Role of phosphodiesterase in glucagon resistance of large adipocytes. The role of phosphodiesterase in glucagon resistance of large adipocytes was investigated. A comparison was made of phosphodiesterase activities of homogenates prepared from isolated small (mean diameter approximately 45 micro m) and large (mean diameter approximately 78 micro m) adipocytes, using various concentrations (5 x 10(-4) to 1 x 10(-7) M) of 3',5'-cAMP. Kinetic analyses revealed two distinct catalytic activities (high and low affinities) in both cell types; however, the activities of both high- and low-affinity enzymes were significantly elevated in large adipocytes. Lipolysis was measured in isolated adipocytes in the presence of different concentrations (0.1-0.6 mM) of the phosphodiesterase inhibitor aminophylline. Large adipocytes were less responsive to low levels of methylxanthine, suggesting that greater amounts of phosphodiesterase must be inhibited before lipolysis can be stimulated. To evaluate the influence of phosphodiesterase during glucagon-stimulated lipolysis, small and large adipocytes were incubated with a maximally effective concentration of glucagon (1.5 x 10(-6) M) in combination with various concentrations (0.1-0.6 mM) of aminophylline. Although the glucagon effect was potentiated in both cell types, the maximum lipolytic response of large adipocytes (at 0.4 mM aminophylline) was approximately 36% lower than that observed in small adipocytes (at 0.2 mM aminophylline). This reduction correlates closely with the decreased glucagon binding present in large cells; therefore, it appears that the glucagon-resistant state is adequately explained by elevations in phosphodiesterase levels and diminished glucagon-cell association.


Ultrastructural and physiological evidence for corticosteroid-induced alterations in hepatic production of very low density lipoprotein particles. The cause of corticosteroid-induced hyperlipoproteinemia was studied in rats and mice. An ultrastructural morphometric method was utilized to demonstrate alterations in hepatocyte very low density lipoprotein content, and Triton WR 1339-treated rats were used to identify changes in the removal of very low density lipoproteins from plasma. The results show that corticosteroid treatment results in (1) an increase in both plasma triglyceride and cholesterol levels, (2) an increase in rate of accumulation of triglyceride after inhibition of very low density lipoprotein removal by Triton, and (3) an increase in the number and size of Golgi-associated very low density lipoprotein particles in hepatocytes. These combined results suggest that corticosteroids induce hyperlipoproteinemia through increased hepatic production of very low density lipoproteins.


Idiopathic arthropathy of the elbow.

Idiopathic arthropathy of the elbow.


Changes of gangliosides and other lipids in skeletal muscle from rabbits with experimental dystrophy. Comparison of the skeletal muscles from vitamin E-deficient and control rabbits showed that the muscles from the deficient animals had lower contents of protein and glycogen but more water and lipid. Increases of individual lipids per unit weight of muscle from deficient animals compared with those from control animals were 2.2-fold for gangliosides, 2.18-fold for cholesterol, 1.74-fold for sulfatides, and 1.45-fold for neutral glycosylceramides. Total phospholipids did not change; this was the result of an increase in sphingomyelin (1.47-fold) and a decrease of phosphatidylcholine to 83% of the control, while the other fractions remained unchanged. When the measurements were referred to total muscle, the contents of cholesterol, gangliosides, sulfatides, neutral glycosylceramides, and sphingomyelin in muscle from vitamin E-deficient rabbits were also above those of the control rabbits, and only the phosphatidylcholine content was decreased. It was not possible to determine whether the alteration of lipid content preceded or followed the onset of signs of muscular dystrophy.


Synthesis and biological activity of 9-beta-D-arabinofuranosyladenine cyclic 3',5'-phosphate and 9-beta-D-arabinofuranosylguanine cyclic 3',5'-phosphate.


Angiotensin II analogs. 11. Further studies on des-aspartyl-angiotensin II.


Antiviral agents. 1-Aralkyloxyadenosines.


13-Alkylpyrimidine nucleosides. Preparation and properties of 5-ethyl-2'-deoxycytidine and related nucleosides.


Phospholipases. I. Effect of n-alkanols on the rate of enzymatic hydrolysis of egg phosphatidylcholine.


Phospholipases. II. Enzymatic hydrolysis of lecithin: effects of structure, cholesterol content, and sonication.


Antipseudomonal effect of polymyxin and phenylethanol.


The anatomy of the parotoid gland in Bufonidae with some histochemical findings. I. Bufo marinus.


Carcinoma of the adrenal gland in children.


Evidence for the action of d-lysergic acid diethylamide, mescaline and bufotenine on 5-hydroxytryptamine receptors in umbilical vasculature.


The effects of dibutyryl cyclic adenosine 3',5'-monophosphate, theophylline and aminophylline on neuromuscular transmission in the rat.


The elimination of 5-hydroxyindoleacetic acid from cerebrospinal fluid: characteristics of the acid transport system of the choroid plexus.


Clostridium perfringens exotoxins. II. Purification and some properties of theta-toxin.


Establishment of two inbred strains of the rat for cancer research in tissue culture.


Release of renal prostaglandin by catecholamines: relationship to renal endocrine function.


Salmonella typhimurium mutants affecting establishment of lysogeny.


Interactions among genes controlling sensitivity to radiation and alkylation in yeast.


Pathobiology of nucleocytoplasmic exchange.


Intercellular junctions in normal and in malignant cells.


Viral and immunologic studies of human neoplasms.


Cellular DNA replication in viral infection.


Arterial infusion chemotherapy of hepatoma.


Thyroidography and thyrolymphography.

Thyroidography and thyrolymphography.


A myoelectric hand splint.

A myoelectric hand splint.


Isolation of an electrophoretically homogeneous glucomannan, using glutaraldehyde-insolubilised concanavalin A.


Photo-affinity labelling of carbohydrate-binding sites in proteins: synthesis of potential inhibitors.


Physiologic and pharmacologic roles for prostaglandins in obstetrics.


Sound deprivation causes hypertension in rats.


Early stages in estrogen control of gene expression and its derangement in cancer.


Microsomal membranes and the translational apparatus of eukaryotic cells.


Solubilization and cellular fatty change.


Virologic and immunologic aspects of major oral ulcerations.


Rare combinations of multiple primary tumours: report of two cases.


Bilateral granular cell myoblastoma of the lip: report of case.


A child with multiple congenital malformations and a 46,XX,t(Bq+;Dq-)-45,XX,-B,-D,+der(B),t(Bq+;Dq-) karyotype.


Influence of hormone therapy on rats treated with the carcinogen ethylmethanesulphonate.


Analysis of morphophysiological developmental processes in mammalian brain.


Water insoluble and soluble glucans produced by extracellular glycosyltransferases from Streptococcus mutans.


The surgical treatment of occult insulinomas: a review of the problem.


Endocrine pancreatic islet disease with diarrhea. Report of a case due to diffuse hyperplasia of nonbeta islet tissue with a review of 54 additional cases.


Clinical evaluations of a histologic examination of the side effects of myelographic contrast media.


Preliminary experience of bone scanning with 99mTc-labelled polyphosphate in malignant disease.


Antiviral antibody responses in patients with renal diseases.


Further evidence for the pool function of ubiquinone as derived from the inhibition of the electron transport by antimycin.


Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study.


Structural properties of the creatine-kinase active site studied by chromophoric-reagent labelling.


Homology between enterotoxin protein and spore structural protein in Clostridium perfringens type A.


Precursor--product relationship of encephalomyocarditis virus-specific polypeptides. Comparisons by tryptic peptide mapping.


Purification, subunit structure and properties of two repressible phosphohydrolases of Bacillus subtilis.


Mutations in the L-arabinose operon of Escherichia coli B-r that result in hypersensitivity to catabolite repression. Two independent mutants resistant to l-arabinose inhibition only in the presence of d-glucose were isolated from an l-arabinose-sensitive strain containing the araD139 mutation. Preliminary mapping studies indicate that these mutations are closely linked to the araIOC region. Addition of d-glucose to growing cultures of these mutants results in a 95 to 98% repression of ara operon expression, as compared to a 50% repression of the parental control. Since cultures of both mutant and parental strains undergo a 50% repression of lac operon expression upon addition of glucose, the hypersensitivity to catabolite repression exhibited by these mutants is specific for the ara operon. Addition of cyclic adenosine monophosphate reverses the catabolite repression of the ara operon in both mutant and parent strains to 70 to 80% of the control. It is suggested that in these mutants the affinity of the ara operon initiator region for the cAMP-catabolite-activator protein complex may have been altered.


Genetic polymorphisms in Finno-Ugrian populations. Finns, Lapps and Maris.


Polymorphic traits in peoples of Eastern Asia and the Pacific.


Investigation of genetic polymorphic traits in jews. A contribution to the study of population genetics.


Derepressed levels of the isoleucine-valine and leucine enzymes in his T 1504, a strain of Salmonella typhimurium with altered leucine transfer ribonucleic acid. A hisT mutant of Salmonella typhimurium was found to have altered regulation of the isoleucine-valine and leucine enzymes. These enzymes in the hisT strain were derepressed two- to eightfold over those of the parent wild-type strain when grown in minimal medium or under repressing conditions. The amount of tRNA(Leu) and the cellular concentration of charged tRNA(Leu) was about the same in the hisT strain and in the wild type. However, leucyl-tRNA from the mutant was chromatographically different from that of wild type, confirming previous reports that hisT strains have altered tRNA(Leu). These results suggest strongly that tRNA(Leu) is involved in repression of the isoleucine-valine and leucine enzymes in S. typhimurium.


Isolation and complementation of mutants in galactose taxis and transport. By using a new screening method, we have obtained 43 new Escherichia coli mutants defective in ring formation on galactose swarm plates, which score for defects in chemotaxis or transport. They were complemented and compared with mutations previously known to lie in the galactose-binding protein or the beta-methylgalactoside (mgl) permease, or both. The mutations were all found to lie in three genes, called mglA, mglB, and mglC. mglB codes for the gene specifying the binding protein. Based on co-transduction experiments, mglA, mglB, and mglC lie close to each other on the bacterial chromosome.


Thalassemia types among Kurdish Jews.

Thalassemia types among Kurdish Jews.


Ethylene glycol-induced alteration of conidial germination in Neurospora crassa. In nutrient medium containing 3.22 M ethylene glycol or glycerol, conidia of Neurospora crassa grow as single cells, without forming the germ tubes characteristic of normal morphological germination. Ethylene glycol is more effective than glycerol in producing this response. After growth in ethylene glycol medium for a suitable time, the cells are easily disrupted by an abrupt decrease in osmotic pressure. Osmotic disruption yields intact nuclei and mitochondria, although mitochondrial fractions obtained in this way show significantly reduced concentrations of cytochromes c + c(1), as compared to those observed for comparable fractions obtained from vegetative hyphae. Cell cultures gradually adapted to lower concentrations of the glycol show a much higher degree of synchrony in the formation of germ tubes than do untreated conidia.


