Search PubMed⌕ Search

Biomedical subjects

K M Johnson

Publications and source records attributed to K M Johnson.

At least 217 records · Page 12Linked to original sources

Stimulation of synaptosomal tyrosine hydroxylation by phencyclidine in vitro.

Phencyclidine (PCP), a potent psychoactive drug, produces some animal behaviors that are believed to be mediated by dopaminergic and/or cholinergic neurons in the basal ganglia. In this study, we have monitored the effects of PCP in vitro on the synthesis, uptake, and release of dopamine (DA) in rat striatal synaptosomes. Using tyrosine hydroxylation as an index of DA synthesis, we observed a concentration-dependent stimulation of DA synthesis by PCP. The stimulatory effect was antagonized by reserpine (1 micro M) and was observed only when synaptosomes were preincubated under conditions which prevented the spontaneous release of [3H]DA. Two hydroxylated metabolites of PCP were also tested and found to have little effect on tyrosine hydroxylation. Like PCP these metabolites are potent inhibitors of synaptosomal [3H]DA uptake, but they apparently lack PCP's ability to release synaptosomal DA. Taken together, these results support our hypothesis that PCP stimulates synaptosomal DA synthesis by releasing DA from an inhibitory pool.

Amphetamine↗

[Antibodies against the Marburg virus among human populations in the southeastern Central African Republic].

A serological survey was carried out in the south-east of the Central African Republic in 1979 to investigate the incidence of Marburg virus in the human population. Serum samples were tested using the indirect immunofluorescence method on infected and inactivated Vero cells (green monkey kidney) on slides prepared by the Center for Disease Control, Atlanta, U.S.A. Out of 499 samples, 7 were positive. Two of them showed a high antibody titre of 1/64. Both patients were retested 10 months later and again found positive at the same titre. These two antibody carriers had never had any haemorrhagic syndrome. This is the first evidence of non-apparent Marburg virus infection in man without any epidemic. These findings constitute a first approach towards the discovery of natural foci of this virus.

Adult↗

Procedure for recovery of enteroviruses from the Japanese cockle Tapes japonica.

The most likely shellfish to be harvested if sportfishing is reinstated in San Francisco Bay is the Japanese cockle Tapes japonica. The virus levels present in these shellfish are unknown and need to be evaluated before the shellfish beds are open. Towards this end, a procedure for recovering and concentrating enteric viruses from these clams has been evaluated. Effective elution of poliovirus from clam tissues was found to occur with pH 9.5 glycine-buffered saline rather than with the pH 7.5 fluid utilized by other investigators on oysters. Poliovirus desorption was combined with Cat-Floc clarification to remove cytotoxicity from clam tissue homogenates. For assay purpose, viruses were concentrated by mixing the glycine supernatant with a beef extract solution, lowering the pH, and suspending the resulting floc in a small volume of phosphate buffer. This simple technique successfully recovered an average of 73% of the poliovirus added to clam homogenates at levels of 93 and 660 plaque-forming units per 100 g. Coxsackievirus B2 was isolated from clams exposed to raw sewage.

Animals↗

Preparation of polyvalent viral immunofluorescent intracellular antigens and use in human serosurveys.

A method is described for preparation of polyvalent antigens for use in rapid screening for immunofluorescent antibodies to Lassa, Marburg, and Ebola viruses. The technique uses mixtures of specifically infected Vero cells placed on Teflon-templated microscopy slides. It was found to be as sensitive as the use of monovalent antigens for detection and quantitation of antibodies to these highly hazardous human pathogens.

Animals↗

Adrenalectomy reverses the effects of delta-9-THC on mouse brain 5-hydroxytryptamine turnover.

Acute administration of certain cannabinoids, including delta 9-tetrahydrocannabinol (delta 9- THC), resulted in elevated levels of plasma corticosterone in mice. The rank order potency of these cannabinoids is the same as others have reported using behavioral tests. The maximally effective dose of delta 9-THC (30 mg/kg) in this test also increased the amount of 3H-tryptophan found in the brains of mice given an intravenous injection of 3H-tryptophan 10 min prior to decapitation. This effect was associated with an increase in the amount of 3H-5-hydroxytryptamine synthesized during the pulse period. Adrenalectomy was found to inhibit these effects of delta 9-THC. The possibility that corticosterone may mediate the effects of delta 9-THC on tryptophan disposition and metabolism is discussed.

