Immunochemical relationships among lysosomal acid phosphohydrolases: DNase II and nonspecific phosphodiesterase.


Electron-nuclear double resonance study of flavodoxin from Peptostreptococcus elsdenii.


Amoebicidal action of bile salts and other surface-active agents on axenically grown Entamoeba histolytica.


Periphal vascular disease in diabetes mellitus.


Paralytic poliomyelitis: clinical and virological studies.


Activation of Na-K activated ATPase in rat brain by catecholamine.


A scanning electron microscope study of surface features of viral and spontaneous transformants of mouse Balb-3T3 cells. Cells of the mouse line Balb/3T3 as well as three virus-induced transformants and two spontaneous transformants grown in vitro have been studied for their topography by scanning electron microscopy. The parent cell in confluent culture closely resembles an endothelial cell in its form and in the structure of its association with adjacent cells. The tumorigenic transformants produced by SV40, murine sarcoma virus, or polyoma viruses are fusiform to pleomorphic and distinctly different from the cell of origin. They show relatively smooth surfaces except for blebs and marginal microvilli. Perhaps most surprising is the similarity they bear to one another. This is made the more singular by the very different form shown by the tumorigenic transformants of spontaneous origin. One of these, S2-4, possesses a thickened rather than the lamellar form of the parent A31 cell and is covered by long microvilli and many spherical blebs. The other, TuT(3), more closely resembles the cell of origin but shows extensive ruffling at its margins. All transformants grow without evidence of contact inhibition. The significance of the surface morphologies and the factors influencing cell form are discussed.


Parenchymal cells from adult rat liver in nonproliferating monolayer culture. II. Ultrastructural studies. Hepatic parenchymal cells from adult rats, established in vitro as a monolayer, have been evaluated by electron microscopy. Within 24 h after the initial seeding, the incubated cells were polygonal and in close apposition with three to six neighboring cells. The ultrastructure of the monolayer cells was examined at this time and after 3 and 10 days of incubation. With the exception of a few enlarged mitochondria, organelles in both the 1- and 3-day monolayer cells were indistinguishable quantitatively and morphologically from those found in the intact liver. After 10 days of incubation, however, the rough-surfaced endoplasmic reticulum (RER) had become dilated and vesiculated. In all cells studied, portions of RER were found in a close spatial relationship to mitochondria. From its frequency, this association appeared to be more than fortuitous, and the organelle complex may represent a functional unit necessary for new membrane formation, as suggested previously. The Golgi complexes of 1- and 3-day cells contained very low density lipoprotein-sized particles, which suggests that the monolayer cells synthesize lipoproteins. These electron microscope observations demonstrate that adult hepatic parenchymal cells in monolayer retain for several days the subcellular structural elements characteristic of normally functioning hepatocytes.


Insulin binding to rat liver Golgi fractions.


Cytochemical identification of phosphatase activity in the contractile vacuole of Acanthamoeba castellanii.


Lesions of the breast.

Lesions of the breast.


The sulcular epithelium as a reservoir for herpes simplex virus in man.


Production of cyclic AMP and adenosine by the brain and prothoracic glands of Manduca sexta.


Parenchymal cells from adult rat liver in nonproliferating monolayer culture. I. Functional studies. Parenchymal cells from adult rat liver have been established in primary monolayer culture. Donor animals are subjected to a partial hepatectomy and, 4 days later, cells are prepared by collagenase perfusion of the regenerated liver. The hepatic parenchymal cells, separated from nonparenchymal material and suspended in serum-free medium, are placed in plastic tissue culture dishes, where they form a monolayer within 24 h. The monolayer cells exhibit minimal mitotic activity and demonstrate several major metabolic functions characteristic of liver in vivo; these include albumin synthesis and secretion, gluconeogenesis from 3-carbon precursors, responsiveness to insulin and glucagon, glycogen synthesis, and activity of two microsomal enzymes. These functions are present in the monolayer cells for several days at activities similar to those observed in the liver in vivo. The findings indicate that hepatic parenchymal cells in this monolayer system are viable and behave in many respects like normal adult rat liver.


Effects of adrenaline, noradrenaline and isoprenaline on the electrical and mechanical responses of the guinea-pig vas deferens to nerve stimulation.


Effects of acetylcholine and some other smooth muscle stimulants on the electrical and mechanical responses of the guinea-pig vas deferens to nerve stimulation.


Lipid and fatty acid modifications in plasma lipoproteins of baboons under atherogenic diet.


Marmota monax: a model for studies of cardiovascular, cerebrovascular and neoplastic disease.


The susceptibility and response of wild waterfowl to duck plague virus.


Anaesthesia, surgery and renal function: immediate and delayed effects.


Auscultation of the abdomen with reference to vascular sounds.


Studies of human amebiasis. 3. Ameboma: a radiologic manifestation of amebic colitis.


Effect of ethanol administration on cyclic 3',5'-adenosine monophosphate metabolism in brain.


Substrate specificity of caeruloplasmin indoles and indole isosteres.


Artifactual subcellular distribution of dopamine beta-hydroxylase. Effects of dilution and non-specific protein on the dopamine beta-hydroxylase activity of membranes of adrenomedullary and sympathetic nerve vesicles.


Response of isolated white fat cells to anti-malarial drugs.


Bone sodium exchange. Effect of rachitism and vitamin D3 treatment on chicks.


A simplified competitive protein-binding assay for adenosine 3',5'-monophosphate in plasma.


Determination of di-(2-ethylhexyl)-phthalate (DEHP) in human plasma.


Catecholamines and vasomotion.

Catecholamines and vasomotion.


Carbon tetrachloride hepatotoxicity: an example of lethal cleavage.


Peripheral neuropathy caused by chemical agents.


Vertebrobasilar aneurysms. Experience with 27 cases.


Limitations of deteriorated tissue for rabies diagnosis.


Occurrence of canine adenovirus antibodies and non-specific inhibitors of haemagglutination in the sera of diverse animal species.


Effect on calves of the intravenous injection of the enterotoxin of Clostridium welchii type A.


Radioimmunoassay of plasma adrenocorticotrophin in Cushing's syndrome.


Influence of testosterone and cyproterone acetate on the rate of mitosis in seminal vesicles of rats.


Circadian periodicity of pituitary-adrenal function after p-chlorophenylalanine administration in the rat.


Effect of hypothalamic releasing factors and steroids on release of gonadotrophins by organ cultures of human foetal pituitaries.


Enzymic activities and sodium, potassium and copper concentrations in mouse brain and liver after cuprizone treatment in vivo.


Activity of cyclic AMP-dependent microsomal protein kinase and phosphorylation of ribosomal protein in rat brain during postnatal development.


Effect of hyperphenylalaninemia on fatty acid composition of lipids of rat brain myelin.


Postsynaptic adrenergic-cyclic AMP control of the serotonin content of cultured rat pineal glands.


Acummulation of cyclic adenosine 3', 5'-monophosphate in cerebral cortical slices from rat and mouse: stimulatory effect of alpha- and beta-adrenergic agents and adenosine.


Some aspects of visual physiology of the honeybee.


Small RNAs of Rous sarcoma virus: characterization by two-dimensional polyacrylamide gel electrophoresis and fingerprint analysis. Approximately 15 to 20 different species of small (4 to 7S) RNAs have been purified by two-dimensional polyacrylamide gel electrophoresis of RNA isolated from virions of Schmidt-Ruppin D strain of Rous sarcoma virus. Each species of small RNA has been isolated free of 70S RNA; nine of them, including 5S and 7S RNAs, were also found associated with the 70S genomic RNA. Most of the 4S RNAs are present at an average of less than one copy per virion. The 4S RNAs have T1 RNase (EC 2.7.7.26) fingerprints, which are very similar to those of tRNAs. One of the smallest 4S RNAs, which can act as a primer for initiation of RNA-directed DNA synthesis, is associated with the 70S RNA in 1 to 2 copies per complex, whereas an additional 6 to 8 copies of this molecule are free.


Primary in vivo transcription of vesicular stomatitis virus and temperature-sensitive mutants of five vesicular stomatitis virus complementation groups. The process of adsorption and RNA transcription by vesicular stomatitis virus (VSV) in cells has been followed by using highly labeled preparations of VSV virions. The initial transcription process (primary parental transcription) is rapid and takes about 4 min to develop complete transcripts of the input genome. The optimal cell temperature for in vivo transcription is between 36 and 39.5 C, although transcription can be detected at 18 C. No negative effect on primary parental transcription was obtained by the presence of actinomycin D, puromycin, or cycloheximide. Demonstrable primary transcription by selected temperature-sensitive mutants of all five complementation groups of VSV was obtained at either 31 and 34 C (permissive temperatures for virus production) or 39.5 C (nonpermissive temperature for virus development). VSV grown in hamster (BHK 21) or chicken embryo cells were more efficiently adsorbed and transcribed in BHK cells.


Analysis of minimal functions of simian virus 40. II. Enhancement of oncogenic transformation in vitro by UV irradiation. After light UV irradiation (5,000 to 10,000 ergs/mm(2)) "complete" and "defective" simian virus 40 (SV40) showed an enhancement of oncogenic transformation capacity in Syrian hamster kidney cells in vitro up to 180 and 270% of the controls, respectively. Simultaneously with the enhancement of transformation, an increase in T-antigen induction was observed in CV-1 cells infected with light UV-irradiated SV40; infectivity, however, was correspondingly reduced by 1 log(10). After strong UV irradiation (10,000 to 80,000 ergs/mm(2)) of "complete" and "defective" SV40, transformation capacity in vitro proved to be the most resistant viral function. It was only slightly reduced in comparison with a 4 to 5 log(10) reduction of infectivity. T-antigen induction of SV40 was also equally resistant to strong UV irradiation. We found no evidence of "multiplicity reactivation" involved in the high resistance of transformation capacity of SV40 after UV irradiation. Syrian hamster kidney cells transformed in vitro by UV-irradiated SV40 contained the SV40-specific T-antigen and showed the same morphology and growth characteristics as cells transformed by non-irradiated "complete" or "defective" SV40. They induced malignant tumors after subcutaneous inoculation into Syrian hamsters.


Restricted replication of vesicular stomatitis virus in human lymphoblastoid cells. Replication of vesicular stomatitis virus (VSV) is restricted in one human lymphoblastoid cell line (Raji), but not in another similar cell line (Wil-2), compared with growth in HeLa cells. This restriction is characterized by a low proportion of cells yielding infectious virus and is associated with limited production of 42S virion RNA. Primary transcription of 13S and 26S VSV-specific RNA is not restricted in Raji cells, and the 13S RNA produced contains adenylate-rich sequences. This suggests that the block in Raji cells involves some step required for the replication of virion RNA.


L protein requirement for in vitro RNA synthesis by vesicular stomatitis virus. The endogenous transcriptase present in purified vesicular stomatitis (VS) virions was solubilized with a Triton X-100 high-salt solution. The polymerase activity was purified on glycerol gradients and by phosphocellulose column chromatography; the viral proteins present in the active enzyme fractions were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was demonstrated that L protein, but not NS protein, was required for in vitro RNA synthesis on the VS viral nucleocapsid template. Solubilized L protein rebinds to the ribonucleoprotein template when the transcription complex is reconstituted, and the RNA synthesized in vitro by purified L protein hybridizes to virion RNA. Cyanogen bromide peptide fingerprints indicate that the large L protein is a unique polypeptide chain. It is concluded that the L protein functions as the transcriptase, and the nucleocapsid NS protein is not essential for in vitro RNA synthesis.