Properties of mutants in galactose taxis and transport. beta-Methylgalactoside (mgl) permease mutants of Escherichia coli, which are defective in three genes, mglA, mglB, and mglC, were assayed for galactose taxis and galactose transport. The mglB product is the galactose-binding protein. Previous evidence, supported by our new findings, shows that the galactose-binding protein is the recognition component for galactose taxis as well as for galactose transport. Most mutants defective in mglB showed strong effects on both chemotaxis and transport; however, a couple showed effects chiefly on one process or the other, thus allowing a separation of chemotaxis and transport. The mglA and mglC products have not yet been identified, but they must be components of the galactose transport machinery since mutants defective in mglA or mglC, or both, showed strongly reduced transport. Although some of these mutants showed little chemotaxis, most gave close to wild-type chemotactic responses. Thus, transport is not required for galactose taxis. The bacteria detect changes in the fraction of binding protein associated with galactose, not changes in the rate of transport.


Biochemical aspects of the pathogenesis of the thalassemia syndromes.


Cyclic adenosine 3',5'-monophosphate and morphogenesis in Mucor racemosus. Yeastlike cells of Mucor racemosus grown under 100% CO(2) underwent morphogenesis to hyphae after exposure to air. The addition of dibutyryl cyclic adenosine monophosphate (dbcAMP) to yeastlike cultures inhibited this morphogenesis in media containing 2% glucose. The maintenance of uniformly spherical, budding cells required 1 mM dbcAMP in a defined medium containing Casamino Acids, and 3 mM dbcAMP in a medium containing yeast extract and peptone. At these concentrations, dbcAMP also induced yeastlike development in young aerobic hyphae grown in media containing 2% glucose. Removal of dbcAMP resulted in hyphal development. The endogenous cyclic AMP (cAMP) content of yeastlike cultures was measured after a shift from CO(2) to air. A fourfold decrease in intracellular cAMP preceded the appearance of hyphal germ tubes. These results indicate that cAMP plays a role in the control of morphogenesis in Mucor racemosus.


Studies of polymorphic traits for the characterization of populations. African populations south of the Sahara.


Genetic control of the 2-keto-3-deoxy-d-gluconate metabolism in Escherichia coli K-12: kdg regulon. 2-Keto-3-deoxy-gluconate (KDG), an intermediate of the hexuronate pathway in Escherichia coli K-12, is utilized as the sole carbon source only in strains derepressed for the specific KDG-uptake system. KDG is metabolized to pyruvate and glyceraldehyde-3-phosphate via the inducible enzymes KDG-kinase and 2-keto-3-deoxy-6-phosphate-gluconate (KDPG) aldolase. However, another inducible pathway, where the KDG is the branch point, has been demonstrated. Genetic studies of the KDG degradative pathway reported in this paper led to the location of KDG kinase-negative and pleiotropic constitutive mutations. The kdgK locus, presumably the structural gene of the kinase, occurs at min 69 and is co-transducible with xyl. The mutants, simultaneously constitutive for the uptake, kinase, and aldolase, define a kdgR locus at min 36 between the co-transducible markers kdgA and oldD. As to the nature of the control exerted by the kdgR product, we have shown the following. (i) Thermosensitive mutants of the kdgR locus are inducible at low temperature but derepressed at 42 C for the three operons-kdgT (transport system), kdgK, and kdgA (KDPG aldolase). (ii) The kdgR(+) allele is dominant to the kdgR constitutive allele. (iii) A deletion in kdgA extending into the regulatory gene, kdgR, leads to a constitutive expression of the nondeleted operons-kdgT and kdgK. These properties demonstrate that the kdg regulon is negatively controlled by the kdgR product. It is presumed that differences in operator and in promotor structures could explain the strong decoordination, respectively, in the induction and catabolic repression, of these three enzymes activities.


Residual polarity and transcription-translation coupling during recovery from chloramphenicol or fusidic acid. Fusidic acid or chloramphenicol was used to inhibit peptide synthesis to 1% of normal in Escherichia coli B, strain AS19. After 10 min of inhibition, peptide synthesis could be quickly restored to 80% of the normal rate after washing the bacteria on a filter. However, even in the presence of adenosine 3'-5'-cyclic-monophosphoric acid to block catabolite repression, beta-galactosidase, the first enzyme of the lactose operon (lac), could only be induced to 10% of normal, and the last enzyme of the operon, galactoside acetyltransferase, even less. The first and last enzymes of the operon for tryptophan synthesis could be derepressed to about 30% of normal. The lac ribonucleic acid (RNA) induced during recovery showed a smaller than normal size distribution on sucrose gradients. The operator-proximal or -distal parts of this RNA were specifically labeled. Hybridization to phi80dlac deoxyribonucleic acid (DNA) suggested that although the distal parts of the lac RNA were barely detectable, initiation was occurring at normal rates in recovery. Either normal levels of distal messenger RNA (mRNA) are made but then rapidly degraded or the mRNA is not completed. The small amount that is made decayed abnormally slowly, probably as a result of slower transcription. Total mRNA decay was multiphasic with all components decaying slower than normal. We propose that there is a residual level of inhibition of peptide synthesis during recovery. The probability that a ribosome is blocked at any codon can be estimated from the data. The longer the message, the less likely its complete translation. We propose that the RNA polymerase can transcribe translatable mRNA for only a finite distance beyond the lead ribosome. Because ribosomes can load at the start of each message in a polycistronic mRNA, the probability that a distal message will be synthesized and translated is a function of the number of more proximal messages and the distances between their ribosome-loading sites.


Binding of streptococcal competence factor by the spheroplast membrane of a group H streptococcus. The binding of streptococcal competence factor (CF) was found to be specific for a strain of streptococcus which was capable of undergoing competence induction. Three other streptococcal strains which could not be induced to competence, did not bind CF. CF binding was independent of time, temperature, age of the culture, and type of growth media employed. Several observations indicated that the receptor sites for CF are located in the bacterial membrane: (i) the retention of CF by spheroplasts, (ii) the binding of CF by isolated membrane fractions, and (iii), the degradation of CF binding capacity of membranes by different chemicals and enzymes.


Globin synthesis in alpha- and beta-thalassemia.


Distribution of certain polymorphic traits in populations of the Indian peninsula and South Asia.


Studies of polymorphic traits for the characterization of populations. The populations of Scandinavia.


Histidyl-transfer ribonucleic acid synthetase in positive control of the histidine operon in Salmonella typhimurium. Histidyl-transfer ribonucleic acid (tRNA) synthetase (HRS), coded by the hisS gene, appears to play two roles in regulation of the histidine operon of Salmonella typhimurium: (i) in synthesis of a critical effector molecule, histidyl-tRNA, and (ii) a more direct effect elicited by the presence of the enzyme protein itself. The specific activity of HRS was elevated either by mutations in the strB locus or in hisS(+) merodiploids of Escherichia coli/S. typhimurium and S. abony/S. typhimurium. In each case, an increase in HRS was accompanied by an increase in histidine operon expression, indicating that HRS may be involved in positive control of the histidine operon. It is unlikely that HRS leads to increased histidine operon expression merely by acting as a "sponge" for charged tRNA. Rather, HRS appears to influence operon expression by interaction with some effector molecule other than charged tRNA or by a direct interaction with the histidine operator-promoter region. The functional level of histidine operon expression has no effect on HRS specific activity.


Studies of respiratory components and oxidative phosphorylation in mitochondria of mi-1 Neurospora crassa. Oxidative phosphorylation has been demonstrated with mitochondria of the mi-1 respiratory mutant of Neurospora crassa. The P/O ratios observed with these mitochondria were approximately 0.8 with citrate and 0.4 with either externally added reduced nicotinamide adenine dinucleotide (NADH), succinate, or ascorbate-tetramethyl-p-phenylenediamine (TPD). These P/O ratios suggest that there are only two sites of phosphorylation in mitochondria isolated from young (20 to 24 h) cultures of the mi-1 mutant. The energy-dependent reduction of NAD(+) with succinate and the phosphorylation associated with ascorbate-TPD oxidation indicate that the first and the third sites of energy coupling are present in this mutant. Difference spectra of mitochondria from young cultures of the mi-1 mutant revealed the presence of cytochrome c. Cytochromes b and a + a(3) were not detected. However, in the presence of antimycin A, a small peak in the Soret region at 430 nm was observed. A carbon monoxide difference spectrum revealed the presence of a component of the respiratory chain with a spectrum similar to that of cytochrome o. It is of interest that respiratory inhibitors such as antimycin A, 2-n-nonylhydroxyquinoline N-oxide, and cyanide abolished phosphorylation but only partially inhibited oxidation. It is postulated that the mi-1 respiratory system contains two pathways of electron transport-the first is associated with a phosphorylating pathway, whereas the second is a non-phosphorylating electron transport pathway.


D-lysine catabolic pathway in Pseudomonas putida: interrelations with L-lysine catabolism. The isolation of several mutant strains blocked in l-lysine degradation has permitted an assessment of the physiological significance of enzymatic reactions related to lysine metabolism in Pseudomonas putida. Additional studies with intact cells involved labeling of metabolic intermediates from radioactive l- or d-lysine, and patterns of enzyme induction in both wild-type and mutant strains. These studies lead to the conclusions that from l-lysine, the obligatory pathway is via delta-aminovaleramide, delta-aminovalerate, glutaric semialdehyde, and glutarate, and that no alternative pathways from l-lysine exist in our strain. A distinct pathway from d-lysine proceeds via Delta(1)-piperideine-2-carboxylate, l-pipecolate, and Delta(1)-piperideine-6-carboxylate (alpha-aminoadipic semialdehyde). The two pathways are independent in the sense that certain mutants, unable to grow on l-lysine, grow at wild-type rates of d-lysine, utilizing the same intermediates as the wild type, as inferred from labeling studies. This finding implies that lysine racemase in our strain, while detectable in cell extracts, is not physiologically functional in intact cells at a rate that would permit growth of mutants blocked in the l-lysine pathway. Pipecolate oxidase, a d-lysine-related enzyme, is induced by d-lysine and less efficiently by l-lysine. Aminooxyacetate virtually abolishes the inducing activity of l-lysine for this enzyme, suggesting that lysine racemase, although functionally inactive for growth purposes, may still have regulatory significance in permitting cross-induction of d-lysine-related enzymes by l-lysine, and vice versa. This finding suggests a mechanism in bacteria for maintaining regulatory patterns in pathways that may have lost their capacity to support growth. In addition, enzymatic studies are reported which implicate Delta(1)-piperideine-2-carboxylate reductase as an early step in the d-lysine pathway.


Further studies on the behavioural and biochemical interaction between caffeine and L-DOPA.


Metabolism of D-arabinose by Escherichia coli B-r. The pathway for d-arabinose metabolism in Escherichia coli B/r has been determined. Evidence is presented to support the following metabolic scheme: d-arabinose d-ribulose right harpoon-up d-ribulose-5-phosphate d-xylulose-5-phosphate.


