cell surface by trypsin, and of the glycoproteins released from the cells into the medium, gave a series of radioactive glycopeptides when either fucose or glucosamine was employed as precursor. 6. After such glycopeptides were fractionated on columns of Sephadex G-50, marked differences in the elution profiles of (3)H and (14)C were noted. Dibutyryl cyclic AMP evidently causes alterations in the overall composition of the carbohydrate components of the cell surface. It was not possible to decide whether this was solely the result of the same glycoproteins being formed but in different proportions, or the result of modifications of oligosaccharide side chains on some of the glycoproteins. 7. Some of the changes were not unlike the reverse of those that accompany the transformation of fibroblasts by oncogenic viruses, and our results lend credence to the idea that the lowered amount of cyclic AMP noted in transformed cells is responsible for their altered surface properties.


Studies on the biosynthesis of cytochrome c. A soluble cytochrome was isolated and purified from the slime mould Physarum polycephalum and identified as cytochrome c by room-temperature and low-temperature (77 degrees K) difference spectroscopy. A close similarity between P. polycephalum and mammalian cytochromes c was suggested by a comparison of the initial rates of oxidation of both proteins by mammalian mitochondria. This similarity was further emphasized by redox titrations and gel-electrophoretic studies which indicated that P. polycephalum cytochrome c has an oxidation-reduction midpoint potential of +257mV at pH7.0 and a molecular weight of 12500+/-1500 (mean+/-maximum deviation for a set of six measurements). P. polycephalum exhibits an absolute requirement for protohaemin for growth. The (59)Fe-labelled haemin was prepared by chemical synthesis from protoporphyrin. The purified product had a specific radioactivity of 0.8+/-0.02muCi/mol. Growth of P. polycephalum in the presence of [(59)Fe]haemin resulted in the incorporation of (59)Fe into the plasmodial cytochrome c. The specific radioactivity of the cytochrome c haem was 0.36+/-0.02muCi/mol. The high specific radioactivity of the cytochrome haem indicates that synthesis of the holoenzyme must proceed by direct attachment of haem to the apoprotein rather than by the intermediate formation of a protoporphyrinogen-apoprotein complex. The observed decrease in the specific radioactivity of the haem group is attributed to exchange of the (59)Fe with unlabelled iron in the plasmodia either before or during attachment of the haem group to the apoprotein.


Heterogeneous distribution of glucose 6-phosphatase in rat liver microsomal fractions as shown by adaptation of a cytochemical technique. 1. A novel technique for the subfractionation of rat liver smooth and rough microsomal fractions according to their content of glucose 6-phosphatase is described. This technique, based on the Gomori lead histochemical procedure, involves incubation of smooth and rough microsomal fractions with low concentrations of Pb(NO(3))(2) and glucose 6-phosphate. Control experiments, in which enzyme was assayed in the presence of various amounts of Pb(NO(3))(2) or in which microsomal fractions were reisolated after incubation with low concentrations of Pb(NO(3))(2) and glucose 6-phosphate, showed that lead does not interfere with glucose 6-phosphatase activity. 2. Discontinuous sucrose-density-gradient centrifugation of microsomal fractions which had previously been incubated with various amounts of Pb(NO(3))(2) and glucose 6-phosphate showed that it is possible to subfractionate both smooth- and rough-microsomal fractions into several bands, owing to a differential modification of the density of the microsomal vesicles by the trapping of lead phosphate within them. 3. When the material in the bands obtained by density-gradient centrifugation of incubated microsomal fractions was assayed for glucose 6-phosphatase activity, it was found that the modification of the density of the microsomal fractions was directly related to their relative enrichment in glucose 6-phosphatase activity. Control experiments, in which microsomal fractions were incubated with Pb(NO(3))(2) and glucose 6-phosphate and then treated with EDTA, showed that the subfractionation was not due to aggregation of microsomal vesicles, lead and glucose 6-phosphate. Thus the resolution of microsomal preparations into subfractions with different glucose 6-phosphatase activities is interpreted as indicating heterogeneity of glucose 6-phosphatase distribution in the microsomal vesicles. 4. Electron micrographs of both smooth- and rough-microsomal subfractions show deposits of lead phosphate within the microsomal vesicles. The frequency and extent of these deposits correlate with the different amounts of glucose 6-phosphatase activity measured biochemically. 5. The nature of the heterogeneous distribution of glucose 6-phosphatase is discussed and the more general applicability of the technique for studying membrane fractions containing a heterogeneous distribution of phosphatases is indicated.