Cleavage of circular, superhelical simian virus 40 DNA to a linear duplex by S1 nuclease. S(1) nuclease, the single-strand specific nuclease from Aspergillus oryzae can cleave both strands of circular covalently closed, superhelical simian virus 40 (SV40) DNA to generate unit length linear duplex molecules with intact single strands. But circular, covalently closed, nonsuperhelical DNA, as well as linear duplex molecules, are relatively resistant to attack by the enzyme. These findings indicate that unpaired or weakly hydrogen-bonded regions, sensitive to the single strand-specific nuclease, occur or can be induced in superhelical DNA. Nicked, circular SV40 DNA can be cleaved on the opposite strand at or near the nick to yield linear molecules. S(1) nuclease may be a useful reagent for cleaving DNAs at regions containing single-strand nicks. Unlike the restriction endonucleases, S(1) nuclease probably does not cleave SV40 DNA at a specific nucleotide sequence. Rather, the sites of cleavage occur within regions that are readily denaturable in a topologically constrained superhelical molecule. At moderate salt concentrations (75 mM) SV40 DNA is cleaved once, most often within either one of the two following regions: the segments defined as 0.15 to 0.25 and 0.45 to 0.55 SV40 fractional length, clockwise, from the EcoR(I) restriction endonuclease cleavage site (defined as the zero position on the SV40 DNA map). In higher salt (250 mM) cleavage occurs preferentially within the 0.45 to 0.55 segment of the map.


Proteins specified by herpes simplex virus. XI. Identification and relative molar rates of synthesis of structural and nonstructural herpes virus polypeptides in the infected cell. Analyses of polypeptides made in HEp-2 cells infected with herpes simplex virus type 1 by high-resolution polyacrylamide gel electrophoresis revealed the synthesis of at least 49 infected cell polypeptides (ICP) ranging in molecular weight from 15,000 to 280,000. Evidence for virus specificity based on increased rates of synthesis postinfection, immunological specificity, and viral control of mobility and rate of synthesis was available for 47 of the ICP. These 47 polypeptides can account for 75% of the virus genetic information assuming a DNA molecular weight of 10(8) and asymmetric transcription. On the basis of their mobility relative to virion proteins, the ICP were classified as structural (S, 23 polypeptides), nonstructural (NS, 16 polypeptides), and unassigned (U, 10 polypeptides). Analysis of the synthesis of the ICP revealed the following. (i) Rapid posttranslational cleavages of HSV proteins were not detected; in parallel experiments rapid posttranslational cleavages were readily demonstrated in poliovirus-infected cells and these were blocked by protease inhibitors. (ii) Slow posttranslational changes in the mobility of at least two polypeptides were observed. (iii) Analysis of the rates of synthesis of ICP examined at four intervals postinfection revealed regulation of the pattern and amount of ICP synthesized. ICP formed six classes (A to F) differing in their kinetics of synthesis. S and NS ICP were distributed nonrandomly among these classes. Thus, of the sum of S protein amino acid sequences apportioned among these kinetic classes, 47%, constituting class A and comprising "late" structural proteins, were characterized by progressively increasing rates of synthesis until at least 12 h postinfection; whereas "early" structural proteins constituting class C, amounting to 31% of the total amino acid sequences, were synthesized with initially increasing rates until 4 h postinfection and with declining rates thereafter. NS polypeptides and remaining S polypeptides were distributed among the other kinetic classes-B, D, E, and F. Control of protein abundance was evident in that the polypeptides were not made in equimolar amounts. However, S and NS polypeptides could not be differentiated on the basis of their molar rates of synthesis. The bulk of the detected polypeptides did not differ by more than eightfold in their molar rates of synthesis.


RNA synthesis of vesicular stomatitis virus. V. Interactions between transcription and replication. The temperature-sensitive mutant ts114 of vesicular stomatitis virus is temperature-sensitive in both primary and secondary transcription, but not in the replication of 40S RNA. The synthesis of 40S RNA is specifically inhibited when protein synthesis is shut off. The addition of cycloheximide to cells infected by ts114, rapidly inhibits RNA replication at the permissive and nonpermissive temperatures. However, the addition of cycloheximide at the nonpermissive temperature also results in almost complete recovery of transcription to the level found at the permissive temperature. Other inhibitors of protein synthesis applied at the nonpermissive temperature result in the same recoverability of the apparent temperature-sensitive lesion. Ribonucleic acid products synthesized by ts114 at the nonpermissive temperature in the presence of cycloheximide are identical to virus-specific messenger RNA by the criteria of size and complementarity to virion RNA. When mutant-infected cells are shifted to the nonpermissive temperature, incubated for a period of time, and then treated with cycloheximide, the ratio of transcriptive to replicative activity varies depending on the time at which radioactive precursor is added to cells. This suggests an interdependence between replication and transcription during virus-specific RNA synthesis.


Defective interfering particles of poliovirus. IV. Mechanisms of enrichment. Infection of HeLa cells by mixtures of standard poliovirus and defective, interfering (DI) poliovirus particles leads to a higher ratio of DI particles in the progeny than in the inoculum. The extent of this enrichment could be varied by various manipulations of the co-infected cells. At any time during the infection cycle, virions made within short times after addition of radioactive uridine were hyperenriched in DI particles; this transient hyperenrichment fell to the equilibrium enrichment level within 45 min after uridine addition. A shift of the temperature of infection from 37 to 31 C also led to a hyperenrichment of DI particles and pulse-labeling revealed a superimposed transient hyperenrichment. By contrast, cells continuously infected at 31 C showed a severe decrement in DI particles apparently because poliovirus DI particles behave as cold-sensitive mutants for RNA synthesis. Cycloheximide treatment early in the infection cycle also led to hyperenrichment. Study of the cycloheximide effect showed that the drug acted as if to change the input ratio of standard to DI particles. These effects on enrichment can be explained as aspects of two different phenomena: enrichment due to preferential DI RNA synthesis and enrichment due to preferential encapsidation of DI RNA. Both mechanisms probably play a role in the normal level of enrichment.


Nucleic acid synthesis in cytoplasm of Yaba monkey tumor virus-infected cells. Yaba tumor virus progeny appeared in cynomolgus monkey kidney cells at 24 h postinfection and reached a plateau at 72 h in the first cycle of replication. Viral DNA synthesis was first detected at about 3 h and reached a peak in 18 h. Maximum coating of viral DNA in infected cells occurred at 4 days postinfection. Rapidly labeled RNA was synthesized in the cytoplasm of virus-infected cells. At 6 h postinfection 7 to 10S RNA was present; this species was present in greater amount at 12 h; at 24 h a truncated peak indicated the presence of 14 to 15S as well as 7 to 10S RNA. Hybridization data indicated that the largest peak of messenger RNA synthesis occurred at 11 to 13 h postinfection and a second, slightly smaller, peak occurred at 21 to 23 h.


Effect of dibutyryl cyclic AMP on the induction of Epstein-Barr virus in hybrid cells. Treatment of Epstein-Barr virus (EBV) negative somatic cell hybrids with 5'-iododeoxyuridine (IUdR) induced synthesis of EBV antigens and virus particles. When dibutyryl cAMP (Bt(2)-cAMP) was present in medium after exposure of cultures to IUdR, the incidence of cells synthesizing EBV early and virus capsid antigens was increased. The time necessary for appearance of EBV particles after induction by IUdR was significantly reduced in the presence of Bt(2)-cAMP. This enhancement was evident to a lesser degree with 3':5' cAMP than with Bt(2)-cAMP and did not occur with any other of the related compounds tested. The response observed was dose dependent. Untreated (no IUdR) EBV negative hybrid cells exposed to Bt(2)-cAMP also synthesized EBV antigens. The concentration of intracellular cAMP may act as one of the control mechanisms selecting for gene expression in this system.


Trypsin action on the growth of Sendai virus in tissue culture cells. 3. Structural difference of Sendai viruses grown in eggs and tissue culture cells. Polypeptides of egg-borne Sendai virus (egg Sendai), which is biologically active on the basis of criteria of the infectivity for L cells and of hemolytic and cell fusion activities, were compared by polyacrylamide gel electrophoresis with those of L cell-borne (L Sendai) and HeLa cell-borne Sendai (HeLa Sendai) viruses, which are judged biologically inactive by the above criteria. Densitometer profiles on the stained gels of egg Sendai resolved six polypeptides (virion protein [VP] 1 to VP6), in which VP2 and VP4 were identified as glycoproteins by PAS stain. Comparative electropherograms of both L Sendai and HeLa Sendai revealed that there were significantly larger amounts in the VP2 region of these viruses but VP4 was present only in greatly reduced amounts as compared to egg Sendai. It was also found that VP2 of L Sendai and HeLa Sendai consisted of two components, VP2a and VP2b, but the one of egg Sendai consisted of only VP2a. A mild trypsin treatment which converts both L Sendai and HeLa Sendai to a biologically active form selectively removed VP2b from these viruses and increased concomitantly the amounts of materials in the VP4 region. The same treatment of egg Sendai affected neither its biological activities nor its electropherogram. Consequently, gross polypeptide profiles on the stained gels of L Sendai and HeLa Sendai after trypsin treatment became favorably comparable to that of egg Sendai. Electrophoresis of labeled L Sendai and HeLa Sendai with a (3)H-amino acids mixture and (14)C-glucosamine resolved at least three glycoproteins, GP1, GP2, and GP3, each corresponding to VP2a, VP2b, and VP4, respectively. The trypsin treatment of these viruses removed almost all the radioactivity of GP2 and simultaneously increased the radioactive counts of GP3 and raised small amounts of rapidly moving heterogeneous glycoprotein, GP4. A possible relationship between the biological modification and the above characteristic polypeptide patterns of Sendai virus was discussed.


RNA-DNA covalent bonds between the RNA primers and the DNA products formed by RNA tumor virus DNA polymerase. Initiation of DNA synthesis by endogenous RNA primer molecules was studied with three different RNA tumor viruses. The influence of the method of virus disruption on the observed RNA-DNA bonds was ascertained. Ether disrupted virions of both murine leukemia virus (MuLV) and the B77 strain of avian sarcoma virus (B77 virus) have rC-dC and rA-dA covalent linkages between RNA primers and newly synthesized DNA. None of the 14 other possible bonds were formed. Ether-disrupted virions of avian myeloblastosis virus (AMV) have rU-dC and rA-dA linkages. In contrast, work reported herein and from other laboratories shows that Nonidet P-40 (NP-40)-disrupted virions of all three viruses have only the rA-dA junction. Studies with virus particles which were first disrupted with ether and then treated with NP-40 indicated that the detergent treatment disallowed the formation of the ribopyrimidine-dC internucleotide bond. The same transfers are found with AMV in the presence or absence of actinomycin D, where only single-stranded DNA is formed. This finding is consistent with the notion that virtually all of the significant primers have been recognized. In contrast to mature virions, transfer experiments with ether-disrupted early harvest (5 min) MuLV showed only the rC-dC bond; the rA-dA bond was absent. The short-time harvest contains a significantly higher proportion of infectious virions than 24-h harvests. Also, since the RNA from early harvest virus is appreciably more homogenous than the RNA of mature MuLV, it is concluded that the ribopyrimidine-dC linkage is the more significant initiation event from a biochemical standpoint.