Antagonism by DL-threo-DOPS of the suppression of a conditioned avoidance response induced by a dopamine-beta-hydroxylase inhibitor.


The effects of perlapine on sleep.

The effects of perlapine on sleep.


Development of cell lines after exposure of chicken embryonic fibroblasts to herpes simplex virus type 2 at supraoptimal temperature.


Metal complex formation and its importance for enzyme regulation.


Herpes simplex virus latency in SV40 hamster tumour cells.


Measurement of personal exposure to 1,1,1-trichloroethane and trichloroethylene using an inexpensive sampling device and battery-operated pump.


Inhibition of virus multiplication by partially hydrolysed RNA: a possible membrane-effect.


Standard quartz dq12 greater than 5 micro m for experimental pneumoconiosis research projects in the Federal Republic of Germany.


Tyrosine crystals in pleomorphic adenomas of the salivary gland.


Letter: Congenital mesoblastic nephroma.


Virus excretion in smallpox. 1. Excretion in the throat, urine, and conjunctiva of patients. Excretion of virus in the throat, urine, and conjunctiva of smallpox patients was studied daily for 2-3 weeks after the onset of fever. The virus titre in the throat and urine of haemorrhagic and confluent cases was higher than in discrete cases. The duration of virus excretion was also greater in confluent cases than in discrete cases. Conjunctival swabs from all 12 smallpox patients with conjunctivitis were positive for virus. The duration and titre of virus excretion in the throat, urine, and conjunctiva of patients were not related to their age or sex and did not depend on whether or not they had received a primary vaccination.


Virus excretion in smallpox. 2. Excretion in the throats of household contacts. Throat swabs of 34 of 328 family contacts of 52 smallpox cases, examined 4-8 days after the onset of the disease in the family, were positive for variola virus. The log titre of virus per swab ranged from 2 to 3.95. A higher proportion of unvaccinated than of vaccinated contacts excreted the virus. Only 4 of the virus-positive contacts developed clinical smallpox; this occurred 5-7 days after their swabs were examined. Excretion of virus in the throats of these contacts, a few of whom were in the incubation period of the disease, suggests the possibility that they could have spread the infection. This possibility, if kept in mind, may help in tracing the source of infection or in determining the incubation period in a few instances when difficulty is experienced.


Evaluation of virological laboratory methods for smallpox diagnosis. Between July 1966 and May 1972 the Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Ga., USA, tested specimens from 849 suspected smallpox cases by at least 2 methods, electron microscopy and chick embryo chorioallantoic membrane (CAM) cultures. A smaller number of specimens was tested by each of 4 methods: electron microscopy, CAM culture, agar gel precipitation, and tissue culture. For specimens handled in the field the CAM culture method was less sensitive than electron microscopy because the adverse conditions often inactivated the virus. CAM cultures were valuable for identifying members of the poxvirus subgroups, however, particularly when supplemented by tissue culture. The agar gel precipitation test was the least sensitive but was of value in confirming the results of electron microscopy. The latter was highly effective for the diagnosis of varicella, but dependably identified only about half of the vaccinia infections; for vaccinia, the CAM technique was essential. The occurrence of human monkeypox cases in West Africa emphasized that the usual smallpox diagnostic methods were inadequate. More sophisticated tests, such as the rabbit dermal sensitivity test, are necessary for accurate diagnosis of these cases as monkeypox.


Effects of insulin, glucagon and adrenocorticotrophin on the levels of corticosteroids, noradrenaline, adrenaline and ascorbic acid in the adrenal glands of cats.


Metabolite synthesis by rat liver cells and rat liver mitochondria.


Characterization of poliovirus isolates in Japan after the mass vaccination with live oral poliomyelitis vaccine (Sabin). From 1962 to 1968, 127 poliovirus isolates (92 from clinical specimens and 35 from healthy subjects) were subjected to intratypic serodifferentiation by the modified Wecker and McBride techniques. The two techniques gave concordant results for 103 strains, 91 of which were classified as vaccine-like, 9 as nonvaccine-like, and 3 as intermediate; 20 were classified as vaccine-like by one technique and as intermediate by the other, and 4 as nonvaccine-like by one technique and as intermediate by the other. The origin of the nonvaccine-like strains is unknown, but it is unlikely that they had been circulating in the community long. An rct/40-marker test of the isolates revealed a higher positivity rate than that found in field trials of Sabin vaccine. The results indicate that wild poliovirus has been almost completely eradicated from Japan.


The cyclic AMP content and karyotype of the somatic hybrids of mouse malignant and nonmalignant cells segregating in vivo and in vitro.


Cystosarcoma phyllodes--a study of 13 cases.


A study of the relationship of virus-like particles and Australia antigen in liver.


Scleroma affecting the middle ear cavity with report of three cases.


Alpha fetoprotein levels in women taking oral contraceptives.


Glomus jugulare tumors. II. A clinicopathologic analysis of the effects of radiotherapy.


Use of cyclofenil (Sexovid) to induce ovulation.


Evaluation of endometrial biopsy in the cycle of conception.


Sub-clinical endometrial inflammation and T-mycoplasma: a possible cause of human reproductive failure.


Anti-Epstein Barr virus antibody in nasopharyngeal carcinoma.


A modified in vitro spermatozoal penenetration test. I. Method.


A modified in vitro spermatozoal penetration test. II. Application in fertility investigations.


Clinical trial and laboratory investigation of a low-dose progestogen-only contraceptive--Exluton.


Characteristics of infection by RSV. I. Non-requirement for the S phase of cellular DNA synthesis.


Characteristics of infection by RSV. II. Dependence on cell events which can occur in the G2 phase and after mitosis.


Studies on a heat-labile variola virus inhibitor in normal sera. I. Detection by the variola focus reduction assay and its general characteristics.


Studies on a heat-labile variola virus inhibitor in normal sera. II. Further characterization of the inhibitor and its activity.


Migraines in childhood.

Migraines in childhood.


Factors associated with deterioration of kidney function in patients with spinal cord injury.


Chondroma of the tibia.

Chondroma of the tibia.


Hyperlipidemia in experimental disseminated intravascular coagulation.


Renal blood flow in the dog. Autoregulation and intrarenal distribution.


Studies on sedimentation characteristics of heterogeneous nuclear RNA.


Formation of choline from phospholipid precursors: a comparison of the enzymes involved in phospholipid catabolism in the brain of the rhesus monkey.


Inhibition of glycolytic metabolism and sleep-waking states in cats.


Spin echo nuclear magnetic resonance in cancerous tissue.


The protein neurotoxins in scorpion and elapid snake venoms.


Intra-arterial hepatography: experimental evaluation of a new contrast agent.


Pharmacoangiography with angiotensin.

Pharmacoangiography with angiotensin.


Poliovirus type 3 isolation from infants with respiratory diseases.


A clinical approach to pain.

A clinical approach to pain.


Mixed leukocyte culture reactions with man-mouse hybrid cells.


Cell-mediated antitumor immune reactions under syngeneic conditions.


Drinking in the monkey evoked by nicotine or angiotensin II microinjected in hypothalamic and mesencephalic sites.


Virus plaque assay and enumeration of effector cells in mixed lymphocyte cultures.


Correlation of MLC reactivity after experimental and clinical transplantation. Virus and cytophilic antibody: sources of false negatives.


Sensitivity of Azotobacter chroococcum to some antibiotics.


Sleep-waking patterns in cats after administration of fenfluramine and other monoaminergic modulating drugs.


Increased production of cyclic AMP in mechanically stressed alveolar bone in cats.


Reactive granular cells in sites of trauma. A cytochemical and ultrastructural study.


Mitochondrial conformation and swelling-contraction reactivity during early liver regeneration. Studies of mitochondrial respiratory control and swelling contraction activity during early cell regeneration after partial hepatectomy have revealed a selective defect in the rate of substrate-supported, phosphate-induced mitochondrial swelling. Swelling profiles induced by Fe(2-) or Cu(2-) revealed no differences between sham-operated and partially hepatectomized mice, which suggests no defects in -SH group composition or ability to form lipid peroxides. The specific activity of mitochondrial cytochrome c oxidase was unchanged. There was no significant mitochondrial swelling in situ as determined from mitocrit and mitochondrial protein ratios. A significant decline in respiratory control and efficiency of oxidative phosphorylation was found in mitochondria from animals 8 and 24 hours after partial hepatectomy, partially reversed by bovine serum albumin. No significant change in ADP:O ratio was noted and the decrease in RCI was due primarily to a significant decline in state 3 respiration rate. In situ electron microscopic studies of mitochondria failed to reveal significant abnormalities during early cell regeneration apart from decrease in numbers of matrix granules, focal matrix rarefaction and predominance of round forms. Electron microscopic studies of mitochondria after in vitro phosphate-induced swelling experiments showed no differences between sham and partially hepatectomized animals, but revealed two distinct populations of mitochondria, the predominant form (type III) showing distortion, matrix lucency and outer membrane rupture. ATP induced a diminished reversal in light scattering in partially hepatectomized mitochondria even when examined at 20 minutes, manifested as an increase in numbers of orthodox mitochondrial forms at the expense of the swollen type III forms. The pathogenesis of the impaired respiratory control and phosphate-induced swelling is unknown, but analogous observations have been found in mitochondria harvested from cells in which abnormal accumulations of free fatty acids have been demonstrated.


Formation of multinucleate giant cells in organized epitheloid cell granulomas. Organized epithelioid cell granulomas were produced experimentally by injecting intradermally dilute suspensions of zirconium and beryllium salts into individuals who had been previously sensitized to these metals. Biopsies were obtained at intervals of between 5 days and 13 months later, and the specimens were fixed and prepared for light and electron microscopy. Tritiated thymidine was injected into a number of the granulomas; the biopsy specimens were secured from 40 minutes to 2 or more weeks later, and the tissues were processed for light microscopic autoradiography. Giant cells occurred commonly, both within organized tubercles and in relation to areas of necrosis, and had markedly different cytoplasmic features from typical secretory epithelioid cells which enabled them to be readily recognized at scanning magnifications. The characteristic hallmark of these giant cells was the presence of myriads of small mitochondria adjacent to nuclei with numerous membrane-lined vesicles in the center of the cell. Giant cells occurred mainly in edematous disrupted tubercles. In these tubercles, epithelioid cells contained cytoplasmic components more like giant cells. Direct evidence of cell fusion was not seen, although fusion of membranes seemed to occur between cells having similar cytoplasmic features. The failure to find labeled nuclei in any giant cells 40 minutes after injection of tritiated thymidine indicates that normal nuclear division does not occur within giant cells. We postulate that epithelioid cells containing vesicles develop in damaged and necrotic areas, and that mainly this type of epithelioid cell fuses to form giant cells.