A comparison of D-inositol 1:2-cyclic phosphate 2-phosphohydrolase with other phosphodiesterases of kidney. 1. The ability to hydrolyse various phosphodiesterase substrates was examined in subcellular fractions of rat kidney and in serial slices of the kidneys of mouse, rat, guinea pig and ox cut from the cortex perimeter inwards. 2. d-Inositol 1:2-cyclic phosphate 2-phosphohydrolase could be clearly distinguished from phosphodiesterases which hydrolyse 2':3'- and 3':5'-cyclic AMP and p-nitrophenyl thymidine 5'-phosphate (phosphodiesterase I). The hydrolysis of sn-glycero-3-phosphorylcholine showed a distribution identical with that of particle-bound d-inositol 1:2-cyclic phosphate 2-phosphodiesterase, but there was a 30-fold difference in the ratio of enzyme activities between the rat and guinea pig. 3. In rat and mouse kidney, d-inositol 1:2-cyclic phosphate 2-phosphohydrolase is virtually all membrane bound and in the outer cortex, whereas in guinea-pig kidney the enzyme is almost entirely soluble and located throughout the kidney tissue. Some properties of the soluble enzyme are described. 4. Distribution and histochemical studies indicated that in the rat and mouse, phosphodiesterase I is associated with the brush borders of the straight portion (pars recta) of the proximal tubule, whereas inositol 1:2-cyclic phosphate 2-phosphohydrolase and probably glycerylphosphorylcholine diesterase are associated with the brush borders of the convoluted part of the tubule (pars convoluta).


The pattern of methylated purines formed in DNA of intact and regenerating liver of rats treated with the carcinogen dimethylnitrosamine.


The synthesis of DNA associated with the nuclear membrane of guinea pig adrenal cells.


An investigation of the phosphoprotein of the bovine dentin matrix.


The interrelationships between vitamin D parathyroid hormone and calcitonin.


Protein hydrophobicity and lipid--protein interaction.


Some indicators of myocardial metabolism in complications caused by heterogeneous blood transfusion.


The ATP pool in Escherichia coli K 12 strains bearing the R1 plasmid.


Pregnant donkey's serum-induced ovulation in immature mice.


Isolation of enteroviruses from sheep.

Isolation of enteroviruses from sheep.


Effect of contraceptive suture on biochemical composition of uterine fluid of protein deficient rats. To study the effect of a protein deficient diet on the biochemical composition and the volume of uterine fluid, 18 rats were maintained on a protein deficient diet and 18 rats on a normal diet.  A surgical silk suture was inserted into the right uterine horn of each rat.  After ovariectomy followed by rest of 7 days and injection of 50 mgm estradiol dipropionate daily for 7 days, the animals were sacrificed and the luminal fluid aspirated and studied.  The presence of the silk suture led to an increase in the amount of albumin present in the fluid.  There were no other alterations of biochemical composition of fluid attributable to the IUD or dietary protein deficiency.  In vivo incorporation of d1-valine-1-carbon-14 into protein lactic acid glycogen, acid-soluble phosphorus, and phosphatase activity was not affected by the presence of the sutures.


Effects of some divalent cations on sympathetic ganglion function.


Biochemical aspects concerning adenine nucleotides and some related enzymes in the concomitant action of cephalin and serotonin of the blood platelets.


Release of enzymes from a rat liver lysosome fraction: inhibition by catecholamines and cyclic3', 5'-adenosine monophosphate, stimulation by cholinergic agents and cyclic 3', 5'-guanosine monophosphate.


A modified pancreaticoduodenectomy.

A modified pancreaticoduodenectomy.


The origin, hormonal nature, and action of hepatotrophic substances in portal venous blood.


Some functional aspects of the plasma apolipoproteins.


Renin-angiotensin in extrarenal tissues.


Ultrastructural studies on cell degeneration in the mouse uterovaginal anlage.


Effects of different hormones on the zoning and sinusoids of the adrenal gland.


The actions of cyclic nucleotides on the toad bladder.


Regulation of gene transcription in Escherichia coli by cyclic AMP.


The role of cyclic AMP in the control of fluid secretion.


Role of cyclic AMP in the action of neurohypophyseal hormones on kidney.


The effect of cholera toxin on intestinal adenyl cyclase.


Role of cyclic AMP in the regulation of gastric secretion in dogs and humans.


Cyclic AMP and vascular smooth muscle.

Cyclic AMP and vascular smooth muscle.


Cyclic AMP as a first messenger.

Cyclic AMP as a first messenger.


Studies on the possible role of cyclic AMP in drug-induced coronary vasodilatation.


Role of cyclic AMP in platelet function.


Role of cyclic AMP and Ca++ in metabolic and mechanical events in smooth muscle.


The positive inotropic effect of cyclic AMP.


Effect of dibutyryl cyclic GMP on cultured beating rat heart cells.


The role of cyclic AMP in the inotropic response to isoprenaline and glucagon.


Inotropic and chronotropic effects of dibutyryl cyclic AMP.


The role of cyclic AMP in visual excitation.


On the mechanism of action of cyclic AMP and its role in synaptic transmission.


Cyclic AMP-dependent protein kinases from skeletal muscle and liver.


Neuroendocrine control of the cyclic AMP system of brain and pineal gland.


Cyclic AMP in the rat brain: microwave irradiation as a means of tissue fixation.


Cyclic AMP-mediated adrenergic synapses to cerebellar Purkinje cells.


Regulation of cyclic AMP metabolism in cultured cells of the nervous system.


Regulation of brain phosphodiesterase activity: Ca++ plus Mg++ -dependent phosphodiesterase and its activating factor from rat brain.