DNA polymerase of murine sarcoma-leukemia virus: lack of detectable RNase H and low activity with viral RNA and natural DNA templates. Kirsten murine sarcoma-leukemia virus (Ki-MSV[MLV]) was found to contain less RNase H per unit of viral DNA polymerase than avian Rous sarcoma virus (RSV). Upon purification by chromatography on Sephadex G-200 and subsequent glycerol gradient sedimentation the avian DNA polymerase was obtained in association with a constant amount of RNase H. By contrast, equally purified DNA polymerase of Ki-MSV(MLV) and Moloney [Mo-MSV(MLV)] lacked detectable RNase H if assayed with two homopolymer and phage fd DNA-RNA hybrids as substrates. On the basis of picomoles of nucleotides turned over, the ratio of RNase H to purified avian DNA polymerase was 1:20 and that of RNase H to purified murine DNA polymerase ranged between <1:2,800 and 5,000. Based on the same activity with poly (A).oligo(dT) the activity of the murine DNA polymerase was 6 to 60 times lower than that of the avian enzyme with denatured salmon DNA template or with avian or murine viral RNA templates assayed under various conditions (native, heat-dissociated, with or without oligo(dT) and oligo(dC) and at different template enzyme ratios). The template activities of Ki-MSV(MLV) RNA and RSV RNA were enhanced uniformly by oligo(dT) but oligo(dC) was much less efficient in enhancing the activity of MSV(MLV) RNA than that of RSV RNA. It was concluded that the purified DNA polymerase of Ki-MSV(MLV) differs from that of Rous sarcoma virus in its lack of detectable RNase H and in its low capacity to transcribe viral RNA and denatured salmon DNA. Some aspects of these results are discussed.


Effects of simian virus 40-induced transformation on isoaccepting species of transfer RNA from mouse fibroblasts. Alterations in isoaccepting species of tRNA in mouse fibroblasts transformed by simian virus 40 were determined for alanine, arginine, histidine, leucine, lysine, phenylalanine, serine, tyrosine, and valine. Significant differences between transformed cells in culture and newborn mouse cells are attributed to tRNA alterations accompanying differentiation of mouse cells.


Influence of complement on the neutralization of murine cytomegalovirus by rabbit antibody. Antiserum against murine cytomegalovirus produced in the rabbit contained complement (C')-requiring neutralizing (CRN) antibody. The proportion of CRN was extremely high (up to 98%) during the early portion of an immunization procedure, whereas the antisera produced late had a much lower proportion that required C'. The antiserum produced was specific for MCMV with or without C'.


Low-molecular-weight RNAs of murine sarcoma virus: comparative studies of free and 70S RNA-associated components. Several low-molecular-weight RNAs were released from mouse leukemia sarcoma virus 70S RNA under conditions of thermal denaturation. One of them, the 70S-associated 8S RNA, exhibits a number of structural properties characteristic of a previously described free viral 8S RNA. This similarity was revealed by polyacrylamide gel electrophoresis and nucleotide composition.


Formation of lipid-nucleotide complex by RNA tumor virus preparations. RNA tumor virus preparations utilize alpha-(32)P-deoxyribonucleoside triphosphates as substrates to form lipid-nucleotide products which are tightly associated with protein.


Location of the T4 gene 32 protein binding site on simian virus 40 DNA. The T4 gene 32 protein, which binds to single-stranded but not duplex DNA, forms a specifically located denaturation loop in covalently closed circular simian virus 40 (SV40) DNA. Cleavage of the SV40 DNA-gene 32 protein complex with a restriction endonuclease from Hemophilus parainfluenzae shows the loop center to be at 0.46 on the SV40 DNA map. This is within one of the regions of SV40 DNA cleaved preferentially by the single-strand-specific nuclease S(1).


Rapid screening assay for revertants derived from MSV-transformed cells.


The effect of prostaglandin E1 on norepinephrine-induced membrane depolarization and cyclic AMP accumulation in brown fat cells.


Diurnal variation of plasma angiotensin II in man.


Plasma lipid and lipoprotein levels in childhood and adolescence.


Estrogen mercapturic acids in the adult male rat.


Estrogen receptor-anti-estrogen complex: atypical binding by uterine nuclei and effects on uterine growth.


The identification of androstenedione and androstenedione 3-enol glucuronide in the blood of a woman with an interstitial cell ovarian tumor after 4-14C-testosterone.


Structural and functional properties of synapses in insects.


Subcellular localization of hexokinase in the rat cortex.


Influence of deafferentation of the medial basal hypothalamus on the sensitivity of the brain to hyperbaric oxygen.


Comparison of visual acuity tests and viewing condition interactions.


Adenoid cystic carcinoma of the male breast: report of a case.


Renin-secreting Wilms' tumor with severe hypertension. Report of a case and brief review of renin-secreting tumors.


Metronidazole combined with diloxanide furoate in amoebic liver abscess.


Studies on polynucleotides containing hybrid sequences. Synthesis of oligonucleotides containing thymidine, adenosine, and a single deoxyribonucleotidyl-(3'-5')-ribonucleotide linkage.


Enzymatic synthesis and crystallographic characterization of an isomorphous derivative of yeast formylatable methionine transfer ribonucleic acid containing iodocytidine.


Inhibition of fumarylacetoacetate fumarylhydrolase by monovalent anions.


Roles of zinc ion and reduced coenzyme in the formation of a transient chemical intermediate during the equine liver alcohol dehydrogenase catalyzed reduction of an aromatic aldehyde.


Observations on the oxidation-reduction properties of bovine erythrocyte superoxide dismutase.


Spin-labeled ribonuclease. A. Selective incorporation of a nitroxide spin label sensitive to active-center geometry.


Conformational studies of angiotensin peptides in aqueous solution by proton magnetic resonance.


Model studies for molybdenum enzymes. Reduction of flavines by mu-oxo-bis(oxodihydroxo(L-cysteinato)molybdate(V)).


Oxidation-reduction potential dependence of low-temperature photoreactions of chloroplast photosystem. II.


Polylysine-enhanced effectiveness of plastocyanin in photosystem. I.


The oxidation mechanisms of thiosulphate and sulphide in Chlorobium thiosulphatophilum: roles of cytochrome c-551 and cytochrome c-553.


Effect of oxidizing treatment on chloroplast photosystem II reactions.


Isolation of cytoplasmic glucocorticoid-binding protein(s) from rat liver by means of affinity chromatography, and its partial characterization.


Progesterone-binding protein in human myometrium. Ligand specificity and some physicochemical characteristics.


Binding of NAD+ to rabbit-muscle glyceraldehydephosphate dehydrogenase. The use of N-methylnicotinamidium chloride as a spectral and conformational probe.


The effects of trypsin on purified myelin.


Cell wall glycopeptides of Candida albicans serotypes A and B.


Structural and functional determinants of Mucor miehei protease. II. Circular dichroic studies on the native and periodate-oxidized enzyme.


Mössbauer spectroscopy of iron in human and rabbit transferrin.


Simulated behavior states: an approach to specificity in psychobiological research.


Reactivity of vascular smooth muscle in hypertensive rats.


Myocardial nucleotide synthesis from purine bases and nucleosides. Comparison of the rates of formation of purine nucleotides from various precursors and identification of the enzymatic routes for nucleotide formation in the isolated rat heart.


Incidence of autoantibodies in cancer patients.


Selective stimulation of renal nerves in the anesthetized dog. Effect on renin release during controlled changes in renal hemodynamics.


Prediction of the burden of released mental patients.


Social approaches to community mental health via intake or central reception services.


Proceedings: Some aspects of freezing and drying of microorganisms on the basis of cellular water.


Chemical screening and evaluation of coronary and coronary-prone patients.


A new national strategy to make health services flexible and responsive.


Attempts to detect homologous autointerference in vivo with influenza virus and vesicular stomatitis virus. Von Magnus particles of influenza virus and defective interfering T particles of vesicular stomatitis virus were unable to provide significant protection of mice from disease or death when inoculated intranasally or intracerebrally along with moderate or high doses of homologous infectious challenge virus. However, yields of infectious virus from the affected organs were reduced as compared to controls inoculated with infectious virus alone. Serial intracerebral passage of vesicular stomatitis virus in mouse brain at high doses failed to produce T particles detectable by in vitro autointerference assays on BHK(21) cells, whether or not T particles were introduced along with B virions at the first passage. When very low challenge doses of infectious B virions were inoculated intracerebrally along with high doses of homologous defective particles, there was significant prolongation of life, although most mice died eventually of slowly progressing disease. Also, the virus yields in the brains of these mice were significantly reduced, and virus was no longer detectable in the brains of "protected" mice surviving for 10 days or more. Our results suggest that although homologous autointerference does occur in vivo, it is a more complex phenomenon than in vitro cell culture experiments might indicate.


Differences in clinical and convalescent-phase antibodies of Rhesus monkeys infected with monkey pox, tanapox, and Yaba poxviruses. Complement-fixing and complement-fixing inhibiting (CFI) antibodies were demonstrated in the clinical and convalescent stages, respectively, of rhesus monkeys infected with either monkey poxvirus, Tanapoxvirus, or Yaba poxvirus. Specificity of the CFI antibody was confirmed by its failure to cross-react with heterologous poxvirus antigens and by experiments demonstrating the CFI test as being antigen dependent. Serum containing CFI antibody neutralized homologous poxvirus but failed to agglutinate antigen-coated, tanned red blood cells. The application of CFI test as a seroepidemiologic tool for studies of poxvirus infection of man and simian monkeys and the biologic role of CFI antibody in pathogenesis were discussed.


Immunity to chlamydial infections of the eye. V. Passive transfer of antitrachoma antibodies to owl monkeys. Previous studies have shown that owl monkeys which have had a trachoma agent infection were subsequently highly resistant to challenge by both homologous and heterologous organisms. In the present study, passive transfer of owl monkey serum containing antitrachoma antibody from immune monkeys did not protect recipient monkeys from infectious challenge with homologous trachoma. Antibody was not detectable in eye secretions of the recipient monkeys until the intensity of infection was waning, suggesting but not proving that local antibody synthesis rather than simple transudation of serum antibody occurs.


Host responses to Epstein-Barr virus and cytomegalovirus infection in leprosy. A study was undertaken in patients with leprosy to assess the contribution of cell-mediated immunity to the host response to Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection. Sixteen of 72 patients (22%) with lepromatous leprosy, with impaired cellular immunity, had anti-EBV titers of 1,640 or higher. Only 4 of 49 patients (8%) with tuberculoid leprosy, with intact cell-mediated immunity, attained the level of 1:640. The anti-EBV antibody titers were significantly higher in patients with lepromatous leprosy (P approximately 0.025). No significant differences were found in the level of anti-CMV antibody titers in patients with the two types of leprosy. The presence of high anti-EBV antibody titers in lepromatous leprosy suggests that cell-mediated immunity is a significant factor in host response to EBV infection. Host immune responses should be taken into consideration when assignment of an etiological role to EBV is based upon seroepidemiological data.