Adrenalectomy↗

Recovery of a Lassa-related arenavirus in Zimbabwe.

Immunofluorescent antibodies to "Mozambique" virus, a close relative of Lassa virus, were found in 11 of 55 Mastomys natalensis and 1 of 13 Aethomys chrysophilus rodents captured near Que Que and Chiredzi, Zimbabwe. Six strains of Mozambique virus, identified by use of specific monoclonal antibodies to the agent, were recovered from visceral tissues of M. natalensis rodents. All Mastomys having virus or antibodies to this agent were of the chromosomal form 2N = 32 (M. natalensis). These data extend the area of geographic occurrence of this virus, which was initially recognized in Mozambique and which may represent a naturally attenuated antigenic variant of human pathogenic West African Lassa virus.

Animals↗

Monoclonal antibodies to lymphocytic choriomeningitis virus react with pathogenic arenaviruses.

Certain arenaviruses have become widely recognized as important human pathogens, the most notable among these being Lassa virus, the causative agent of Lassa fever. Two other members of the group, Junin and Machupo virus, are the aetiological agents of Argentine and Bolivian haemorrhagic fevers, respectively. All these agents share both morphological features and to varying degrees serological cross-reactivity with other non-pathogenic arenaviruses. Despite the evident clinical importance of these viruses, work to define their physiochemical structure and to develop rapid and precise diagnostic techniques has been slow. Consequently, the definitive relationships among West African Lassa strains, strains of a related agent from Mozambique and of an Old World arenavirus, lymphocytic choriomeningitis (LCM), have not been established. This problem is of more than simple taxonomic importance in view of the fact that a Mozambique virus strain produced subclinical infection in experimental monkeys which were then resistant to challenge with monkey and human virulent Lassa virus from Sierra Leone. We have explored the use of monoclonal hybridoma antibodies generated against relatively less hazardous arenaviruses to define antigens cross-reactive with the important human pathogens of the group. Here we describe the use of monoclonal antibodies directed against LCM, virus to define antigenic specificities shared among LCM, Lassa and Mozambique viruses.

Antibodies, Viral↗

Lassa virus infection of rhesus monkeys: pathogenesis and treatment with ribavirin.

Rhesus monkeys were experimentally infected with Lassa virus to establish their suitability as a nonhuman primate model for the human disease and to test the protective efficacy of ribavirin, an antiviral drug. Six of 10 untreated control monkeys died after subcutaneous inoculation of 10(6.1) plaque-forming units of Lassa virus (strain Josiah). Infectivity titrations of tissue homogenates from the six dead monkeys indicated significant replication in all tissues tested except the central nervous system. This distribution of virus was confirmed by direct immunofluorescence examination of cryostat-sectioned tissues. Ribavirin was beneficial in the treatment of two groups of infected monkeys. Four monkeys first treated on the day of viral inoculation experienced only mild clinical disease; four monkeys first treated five days later experienced a more severe illness. None of the eight monkeys treated with ribavirin died. Viremia titers and elevations of levels of serum transaminases in treated monkeys were significantly lower than in controls. Ribavirin may be beneficial in the treatment of humans exposed to this life-threatening virus.

Adrenal Glands↗

Ebola hemorrhagic fever: Tandala, Zaire, 1977-1978.

Ebola virus was recovered from a nine-year-old girl who died of acute hemorrhagic fever in June 1977 at Tandala Hospital in northwestern Zaire, in the first reported recognized case of this disease since the discovery epidemics of 1976 in Zaire and Sudan. Investigations undertaken in the Tandala region revealed that two previous clinical infections with Ebola virus had occurred in 1972 and that about 7% of the residents had immunofluorescent antibodies to the virus. Females younger than 30 years of age had a higher prevalence of antibodies than males of comparable age, but above the age of 30 years there was no sex difference. No other clues to the still-mysterious natural reservoir of Ebola virus were uncovered.