Prostaglandin--adenyl cyclase relationships.


The role of cyclic AMP in activation of hormone-sensitive lipase of adipose tissue.


Cyclic AMP and prostaglandins in hormone action.


Functional relations between cyclic AMP, prostaglandins, and luteinizing hormone in rat pituitary and ovary.


The role of cyclic AMP in lysosome mobilization and their nucleotropic translocation in steroid hormonal target cells.


A study of the bioloical activity and resistance to phosphodiesterase of some derivatives and analogues of cyclic AMP.


Levels of cyclic AMP and rate of fat mobilizing lipolysis in human adipose tissue in response to different adrenergic stimulators.


Studies on the role of cyclic AMP in human lipolysis.


The role of cyclic AMP in the control of hepatic glucose production by glucagon and insulin.


Determination of alpha-quartz in the respirable portion of airborne particulates by X-ray diffraction.


Animal model of human disease. Liver cell carcinoma, hepatocellular carcinoma, hepatoma.


The functional significance of surface structures on lymphocytes.


Immunologic properties of ferritin.

Immunologic properties of ferritin.


Hepatic arterial patency and complications after catheterization for infusion chemotherapy.


Muscular tumors of the stomach: clinical and pathological study of 113 cases.


Abdominal aortography in the newborn via the umbilical artery.


Murine erythroblastosis by a novel viral agent.


Chemotherapy of lymph node metastasis by thigh and footpad inoculation of mouse leukemia L-1210 cells.


Molecular weight of cytochrome oxidase.

Molecular weight of cytochrome oxidase.


A rabies-induced serum factor inhibiting Rous sarcoma virus in chicks.


Temperature-sensitive mutants of vesicular stomatitis virus; homology and nomenclature.


Host range conversion of the murine sarcoma-leukaemia complex.


The role of antibody and host cells in the resistance of mice against infection by coxsackie B-3 virus.


Evidence for a group protein in foot-and-mouth disease virus particles.


Properties of mouse embryo cells infected with murine sarcoma virus and simian virus 40 simultaneously in vitro.


Haemagglutination by type SAT 2 foot-and-mouth disease viruses.


Restoration of the fusion activity of L cell-borne Sendai virus by trypsin.


Primary carcinoma of the liver: a study of 282 cases in Ugandan Africans.


Actions of 1,25-dihydroxycholecalciferol in patients with hypophosphatemic, vitamin-D-resistant rickets.


Familial hypophosphatemia: the dilemma of treatment.


Metabolism of the myocardium at cellular level.


Ventilatory pumping of human pulmonary lymphatic vessels.


The role of diet in the management of hyperlipoproteinaemias.


Time course of decrease in blood pressure and in blood pressure response to vasopressor agents during pregnancy in the rat.


Delay in bone age in children with cyanotic congenital heart disease.


Use of ultrasonography to follow regression of theca lutein cysts.


Granuloma formation.

Granuloma formation.


Contraception.

Contraception. The article reviews the putative effects of oral contraceptives on the metabolism, hepatic function, thyroid gland, adrenal gland, carbohydrate and lipid metabolism, blood pressure and coagulation, and thromboembolic disease.  Assessing risks by interpretation of mortality rates is briefly discussed and it is concluded that the risks in oral contraception are acceptable.


Suppression of the defect in cell division in the histidine regulatory mutants of Salmonella typhimurium.


A case of juvenile angiofibroma.

A case of juvenile angiofibroma.


The amino acid sequence of cytochrome c from Nigella damascena L. (love-in-a-mist). The amino acid sequence of cytochrome c from Nigella damascena L. was determined on 0.2mumol of protein. Peptides from a single chymotryptic digest were analysed by the dansyl-Edman procedure. These peptides were ordered by reference to the sequences of other plant cytochromes c, assuming that the Nigella cytochrome is homologous with the other cytochromes. Many of the Nigella peptides were one or two residues short when compared with the corresponding chymotryptic peptides from other plant cytochromes c. These residues are assumed to have been removed by an endogenous carboxypeptidase, and the identification and placing of these residues is entirely based on homology. These residues are numbered 3, 18, 42, 43, 44, 54, 67, 72, 73, 82 and 105. A number of other positions are almost entirely placed by homology. These are positions which could not be placed definitely by dansyl-Edman analysis or by dansylation after digestion with carboxypeptidase A, and are numbered 14, 15, 16, 39, 40, 85, 86, 87 and 88. Except for residue 15, all residues based entirely, or nearly so, on homology have been previously found invariant in sequences of plant cytochromes c. Experimental details are given in a supplementary paper that has been deposited as Supplementary Publication SUP 50017, at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1973) 131, 5.