Further studies on the carbohydrate metabolism of immature Schistosoma mansoni.


An e.s.r. study of free-radical conversions in irradiated single crystals of N-acetylglycine in the temperature range 77-300 K.


An enzyme histochemical study of mesothelial cells in rodents.


Effects of acetazolamide on the urinary excretion of cyclic AMP and on the activity of renal adenyl cyclase. Acetazolamide, an inhibitor of the enzyme carbonic anhydrase, increased the urinary excretion of cyclic AMP in normal and parathyroidectomized rats. The increase was greater in rats with intact parathyroid glands than in parathyroidectomized rats. This rise in the urinary excretion of cyclic AMP was not due to an increase in urine flow or a change in urine pH. Furosemide caused an increase in urine flow, but did not affect the excretion of cyclic AMP or phosphate. Alkalinization of the urine with bicarbonate did not increase the urinary excretion of phosphate or cyclic AMP. Acetazolamide increased the productionof cyclic AMP by rat renal cortical slices in vitro. This effect was dose-dependent. Acetazolamide also stimulated the activity of renal cortical adenyl cyclase in a dose-dependent manner but had no effect on the activity of cyclic nucleotide phosphodiesterase. The pattern of urinary excretion of cyclic AMP and phosphate after administration of acetazolamide was similar to that observed in rats given parathyroid hormone. It is suggested that acetazolamide stimulates the renal production of cyclic AMP by activating adenyl cyclase and that this may be the mechanism by which this inhibitor of carbonic anhydrase produces phosphaturia.


Plasma clearance rates and renal clearance of 3H-labeled cyclic AMP and 3H-labeled cyclic GMP in the dog. Previously, in an attempt to understand the mechanisms involved in the regulation of plasma cyclic nucleotides, we measured concentrations of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in plasma from selected blood vessels of anesthetized dogs. The observation that the renal venous plasma concentrations of both cyclic nucleotides were less than arterial concentrations suggested that the kidney might be an important site for the elimination of these compounds from plasma and prompted further investigation of the renal handling of these compounds. Tracer doses of either [(3)H]cAMP or [(3)H]cGMP were administered to anesthetized dogs by constant intravenous infusion, and metabolic clearance rates were determined. Concentrations of endogenous cyclic nucleotide and of cyclic nucleotide radioactivity were measured in aortic and renal venous plasma as well as in urine. Renal venous plasma [(3)H]cGMP was 39% and [(3)H]cAMP was 65% of the concentration in arterial plasma. Endogenous cyclic nucleotide levels showed a similar relationship. The plasma clearance rates (PCR) were 271+/-27 ml/min (mean+/-SE) for cGMP and 261+/-17 for cAMP. The total kidney clearance (calculated as the renal plasma flow x renal cyclic nucleotide extraction ratio) accounted for 52+/-4% and 30+/-2% of the PCR for cGMP and cAMP, respectively. Only about two-thirds of the total kidney clearance of each cyclic nucleotide could be accounted for by urinary excretion, the remainder presumably being the result of renal metabolism. The urinary clearances of (3)H-labeled cGMP (40.9+/-4.2 ml/min) and endogenous cGMP (45.0+/-2.3 ml/min) were not significantly different from each other. Both were approximately 50% greater than the glomerular filtration rate, which was 27.1+/-2.0 ml/min, indicating that a significant amount of urinary cGMP is derived from plasma by tubular secretion. In contrast, the urinary clearances of (3)H-labeled cAMP (23.7+/-1.9 ml/min) and endogenous cAMP (27.2+/-2.6 ml/min) were nearly equal both to each other and to the glomerular filtration rate, which was 24.6+/-1.7 ml/min. Thus, in the dog, glomerular filtration of plasma cAMP appears to be responsible for most of the cAMP found in urine. Renla production of cAMP, which in humans contributes from a third to a half of the urinary cAMP, was quantitatively of minor importance in the dog.Thus, under the conditions of these experiments in dogs, renal elimination appears to be responsible for half of the PCR of cGMP and about a third of the PCR of cAMP. About a third of the renal elimination of both cyclic nucleotides appears to be due to metabolic degradation within the kidney, and the balance is due to excretion in the urine.


Hemolytic plaque formation by leukocytes in vitro. Control by vasoactive hormones. Histamine, beta-adrenergic amines, and prostaglandins inhibited hemolytic plaque formation by splenic leukocytes from immunized mice. The same agents had previously been shown to prevent both the IgE-mediated release of histamine from human basophils and the immunologically specific cytolytic activity of murine lymphocytes, through stimulation of the production of cyclic AMP in leukocytes. We therefore tested the hypothesis that cyclic AMP might mediate an inhibitory effect of these drugs by comparing the ability of these agents to inhibit plaque formation with their effects on cyclic AMP accumulation in leukocytes. In splenic cells from three mouse strains, the dose-dependent effects of these agents of cyclic AMP correlated with their inhibition of plaque formation. Beta- but not alpha-adrenergic agonists were effective in both systems, and the effects of isoproterenol were inhibited by propranolol. Histamine was approximately equipotent with isoproterenol in both systems. Two prostaglandins (E(1) and E(2)) were effective in both systems, but prostaglandin F(2alpha) was not. Dibutyryl cyclic AMP, a lipid-soluble analog of the endogenous nucleotide, inhibited plaque formation by cells of all three strains. Theophylline, an inhibitor of cyclic AMP degradation, inhibited plaque formation slightly, but potentiated the effects of histamine, isoproterenol, and the prostaglandins on both cyclic AMP accumulation and plaque formation. Finally, cholera enterotoxin, a potent activator of adenyl cyclase, produced a delayed inhibition of plaque formation and a parallel increase in leukocyte cyclic AMP content; both effects of the toxin were blocked by canine antitoxin. These results suggest that leukocyte cyclic AMP may act as a "second messenger" to suppress plaque formation in vitro. The inhibitory effects of hormones and cyclic AMP on plaque formation are strikingly similar to their effects on in vitro models of immediate and cell-mediated hypersensitivity. The physiologic significance of these findings is not yet known.


Effect of glucagon on net splanchnic cyclic AMP production in normal and diabetic men. Glucagon activates hepatic adenylate cyclase, thereby increasing acutely the liver content of cyclic AMP (cAMP) as well as the release of cAMP into the hepatic vein. Insulin, on the other hand, antagonizes this glucagon-mediated cAMP production, thus providing a hypothetical mechanism through which insulin might correct some of the metabolic abnormalities of diabetes. To study this hormonal interaction in man, net splanchnic cAMP production (NScAMPP) was investigated in normal and insulin-dependent diabetic men under basal conditions and in response to intravenous glucagon, 50 ng/kg/min for 2 h. In normals (n=19), basal hepatic vein cAMP concentration was 23.6+/-1.1 nM and NScAMPP was 1.7+/-0.6 nmol/min. Glucagon stimulated NScAMPP in four normal subjects to a peak of 99.6+/-43 nmol/min at 25 min with a subsequent fall to 12.4+/-5.1 nmol/min by 90 min despite continuing glucagon infusion. Endogenous insulin secretion was stimulated as indicated by rising levels of immunoreactive insulin and C-peptide (connecting peptide) immunoreactivity, raising the possibility that endogenous insulin might be responsible for the fall in NScAMPP that followed the initial spike. In the diabetics (n=8), basal hepatic vein cAMP concentration was 24.7+/-1.2 nM and NScAMPP was undetectable. Glucagon stimulated NScAMPP in five diabetics to a peak of 169.9+/-42.6 with a subsequent fall to 17.4+/-3.9 nmol/min by 90 min even though endogenous insulin secretion was not stimulated (no rise in C-peptide immunoreactivity). Although the mean increase in NScAMPP was greater in the diabetics, the two groups did not differ significantly.Conclusions. In normal resting man the liver is a significant source of circulating cAMP. Diabetics do not release abnormally large amounts of hepatic cAMP under basal conditions. Glucagon markedly enhances hepatic cAMP release with a spike-decline pattern in both normal and diabetic men. The decline in hepatic cAMP release despite continuing glucagon stimulation is due to factors other than a stimulation of insulin secretion.


Sources of cyclic nucleotides in plasma. In order to determine the sites of net production and removal of the cyclic nucleotides in plasma, various blood vessels were catheterized in 17 anesthetized dogs and arterial and venous concentrations of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) were measured by radioimmunoassay. Aortic cAMP was 30+/-2 nM (mean+/-SE) and cGMP was 13+/-1 nM. There were no significant differences for either cyclic nucleotide between the concentration in the aorta and that in the inferior vena cava, coronary sinus, hepatic vein, and femoral vein. The concentration of cAMP in renal venous plasma was 25% lower than in aortic plasma, and renal venous cGMP was 51% lower than in the aorta. The pulmonary arterial concentrations of cAMP and cGMP were slightly lower than in the aorta. The concentration of cGMP in the superior mesenteric vein plasma was 83% greater than in aortic plasma; the concentration of cAMP in this vessel was only 16% greater than that in the aorta. Superior vena cava concentrations of both cyclic nucleotides were slightly greater than arterial concentrations. THE RESULTS SUGGEST THAT: (a) the kidneys are a major site of removal of both cyclic nucleotides from plasma. (b) The lungs may be a site of net addition of both cyclic nucleotides to plasma. (c) The small intestine is a site of net production of both cyclic nucleotides, particularly cGMP. (d) The liver probably removes cyclic nucleotides from plasma. (e) Since no other organs or regions studied added detectable net amounts of cyclic nucleotides to plasma, and since the turnover of these compounds in plasma is known to be rapid, the production of plasma cyclic nucleotides under basal conditions may well be the result of small net contributions may well be the result of small net contributions from many tissues or bidirectional fluxes between tissues and plasma, or both.


Induction of the platelet release reaction by phytohemagglutinin. We have previously shown that the erythroagglutinating phytohemagglutinin (E-PHA) from Phaseolus vulgaris binds to the surface of intact human platelets and that adenylate cyclase activity in the particulate fraction of E-PHA-treated platelets is lower than in comparable controls. We now find that E-PHA induces release of [(14)C]serotonin from platelets. Release follows binding of E-PHA, and a haptenic inhibitor of E-PHA binding prevents induction of release. E-PHA does not produce platelet lysis and has little effect on [(14)C]serotonin uptake. Platelets possess approximately 300,000 receptor sites of E-PHA per cell, and we estimate that about 15% of these sites must be occupied by E-PHA to initiate the release reaction. Prior incubation of platelets with prostaglandin E(1), theophylline, or dibutyryl cyclic AMP prevents E-PHA-induced release, although these agents have little effect on E-PHA binding to platelets. Thrombin and E-PHA produce different rates and extents of serotonin release. Thrombin (1 U/ml) causes release of 75-85% of platelet [(14)C]-serotonin, with half-maximal release occurring less than 0.5 min after thrombin addition. E-PHA, however, induces release of only 30-60% of platelet serotonin at a 10-fold slower rate. In addition, utilizing electron microscopy, we have observed striking differences in the morphological changes that occur in platelets exposed to E-PHA as compared with thrombin. Thus, the platelet release reaction may be triggered in part by binding of E-PHA to the cell surface, but this reaction only partially resembles that produced by thrombin.