Electron microscopic and chemical studies of the vascular changes and edema of lead encephalopathy. A comparative study of the human and experimental disease. Lead encephalopathy was induced in suckling rats by administering lead to the mother. The brains were studied by light and electron microscopy, and the results were compared with observations in the human disease as well as in cases of cerebral ischemia in children. In their severe forms, both human and experimental lead encephalopathies are characterized by exudative extracellular edema and perivascular PAS-positive globules. The latter consist of osmiophilic non-membrane-limited cytoplasmic inclusions located, in the rat exclusively and in the human predominantly, in perivascular astrocytes. Intervascular strands are also found in both forms of the disease. In the rat these consist of basement membrane surrounding endothelial cytoplasm. Chemically, experimental lead encephalopathy with morphologically demonstrable edema is associated with an increase in brain water, sodium and serum albumin. Relative to the serum concentration, the increase in water is disproportionately greater than the sodium or albumin. There were no demonstrable changes in chloride or potassium.


Separation of cells having histochemically demonstrable glucose-6-phosphatase from suspensions of hamster kidney cells in an isokinetic density gradient of Ficoll in tissue culture medium. Suspensions of enzymatically disaggregated hamster kidney cells were separated primarily according to differences in diameter using velocity sedimentation in a previously described isokinetic density gradient and according to differences in density in an isopycnic density gradient. Cells which contained histochemically demonstrable glucose-6-phosphatase were thought to be cells from proximal tubules and constituted 46.5 +/- 14.1% of the cells in the starting sample suspension of disaggregated kidney cells. The purest gradient fractions from experiments using velocity sedimentation contained 98.0 +/- 0.6% cells which demonstrated glucose-6-phosphatase activity. More than 99.0% of these cells excluded trypan blue. Isopycnic sedimentation was not an effective means of purifying proximal tubule cells.


Lesions of the islets of Langerhans in encephalomyocarditis virus-infected mice with diabetes mellitus-like disease. I. Acute lesions. Mice infected with the M variant of the encephalomyocarditis (EMC) virus develop lesions of the islets of Langerhans associated with a diabetes mellitus-like disease. Ultrastructural alterations become evident in capillaries and beta cells at a time when large amounts of virus are present in the pancreatic tissue. Although some beta cells become necrotic, degranulation and contraction of intact cells is the prominent lesion. Changes in the capillaries appear early in the course of the infection and later are associated with interstitial fibrosis in and around the islets. During early convalescence, beta cells are degranulated and exhibit striking alterations of cytoplasmic organelles. These changes appear to be consequent to increased metabolic activity by the residual insular tissue. Interestingly enough, specific lesions of the alpha cells are not observed.


Clinical evaluation of live, oral types 1, 2, and 5 adenovirus vaccines.


Histopathology of early myocardial infarcts. A new approach. The histopathology of human myocardial infarcts is reviewed in a series of 46 cases ranging from sudden death to a clinical age of 3 days. A set of histopathologic features is described whereby the diagnosis of acute myocardial infarction can be made, even in cases of sudden death, on routine sections and even after considerable autolysis. This is primarily a stretching and waviness of the myocardial fibers, especially at the border of the infarcted area. Its mechanism is probably twofold: the rythmical pull exerted by the normal myocardium against the infarcted paralyzed area and the outward bulging of this area at every systole. On the basis of human material alone, it may be inferred that this pattern develops very rapidly: surely less than 1 hour and perhaps a few minutes after the local circulation has failed.


Airways function during mild viral respiratory illnesses. The effect of rhinovirus infection in cigarette smokers.


Moderate ethanol ingestion and plasma triglyceride levels. A study in normal and hypertriglyceridemic persons.


Hypercalcemia in bronchogenic carcinoma. A prospective study of 200 patients.


1,25 Dihydroxy-vitamin D3 in normal man and patients with renal failure.


Letter: Hypercalcemia and streptozotocin.


Letter: Hypercalcemia and streptozotocin. In comment.


Electron spinal resonance analysis of the nitroxide spin label 2,2,6,6-tetramethylpipidone-N-oxyl (Tempone) in single crystals of the reduced Tempone matrix. The nitroxide spin label Tempone (2,2,6,6-tetramethylpiperidone-N-oxyl) can be reduced with ascorbic acid to give a nonparamagnetic species. Single crystals of reduced Tempone serve as a suitable host matrix to orient trace quantities of Tempone for ESR analysis. In these crystals the majority of the Tempone molecules are well-oriented, but a smaller fraction of the molecules tumble freely to give an isotropic electron spin resonance (ESR) spectrum. ESR transitions for the oriented molecules are saturated at much lower microwave power levels than for the tumbling molecules. For the oriented molecules, an analysis of the anisotropy of the spectroscopic splitting factor (g) gives principal values of g(1) = 2.0094, g(2) = 2.0061, g(3) = 2.0021. The hyperfine coupling tensor is nearly axially symmetric, with principal values (in gauss) of A(1) = 6.5, A(2) = 6.7, A(3) = 33.0. Within experimental error, the principal axis systems for the g tensor and the hyperfine tensor are identical. Comparison of the average values of g and A with the isotropic values of these parameters for Tempone in solvents of different polarity suggests a method for choosing the most appropriate tensor elements to be used for spin label experiments in various solvent systems.


Sequential enzymolysis of ligament and resultant stress-strain behavior.


Electrochemical properties of hydrated cation-selective glass membrane. A model of K+ and Na+ transport. Electrochemical properties of cation-selective glass microelectrodes made from NAS(27-04) were studied. There was a marked fall in electrical resistance of the microelectrodes stored in 3 M KCl solution (aging). The resistance was in the range of 2 x 10(7) to 10(9) Omega, which were much lower than those estimated from the electrical resistivity of dry glass for the equivalent dimensions of microelectrode working tips. This fall in resistance was accompanied by an increase in microelectrode selectivity for K(+). The low resistance and increased K(+) selectivity are desirable features that make the microelectrode more suitable for application to biologic studies. The changes in microelectrode resistance and selectivity were interpreted to be due to hydration of the entire thickness of the glass membrane, resulting in a change in the field strength of anionic sites and formation of ionic channels in the glass membrane. Thus, the fall in resistance is explained by decrease in energy barrier, which is equivalent to the activation energy of interaction between the cations and anionic sites in the glass membrane. Some of the microelectrodes showed a transient depolarization that resembled the action potential of a biological membrane. This transient depolarization was associated with the changes in microelectrode resistance and selectivity. The transient depolarizations suggest the temporary development of wide channels in the membrane permitting free movement of hydrated cations according to the bulk electrochemical gradient.


Letter: Type IV hyperlipidaemia in cord blood.


Plasma testosterone: an accurate monitor of hormone treatment in prostatic cancer.


The effect of diphenylhydantoin on insulin response.


Affinity of calciferol analogues for 25-hydroxycholecalciferol receptors.


Effects of angiotensin on plasma electrolyte concentrations in rabbits and in man.


Proceedings: Pressor sensitivity to angiotensin II in relation to sodium.


The effect of modifying the combination of insulin with rat adipose cells on the intracellular levels of cyclic AMP.


The effect of a distant reparative process on rat liver function.


Effects of sodium, angiotensin, and steroids on vascular reactivity in man.


Derivation of TK- clones from revertant TK+ mammalian cells. In order to obtain a large collection of Chinese hamster cell clones defective in thymidine kinase (TK(-)), BrdU(r) selection experiments have been performed on wild-type and revertant TK(+) cell lines. No clones (< 10(-9)) were obtained from the wild-type TK(+) cell line by single-step selection. In contrast, revertant TK(+) clones readily gave rise to stable TK(-) derivatives (1 - 2 x 10(-4)). Both wild-type and revertant TK(+) clones spontaneously yielded 8-AG(r) colonies with the same frequency (1 - 5 x 10(-6)), suggesting that the differences between wild-type and revertant cell lines specifically affected selection of the TK(-) phenotype. The increased frequency of TK(-) clones reflects perhaps the number (ploidy) or character of the autosomal TK loci in TK(+) revertants, or perhaps the mechanisms which regulate expression of the TK genes. Several mutagens, EMS, MNNG and UV, stimulated the TK(+) revertants' frequency of TK(-) subclones only slightly (< 3-fold). Biochemical and genetic data indicated that the TK(-) clones derived from one revertant are phenotypically different. The phenotypes displayed by these cell lines are stable and do not depend upon the continued presence of the selective agent.


Low gene variation in Drosophila busckii. Study of allozyme variation in D. busckii at thirty loci gives the proportion of polymorphic loci =.166 and the proportion of loci heterozygous per individual =.044. D. busckii has a narrower seasonal and food niche than the other domestic species D. melanogaster which has more allozyme variation. It is suggested that the low gene variation in D. busckii might be due to adaptation of this species to a narrow niche.


Defective virions of herpes simplex viruses.


In vitro transcriptase activity of vesicular stomatitis virus B and T particles: analysis of product.


Resistance of hamster cells transformed by herpes simplex virus type 2 to superinfection by herpes simplex viruses.


Biochemical and biophysical characterization of calicivirus isolates from pinnipeds.


Agglutinability of Rous cells by concanavalin A: study with a temperature-sensitive RSV mutant and inhibitors of macromolecular synthesis.


Control of gene expression in rat cells transformed by a cold-sensitive murine sarcoma virus (MSV) mutant.


Differential phosphorylation and turnover of nuclear acidic proteins during the cell cycle of synchronized HeLa cells.


Binding of adenosine diphosphate by isolated membranes from human platelets.


Fish liver fructose 1,6-diphosphatase. 3. The effect of temperature on the regulatory properties of the carp (Cyprinus carpio) liver enzyme.


Nuclear protein kinases. Evidence for their heterogeneity, tissue specificity, substrate specificities, and differential responses to cyclic adenosine 3':5'-monophosphate.


Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia.


Near ultraviolet circular dichroism and absorption spectra of chicken ovomucoid and acetylated derivatives at 297 and 77 degrees K.


Properties of angiotensin II receptors in the bovine and rat adrenal cortex.


Nuclear deoxyribonucleic acid polymerase. Purification and properties of the homogeneous enzyme from human KB cells.


Induction of delta-aminolevulinic acid synthetase in isolated rat liver cell suspensions. Adenosine 3':5'-monophosphate dependence of induction by drugs.


Induced reoxidation and reactivation of a reduced uridine diphosphate galactose-4-epimerase complex.


Molecular basis of the biological function of molybdenum. Effect of tungsten on xanthine oxidase and sulfite oxidase in the rat.


The metabolism of cyclopropane fatty acids by Tetrahymena pyriformis.


Evidence for randon distribution and translational movement of cytochrome b5 in endoplasmic reticulum.


Structural analyses of mammalian ribosomal ribonucleic acid and its precursors. The distribution of polypyrimidine sequences in ribosomal 28 S ribonucleic acid.


Anomeric specificity of the alkaline form of fructose 1,6-diphosphatase from rabbit liver.


Multiple forms of flounder muscle glyceraldehyde 3-phosphate dehydrogenase. Subunit composition, properties, and tissue distribution of the forms.