The formation of a  -(1 leads to 4)-D-galactan chain catalysed by a Phaseolus aureus enzyme. With a particulate enzyme preparation from Phaseolus aureus hypocotyls, UDP-alpha-d-[U-(14)C]galactose served as a precursor for a number of products. One of these products was characterized as a beta-(1-->4)-linked galactan. The ADP-, GDP-, TDP- and CDP- derivatives of alpha-d-galactose did not serve as biosynthetic precursors for any products insoluble in 70% ethanol, nor as substrates for a sugar nucleotide 4-epimerase which is present in the particulate enzyme preparation. The (14)C-labelled beta-(1-->4)-galactan is alkali-insoluble and was characterized by analysis of partial acetolysis products. The labelling pattern of the [(14)C]oligosaccharides derived from acetolysis indicates that (1) only slightly more than two [(14)C]galactose moieties are added to the growing polysaccharide chain on average, and (2) these additions take place at the reducing end of the polysaccharide chain. The radioactive beta-(1-->4)-linked galactan chain represented 8.5% of the radioactivity initially added, and 20% of the water- and butanol-insoluble products derived from UDP-alpha-d-[(14)C]galactose. Total hydrolysis of the alkali-insoluble fraction of Phaseolus aureus hypocotyl yielded d-glucose and d-mannose in a 5:1 ratio but no detectable quantities of d-galactose. A trace quantity of a radioactive disaccharide, identified as (1-->3)-linked galactobiose, was isolated from the partial acetolysate of the alkali-insoluble [(14)C]polysaccharide material. Also isolated from this partial acetolysate was a C-1 derivative of [(14)C]galactose, which could not be identified. An alkali-soluble galactose-containing polysaccharide was also synthesized in this enzymic reaction, and represented 20% of the water- and butanol-insoluble products derived from UDP-alpha-d-[(14)C]galactose. The spectrum of radioactive oligosaccharides produced by partial acetolysis of this alkali-soluble polysaccharide material was different from that obtained from the alkali-insoluble polysaccharide, indicating a different structure.


The association between phosphatidylinositol phosphodiesterase activity and a specific subunit of microtubular protein in rat brain. 1. Supernatant proteins from rat brain were separated into two fractions containing phosphatidylinositol phosphodiesterase activity by chromatography on DEAE-Sephadex A-50. 2. The first fraction sediments in linear sucrose density gradients in two bands corresponding to molecular weights of 66000 and 36000. There was presumptive evidence that the lighter protein constituted the monomeric form of the enzyme. The second fraction sediments predominantly as a single protein of molecular weight 86000. 3. Treatment of rat brain supernatant with [(3)H]colchicine abolished the second DEAE-Sephadex peak and removed the lighter protein from the first peak. These proteins emerged in the same position as the protein binding [(3)H]colchicine at high salt concentration; phospholipase activity was recovered from linear sucrose density gradients in positions corresponding to molecular weights 88000 and 43000, together with an aggregate of molecular weight 140000. Electrophoresis on sodium dodecyl sulphate-urea-polyacrylamide gels of this fraction revealed only three proteins: the alpha and beta-subunits of microtubular protein, of molecular weights 56000 and 52000 respectively, and a protein of molecular weight 38000. 4. A sample of microtubular protein from mouse, labelled in vivo with [(3)H]proline and (32)P(i), was added to rat brain supernatant together with an equal amount of the same microtubular protein treated with cyclic AMP and [gamma-(32)P]ATP and the mixture subsequently characterized by ion-exchange chromatography. Some phospholipase activity characteristic of the second peak from DEAE-Sephadex was associated with one fraction of added microtubular protein. This fraction was identified on the basis of the (3)H:(32)P ratio as the beta subunit of the protein treated with ATP and cyclic AMP. The subunit of added microtubular protein untreated with nucleotides was not associated with phospholipase activity.


A collagenase in extracts of the invertebrate Bipalium kewense. The localization, isolation and partial characterization of a collagenolytic enzyme from the land planarian Bipalium kewense is described. This enzyme can be obtained by direct extraction of the organism, and can be separated from non-collagenous proteolytic activity by (NH(4))(2)SO(4) precipitation and Sephadex-gel chromatography. Its mode of attack on collagen and sensitivity to a variety of inhibitors indicate that this enzyme differs from vertebrate collagenases and a previously described invertebrate collagenase.


Lack of temperature-sensitivity of rat liver pyruvate kinase. Rat liver pyruvate kinase, prepared by Sephadex treatment of a 10(5)g supernatant in phosphate buffer, is quite stable and gives reproducible results when a variety of parameters are altered in the enzyme assay. Incubation of this preparation at 25 degrees C or 0-2 degrees C has no effect on the activation by fructose 1,6-diphosphate or inhibition by ATP or alanine.


A radiographic survey of monumental masonry workers in Aberdeen.