Adolescent↗

Ebola virus: identification of virion structural proteins.

Polyacrylamide gel electrophoresis of purified Ebola virus revealed the presence of four major virion structural proteins which we have designated VP1, VP2, VP3 and VP4. Vesicular stomatitis virus (VSV) proteins were used as mol. wt. markers, and the virion proteins were found to have mol. wt. of 125000 (VP1), 104000 (VP2), 40000 (VP3) and 26000 (VP4). VP1 was labelled with glucosamine and is probably a glycoprotein. The density of the Ebola virion was approx. 1.14g/ml in potassium tartrate. Virus nucleocapsids with a density of 1.32g/ml in caesium chloride were released when virions were treated with detergents. Proteins VP2 and VP3 were consistently associated with released nucleocapsids and are probably the major structural nucleocapsid proteins analogous to the N protein of VSV. Protein VP4 was reduced or absent in released nucleocapsids and is probably analogous to the membrane (M) protein of VSV and similar viruses. The glycoprotein (VP1) is larger than the glycoprotein of any known negative-strand RNA virus and is not labelled well with 35S-methionine. VP1 is solubilized by detergent treatment, suggesting that it is a component of the virion spikes and analogous to the G protein of VSV. Our results, in conjunction with analysis of Ebola virion RNA (Regnery et al. 1980), strongly suggest that the virus is a negative-strand RNA virus and, along with marburg virus, may constitute a new taxon within this group.

Capsid↗

Preparation and use of erythrocyte-globulin conjugates to Lassa virus in reversed passive hemagglutination and inhibition.

Conditions were defined for functional covalent coupling of anti-Lassa virus globulins to glutaraldehyde-fixed chicken erythrocytes. Tolylene-2,4-diisocyanate in a reaction mixture containing not more than 0.01 M NaCl produced uniformly good conjugates which were used in reversed passive hemagglutination (RPH) and reversed passive hemagglutination inhibition (RPHI) tests to detect Lassa virus antigens in infected cell cultures and specific antigens in Vero cell cultures. Identical results were obtained with this method and with immunofluorescent-antibody (IFA) staining in the detection and identification of Lassa virus isolated from human and rodent specimens from West Africa. The RPHI method was equal to IFA for serological diagnosis of acute human Lassa virus infection and superior to IFA, complement fixation, and a radioimmunoassay procedure for detection of Lassa virus antibodies in a human population where this infection is endemic.

Animals↗

Virion nucleic acid of Ebola virus.

The virion nucleic acid of Ebola virus consists of a single-stranded RNA with a molecular weight of approximately 4.0 x 10(6). The virion RNA did not bind to oligodeoxythymidylic acid-cellulose under conditions known to bind RNAs rich in polyadenylic acid and was not infectious under conditions which yielded infectious RNA from Sindbis virus, suggesting that Ebola virus virion nucleic acid is a negative-stranded RNA.

Ebolavirus↗

Induction of xenobiotic metabolism in rat liver by chlorinated biphenyl ether isomers.

Chlorinated diphenyl ether isomers were administered to rats at doses of 10 mumols/kg/day po for 3 days. Decachlorodiphenyl ether caused increases in EPN detoxification, NADPH cytochrome c reductase and cytochrome P-450 but did not alter aryl hydrocarbon hydroxylase (AHH). It caused a shift in P450 absorption to 448 nm. 2,4,5,2',4'-Pentachlorodiphenyl ether increased EPN detoxification and cytochrome P-450. 2,4,5,3',4'-Pentachlorodiphenyl ether increased AHH and cytochrome P-450 and caused a shift in the absorption maximum to 448 nm. 3,4,2',4'-Tetrachlorodiphenyl ether induced AHH. 2,4'-Dichlorodiphenyl ether, 4,4'-dichlorodiphenyl ether, 2,4,2'-trichlorodiphenyl ether, 2,4,4'-trichlorodiphenyl ether, 3,4,2'-trichlorodiphenyl ether and 3,4,2',4'-tetrachlorodiphenyl ether did not alter any of these parameters. The position and degree of chlorination are important in determining the extent of induction and pathways induced.

Animals↗