Communication: Coacervation of tropoelastin results in fiber formation.


Induction of cellular immunity to herpes simplex virus: relationship to the humoral immune response.


Host response to tumor-associated fetal antigens.


In vitro immune stimulation-inhibition to spontaneous canine tumors of various histologic types.


In vitro study of antiviral activity of immune spleen cells in experimental Venezuelan equine encephalomyelitis infection in mice.


The production of interferon by malignant plasma cells from patients with multiple myeloma.


Acid lability of rhinoviruses: loss of C and D antigenicity after treatment at pH 3.0.


Immunochemical quantitation of cell bound C4.


A basis for extracellular current density analysis in cerebellar cortex.


In vivo suppression by cholera toxin of cell-mediated and foreign body inflammatory responses.


Organization of vestibular nystagmus in oblique oculomotor system.


Identification of unitary potentials in turtle cerebellum and correlations with structures in granular layer.


Observations on phase-sensitive neurons of anteroventral cochlear nucleus of the cat: nonlinearity of cochlear output.


Hepatic ultrastructural changes in murine lupinosis.


Response characteristics of single units in the rat's trigeminal nuclei to vibrissa displacements.


Ultrastructure of the alveolar-capillary wall in mitral stenosis.


Cell death in the normal neonatal rat adrenal cortex.


An ultrastructural study of the effect of ultrasound on arterial tissue.


Studies on the pathogenesis of corneal arcus formation. I. The human corneal arcus and its relation to atherosclerosis as studied by immunofluorescence.


Poliovirus antibody in urban school children.


Antibody titers to polioviruses in patients ten years after immunization with sabin vaccine.


Wilms' tumor metastasis to uncommon sites.


Fever and petechiae with adenovirus type 7 infection.


Responsiveness to flickering light in waking and sleeping infants.


A micromethod for the measurement of human plasma renin activity.


Plasma renin activity in the newly born and in young infants.


N-acetyl-2-O-methyl-tyrosine-oxytocin: a specific antagonist of oxytocin.


Drinking elicited by intracranial microinjection of angiotensin in the cat.


Treatment of chondritis in the burned ear by the local instillation of antibiotics.


Congenital epulis tumor. Case report.

Congenital epulis tumor. Case report.


6-OHDA lesions of the hypothalamus: interaction of aphagia, food palatability, set-point for weight regulation, and recovery of feeding.


Persistence of abnormal REM sleep response to ethanol as a result of previous ethanol ingestion.


Taming effect of nonnarcotic analgesics on the septal syndrome in rats.


Persistence of cadmium-induced metabolic changes in liver and kidney. Daily intraperitoneal injection of cadmium chloride (1 milligram per kilogram) for 45 days enhanced gluconeogenesis as evidenced by significant increases in the activities of liver and kidney cortex pyruvate carboxylase, phosphopyruvate carboxylase, hexosediphosphatase, and glucose-6-phosphatase, the quartet of key, rate-limiting enzymes involved in the biotransformation of noncarbohydrate precursors into glucose. Whereas cadmium treatment decreased the level of hepatic glycogen, the concentration of blood glucose and urea was significantly elevated by this heavy metal. Discontinuation of the heavy metal treatment for 28 days, in rats previously injected with cadmium for 45 days, failed to restore the observed biochemical alterations in hepatic and renal carbohydrate metabolism to control values. Evidence indicates that cadmium augments the glucose-synthesizing capacity of liver and kidney cortex and that various metabolic changes persist even after a 4-week period of withdrawal from exposure to the heavy metal.


Lever-pressing behavior caused by intraseptal angiotensin II in water satiated rats.


Intravenous infusion of hydrochloric acid for treatment of severe metabolic alkalosis.


Cold lymphocytotoxins in infections and parasitic infestations.


Bacterial pneumonia complicating adenoviral pneumonia. A comparison of respiratory tract bacterial culture sources and effectiveness of chemoprophylaxis against bacterial pneumonia.


Diagnostic and surgical aspects of insulinoma. A review of twenty-seven cases.


Studies on clonazepam, flunitrazepam, and related benzodiazepines in cat and monkey.


Effect of prostaglandin F2alpha on responses on vascular smooth muscle to serotonin, angiotensin and epinephrine.


Complement-fixing antibodies to the AD-169 strain of cytomegalovirus in banked blood.


Subcutaneous mastectomy and immediate prosthetic implantation as an alternative to simple mastectomy.


Fibrinous pseudointimas within impermeable silastic-nylon velour. I. Ultrastructure of cell components at initial stages and cell population changes in the earlier pseudointima.


Registers and registries: a review.

Registers and registries: a review.


Immunization during pregnancy against poliomyelitis and influenza in relation to childhood malignancy.


Peculiar lipid inclusions in the hepatic parenchymal cell of a patient with hereditary spherocytosis.


Stimulation of phagocytic release of neutral protease from human neutrophils by cholinergic amines and cyclic 3',5'-guanosine monophosphate.


Letter: Prevention of postsurgical ulnar neuropathy.


Homozygous type II hyperlipoproteinemia treatment. Partial ileal bypass in two children.


Ear piercing and hepatitis. Nonsterile instruments for ear piercing and the subsequent onset of viral hepatitis.


Ovarian tumors. Tumors and tumor-like conditions of the ovaries, fallopian tubes and ligaments of the uterus.


The baboon. Microbiology, clinical chemistry and some hematological aspects.


NIMH-sponsored chemical synthesis program.


Forty-day fever. An epidemic of cytomegalovirus disease in a renal transplant population. An epidemic of cytomegalovirus disease (CMV) occurred in 38 percent of 34 renal transplant recipients during an 18-month period. A characteristic clinical pattern was noted: 40 days following transplantation, daily fevers recurred for periods of four to six weeks. This fever in conjunction with a diffuse interstitial pneumonitis and impaired hepatic and renal function constituted a diagnostic tetrad. Of all the laboratory techniques, throat and urine cultures were the most consistent in confirming the diagnosis. Analysis of the epidemic implicated the communal hemodialysis unit as the source of exposure to the virus. CMV was not seen in the first 86 patients who received transplants in the program, but with increasing use of hemodialysis, the percentage of patients with positive serologic reaction for CMV increased dramatically.


Mixed mesodermal tumors of the uterus.

Mixed mesodermal tumors of the uterus. Two of five women with mixed mesodermal tumor of the uterus are well more than ten years after therapy. A third was well when last seen two years after therapy and died at age 84 but autopsy was not done. Review of the literature and the reported experience indicates that this diagnosis should be suspected more often. Since histologic features may vary from one place to another within the lesion, accurate assessment requires examination of adequate specimens of the tumor. The mere presence of heterologous elements in an endometrial carcinoma changes the five-year survival rate from 85 percent to less than 35 percent. While total abdominal hysterectomy with bilateral salpingo-oophorectomy is mandatory, radiation therapy should be added more often than in the past, as it has been clearly shown that many of these tumors are radiosensitive.


Specialty conference: potpourri of adenoviral infections.


The ubiquitous adenovirus.

The ubiquitous adenovirus.


Effect of hyper- and hypothyreosis on cytochrome oxidase and succinic dehydrogenase activities of the rat kidney.


Induced cellular autophagy in the epithelial cells of seminal vesicle of mice treated with actinomycin D.


Morphological aspects of protein synthesis.


Control of protein synthesis in anterior pituitary gland.


Protein synthesis in reproductive tissue. Transactions of the sixth symposium held in Geneva on May 21-23, 1973.


Oestrogen induced synthesis of a protein in avian liver.


Amebiasis presenting as an acute abdomen.


Milk-rejection sign of breast cancer.

Milk-rejection sign of breast cancer.


Galactography in the examination of secretory breasts.


Initiation of free radical reactions and hepatotoxicity in rats poisoned with carbon tetrachloride or bromotrichloromethane.


Effects of various mitogens on the phospholipid metabolism of human peripheral lymphocytes.


On the metabolic conversion of human plasma very low density lipoprotein to low density lipoprotein.


Metabolism of rat plasma very low density lipoprotein. II. Fate in circulation of apoprotein subunits.


Metabolism of rat plasma very low density lipoprotein. I. Fate in circulation of the whole lipoprotein.


Identification of lipoprotein families in familial lecithin: cholesterol acyltransferase deficiency.


The effect of K+ and pH on protein-dodecylsulphate complexes.


Comparative studies on adrenal iron-sulfur protein and its selenium derivatives by electron nuclear double resonance.


The intracellular distribution of the radiocopper derived from ceruloplasmin and from albumin.


Application of the fluorescent antibody technique to the diagnosis of avian encephalomyelitis. A direct fluorescent antibody test was applied to the diagnosis of avian encephalomyeltis in experimental chicks and in chicks from three natural outbreaks of the disease. Intracerebrally inoculated chicks exhibited maximum fluorescence in brain tissue during the early clinical stages of the disease and similar observations were made on natural cases. Best fluorescence was obtained with frozen sections of cerebellum and pancreas from chicks approximately three weeks of age, but after four weeks of age it was not possible to diagnose the naturally-occurring (field) disease by this method. In these cases a diagnosis of avian encephalomyelitis was confirmed by the application of the fluorescent technique to the brains of either (a) chicks which had hatched from eggs inoculated with brain homogenates from the field cases or (b) hatched chicks which had been inoculated with the homogenates by the intracerebral route.


Experimental alkylmercurial poisoning in swine. Lesions in the peripheral and central nervous systems. The effects of alkylmercurial poisoning were studied in 16 pigs poisoned with daily oral doses of a fungicide containing methylmercury 2, 3-dihydroxy propyl mercaptide and methylmercury acetate. Clinical signs included weakness, wobbling gait, blindness, recumbency and death. Microscopic studies of the peripheral nervous system revealed Wallerian degeneration in sensory fibers and neuronal degeneration in dorsal root ganglia. In the central nervous system, there were neuronal degeneration of ischemic type, glial degeneration, gliosis and necrosis of the media of meningeal arterioles. The last mentioned lesion was not extensive.The sequential development o lesions and the absence of segmental demyelination suggest that the primary lesion in the peripheral nervous system was neuronal-axonal degeneration rather than degeneration of the Schwann cell and myelin sheath.


Effects of dietary cholesterol on bile acid synthesis in liver and hepatomas.


Spectrophotometric analysis of cytochromes in rat liver during carcinogenesis.


Inhibition of purine ribonucleotide and phosphoribosyl pyrophosphate synthesis by 6-cyclopentylthio-9-hydroxymethylpurine and structurally related compounds.


Lack of syncytium formation by a type C virus-producing XC cell line in the mixed culture cytopathogenicity test.


An electron microscopic study of spontaneous and experimentally induced leukemia in ICRC mice.


Prevention of 334C murine virus-induced leukemia by transmission of maternal immunity to offspring.


Effect of a carcinogenic oral dose of 7, 12-dimethylbenz(a)anthracene on receptor binding of estradiol-17 beta in uterus and mammary tissue throughout lactation in the rat.