A comparaive study of the effects of chemical modification on the immunochemical and optical properties of human plasma low-density lipoprotein(s) and apoproteins. 1. The structure of human plasma low-density lipoprotein(s) [LD lipoprotein(s)] was investigated by several immunological and optical techniques. The effects of delipidation and of chemical modification by 3-carboxypropionylation, acetylation, diazotization and amidination were examined. A sensitive double-antibody radioimmunoassay for human LD lipoproteins is presented and is used to assess the extent of immunochemical modification. A computer best-fit analysis is used to analyse circular-dichorism (c.d.) spectra. These methods permit comparisons of the relative effects of chemical modification and delipidation of LD lipoprotein under similar experimental conditions. 2. 3-Carboxypropionylation, acetylation or diazotization produces qualitative and quantitative changes in the immunochemical properties of LD lipoprotein. Amidination causes minor changes detected by radioimmunoassay but not by double-diffusion experiments. In general, the order of effectiveness in displacing (125)I-labelled LD lipoprotein is amidinated>diazo or acetyl>3-carboxypropionyl derivatives. 3. The order of the extent of conformational alteration induced in apoLD lipoprotein and LD lipoprotein, as judged by c.d. analyses, was 3-carboxypropionylation>diazotization>acetylation or amidination. 4. Delipidation of LD lipoprotein results in immunological alterations that are qualitatively detected by antisera to LD lipoprotein. Four of five antisera to apoLD lipoprotein form precipitin lines of identity between native LD lipoprotein and apoLD lipoprotein in double-diffusion experiments. An anti-(apoLD lipoprotein) serum that forms precipitin lines of complete identity between LD lipoprotein and apoLD lipoprotein reacts differently with these two antigens in radioimmunoassay. ApoLD lipoprotein is only one-fourth to one-half as effective as LD lipoprotein, on a protein basis, in the displacement of (125)I-labelled LD lipoprotein from this anti-(apoLD lipoprotein). 5. Conformational analysis indicates that apoLD lipoprotein retains a high proportion of the structural integrity of the native lipoprotein. Delipidation induces a small decrease in the content of beta-structure and a small increase in disordered structure, without greatly affecting the alpha-helical content. Chemical modification produces more severe conformational changes of apoLD lipoprotein than of LD lipoprotein. Computer analysis of the c.d. spectra of apoLD lipoprotein indicates that addition of high concentrations of sodium decyl sulphate abolishes most of the beta-conformation concomitant with increases in alpha-helical and disordered structure. 6. There is parallelism between the alteration of the charge of LD lipoprotein and apoLD lipoprotein and the extent of immunochemical and conformational changes.


The effects of pargyline on overflow of transmitter and uptake of noradrenaline in the cat spleen. 1. Twenty minutes after the addition of pargyline (5 x 10(-4)M) to blood perfusing the isolated spleen of the cat, the overflow of transmitter resulting from stimulation of the sympathetic nerves increased 2.3-3-fold. Lower doses of pargyline did not significantly affect overflow.2. Monoamine oxidase activity, measured with either radioactively labelled tyramine or noradrenaline as substrate, was almost completely inhibited by doses of pargyline in the range of 10(-4)M to 5 x 10(-4)M. Inhibition of enzyme activity was not correlated with the effect on overflow. Pargyline had only a slight inhibitory effect on catechol-O-methyl transferase.3. Uptake of a 1 mug injection (pulse) of labelled noradrenaline, following pargyline (5 x 10(-4)M), was increased to 199.1% of that found in control experiments.4. Pargyline significantly reduced the vascular responses to nerve stimulation but had no significant effect on capsular responses.5. The inhibitor had no effect on resting overflow of labelled noradrenaline from the spleen but doubled the overflow of labelled noradrenaline following nerve stimulation.6. It is suggested that the effect of pargyline on overflow is due to increased release of transmitter during nerve stimulation.7. The possible clinical significance of these findings is discussed.


Effect of phospholipase C on calcium release from epithelia treated with antidiuretic hormone. 1. Addition of antidiuretic hormone (ADH) to the bladders of toads (Bufo marinus) preloaded with (45)Ca causes an increase in the rate of calcium efflux.2. Pretreatment of the serosal surfaces of bladders with phospholipase C prevents the action of ADH on calcium efflux.


Does methaqualone cause neuropathy?

Does methaqualone cause neuropathy?


Smooth muscle autoantibodies in infectious mononucleosis. Smooth muscle antibodies (S.M.A.) were found in the sera of 81% of 126 patients over 10 years old with seropositive infectious mononucleosis tested within one month of onset. In 27 patients presenting clinically with infectious mononucleosis but having negative Paul-Bunnell tests the incidence of S.M.A. was 44%. In children 10 years of age or less in these two categories S.M.A. were present in 75% and 25% respectively, while in children of similar age not suspected of having infectious mononucleosis the incidence of S.M.A. was 10%. Among 45 adults with past histories of seropositive infectious mononucleosis more than one year before the incidence of S.M.A. was 33%, in contrast to 14% in 98 subjects with a negative history for infectious mononucleosis.


Dextran-coated charcoal technique to make the hormone-free serum as a diluent for standard curve of radioimmunoassay.


Effect of sex hormones on the activity of protein kinases in rat ventral prostate and uterus.


Study on the systematic use of serial estimation of human placental lactogen (hPL) and human chorionic gonadotropin (hCG) for the management of trophoblastic neoplasia.


Effects of ACTH and its synthetic analogues on water balance in rats.


Improvement by exogenous cyclic AMP of hereditary vasopressin-resistant diuresis in mice with normal adenyl cyclase system of the kidney cells.


Operantly conditioned firing patterns of epileptic neurons in the monkey motor cortex.