Separation of specific antibody-forming mouse cells by their adherence to insolubilized endogenous hormones. Spleen cells from mice immunized with sheep red cells were separated by differential adherence to insolubilized histamine, catecholamines, and prostaglandins. The hormones were insolubilized by linking them to Sepharose beads through a protein carrier. We measured hemolytic plaque formation (per million splenic leukocytes) of cells which passed through columns of hormone-carrier-Sepharose beads (i.e., those cells that failed to bind). As compared with control (no column) cells, the number of plaque-forming cells was substantially reduced by passage through histamine, epinephrine, isoproterenol, and prostaglandin-E(2) columns. Plaque-forming cells were not significantly reduced by passage through carrier Sepharose (another control) or norepinephrine- and prostaglandin-F(2alpha)-carrier Sepharose columns. Thus, the ability of an insolubilized hormone preparation to subtract plaque-forming cells roughly correlated with the presence of pharmacologic receptors for the corresponding free hormones, as judged by stimulation of cyclic AMP accumulation in the same cells, reported previously. Both 19S and 7S plaque-forming cells were subtracted by columns prepared from pharmacologically active hormones, but none of the insolubilized hormones stimulated accumulation of intracellular cyclic AMP. The cell membrane phenomenon that allows adherence to a given hormone-carrier-bead column may be identical with the cell receptor.


Mechanisms of lysosomal enzyme release from human leukocytes. II. Effects of cAMP and cGMP, autonomic agonists, and agents which affect microtubule function. Selective release of inflammatory materials from leukocyte lysosomes is reduced by compounds which increase cyclic 3',5'-adenosine monophosphate (cAMP) levels in suspensions of human leukocytes and is augmented by agents which increase cyclic 3',5'-guanosine monophosphate (cGMP) levels in these cell suspensions. Lysosomal enzymes are released in the absence of phagocytosis when cytochalasin B (5 mug/ml) converts polymorphonuclear leukocytes (PMN) to secretory cells: lysosomes merge directly with the plasma membrane upon encounter of PMN with zymosan, and cells selectively extrude substantial proportions of lysosomal, but not cytoplasmic enzymes. beta-Adrenergic stimulation of human leukocytes produced a dose-related reduction in beta-glucuronidase release (blocked by 10(-6) M propranolol) whereas alpha-adrenergic stimulation (phenylephrine plus propranolol) was ineffective. In contrast, the cholinergic agonist carbamylcholine chloride enhanced enzyme secretion, an effect blocked by 10(-6) M atropine. Incubation of cells with exogenous cAMP or with agents that increase endogenous cAMP levels (prostaglandin E1, histamine, isoproterenol, and cholera enterotoxin) reduced extrusion of lysosomal enzymes; in contrast, exogenous cGMP and carbamylcholine chloride (which increases endogenous cGMP levels), increased beta-glucuronidase release. Whereas colchicine (5 x 10(-4) M), a drug which impairs microtubule integrity, reduced selective enzyme release, deuterium oxide, which favors microtubule assembly, enhanced selective release of lyosomal enzymes. The data suggest that granule movement and acid hydrolase release from leukocyte lysosomes requires intact microtubules and may be modulated by adrenergic and cholinergic agents which appear to provoke changes in concentrations of cyclic nucleotides.


The rapid changes of hepatic glycolytic enzymes and fructose-1,6-diphosphatase activities after intravenous glucagon in humans. Glucagon (0.04-0.09 mg/kg/min) was given intravenously for either 2 or 3 min to eight patients with fasting-induced hypoglycemia. One child had hepatic phosphorylase deficiency, two children had glucose-6-phosphatase deficiency, two children had debrancher enzyme (amylo-1,6-glucosidase) deficiency, and two children and one adult had decreased hepatic fructose-1,6-diphosphatase (FDPase) activity. Liver biopsy specimens were obtained before and immediately after the glucagon infusion. The glucagon caused a significant increase in the activity of FDPase (from 50+/-10.0 to 72+/-11.7 nmol/mg protein/min) and a significant decrease in the activities of phosphofructokinase (PFK) (from 92+/-6.1 to 41+/-8.1 nmol/mg protein/min) and pyruvate kinase (PK) (from 309+/-39.4 to 165+/-23.9 nmol/mg protein/min). The glucagon infusion also caused a significant increase in hepatic cyclic AMP concentrations (from 41+/-2.6 to 233+/-35.6 pmol/mg protein). Two patients with debrancher enzyme deficiency who had biopsy specimens taken 5 min after the glucagon infusion had persistence of enzyme and cyclic AMP changes for at least 5 min. One child with glucose-6-phosphatase deficiency was given intravenous glucose (150 mg/kg/min) for a period of 5 min after the glucagon infusion and biopsy. The plasma insulin concentration increased from 8 to 152 muU/ml and blood glucose increased from 72 to 204 mg/100 ml. A third liver biopsy specimen was obtained immediately after the glucose infusion and showed that the glucagon-induced effects on PFK and FDPase were completely reversed. The glucagon infusion caused an increase in hepatic cyclic AMP concentration from 38 to 431 pmol/mg protein but the glucose infusion caused only a slight decrease in hepatic cyclic AMP concentration (from 431 to 384 pmol/mg protein), which did not appear to be sufficient to account for the changes in enzyme activities. Hepatic glucose-6-phosphatase and fructose-1,6-diphosphate aldolase activities were not altered by either the glucagon or the glucose infusion in any patients. Cyclic AMP (0.05 mmol/kg) was injected into the portal vein of adult rats and caused enzyme changes similar to those seen with glucagon administration in humans. Our findings suggest that rapid changes in the activities of PFK, PK, and FDPase are important in the regulation of hepatic glycolysis and gluconeogenesis, respectively, in humans and that cyclic AMP may mediate the glucagon- but probably not the glucose-insulin-induced changes in enzyme activities.


Cholinergic and beta-adrenergic compounds in the control of drinking behavior in the rat.


Effects of weight reduction on obesity. Studies of lipid and carbohydrate metabolism in normal and hyperlipoproteinemic subjects. Considerable controversy exists over the purported role of obesity in causing hyperglycemia, hyperlipemia, hyperinsulinemia, and insulin resistance; and the potential beneficial effects of weight reduction remain incompletely defined. Hypertriglyceridemia is one of the metabolic abnormalities proposed to accompany obesity, and in order to help explain the mechanisms leading to this abnormality we have proposed the following sequential hypothesis: insulin resistance --> hyperinsulinemia --> accelerated hepatic triglyceride(TG) production --> elevated plasma TG concentrations. To test this hypothesis and to gain insight into both the possible role of obesity in causing the above metabolic abnormalities and the potential benefit of weight reduction we studied the effects of weight loss on various aspects of carbohydrate and lipid metabolism in a group of 36 normal and hyperlipoproteinemic subjects. Only weak to absent correlations (r = 0.03 - 0.46) were noted between obesity and the metabolic variables measured. This points out that in our study group obesity cannot be the sole, or even the major, cause of these abnormalities in the first place. Further, we have observed marked decreases after weight reduction in fasting plasma TG (mean value: pre-weight reduction, 319 mg/100 ml; post-weight reduction, 180 mg/100 ml) and cholesterol (mean values: pre-weight reduction, 282 mg/100 ml; post-weight reduction, 223 mg/100 ml) levels, with a direct relationship between the magnitude of the fall in plasma lipid values and the height of the initial plasma TG level. We have also noted significant decreases after weight reduction in the insulin and glucose responses during the oral glucose tolerance test (37% decrease and 12% decrease, respectively). Insulin and glucose responses to liquid food before and after weight reduction were also measured and the overall post-weight reduction decrease in insulin response was 48% while the glucose response was relatively unchanged. In a subgroup of patients we studied both the degree of cellular insulin resistance and the rate of hepatic very low density (VLDL) TG production before and after weight reduction. These subjects demonstrated significant decreases after weight reduction in both degree of insulin resistance (33% decrease) and VLDL-TG production rates (40% decrease). Thus, weight reduction has lowered each of the antecedent variables (insulin resistance, hyperinsulinemia, and VLDL-TG production) that according to the above hypothesis lead to hypertriglyceridemia, and we believe the overall scheme is greatly strengthened. Furthermore, the consistent decreases in plasma TG and cholesterol levels seen in all subjects lead us to conclude that weight reduction is an important therapeutic modality for patients with endogenous hypertriglyceridemia.


Calciferol metabolism and intestinal calcium transport in the chick with reduced renal function.


Connective tissue activation. VI. The effects of cylic nucleotides on human synovial cells in vitro.


Effect of estrogens and a progestogen on platelet adhesiveness and aggregation in rabbits.


Phosphorylative capacity of liver mitochondria with an elevated ratio of cytochrome c+c1 to cytochrome a(+a3).


Sarcoplasmic reticulum in the portal vein heart and ventricle of the cyclostome Myxine glutinosa (L.).


Phosphorylation of cardiac native tropomyosin and troponin: inhibitory effect of actomyosin and possible presence of endogenous myofibrillar-located cyclic-AMP-dependent protein kinase.


Parotid tumors and the orbital apex syndrome.


Enhanced detection of a skeletal lesion with delayed 99mTc-polyphosphate bone scanning.


Effect of various steroids and ACTH on distribution of zoxazolamine in rats.


Lipid infusions in man. Ultrastructural studies on blood platelet uptake of fat particles.


In vitro effects of lipids on fibrinolysis.


mRNA transcription linked to the morphological and plasma membrane changes induced by cyclic AMP in tumour cells.


The effect of clonazepam (Ro 5-4023) in the syndrome of infantile spasms with hypsarrhythmia and in petit mal variant of Lennox syndrome. Preliminary report.


Optical recording of impulses in individual neurones of an invertebrate central nervous system.


Adenyl cyclase.

Adenyl cyclase.


The chemistry and biological properties of nucleotides related to nucleoside 3',5'-cyclic phosphates.


Clinical studies and applications of cyclic nucleotides.


Analysis of the photochemical isomers of ergosterol by column chromatography.


Protein kinases and protein kinase substrates.


Determination of nicotinamide in some injections of B-complex vitamins by thin-layer chromatography.


Male infertility caused by abnormal androgen production in the adrenal cortex.


Growth of Clostridium perfringens in food proteins previously exposed to proteolytic bacilli. Proteolytic sporeforming bacteria capable of surviving processing heat treatments in synthetic or fabricated protein foods exhibited no antagonistic effects on growth of Clostridium perfringens, but instead shortened the lag of subsequent growth of C. perfringens in sodium caseinate and isolated soy protein. Bacillus subtilis A cells were cultured in 3% sodium caseinate or isolated soy protein solutions. The subsequent effect on the lag time and growth of C. perfringens type A (strain S40) at 45 C was measured by colony count or absorbance at 650 nm, or both. B. subtilis incubation for 12 h or more in sodium caseinate reduced the C. perfringens lag by 3 h. Incubation of 8 h or more in isolated soy protein reduced the lag time by 1.5 h. Molecular sieving of the B. subtilis-treated sodium caseinate revealed that all molecular sizes yielded a similar reduced lag time. Diethylaminoethyl-Sephadex ion exchange fractionation and subsequent amino acid analysis indicated that the lag time reduction caused by B. subtilis incubation was not related to charge of the peptides nor to their amino acid composition. Apparently the shortened C. perfringens lag in these B. subtilis-hydrolyzed food proteins was a result of the protein being more readily available for utilization by C. perfringens.