Effect of aminonucleoside on serum stimulation of nonhistone nuclear protein and DNA synthesis in normal and SV40-transformed human fibroblats.


Inhibition of ribosomal RNA maturation in Novikoff hepatoma cells by toyocamycin, tubercidin, and 6-thioguanosine.


Glucocorticoid receptors and mechanism of resistance in the cortisol-sensitive and -resistant lines of lymphosarcoma P1798.


Imbalance in ornithine metabolism in hepatomas of different growth rates as expressed in behavior of L-ornithine:2-oxoacid aminotransferase (ornithine transaminase, EC 2.6.1.13).


Identity of the paramagnetic element found in increased concentrations in plasma of cancer patients and its relationship to other pathological processes.


Transfer RNA base composition studies in Morris hepatomas and rat liver.


On the pathological modification of serum high density lipoproteins in liver diseases. An alteration in the binding mode of indocyanine-green with human serum proteins.


The inorganic pyrophosphatase activity associated with the forms of alkaline phosphatases isolated from human serum.


Cyclic AMP stimulated phosphorylation of erythrocyte membranes from cystic fibrosis and control subjects.


5'nucleotidase: recent advances in cell biology, methodology and clinical significance.


Computer extraction of an ultradian cycle in sleep from manually scored sleep stages.


Screening for primary liver cancer. The relationship between the time of appearance of alpha-foetoprotein in the serum and clinical symptoms in nine cases.


Glomus tumor. A case report.

Glomus tumor. A case report.


Bovine enteroviruses in the calf: an attempt at serologic, biologic, and pathologic classification.


Preslaughter treatment affecting intramuscular and plasma lipids. I. Effect of ACTH in rabbits.


Genetic manipulation of motor output in shaker mutants of Drosophila.


The derivation of plasma-free fatty acids from dietary neutral fat in man.


Leroy's l-cell disease: markedly increased activity of plasma acid hydrolases.


Some physiological and biochemical features of striated muscles reinnervated by preganglionic sympathetic fibers.


Identity of "dumbbell" profiles in synaptosomal fractions from rat brain.


Changes in the excitability of Renshaw cells due to orthodromic tetanic stimuli.


T-shaped cells of dorsal ganglia can influence the pattern of afferent discharge.


RNA viruses: the age of innocence ends.

RNA viruses: the age of innocence ends.


Visna virus infection of American lambs. Random-bred fetal and 4-week-old American lambs, inoculated intracerebrally with visna virus, developed a persistent infection in the brain and sometimes in the lung. The pathologic changes present in these lambs were similar to the early lesions of visna in Icelandic sheep, thus providing a possible model for the study of virus-induced demyelinating disease.


Congenital infections due to reovirus type 3 in hamsters.


Future directions for automated analysis.


Effect of furosemide administration and upright position on plasma renin activity and angiotensin II in hypertension.


Primary linitis plastica of the rectum. Report of two cases.


The structure of novel C35 pentacyclic terpenes from Acetobacter xylinum. A novel C(35) terpene and its monounsaturated analogue were isolated from cultures of Acetobacter xylinum, together with traces of their C(36) homologues. These substances were found to be hopane derivatives substituted by a five-carbon chain bearing four vicinal hydroxyl groups. For the parent hydrocarbon the term bacteriohopane is proposed. The elucidation of the structures utilized high-resolution mass spectrometry of the terpenes, degradation to C(32) hydrocarbons and detailed mass-spectrometric comparison of these with C(32) hydrocarbons synthesized from known pentacyclic triterpenes. High-resolution mass-spectral data of the terpenes are presented. N.m.r. data are in agreement with the proposed structures, which are further supported by the isolation from the same organism of 22-hydroxyhopane and derivative hopene(s).


The nature of the electrophoretically separable multiple forms of rat liver monoamine oxidase. 1. Treatment of a partly purified preparation of rat liver monoamine oxidase with the chaotropic agent sodium perchlorate caused the enzyme to migrate as a single band of activity of polyacrylamide-gel electrophoresis, whereas the untreated enzyme separated into a number of bands. 2. Treatment with the chaotropic agent caused no loss of enzyme activity towards benzylamine, dopamine or tyramine. 3. The activities of the untreated preparation towards different substrates were inhibited to different extents by heat treatment and by some inhibitors. No such differences could be detected after the enzyme preparation had been treated with sodium perchlorate. 4. Lipid material, which could be separated by gel filtration, was liberated from the enzyme preparation by sodium perchlorate treatment. 5. The molecular weight of the treated enzyme was found to be 380000+/-38000. 6. Perchlorate treatment altered the solubility of the enzyme. 7. A continuous assay method for monoamine oxidase is described.


The structure of a beta-(1 leads to 3)-D-glucan from yeast cell walls. Yeast glucan as normally prepared by various treatments of yeast (Saccharomyces cerevisiae) cell walls to remove mannan and glycogen is still heterogeneous. The major component (about 85%) is a branched beta-(1-->3)-glucan of high molecular weight (about 240000) containing 3% of beta-(1-->6)-glucosidic interchain linkages. The minor component is a branched beta-(1-->6)-glucan. A comparison of our results with those of other workers suggests that different glucan preparations may differ in the degree of heterogeneity and that the major beta-(1-->3)-glucan component may vary considerably in degree of branching.


The kinetics of the interconversion of intermediates of the reaction of pig muscle lactate dehydrogenase with oxidized nicotinamide-adenine dinucleotide and lactate. Oxamate competes with pyruvate for the substrate binding site on the E(NADH) complex of pig skeletal muscle lactate dehydrogenase. When this enzyme was mixed with saturating concentrations of NAD(+) and lactate in a stopped-flow rapid-reaction spectrophotometer there was no transient accumulation of enzyme complexes with the reduced nucleotide. The steady-state rate of formation of free NADH was reached within the dead-time of the instrument (3ms). When oxamate was added to inhibit the steady state and to uncouple the equilibration: [Formula: see text] through the rapid formation of E(NADH) (Oxamate), the rate of formation of E(NADH) could be measured by observation of the first turnover. This pH-dependent transient is controlled by the rate of dissociation of pyruvate and the fraction of the enzyme in the form E(NADH) (Pyruvate).


The purification and regulatory properties of alpha-oxoglutarate dehydrogenase from Acineobacter iwoffi. The alpha-oxoglutarate dehydrogenase multienzyme complex was purified from Acinetobacter lwoffi to a high degree of homogeneity as shown by gel electrophoresis and analytical ultracentrifugation. Sedimentation-velocity analyses gave s(20,w) values which increased with increasing protein concentration, suggesting dissociation of the complex in dilute solution. The maximum s(20,w) value thereby obtained and the value determined by active enzyme centrifugation were both in the range 28-29S. Electron micrographs of the complex indicated a molecular diameter of 20-22nm (200-220A). The overall activity of the complex was inhibited by NADH, and kinetic studies indicated sites of action on the first and third enzyme components. AMP and ADP relieved this inhibition and also stimulated enzyme activity. Assays specific for the first enzyme component showed this to be the site of action of the adenylates. The activity of the complex varied with energy charge in a manner consistent with its role in energy metabolism.


Evidence that chick tendon procollagen must be denatured to serve as substrate for proline hydroxylase. The ability of chick-embryo proline hydroxylase to hydroxylate [(14)C]proline-labelled procollagen was investigated between 23 degrees and 37 degrees C. The amount of hydroxy[(14)C]proline that could be formed increased sharply between 26 degrees and 30 degrees C. This corresponded to the temperature interval in which the [(14)C]procollagen substrate was thermally denatured, and the results therefore indicate that only denatured molecules can be hydroxylated.


Editorial: New assays for old.

Editorial: New assays for old.


Nervous system involvement in ankylosing spondylitis. In a review of 45 patients with ankylosing spondylitis 10 had neurological symptoms and signs and three of them had two separate neuropathological disorders. The neurological profiles fell into five main categories-multiple sclerosis, the cauda equina syndrome, focal epilepsy, vertebrobasilar insufficiency, and peripheral nerve lesions. An association between ankylosing spondylitis and multiple sclerosis is suggested, possibly due to an immunological defect or to one being a complication of the other.


Changes in antigenic nature of lymphocytes caused by common viruses. Healthy human lymphocytes were incubated in the presence of influenza A2/Singapore/57, herpes simplex type 1, or adenovirus type 2. After two days the cultures were inactivated by irradiation. Fresh lymphocytes taken from the same donor were then found to react to the virus-treated cells in short-term cultures. We suggest that this reactivity is due to a change in the surface characteristics of the lymphocytes brought about by the presence of the virus. This may account for anomalous reactions in mixed lymphocyte cultures, and a similar effect in vivo might cause accelerated graft rejection.


Repression, interference, and field dependence as factors in dream forgetting.


Determination of iron in low-iron diets by colorimetric and atomic absorption procedures.


Gas-liquid chromatographic method for the determination of dimethoate and dimethoxon residues in plant and animal tissues, milk, and eggs.


The rapid chromatographic analysis of the free nucleotides from rat brain.


Simple separation of neutral lipid classes with two dimensional thin-layer chromatography.


The rapid liquid chromatographic analysis of mixtures of 5'-nucleotides and mixtures of flavin nucleotides and 5'-AMP.


Separation of mammalian neutral lipids by chromatography on glass-fiber paper impregnated with silica gel.


Application of vapor phase chromatography to the quantitative determination of conjugated estrogens in drugs.


Reversal of cyclic AMP-mediated intestinal secretion by ethacrynic acid. Ethacrynic acid (EA) has been reported to reduce cholera toxin-induced intestinal fluid secretion in the intact animal. We explored the nature of this inhibition in vitro by measuring unidirectional, transmural fluxes of (22)Na and (36)Cl across isolated rabbit ileal mucosa. Under control conditions (short-circuited mucosa bathed in bicarbonate-Ringer), there was net absorption of Na and Cl. Theophylline (10 mM), cyclic AMP (5 mM), and cholera toxin (added in vivo) abolished net Na flux and produced net Cl secretion. In the presence of either theophylline or cAMP, addition of 0.1 mM EA to the serosal bathing solution abolished net Cl secretion and restored net Na absorption. Cholera toxin-treated mucosa was exposed to 0.05 and 1.0 mM EA. The lower concentration restored net Na absorption but did not significantly reduce Cl secretion. The higher concentration abolished net transport of both Na and Cl. Short-circuit current and Na flux measurements in the presence and absence of glucose indicated that 0.1 mM EA does not inhibit glucose-coupled Na transport. Short-circuit current measurements in the presence of 1.0 mM EA suggested that even this concentration of EA does not inhibit glucose-coupled Na transport. Thus EA appears to specifically inhibit Cl (or NaCl) secretion without inhibiting the absorptive Na "pump." The anti-secretory effect of 0.1 mM EA does not appear to result from inhibition of adenylate cyclase since secretion stimulated by addition of 5 mM cAMP was abolished. Furthermore, 0.1 mM EA did not significantly reduce theophylline-augmented and cholera toxin-augmented cAMP levels in ileal mucosa. We conclude that EA interacts specifically with the active Cl (or NaCl) secretory mechanism of the small intestine at a step beyond generation of cAMP.