Intrinsic connections of caudate neurons. Locally evoked intracellular responses.


Acoustic responses and plasticity of limbic units in cats.


Spontaneous and evoked bioelectric activity in organized cerebellar tissue cultures.


Recruitment of motor units in voluntary contraction of a finger muscle in man.


Firing rate of individual motor units in voluntary contraction of abductor digiti minimi muscle in man.


The inhibition mechanism of the cytochrome oxidase reaction. IV. The nature of the kinetically inactive complex of cytochrome oxidase with cyanide.


Formation and decomposition of pyrophosphate related to bacterial photophosphorylation.


Role of oleate in the regulation of "neutral" rabbit liver fructose 1,6-diphosphatase activity.


Interaction between adenosine triphosphate and glyceraldehyde 3-phosphate dehydrogenase. 3. Mechanism of action and metabolic control of the enzyme under simulated in vivo conditions.


Effect of beta-adrenergic catecholamines on sodium transport in turkey erythrocytes.


Regulation of glyceraldehyde 3-phosphate dehydrogenase by phosphocreatine and adenosine triphosphate. IV. Factors affecting in vivo control of enzymatic activity.


Specific binding of phosphorylated non-histone chromatin proteins to deoxyribonucleic acid.


L-Glycerol 3-phosphate dehydrogenases. II. Effects of phosphorylated compounds on nicotinamide adenine dinucleotide linked enzyme from rabbit liver.


Inactivation of melanocyte-stimulating hormone release-inhibiting factor by a manganese-stimulated bovine brain aminopeptidase.


Arginase isozymes of rat mammary gland, liver, and other tissues.


Expression of the mitochondrial genome in HeLa cells. XVII. Heterogeneity of isolated HeLa cell mitochondria as assayed for their enzymatic and in vivo biosynthetic activities.


Plasma membrane cyclic adenosine 3':5'-monophosphate phosphodiesterase of cultured cells and its modification after trypsin treatment of intact cells.


Partial resolution of the enzymes catalyzing oxidative phosphorylation. XXXIX. Reconstitution of the third segment of oxidative phosphorylation.


Early events in glucocorticoid action. Activation of the steroid receptor and its subsequent specific nuclear binding studied in a cell-free system.


Neuroendocrine responses to physical and psychological stress.


Nature of nuclear acceptor sites for glucocorticoid- and estrogen-receptor complexes.


Recruitment deafness: functional effect of priming-induced audiogenic seizures in mice.


Genetic and enzymatic characterization of a conditional lethal mutant of Escherichia coli K12 with a temperature-sensitive DNA ligase.


Genetics and function of DNA ligase in Escherichia coli.


Spontaneous skin potential responses during natural sleep in monkeys.


Interferon production by Bordetella pertussis components in rabbits and in rabbit cell cultures.


Chronic lead nephropathy.

Chronic lead nephropathy.


Molecular conformation of guanosine 3,'5-cyclic monophosphate.


Incorporation of (1-14c)-oleic acid into neutral glycerides and phosphoglycerides of mouse brain.


Preferential labeling of phosphatidylcholine during phospholipid synthesis by bovine mammary tissue.


Post-tetanic potentiation and facilitation do not share a common calcium-dependent mechanism.


Windowless semiconductor radiation detectors for measurement of low-energy beta-emitters in vivo and in vitro.


Insomnia with sleep apnea: a new syndrome. A new clinical syndrome, sleep apnea associated with insomnia, has been characterized. Repeated episodes of apnea occur during sleep. Onset of respiration is associated with general arousal and often complete awakening, with a resultant loss of sleep. An important clinical implication is that patients complaining only of insomnia may be suffering from this syndrome.


Photopic suppression of monkey's rod receptor potential, apparently by a cone-initiated lateral inhibition.


Plasma membranes: isolation from naturally fused and lysolecithin-treated muscle cells. A medium containing bicarbonate and calcium was used to isolate plasma membranes of cultured muscle cells. Membranes from differentiated myotubes, as well as the labile, largely unfused, lysolecithin-treated cells from the same culture could be isolated by identical manipulations. Adenylate cyclase of high specific activity was assayed in plasma membranes from both types of cells. Lysolecithin treatment apparently interferes with the metabolism and turnover of membrane phospholipids and thus prevents the natural fusion of muscle cells.


Ultradian rhythms in human telemetered gross motor activity.


Circadian rhythms of free radical state concentrations in the organs of mice.


Aftereffects of alcohol on the perception and control of pitch attitude during centripetal acceleration.


Herpes zoster in children with cancer.

Herpes zoster in children with cancer.


Wilms tumor in right atrium.

Wilms tumor in right atrium.


Six year follow-up of a child with Bartter syndrome.


Benign nasal tumor appearing as neonatal respiratory distress. First reported case of nasopharyngeal fibrous histiocytoma.


Physiological psychology: sleep.

Physiological psychology: sleep.


Instantaneous decompression and the skin.


24-Hour sleep patterns. A comparison between 2- to 3-year-old and 4- to 6-year-old children.