Identification of the toxic principle in a sample of poaefusarin. A sample of poaefusarin (a mycotoxin suspected of being one of the toxins involved in alimentary toxic aleukia in the U.S.S.R.) was received from a Soviet scientist for evaluation and comparison with other mycotoxins. Although poaefusarin is presumed to be a steroid, analyses by thin-layer chromatography, gas-liquid chromatography, and infrared, ultraviolet, and mass spectrometry could not confirm the presence of a steroid structure. However, 2.5% of the sample was made up of the trichothecene T-2 toxin, an amount sufficient to explain the toxicity found in the rat and rabbit skin toxicity tests. In addition, neosolaniol (0.14%), T-2 tetraol (0.6%), and zearalenone (F-2) (0.43%) were present in the sample. Since the toxicity was found to be associated only with T-2 toxin, no attempt was made to determine the nature of the other nontoxic components of the sample.


Inactivation of foot-and-mouth disease virus with ethylenimine. Foot-and-mouth disease virus (FMDV) was inactivated by ethylenimine (EI) at three concentrations and two temperatures. Comparison of inactivation kinetics and the antigenic and immunogenic potency of EI and N-acetylethylenimine (AEI)-inactivated FMDV indicates that EI has nearly optimal characteristics as an inactivant for FMDV vaccine preparation. Although AEI-inactivated FMDV has proved to be a potent specific immunogen, an equivalent percentage of EI inactivated FMDV at substantially faster rates and produced an equally potent immunogen. In addition, EI inactivated FMDV at rates that were essentially linear throughout the loss of nearly all measurable infectivity.


Simplified method for purification of Clostridium perfringens type A enterotoxin. Purification of Clostridium perfringens type A enterotoxin from sporulated cells was simplified. The method consisted of precipitation of the enterotoxin from the extract of sonically treated cells at 40% saturation of ammonium sulfate at pH 7, differential solubilization in 0.02 M phosphate buffer, pH 6.7, and repeated gel filtration on Sephadex G-200. The purified enterotoxin was at least 98% pure in ultracentrifugation, polyacrylamide gel electrophoresis, and agar gel double diffusion. Recovery was over 74% from the sporulated cell extract. The toxin had biological activities of at least 4,700 mouse intravenous minimal lethal doses/mg of N, 3,900 capillary permeability-increasing U/mg of N in the guinea pig skin, and 210 rabbit intestinal loop distension U/mg of N. The toxin, containing no hexose, lipid, or nucleic acid, appeared to be identical in sedimentation constant, isoelectric point, and ultraviolet absorption spectrum to the toxin purified previously by different procedures.


Proton magnetic double-resonance study of angiotensin II (Asn1Val5) in aqueous solution employing correlation spectroscopy. Assignment of peptide NH resonances and transfer of saturation from water.


Kinetic studies of fluoride binding by cytochrome c peroxidase.


Kinetic and equilibrium studies of cyanide binding by cytochrome c peroxidase.


Functional groups of diphosphopyridine nucleotide linked isocitrate dehydrogenase from bovine heart. II. Studies of an active amino group by reaction with aldehydes.


Functional groups of diphosphopyridine nucleotide linked isocitrate dehydrogenase from bovine heart. I. Studies of an active amino group by amidination, arylation, acetylation, and carbamylation.


An unproductive binary complex of liver alcohol dehydrogenase and a chromophoric aldehyde.


Electronic substituent effects during the liver alcohol dehydrogenase catalyzed reduction of aromatic aldehydes.


Regulation of pea leaf ribulose-5-phosphate kinase activity.


Modulation of succinate dehydrogenase in response to environmental stress conditions of hypobaria and hypoxia.


Phosphorylation of muscle proteins by cyclic adenosine 3',5'-monophosphate-dependent protein kinase from muscle.


Adenylate kinase from Thiobacillus neapolitanus. Unique properties, possibly designed to serve a unique metabolic function.


A surface p-nitrophenyl phosphatase of frog gastric mucosa.


Further characterization of a specific p-nitrophenylphosphatase from baker's yeast.


Purification of phospholipase C (alpha-toxin) from Clostridium perfringens.


Distribution of lysosomal enzymes between parenchymal and Kupffer cells of rat liver.


The integrity of human lymphoblastoid RNA after incorporation by human skin fibroblasts.


Hydroxylamine-O-sulfonic acid: in vitro and possible in vivo reaction with DNA.


Platelet function studies in coronary artery disease.


Changes in microsomal enzyme activities during DAB carcinogenesis.


Hyper-low density lipoproteinemia in United States Air Force recruits.


A study on the role of pituitary ACTH in the aldosterone production of sodium depleted rats.


Adrenocortical responsiveness after long-term corticosteroid therapy in childhood nephrosis.


Familial congenital adrenal hypoplasia.

Familial congenital adrenal hypoplasia.


Alteration of binding specificity of murine myeloma protein-315 to 2,4-dinitrophenyl and 2,4,6-trinitrophenyl ligands.


Letter: A phosphodiesterase from Enterobacter aerogenes.


Surface markers on human B and T lymphocytes. II. Presence of Epstein-Barr virus receptors on B lymphocytes. Human peripheral lymphocytes were investigated for receptors binding Epstein-Barr virus (EBV) because of the regular association of this virus with infectious mononucleosis and Burkitt's lymphoma. This was done by a cytoadherence technique where virus-producing cells, displaying fresh viral determinants in their cytoplasmatic membrane, were mixed with lymphocytes. Unfractionated lymphocytes were found to adhere to these cells in contrast to column-purified T lymphocytes. The specificity of the binding was confirmed by blocking experiments that showed that sera containing high titers of antibodies directed against the virus could partially inhibit the adherence in contrast to low-titer sera. It is concluded that B lymphocytes, in contrast to T lymphocytes, have receptors for EBV. In a second line of experiments it was found that established human lymphoblastoid lines that carry the EBV genome had receptors characteristic for B lymphocytes and did not form T-lymphocyte rosettes. In contrast, a line of known T-lymphocyte origin that did not carry the EBV genome had receptors characteristic for T lymphocytes. EBV-transformed simian lymphoblastoid lines had surface markers indicating a B-lymphocyte origin in contrast to HVS-transformed simian lines that lacked surface immunoglobulin but carried receptors for sheep red blood cells.


Comparison of the yield of infectious virus from clones of human and simian lymphoblastoid lines transformed by Epstein-Barr virus. Three lymphoblastoid cell lines, of human, squirrel monkey, and marmoset origin, all transformed by the same strain of Epstein-Barr virus (EBV), differed markedly in their content of infectious virus. Single cell clones were obtained from each line to learn whether these differences were dependent upon factors shared by all cells in each line or upon factors present only in a proportion of the total cell population. A total of 17 primary clones were examined: 6 human, 6 squirrel monkey, and 5 marmoset. Cloning efficiency on human placental cell feeder layers varied from 16 to 24%. EBV antiserum, present in the cloning suspension, was shown to neutralize all extracellular virus. 15 of the 17 clones released EBV as measured by the transformation assay. Titers of infectious virus released by daughter clones paralleled titers of virus in the parent line. The median virus titers from human, squirrel monkey, and marmoset clones were respectively 10(1.5), 10(3.0), and 10(4.3) 50% transforming doses per 0.2 ml. The median yield of virus from clones of the three species was, respectively, 4, 96, and 786 transforming units per 1,000 cells containing viral capsid antigen. Two nonproducer clones (one human and one squirrel monkey) did not release infectious virus after treatment with 5'-bromodeoxyuridine, or with X ray followed by co-cultivation with marmoset leukocytes. The nonproducer clones could not be superinfected by biologically active EBV. These results show that differences in production of infectious EBV among the lines tested are reflected in the majority of cells of these lines. The data imply that the mechanism for regulation of the expression of the EBV genome is cellular rather than viral in origin. There are presumably genetic differences among primate species in this regulatory process.


Adaptations of energy metabolism in the cultivated macrophage. Adaptive changes in energy metabolism, as reflected by pyruvate kinase and cytochrome oxidase activities, were examined during in vitro differentiation of the cultivated macrophage. Serum concentrations of tissue culture media, which directly influence endocytic activity, and ambient oxygen tension were both shown to influence pyruvate kinase and cytochrome oxidase activities. Cells maintained in high serum concentrations (30% newborn calf serum [NBCS]) exhibited a 300-400% increase in pyruvate kinase activity and a 40% increase in cytochrome oxidase activity, whereas cells maintained in low serum concentrations (2% NBCS) exhibited a lesser increase (65%) in pyruvate kinase activity and no change in cytochrome oxidase activity. Anaerobiosis resulted in additional alterations in pyruvate kinase and cytochrome oxidase activities. Cells maintained for 48-72 h under anaerobic conditions exhibited a 500-600% increase in pyruvate kinase activity and a 40% decrease in cytochrome oxidase activity. Increased pyruvate kinase activity was dependent on continued protein synthesis. Enzyme increases occurred in anaerobically cultured cells despite an overall reduction in cell protein synthesis. It is suggested that adaptive changes in pyruvate kinase and cytochrome oxidase activity resulting from alterations in either serum concentration or ambient oxygen tension are regulated by two independent mechanisms. One mechanism is aimed at providing energy for endocytic activity and the other in compensating for impaired oxidative metabolism during anaerobiosis.


Study of methyl-CCNU(NSC-95441) in the treatment of lung cancer.


A suppression of cellular immunity in patients with multiple sclerosis.


Preparation and characterization of an immuno-electron microscope tracer consisting of a heme-octapeptide coupled to fab. A heme-octapeptide (mol wt 1,550) has been obtained from cytochrome c by successive pepsin and trypsin hydrolysis and purified by gel filtration and countercurrent distribution. It possesses peroxidatic activity characterized by an apparent K(m) of 0.2 M, an apparent v(max) of 4 mmol/min per mg of peptide, and a pH optimum of 7.0. Using a novel two-step conjugation procedure, the heme-octapeptide was coupled to rabbit Fab antibody fragments by first derivatizing it with the N-hydroxysuccinimide ester of p-formylbenzoic acid and subsequently allowing it to form a Schiff base with the amino groups of Fab. Stable covalent linkages were then obtained by reduction of the Schiff bases with sodium borohydride. The conjugate consists of approximately 2 heme-octapeptides attached to each Fab molecule. The molecular weight is 45,000 daltons when coupled to sheep Fab and 50,000 daltons with a Stokes radius of 32 A, when conjugated to rabbit Fab. Its peroxidatic activity is characterized by an apparent K(m) of 0.4 M, an apparent v(max) of 0.4 mmol/min and per mg of attached heme-octapeptide and a pH optimum of 7.0. The conjugate has been used for the localization at the electron microscope level of secretory immunoglobulins in the mammary gland of lactating rabbits.


Renin content in subcellular fractions of normal rat kidney extract.


Role of cyclic AMP in the action of antidiuretic hormone on kidney.


Uptake of estradiol by the rat pineal organ. Effects of cervical sympathectomy, stage of the estrous cycle and estradiol treatment.