Vitamin B6 metabolism in chronic alcohol abuse. Pyridoxal phosphate levels in plasma and the effects of acetaldehyde on pyridoxal phosphate synthesis and degradation in human erythrocytes. The plasma pyridoxal-5'-phosphate (PLP) level of alcoholic subjects has been compared with that of non-alcoholic individuals in order to ascertain the incidence of abnormal vitamin B(6) metabolism in chronic alcohol abuse. 66 alcoholic subjects were selected on the basis that they did not exhibit abnormal liver function tests and hematologic findings. 35 of them had plasma PLP concentrations less than 5 ng/ml, the lowest value encountered in 94 control subjects, indicating a high incidence of deranged PLP metabolism in alcoholic patients even when hepatic and hematologic abnormalities are absent. The biochemical basis for the altered PLP metabolism in chronic alcohol abuse was examined. Low plasma PLP levels in alcoholics were not accompanied by decreased pyridoxal kinase and pyridoxine phosphate oxidase activities in erythrocytes. Further studies with erythrocytes demonstrated that the cellular content of PLP is determined not only by the activities of these PLP-synthesizing enzymes but also by the activity of a phosphate-sensitive, membrane-associated, neutral phosphatase, which hydrolyzes phosphorylated B(6) compounds.Acetaldehyde, but not ethanol, impaired the net formation of PLP from pyridoxal, pyridoxine, and pyridoxine phosphate by erythrocytes. However, when the B(6)-phosphate phosphatase activity was inhibited by 80 mM phosphate, this effect of acetaldehyde was abolished. By the use of broken cell preparations, it was possible to demonstrate directly that the action of acetaldehyde is mediated by the phosphatase, resulting in an acceleration of the degradation of the phosphorylated B(6) compounds in erythrocytes.


Direct inhibitory effect of hypercalcemia on renal actions of parathyroid hormone. The effects of calcium on the renal actions of parathyroid hormone (PTH) were studied in vivo and in vitro. In parathyroidectomized rats, variable levels of blood calcium concentration were induced by intravenous infusion of calcium. The renal responses to the injected PTH, i.e. phosphate and cyclic AMP excretion, were compared in these animals. After PTH injection, the increases of both phosphate and cyclic AMP excretion were less in the calcium-infused animals than in the control group without calcium infusion. There was an inverse correlation between the renal responses to PTH and plasma calcium concentration of 4.2-13.5 mg/100 ml. But calcium had no effect on phosphate excretion induced by infusion of dibutyryl cyclic AMP. In the in vitro experiments, the increase of cyclic AMP concentration in response to PTH was less in renal cortical slices taken from the calcium-infused animals than in ones from the control group without calcium infusion. Calcium also inhibited the activation of renal cortical adenylate cyclase in response to PTH, but calcium had no effect on phosphodiesterase. The data indicate that calcium directly inhibits renal actions of PTH both in vivo and in vitro. Such inhibitory mechanism is probably at or before the step of PTH-dependent cyclic AMP generation in the kidney.


Effects of ethacrynic acid on the isolated collecting tubule. Effects of the diuretic ethacrynic acid on osmotic water permeability were investigated in the isolated perfused collecting tubule of the rabbit kidney. The base-line water permeability of the collecting tubule was not affected when the drug (10(-4)M) alone was added to the bathing medium. Vasopressin alone in the bathing medium (2, 5 muU/ml) elicited a significant increase in osmotic water absorption. With vasopressin kept in the bathing medium, the addition of 10(-5)M ethacrynic acid depressed the hydro-osmotic effect of vasopressin by 50%. This inhibitory effect of low concentrations of ethacrynic acid could be surmounted by high, supramaximal dosage levels of vasopressin. When 10(-4)M ethacrynic acid was added to the bathing medium before vasopressin, the hydro-osmotic effect of vasopressin and the diuretic in combination was insignificant.Dibutyryl adenosine 3'5'-monophosphate (10(-4)-10(-2)M) alone in the bathing medium significantly increased baseline osmotic water flow, mimicing the effect of antidiuretic hormone. When ethacrynic acid was added together with the nucleotide, the permeability remained at the same high level. Theophylline, like the nucleotide and vasopressin, produced a significant hydro-osmotic effect. The magnitude of this response was not affected by further addition of ethacrynic acid (10(-4)M). It was concluded that ethacrynic acid is an antagonist of antidiuretic hormone. The antagonism probably occurs at the level of the receptor site of the hormone on the peritubular membrane. Antagonism to circulating antidiuretic hormone may therefore be one of the factors involved in the loss of renal concentrating ability brought about by ethacrynic acid diuresis.


Study of the renal tubular interactions of thyrocalcitonin, cyclic adenosine 3',5'-monophosphate, 25-hydroxycholecalciferol, and calcium ion. Acute clearance studies were performed in thyroparathyroidectomized animals to determine the actions and interactions of thyrocalcitonin (TCT), cyclic adenosine 3'5'-monophosphate (cAMP), 25-hydroxycholecalciferol (25HCC), and calcium ion on the reabsorption of phosphate, calcium, sodium, and potassium by the kidney. The infusion of 25HCC in a dosage of 60 U/h to moderately saline-expanded animals (2.5% body weight) induced a fall in the excretion of all of the ions under study after 90-120 min similar to that observed in previous experiments from this laboratory. Mean decrements in fractional excretion were: phosphate, 42.0% (P < 0.005); calcium, 25.0% (P < 0.005); sodium, 23.4% (P < 0.001); and potassium, 14.7% (P < 0.005). The superimposition of either porcine or salmon TCT (1-100 MRC U/h for 2 h) resulted in no further alterations in electrolyte excretion. However, the infusion of TCT during steady-state saline expansion, before the administration of 25HCC, obviated the renal transport effects of the vitamin D metabolite. Both in the latter studies, as well as those in which similar doses of TCT were given to hydropenic animals, the hormone itself failed to induce any consistent alteration in electrolyte excretion. Cyclic AMP (50 mg/h) caused an increase in the excretion of phosphate, sodium, and potassium and no change in calcium excretion. Like TCT, the nucleotide blocked the action of 25HCC on the kidney. Raising the mean level of serum ultrafilterable calcium to 3.02+/-0.25 mEq/liter from 1.62+/-0.17 mEq/liter likewise prevented enhanced ionic reabsorption due to 25HCC.


Ultrastructure of taper hepatoma ascites cells.


Effects of prostaglandins and cholera enterotoxin on intestinal mucosal cyclic AMP accumulation. Evidence against an essential role for prostaglandins in the action of toxin. Both cholera enterotoxin and certain prostaglandins have been shown to stimulate intestinal fluid secretion in vivo, to cause ion flux changes in vitro similar to those caused by addition of cyclic 3',5'-adenosine monophosphate (cyclic AMP), and to activate intestinal mucosal adenyl cyclase. It has been suggested that the effects of the enterotoxin on intestinal cyclic AMP metabolism may be indirect, and that locally synthesized prostaglandins may serve as required intermediates for the effects of the enterotoxin in activating intestinal mucosal adenyl cyclase. In order to clarify certain aspects of the mechanisms by which these two agents alter intestinal mucosal cyclic AMP metabolism and ion transport, their effects on cyclic AMP accumulation in rabbit ileal mucosa were examined in vitro. Addition of 5 mug per ml (75 mug per 150 mg mucosa) of purified cholera enterotoxin produced a peak increase in cyclic AMP level in 3 h but there was a time delay of at least 30 min before any effect was observed. Inhibition of cyclic nucleotide phosphodiesterase with theophylline failed to reduce this time delay. In contrast, addition of prostaglandin E(1) (PGE(1)) increased the cyclic AMP level rapidly, a peak effect being observed in 2 min. The time of the peak prostaglandin-induced changes in cyclic AMP level and short-circuit current correlated closely. A maximal increment in cyclic AMP level was achieved with 5 x 10(-5) M PGE(1). When 10(-4) M PGE(1) was added to mucosa already maximally stimulated with cholera toxin, the resulting cyclic AMP level was equal to the sum of the levels reached when each agent was added alone. Furthermore, the effects of the enterotoxin on mucosal cyclic AMP levels were not influenced by indomethacin under conditions where mucosal prostaglandins synthesis was inhibited. The results suggest that endogenous prostaglandins do not provide an essential link in the activation of intestinal mucosal adenyl cyclase by cholera enterotoxin. The present study also indicates that the effect of cholera enterotoxin on intestinal mucosal cyclic AMP metabolism involves a definite time delay which is not due to cyclic nucleotide phosphodiesterase activity.


Effects of oestrogen antagonists on mitosis and (3H)oestradiol binding in the mouse uterus.


Inhibition by dexamethasone of adrenocorticotrophin and cortisol release induced by intravenous infusion of ATP and dibutyryl cyclic AMP in piglets.


The mechanism of androgen uptake and concentration by rat ventral prostate in organ culture.


Genetic and physiological properties of temperature-sensitive mutants of Cocal virus. Temperature-sensitive (ts) mutants of Cocal virus (VSV Cocal) were isolated after treatment with the base analogue mutagen, 5-fluorouracil. These mutants could be classified into four mutually complementing groups. Weak complementation was detected between certain pairs of VSV Cocal ts mutants and ts mutants of vesicular stomatitis virus (VSV) Indiana, but no complementation was observed with ts mutants of VSV New Jersey. Two complementing ts mutants of Chandipura virus, an unrelated rhabdovirus, did not complement any VSV mutant, Thus, ability to complement in the VSV group appears to be correlated with serological relationships. The RNA and protein-synthesizing capacities of these ts mutants have been determined, and it is possible to establish a correspondence between the VSV Cocal and the VSV Indiana complementation groups.


Unwinding of parental strands during simian virus 40 DNA replication. Pools of young (less than 60% replicated) and mature (60-90% replicated) replicating molecules of simian virus 40 (SV40) DNA have been treated at pH 12.2 in order to dissociate growing chains from the parental strands. The molecules are neutralized so that the parental strands can reassociate and they have then been isolated. They are covalently closed structures which sediment rapidly in alkaline sucrose gradients; however, the sedimentation rates are less than the sedimentation rate of SV40 DNA I. Isopycnic banding in CsCl-ethidium bromide and sedimentation velocity studies in the presence of various amounts of ethidium bromide indicate that these structures contain negative superhelical turns and several-fold-higher superhelix densities than SV40 DNA I (the covalently closed DNA molecule). These structures are those that would be predicted if nicking, unwinding, and sealing of the parental strands occurred as replication proceeded. These experiments provide a direct demonstration that there is a progressive decrease in the topological winding number which accompanies SV40 DNA replication.