Chinese psychiatry. A visit to a Chinese mental hospital.


Sleep EEG studies in untreated, long-term schizophrenic patients.


The surgical management of amoebiasis in children.


Barbiturate-induced transmitter release at a frog neuromuscular junction. 1. The influence of barbiturates on neuromuscular transmission at end-plates of frog sartorius muscles was investigated electrophysiologically on preparations bathed in Ringer solution containing a low concentration of calcium and a high concentration of magnesium.2. Effects of a convulsant barbiturate, 5-(2-cyclohexylideneëthyl)-5-ethyl barbituric acid (CHEB), were compared with those of phenobarbitone.3. CHEB and phenobarbitone increased the mean quantum content of the end-plate potentials and decreased the mean amplitude of the miniature end-plate potentials.4. Both barbiturates enhanced the duration of the nerve-terminal action potential and had little or no effect on the effective resistance of the skeletal muscle membrane.


Pituitary ACTH and GH content associated with the loss of acidophils following thyroidectomy.


Relation between changes in the acid-base and the energy metabolism of the brain in hepatic coma.


Changes in collagen with age. V. Modification of mouse skin collagen by whole body x-irradiation.


Pathophysiology of human tears.

Pathophysiology of human tears.


Pathophysiology and diagnosis of tear film abnormalities. Surfacing abnormalities.


Renal stone crystals grown in gel systems. A preliminary report.


Oxidation of a ferrocytochrome c in the crystalline state--structural change and anion binding.


The sucrose-gap technique. Autonomic drugs and electrical characteristics of the ureter.


Inhibitory effect of Na+ on phosphorylation of proteins in brain microsomes and synaptic membranes.


Ferredoxin-linked nitrate reductase from Clostridium perfringens.


Combined transmission electron microscopy and X-ray micro-analysis of ultrathin frozen dried sections--an investigation to determine the normal elemental composition of mammalian tissue.


Fluidity of phospholipid bilayers and membranes after exposure to osmium tetroxide and gluteraldehyde.


Subcellular site of the phosphatidylinositol effect. Distribution on density gradients of labelled lipids from resting and active sympathetic ganglia of the rat.


Influence of neuroleptic drugs and apomorphine on dopamine-sensitive adenylate cyclase of retina.


Hexagonal arrangement of filaments in herpes simplex virus type 2-infected cells.


Effect of angiotensin on blood pressure in normal and cirrhotic rats.


Pharmacological study of hydroxy bis-[2-(p-chlorophenoxy)-isobutyric acid] aluminium. II. The effect of hydroxy bis-[2-(-chlorophenoxy)-isobutyric acid] aluminum on lipid metabolism in hypercholesterolimic rats.


Pituitary-adrenal responsiveness during lactation in rats.


Postweaning development of negative feedback in the pituitary-adrenal system of the rat.


Diagnostic problems of trophoblastic disease in women aged 50 or more.


Simultaneous laparoscopy and hysteroscopy for intrauterine adhesions.


Ovarian lutein cysts in pregnancy.

Ovarian lutein cysts in pregnancy.


Pregnancy and delivery post radical hemipelvectomy.


Safety and antigenicity of temperature sensitive (TS) mutant respiratory syncytial virus (RSV) in infants and children.


Comparative studies on the pathogenicity for mice of tumour homogenates and of nucleic acid extracted from chicken sarcomas induced by the Bryan strain of Rous sarcoma virus.


The possibility to overcome species and age resistance in the induction of a neoplastic process by an avian tumour virus.


Particularities of cytomegalovirus (CMV)-induced cytophagia.


Photoacoustic spectroscopy of biological materials. A new technique for performing optical spectroscopy on solids has been developed. Photoacoustic spectra of cytochrome c and hemoglobin show how this technique can be used to obtain information about optical absorptions and subsequent de-excitations in solid biological materials, particularly those which cannot readily be studied by conventional means.


Insecticide inhibition of 5alpha-dihydrotestosterone binding in the rat ventral prostate. The chlorinated hydrocarbon insecticides dieldrin and o,p'-DDT inhibit binding of 5alpha-dihydrotestosterone to specific receptor proteins in rat prostate cytosol. Dieldrin is less inhibitory than o,p'-DDT.


Murine C-type RNA virus from spontaneous neoplasms: in vitro host range and oncogenic potential. Strain BALB/c mice harbor at least two host range variants of marine leukemia virus. One variant, which is host-cell tropic, is the predominant isolate from neoplastic tissues and produced lymphoreticular neoplasms when injected into BALB/c newborn mice. A second variant, whicht is isolated throughout life, grows poorly in host embryonic cells in culture and was not associated with lymphoreticular neoplasm induction when injected into newborn BALB/c mice.


Alterations in the ontogeny and specific activity of phosphomonoesterases associated with abnormal chondrogenesis and osteogenesis in the limbs of fetuses from folic acid-deficient pregnant rats.