Synthesis and toxicity evaluation of aflatoxin P.


New applications of electron spin resonance to problems in biochemistry and pharmacology.


Enigma and dilemma of the pulmonary nodule.


Aldosterone: review of its physiology and diagnostic aspects of primary aldosteronism.


Dissociation between human platelet agglomerating activity and factor VIII procoagulant activity of bovine plasma preparations by chemical treatment. II. Effect of periodate oxidation.


The influence of p,p'-DDT, alpha-chlordane, heptachlor and endrin on hepatic and renal carbohydrate metabolism and cyclic AMP-adenyl cyclase system.


Feline viral rhinotracheitis (FVR).

Feline viral rhinotracheitis (FVR).


Feline viral infections.

Feline viral infections.


Ultrastructural and histochemical demonstration of myoepithelium in mixed tumors of the canine mammary gland.


Immunologic response of the bovine fetus to inactivated infectious bovine rhinotracheitis-infectious pustular vulvovaginitis virus.


Lithium carbonate and sleep in affective disorders. Further considerations.


Role of horse fly (Tabanus fuscicostatus Hine) and stable fly (Stomoxys calcitrans L.) in transmission of equine infectious anemia to ponies in Louisiana.


Respiration-driven proton translocation by yeast mitochondria with differing efficiencies of oxidative phosphorylation. Measurements were made of the stoicheiometry of proton translocation coupled to respiration in mitochondria from Candida utilis where the number of functional energy-conservation sites between intramitochondrial NADH and oxygen was one in a mutant with a novel oxidase (Downie & Garland, 1972), two in sulphate-deficient cells (Haddock & Garland, 1971) or three in glycerol-limited cells (Light & Garland, 1971). The stoicheiometries of protons translocated per atom of oxygen utilized (i.e. -->H(+)/2e(-) ratio; Mitchell, 1966) were close to 2.0, 4.0 and 6.0 respectively. Thus by using the same substrate (intramitochondrial NADH) and oxygen throughout, the -->H(+)/2e(-) ratio is shown to be 2.0 per energy-conservation site when the number of such sites is varied from one to three.


An antimycin A- and cyanide-resistant variant of Candida utilis arising during copper-limited growth. 1. During copper-limited growth of Candida utilis in continuous culture on a non-fermentable carbon and energy source there is a selective pressure favouring the emergence of variants that are less dependent on copper. 2. We describe the properties of such a variant that by-passes cytochrome oxidase (EC 1.9.3.1) by utilizing an alternative oxidase communicating with the respiratory chain at about the level of cytochrome b. 3. Both direct studies of isolated mitochondria and calculations based on growth parameters showed that only one of the normal three phosphorylation sites was active. This site was localized between NADH and the cytochromes. 4. Growth of the variant with copper-supplemented media resulted in the return of cytochrome oxidase but not the loss of the alternative oxidase. 5. The alternative oxidase is inhibited by substituted benzhydroxamic acids. 6. Submitochondrial particles from the variant did not exhibit any novel electron-paramagnetic-resonance-spectroscopy features at about g=2.0 either at 80 degrees K or 12 degrees K.


Biochemical effects of the porphyrinogenic drug allylisopropylacetamide. A comparative study with phenobarbital. Successive administrations of allylisopropylacetamide, a potent porphyrinogenic drug, increase liver weight, microsomal protein and phospholipid contents. There is an increase in the rate of microsomal protein synthesis in vivo and in vitro. The drug decreases microsomal ribonuclease activity and increases NADPH-cytochrome c reductase activity. Phenobarbital, which has been reported to exhibit all these changes mentioned, is a weaker inducer of delta-aminolaevulinate synthetase and increases the rate of haem synthesis only after a considerable time-lag in fed female rats, when compared with the effects observed with allylisopropylacetamide. Again, phenobarbital does not share the property of allylisopropylacetamide in causing an initial decrease in cytochrome P-450 content. Haematin does not counteract most of the biochemical effects caused by allylisopropylacetamide, although it is quite effective in the case of phenobarbital. Haematin does not inhibit the uptake of [2-(14)C]allylisopropylacetamide by any of the liver subcellular fractions.


Glucose metabolism in the newborn rat. Hormonal effects in vivo. 1. The concentrations of liver glycogen and plasma d-glucose were measured in caesarian-delivered newborn rats at time-intervals up to 3h after delivery after treatment of the neonatal rats with glucagon, dibutyryl cyclic AMP, cortisol or cortisol+dibutyryl cyclic AMP. Glycogenolysis was promoted by glucagon or dibutyryl cyclic AMP in the third hour after birth but not at earlier times. Cortisol and dibutyryl cyclic AMP together (but neither agent alone) promoted glycogenolysis in the second hour after birth, but no hormone combination was effective in the first postnatal hour. 2. The specific radioactivity of plasma d-glucose was measured as a function of time for up to 75 min after the intraperitoneal injection of d-[6-(14)C]glucose and d-[6-(3)H]glucose into newborn rats at delivery and after treatment with glucagon or actinomycin D. Glucagon-mediated hyperglycaemia at this time was due to an increased rate of glucose formation and a decreased rate of glucose utilization. Actinomycin D prevented glucose formation and accelerated the rate of postnatal hypoglycaemia. 3. The specific radioactivity of plasma l-lactate and the incorporation of (14)C into plasma d-glucose was measured as a function of time after the intraperitoneal injection of l-[U-(14)C]lactate into glucagon- or actinomycin D-treated rats immediately after delivery. The calculated rates of lactate formation were unchanged by either treatment, but lactate utilization was stimulated by glucagon administration. Glucagon stimulated and actinomycin D diminished (14)C incorporation into plasma d-glucose. 4. The factors involved in the initiation of glycogenolysis and gluconeogenesis in the rat immediately after birth are discussed.


Changes in enzyme activities in tissues of rats exposed to hypoxia. Rats were exposed to various degrees of hypoxia and enzyme activities in their tissues were determined. In general, oxidative metabolism was not increased in response to hypoxia, nor was anaerobic metabolism. Physiological and anatomical changes were concluded to be more important than changes in cellular enzyme activities in the overall adaptation to acute hypoxia.


Cell-surface mucosubstances from trypsin diaggregation of normal and virus-transformed lines of baby-hamster kidney cells. Cell disaggregation by trypsin solubilizes significantly less mucosubstance from the surface of polyoma-virus-transformed baby-hamster kidney cells than from the same non-transformed cell line. The mucosubstance, which consists of both acid mucopolysaccharides and mucoproteins, also differs qualitatively in the two cell lines.


Hormonal regulation of glycogen metabolism in neonatal rat liver. 1. The development of active and inactive phosphorylase was determined in rat liver during the perinatal period. No inactive form could be found in tissues from animals less than 19 days gestation or older than the fifth postnatal day. 2. The regulation of phosphorylase in organ cultures of foetal rat liver was examined. None of the agents examined [glucagon, insulin or dibutyryl cyclic AMP (6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate)] changed the amount of phosphorylase activity. 3. Glycogen concentration in these explants were nevertheless decreased more than twofold by 4h of incubation with glucagon or dibutyryl cyclic AMP. Incubation with insulin for 4h increased the glycogen content twofold. 4. Glycogen synthetase activity was examined in these explants. I-form activity (without glucose 6-phosphate) was found to decrease by a factor of two after 4h of incubation with dibutyryl cyclic AMP, whereas I+D activity (with glucose 6-phosphate) remained nearly constant. Incubation for 4h with insulin increased I-form activity threefold, with only a slight increase in I+D activity. 5. When explants were incubated with insulin followed by addition of dibutyryl cyclic AMP, the effects of insulin on glycogen concentration and glycogen synthetase activity were reversed. 6. These results indicate that the regulation of glycogen synthesis may be the major factor in the hormonal control of glycogen metabolism in neonatal rat liver.


Microbial metabolism of amino alcohols. Metabolism of ethanolamine and 1-aminopropan-2-ol in species of Erwinia and the roles of amino alcohol kinase and amino alcohol o-phosphate phospho-lyase in aldehyde formation. 1. Growth of Erwinia carotovora N.C.P.P.B. 1280 on media containing 1-aminopropan-2-ol compounds or ethanolamine as the sole N source resulted in the excretion of propionaldehyde or acetaldehyde respectively. The inclusion of (NH(4))(2)SO(4) in media prevented aldehyde formation. 2. Growth, microrespirometric and enzymic evidence implicated amino alcohol O-phosphates as aldehyde precursors. An inducibly formed ATP-amino alcohol phosphotransferase was partially purified and found to be markedly stimulated by ADP, unaffected by NH(4) (+) ions and more active with ethanolamine than with 1-aminopropan-2-ol compounds. Amino alcohol O-phosphates were deaminated by an inducible phospho-lyase to give the corresponding aldehydes. This enzyme, separated from the kinase during purification, was more active with ethanolamine O-phosphate than with 1-aminopropan-2-ol O-phosphates. Activity of the phospho-lyase was unaffected by a number of possible effectors, including NH(4) (+) ions, but its formation was repressed by the addition of (NH(4))(2)SO(4) to growth media. 3. E. carotovora was unable to grow with ethanolamine or 1-aminopropan-2-ol compounds as sources of C, the production of aldehydes during utilization as N sources being attributable to the inability of the microbe to synthesize aldehyde dehydrogenase. 4. Of seven additional strains of Erwinia examined similar results were obtained only with Erwinia ananas (N.C.P.P.B. 441) and Erwinia milletiae (N.C.P.P.B. 955).


Adenosine metabolism in Micrococcus sodonensis.


Pharmacologic and toxicologic studies with the polymyxins. I. A gas chromatographic procedure for the analysis of colistin in urine by its content of D-leucine.


Pharmacologic and toxicologic studies with the polymyxins. II. Comparative pharmnacologic studies of the sulfate and methanesulfonate salts of polymyxin B and colistin in dogs.


Pharmacologic and toxicologic studies with the polymyxins. 3. Consideration regarding clinical use in dogs.


Effects of mebutamate on the electroencephalographic sleep profile.


Interaction of Sendai virus with human erythrocytes. II. The fusion reactions.


Interaction of Sendai virus with human erythrocytes. I. The ultrastructure of untreated and pyridine-treated virions and their relationship with erythrocyte surface during hemagglutination.


Elevation of plasma glucose levels by mammalian ACTH in the spiny dogfish shark (Squalus acanthias).


Effects of ACTH on the pituitary-interrenal axis and abundance of white blood cell types in juvenile coho salmon, Oncorhynchus kisutch.


Sodium-retaining bioassay of prolactin in the intact teleost Tilapia mossambica acclimated to sea water.


Cyclic adenosine 3':5'-monophosphate-dependent protein kinase.


Pituitary regulation of serum calcium levels in the killifish, Fundulus heteroclitus L.


Kinetic studies of the activation of muscle phosphorylase phosphatase.


Kinetic studies of the inhibition of muscle phosphorylase phosphatase.


Alpha-keto acid dehydrogenase complexes. XX. A kinetic study of the pyruvate dehydrogenase complex from bovine kidney.


Similarity of the active site of phosphorylation of the adenosine triphosphatase from transport of sodium and potassium ions in kidney to that for transport of calcium ions in the sarcoplasmic reticulum of muscle.