Phosphorylation of simian virus 40 proteins in a cell-free system. We have shown previously that all the structural proteins of simian virus 40 (SV40) are phosphoproteins. Virus phosphorylated in vivo could be further phosphorylated with exogenous cellular protein kinases in a cell-free system containing gamma-(32)P-ATP as phosphate donor. In intact infectious virus only polypeptides 1 and 2 (mol wt 49,000 and 40,800, respectively) were further phosphorylated in vitro. However, when infectious SV40 was partially disrupted, treated with nucleases, and then phosphorylated in vitro, all five structural polypeptides accepted additional phosphate groups. Similarly, all polypeptides of intact empty capsids, derived from infected cells, were further phosphorylated in vitro. Phosphorylation of empty capsids and infectious SV40 in vitro was enhanced from 4- to 11-fold after prior treatment of virus with alkali. The phosphate group was linked only to serine residues of the viral polypeptides phosphorylated both in vitro and in vivo.


Integrated state of oncornavirus DNA in normal chicken cells and in cells transformed by avian myeloblastosis virus. The covalent linkage of oncornavirus-specific DNA to chicken DNA was investigated in normal chicken embryo fibroblasts (CEF) and in virus-producing leukemic cells transformed by avian myeloblastosis virus (AMV). The virus-specific sequences present in cellular DNA fractionated by different methods were detected by DNA-RNA hybridization by using 70S AMV RNA as a probe. In CEF and in leukemic cells, the viral DNA appeared to be present only in the nucleus. After cesium chloride-ethidium bromide density equilibrium sedimentation, the viral DNA was present as linear, double-stranded molecules not separable from linear chicken DNA. After extraction by the Hirt procedure, the viral DNA precipitated with the high-molecular-weight DNA. After alkaline sucrose velocity sedimentation, the viral DNA cosedimented with the high-molecular-weight cellular DNA. The results indicate that in both types of cells studied, the oncornavirus-specific DNA sequences were linked by alkali stable bonds to nuclear cellular DNA of high molecular weight and did not appear to be present in free form of any size.


Partial transcription of murine type C viral genomes in BALB c cell lines. The mouse cell line, BALB/c 3T3, and its derivatives transformed either spontaneously or by treatment with a variety of external agents, were analyzed for cytoplasmic RNA complementary to DNA products prepared from the Kirsten strain of murine sarcoma-leukemia virus, and from an endogenous type C virus of BALB/c 3T3. Although none of these cell lines spontaneously releases complete type C virions, they all contain RNA which is partially homologous to a portion of the 35S RNA isolated from these viruses. The parental cell line, BALB/c 3T3, contains a low level of viral-related RNA, and there is an increased amount of this RNA in some of the transformed cells. The RNA detected represents only a fraction of the viral RNA found in virus-producing cells. The formation of RNA:DNA hybrids was detected by equilibrium centrifugation in Cs(2)SO(4) density gradients and by analysis with a single-strand-specific nuclease from Aspergillus oryzae. Viral DNA products prepared either from an endogenous reaction with whole virus in the presence of actinomycin D or from purified 70S viral RNA as template using avian myeloblastosis virus DNA polymerase yield comparable data. In addition, all of the BALB/c lines examined produce detectable levels of murine type C virus group-specific antigen.


Reassortment of simian virus 40 DNA during serial undiluted passage. Alterations occur in the supercoiled form of viral DNA after the serial undiluted passaging of simian virus (SV) 40. We have identified a portion of the viral genome which is amplified during this process. These SV40 DNA sequences represent about 30% of the viral genetic information and are present in a reiterated form in twisted circular molecules prepared from purified virions. In addition, reiterated and unique green monkey DNA sequences are incorporated into supercoiled viral DNA. The cellular DNA appears to be inserted at numerous locations in the DNA I molecules.


Separation of Herpes simplex virus-induced antigens by Concanavalin A affinity chromatography. Biologically active herpes simplex virus (HSV)-induced antigens were selectively removed from extracts of infected BHK cells by affinity chromatography by utilizing an insoluble form of concanavalin A (Con A). Soluble extracts of (3)H-glucosamine-labeled, HSV-infected cells were absorbed to a Con A column. Bound material was eluted with alpha-methyl-d-mannoside (alphaMM) and NaCl. The specific activity of the eluted glycoproteins increased by 10-fold. Two broad groups of viral-induced antigens were isolated from Con A. Group I includes two antigens which bind to Con A by a specific mechanism because the antigens are dissociated by alphaMM. Group II contains three antigens which bind to Con A but apparently by a nonspecific or electrolytic mechanism. One antigen in group I was identified as the glycoprotein antigen, CP-1, described previously.


Comparison of in vitro and cell-mediated alteration of a human Rhinovirus and its inhibition by sodium dodecyl sulfate. After human rhinovirus type 2 (HRV-2) attaches to HeLa cells, two types of subviral particles are formed which closely resemble particles produced in vitro by acid or heat. One type of particle contains RNA whereas the second sediments as an empty capsid and is RNA-deficient. Sodium dodecyl sulfate (SDS) at 10(-4) M inhibits the cell-mediated formation of these particles from HRV-2 virions and the ability of HRV-2 to form plaques, but it does not inhibit the formation of plaques by human rhinovirus 14 (HRV-14). SDS also stabilizes HRV-2 against inactivation by acid or heat to a much greater extent than it does HRV-14. In a similar manner, SDS protects against the acid inactivation of the subpopulation of HRV-2 natural top component particles which attach to virus-specific cellular receptors. This suggests that the loss of native properties of natural top component particles and of virion are related processes. The basis for this alteration and also its role in infection are discussed.


Polypeptide composition of Influenza B viruses and enzymes associated with the purified virus particles. Influenza B/LEE/40, B/Rome/1/67, B/Hong Kong/8/73, and B/Victoria/98926/70 viruses have a similar polypeptide composition as analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. These viruses are composed of six or seven polypeptides, depending on whether one or two high-molecular-weight polypeptides are resolved, ranging in molecular weights from 27,000 to 90,400. Three of these polypeptides, namely the heavy and light hemagglutinin chains and the neuraminidase, have attached carbohydrate. Highly purified influenza B/LEE/40 and B/Rome/1/67 virus preparations have RNA-dependent RNA polymerase activity equivalent to the incorporation of 100 and 30 pmol, respectively, of (3)H-UMP per mg of virus protein per h at 37 C, which is demonstrated only in detergent-treated virus suspensions. However, no RNA-dependent DNA polymerase enzyme activity was detected in the two viruses although virus suspensions were "activated" by heat, alpha-chymotrypsin, and detergents. Other enzymatic activities were associated with purified preparations of influenza B virus and were attributed to minor contamination of virus with host cell enzymes. Thus, nucleoside and deoxynucleoside phosphohydrolase enzymes were active in the absence of detergents and catalyzed the release of 1,200 and 1,800 nmol of P(i) per mg of virus protein in 30 min at 37 C from ATP and dATP substrates. Thin-layer chromatography indicated that the products of the phosphohydrolase enzymes of influenza B/LEE/40 were mainly nucleoside diphosphate and monophosphate. The latter enzymes were tightly bound to influenza B/LEE/40 virus and could not be removed completely by repeated centrifugation, including centrifugation of the virus to equilibrium in density gradients of 25 to 40% (wt/vol) cesium chloride. A low degree of RNase (approximately 0.01 mug% contamination) and phosphatase (10-30 nmol of P(i) released per mg of virus protein per 30 min) activity was detected in some, but not all, influenza B/LEE/40 virus preparations.


Studies of nondefective Adenovirus 2-Simian virus 40 hybrid viruses. 8. Association of Simian virus 40 transplantation antigen with a specific region of the early viral genome. Two of the five nondefective adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrids induce SV40 transplantation resistance in immunized hamsters. These two hybrids, Ad2(+)ND(2) and Ad2(+)ND(4), contain 32 and 43% of the SV40 genome, respectively. The pattern of induction of SV40 transplantation antigen (TSTA) by the various hybrids differentiates TSTA from both SV40 U and T antigens. Since the SV40 RNA induced by both these hybrids is early SV40 RNA, these findings confirm that TSTA is an early SV40 function. By combining available data on SV40 antigen induction by these hybrids with electron microscopy heteroduplex mapping studies, the DNA segment responsible for the induction of SV40 TSTA can be inferred to lie in the region between 0.17 and 0.43 SV40 units from the site on the SV40 chromosome cleaved by E. coli R(1) restriction endonuclease.


SP62, a viable mutant of bacteriophage T4D defective in regulation of phage enzyme synthesis. SP62 is a mutant of bacteriophage T4D that was discovered because it produces fewer phage than the wild type in the presence of 5-fluorodeoxyuridine. In the absence of phage DNA synthesis, SP62 solubilizes host DNA slower than normal; this may explain the sensitivity to 5-fluorodeoxyuridine. In Escherichia coli B at 37 C in the absence of drugs, SP62 makes DNA at a normal rate and the kinetics of appearance of phage are nearly normal. Under the same conditions, SP62 produces T4 lysozyme (gene e) at a normal rate until 20 min, but then produces it at twice the normal rate until at least 60 min. It has long been known that, when T4 DNA synthesis is blocked (DNA(-) state) in an otherwise normal infection, the synthesis of a number of early enzymes continues beyond the shutoff time of about 12 min seen in the DNA(+) state, but still stops at about 20 min. We have termed the 12-min shutoff event S1 and the 20-min shutoff event S2. We show here that, in the DNA(+) state, SP62 makes four early enzymes normally, i.e., S1 occurs. However, in the DNA(-) state (where S1 is missing), SP62 continues to make dCTPase (gene 56), dCMP hydroxymethylase (gene 42), and deoxynucleotide kinase (gene 1) for at least an hour; this results in production of up to 13 times the normal level of dCTPase at 60 min after infection, or 6 times the DNA(-) level. We conclude that SP62 is defective in the second shutoff mechanism, S2, for these three enzymes. In contrast, SP62 causes premature cessation of dTMP synthetase production in the DNA(-) state; the result is a twofold underproduction of dTMP synthetase. Autoradiograms of pulse-labeled proteins separated by slab-gel electrophoresis in the presence of sodium dodecyl sulfate show that a number of other T4 early proteins, including the products of genes 45, 46, and rIIA, are synthesized longer than normal by SP62 in the DNA(-) state. Few late proteins are made in the DNA(-) state, but in autoradiograms examining the DNA(+) state there is little or no effect of the SP62 mutation on the synthesis of T4 late or early proteins. Circumstantial evidence is presented favoring a role for the gene of SP62 in translation of certain mRNAs. At very high temperatures (above 43 C) in the absence of drugs, phage production, but not DNA synthesis, is much reduced in SP62 infections relative to wild-type T4 infections; this temperature sensitivity is greater on E. coli CR63 than on E. coli B. This property has facilitated recognition of the SP62 genotype and aided in complementation testing and genetic mapping. A later publication will provide evidence that SP62 defines a new T4 gene named regA, which maps between genes 43 and 62.