Human papovavirus (JC): induction of brain tumors in hamsters. Eighty-three percent of hamsters inoculated at birth with JC virus, a human papovavirus isolated from brain tissue of a case of progressive multifocal leukoencephalopathy, developed malignant gliomas within 6 months. Three brain tumors have been serially transplanted as subcutaneous tumors. JC virus was isolated from five of seven tumors tested. Cells from four tumors were cultivated in vitro. These cells contained an intranuclear antigen with the characteristics of a T antigen, and this antigen was antigenically related to SV40 T antigen. Although virus was not recovered from extracts of serially cultured tumor cells, JC virus was rescued when one tumor cell line was fused with permissive cells.


Primary pulmonary cavitating carcinomas.


A rapid separation of the four major deoxynucleosides and deoxyinosine by high-pressure liquid cation-exchange chromatography.


Quantitation of radio-ligand binding data using a desk-top calculator in the program mode.


Tissue collagenase: a simplified, semiquantitative enzyme assay.


Micro method for determination of borohydride with NAD+.


A sensitive method for estimating 5-phosphoribosyl 1-pyrophosphate in Escherichia coli.


Isolation of rat liver microsomes by gel filtration.


Characterization of neuromuscular block produced by streptomycin.


The effect of angiotensin II and other vasoactive drugs on isolated portal vein preparations.


Effect of propranolol on the isolated phrenic nerve-diaphragm preparation of the rat.


Alkaline ribonuclease and phosphodiesterase activity in rat liver plasma membranes. The ribonuclease and phosphodiesterase activities of rat liver plasma membranes, purified from the crude nuclear fraction by centrifugation in an A-XII zonal rotor and flotation, were examined and compared. The plasma membrane is responsible for between 65 and 90% of the phosphodiesterase activity of the cell and between 25 and 30% of the particulate ribonuclease activity measured at pH8.7 in the presence of 7.5mm-MgCl(2). Both enzymes were most active between pH8.5 and 8.9. Close to the pH optimum, both enzymes were more active in Tris buffer than in Bicine or glycine buffer. Both plasma-membrane phosphodiesterase and ribonuclease were strongly activated by Mg(2+), there being at least a 12-fold difference between the activity in the presence of Mg(2+) and of EDTA. There is, however, a difference in the response of the enzymes to Mg(2+) and EDTA in that the phosphodiesterase is fully activated by 1.0mm-MgCl(2) and fully inhibited by 1.0mm-EDTA, whereas the ribonuclease requires 7.5mm-MgCl(2) for full activation and 5mm-EDTA for full inhibition. Density-gradient centrifugation has indicated that on solubilization in Triton X-100 most of the ribonuclease activity is released into a small fragment of the same size as that containing the phosphodiesterase activity. The relationship between the two activities is discussed in view of these results.


Turnover of protein-bound serine phosphate in respiring slices of guinea-pig cerebral cortex. Effects of putative transmitters, tetrodotoxin and other agents. 1. The effect of various agents on the turnover of protein-bound phosphorus in respiring slices of cerebral cortex was studied. 2. Confirming previous work turnover was increased by the application of electrical pulses for 10s to the tissue. 3. Turnover was also increased by exposure of the slices for 10min to noradrenaline (0.5mm), 5-hydroxytryptamine (1mum) and histamine (0.1mm). 4. When slices were stimulated by electrical pulses in the presence of histamine the increase in turnover was the sum of the responses given by each agent above, suggesting that different phosphorylating systems were involved. 5. Tetrodotoxin (0.5mum) blocked the increased turnover due to electrical pulses, but not that due to histamine. Tetrodotoxin also prevented the increase in tissue cyclic AMP content caused by the application of electrical pulses. 6. Phosphoprotein turnover was not affected by adenosine, despite the increase in tissue cyclic AMP content given by this agent. 7. Adenosine blocked the phosphoprotein response to histamine, but did not affect the response to electrical pulses. 8. The results are discussed in relation to the hypothesis that the stimulation of protein phosphorus turnover by electrical pulses is secondary to the release of cyclic AMP in the tissue.


Protein kinase activity in membrane preparations from ox brain. Stimulation of intrinsic activity by adenosine 3':5'-cyclic monophosphate. 1. Properties of the stimulation by cyclic AMP of the intrinsic protein kinase activity of membrane fragments from ox brain were studied. 2. Stimulation of activity declined from about 100% at 1min to less than 20% at 10min. The time-course was explained by the observation that cyclic AMP did not stimulate turnover of protein-bound serine phosphate once the membrane protein was fully phosphorylated. 3. Cyclic AMP accelerated the activity of a component of the basal activity rather than activating a different kinase. 4. The pH optimum for both the stimulated and basal activities was 7.2-7.4. NaCl (100mm) and KCl (10-100mm) inhibited the stimulated activity but did not affect the basal activity. 5. Strychnine and theophylline inhibited both activites equally, but the stimulated activity was more sensitive to inhibition by adenosine, bicuculline, vinblastin, veratrine, N-ethylmaleimide and cysteine. 6. No firm evidence for a role for endogenous cyclic AMP in the basal activity was found, but the possibility was not excluded. 7. Some 90% of both the stimulated and basal activities remained in an insoluble form after treatment of the membrane fragments with Triton X-100 (0.5%).