Human plasma high density lipoprotein. Interaction of the cyanogen bromide fragments from apolipoprotein glutamine II (A-II) with phosphatidylcholine.


Antifreeze glycoprotein from an Antarctic fish. Effects of chemical modifications of carbohydrate residues on antifreeze and antilectin activities.


Concerted feedback inhibition. Purification and some properties of aspartokinase from Pseudomonas fluorescens.


Concerted feedback inhibition. Modifier-induced oligomerization of the Pseudomonas fluorescens aspartokinase.


Oxidation of 21-dehydrocorticosteroids to steroidal 20-Oxo-21-oic acids by an aldehyde dehydrogenase of sheep adrenal.


Studies on bovine hepatic fructose 1,6-diphosphatase. Substrate inhibition and the kinetic mechanism.


The development of a TRIC agent (Chlamydia trachomatis) and its associated polysaccharide in suspended cell cultures.


Interaction between viruses and platelets: requirement of haemolytic activity for platelet aggregation induced by paramyxoviruses.


Chicken liver phosphofructokinase. II. Cold inactivation.


Synthesis of ribonucleic acids in KB cells infected with rhinovirus type 14.


Characterization of temperature-sensitive mutants of SV40.


Homology of surface receptors for poliovirus on mammalian cell lines.


The effect of rifampicin, actinomycin D and mitomycin C on poliovirus and foot-and-mouth disease virus replication.


Inhibition by interferon of polyoma virus-induced cell DNA synthesis in mouse peritoneal macrophages.


The lipid content of two iridescent viruses.


The distribution of virus proteins in BHK 21 cells infected with vesicular stomatitis virus (Indiana C).


The morphology, morphogenesis, and serological characterization of the rhabdoviruses Navarro, Kwatta, and Mossuril.


Cytochalasin B-induced activation in the synthesis of L-cell virus particles.


Characterization of segmented double-helical RNA from bacteriophage phi6.


A human cell line from a pleural effusion derived from a breast carcinoma.


Case-control study of Hodgkin's disease. II. Herpesvirus group antibody titers and HL-A type.


In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors.


Limited capacity for motor activity as a cause for declining food intake in cancer.


In vivo and in vitro studies on the morphogenesis of tumors induced by murine sarcoma virus (Harvey).


Combined neoplastic effects of vaccinia virus and 3-methylcholanthrene. 3. Susceptibility and resistance in transplanted mouse skin.


Analysis by immunoelectron microscopy of type-C viruses associated with primary and short-term transplanted mouse plasma cell tumors.


Malignant mouse-liver tumors resembling human hepatoblastomas.


Enzyme activities and extrinsic proteins in plasma membranes from normal liver and Morris hepatoma 5123tc.


Comparison of three mammary tumor viruses in genetically similar susceptible mice.


Quantitative lung colony assay for tumor immunity in mice.


Acute alcoholic myopathy. Enzyme histochemistry and electron microscopic findings.


Sural nerve conduction velocity in peripheral neuropathies and subacute myelo-optico-neuropathies (SMON).


Cyclic nucleotides as intracellular mediators of the expression of antigen-sensitive cells.


Phagocytic release and activation of human leukocyte procollagenase.


Psycho-analytic group interview and short-term group psychotherapy with post-myocardial infarction patients.


A sensitive in vitro bioassay method for luteinizing hormone (LH) activity.


Stimulating effect of dibutyryl cyclic adenosine 3',5' monophosphate on protein synthesis in a thyroidal cell-free system at low potassium and sodium concentrations.


Phagocytosis of supernumerary spermatozoa by two-cell embryos.


Fine structure of the urinary bladder of the bullfrog. (Rana catesbiana).


Bacterial endophthalmitis after cataract extraction. II. Incidence in 36,000 consecutive operations with special reference to preoperative topical antibiotics.


Freeze-fracture studies of gap junctions of normal and neoplastic astrocytes.


Collagenase inhibitors in Pseudomonas keratitis. Adjuncts to antibiotic therapy in rabbits.


Viral isolate in superficial punctate keratitis.


Adaptive response of hepatic carbohydrate metabolism to oral administration of p,p'-1,1,1-trichloro-2,2-bis (p-chlorophenyl)ethane in rats.


Inhibition of purine biosynthesis de novo in sarcoma 180 ascites cells by mercapto and seleno purine analogs.


Vitamin C--effects on the Na+, K+ adenosine triphosphate phosphohydrolase complexes of several tissues.


Effect of cyclic nucleotides on activity of cyclic 3',5'-adenosine monophosphate phosphodiesterase.


Action of organophosphorus compounds on cell organelles. I. Effect of tetraethyl dithio pyrophosphate on lysosomal hydrolases.


Leukopenia, leukoagglutinins, and low IgM in a family with severe febrile illnesses.


Studies of the Epstein-Barr virus-host relationship: autochthonous and allogeneic lymphocyte stimulation by lymphoblast cell lines in mixed cell culture.


Identification and partial characterization of specific estrogen receptors in the vole (Microtus montanus).


Species specificity of the inhibition of adenylate cyclase activation by products of ACTH-stimulated fat cells.


The lactate dehydrogenase system in the heart and skeletal muscle of fish: a comparative study.


Phosphatase activity in epiphyseal cartilage of the chicken (Gallus gallus).


A spin-label study of horse erythrocyte carbonic anhydrases C and D.


Effects of estradiol and testosterone on the immature female chicken (Gallus domesticus). II. Immunodiffusional patterns of yolk lipoproteins in the liver and plasma.


Metabolism in porifera. II. Distribution of sterols.


Pathogenesis of genetic diabetes mellitus: further development of a hypothesis.


In vitro biosynthesis of human placental lactogen (HPL) by chorionic tissue and the diagnostic value of HPL in trophoblastic disease.


Radiation myelopathy.

Radiation myelopathy.


Protein kinase and cyclic AMP-binding activities in liver and adipose tissue of normal, streptozotocin-diabetic and adrenalectomized rats.


Pathohistological findings in the peripheral nervous system (nn. ischiadici) after experimental carbon tetrachloride intoxication in bastard rabbits.


Sequence analysis of polyribonucleotides by continuous directional degradation--a study of the course of the reaction at nucleotide concentrations between 10-7 and 10-5 molar.


Evaluation of the energetics of cytochrome C oxidase in the absense of cytochrome C.


Biosynthesis of sideramines in fungi. Fusigen synthetase from extracts of Fusarium cubense.


Poly (ADP-ribose) glycohydrolase in mouse fibroblast cells (LS cells).


The inhibition of Azotobacter vinelandii terminal oxidases by cyanide.


Improvement of the spin-labelling technique by the use of a radioactive spin label.


Pyruvate metabolism and nitrogen fixation in Azotobacter.


Two ACTH species in rat pituitary gland.


Solid-phase Edman degradation of a protein: N-terminal sequence of cytochrome c from Candida krusei.


Novel type of catabolite repression in the pathway of gamma-aminobutyrate breakdown in Escherichia coli K-12.


Cytochromes of two methane-utilizing bacteria.


Stimulation of adipose tissue triglyceride lipase activity after in vivo administration of dibutyryl cyclic AMP or norepinephrine.


The solid-phase synthesis of human and monkey beta-melanotropins.


A preparative method for the isolation of carboxyl terminal tryptic peptides from proteins.


Effects of synthetic ACTH on corticosteroid-induced growth suppression.


Plasma-cell mastitis: case report.

Plasma-cell mastitis: case report.


Cyclic AMP metabolism in asthma: studies with leukocytes and lymphocytes.


Muscle fiber type, rigor development and bone strength in dobule muscled cattle.


Metabolic pathways of biuret degradation and formation of a biuret-complex in the rumen.


Letter: Optimal postfixation washing time for ultrastructural demonstration of glucose 6-phosphatase activity.


Metabolism of biuret by ruminants: in vivo and in vitro studies and the role of protozoa in biuretolysis.


Conformation of coenzyme fragments when bound to lactate dehydrogenase.


Fine structure of the contractile vacuole pore in Paramecium.


Breeding of European hamsters.

Breeding of European hamsters.


Establishment by selective inbreeding of the IVCS strain and related sister strains of the mouse, demonstrating regularly repeated 4-day estrous cycles.


Simian virus 16 associated with an epizootic of obscure neurologic disease.


Maintenance and husbandry of armadillo colonies.


Preventive medicine in anthropoids: parasite control.


The pathogenesis of the alopecia due to hair-chewing in mice.


Humoral immune response of the adult chinchilla.


Protein requirement of growing gerbils.

Protein requirement of growing gerbils.


Establishment of a helminth-free opossum colony.


An epizootic of protozoan enteritis in a closed mouse colony.


Blood acid-base status in normal albino rats.


A durable housing facility for reptiles.


An apparatus for anesthetizing small laboratory rodents.


Pediculosis of spider monkeys: a case report with zoonotic implications.


Versatile cage for environmental protection housing of research animals.


A combination sterilizing chamber and transfer and housing isolator for use in gnotobiotic laboratories.


Measurement of blood cholinesterase activity in laboratory animals utilizing dimethylbutyl acetate as a substrate.


Indirect measurement of arterial blood pressure in the laboratory pony.


Hematologic changes to 60 days of age in clinically normal beagles.


A case of conjoined twins in the Sprague-Dawley rat.


Microbial flora and viral contact status of Chinese hamsters (Cricetulus griseus).


The Epstein-Barr virus carrier state in infectious mononucleosis.


Pathogenesis of hereditary vitamin-D-dependent rickets. An inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D.


Strand orientation of SV40 transcription in cells infected by non-defective adenovirus 2-SV40 hybrid viruses.


Morphine blockade of amino acid putative transmitters on cat spinal cord sensory interneurones.


Effect of aminoglutethimide and glutethimide on the pituitary-adrenal system.


Suppression of pituitary-adrenal activity and shock-induced fighting in rats.


Adrenocortical influences upon the extinction of an appetitive runway response.


Hydration releases inhibition of feeding produced by intracranial angiotensin.


Homology between type-C viruses of various species as determined by molecular hybridization. Two strains of feline leukemia virus, two endogenous feline type-C viruses (RD/CCC group), several endogenous and laboratory strains of murine "leukemia" virus, two rat viruses, two primate viruses (woolly monkey and gibbon ape), as well as hamster, pig, and avian type-C viruses were examined for their relatedness to one another by molecular hybridization. The extent of nucleic-acid homology was determined by hybridization of the various viral RNAs to a [(3)H]DNA product synthesized from each virus. Among the murine type-C viruses (Rauscher, Kirsten, AT-124, and endogenous BALB/c virus) a high degree of homology is observed, although the viruses are not identical. The two primate viruses are also closely related to one another. The feline, rat, hamster, and pig endogenous viruses can be readily distinguished from one another and from the murine and primate viruses since their DNA products share very little or no nucleic-acid homology. However, the murine and primate type-C virus groups possess a surprising degree of relatedness. Feline type-C viruses fall into two distinct groups, the feline leukemia virus group and the RD-114/CCC group, with little detectable nucleic-acid homology between them. Infection of feline or rat cells with type-C virus results in production of the endogenous type-C virus of the species along with the infecting virus.


Electrophysiological investigation of natural sleep and waking in turtles and hens.