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Biomedical subjects

K M Johnson

Publications and source records attributed to K M Johnson.

At least 181 records · Page 10Linked to original sources
PubMed1985

Selection of test methods to assess ecological effects of mixed aerosols.

Components of the mixed aerosols generated during military training are known to be of toxicological and/or ecological significance. There are few studies, however, quantifying mixed aerosol effects on ecosystems. Prompted by our finding that one or more of the compounds in the mixed aerosols commonly encountered in military training areas showed mutagenic effects in several species, a multiyear effort is evaluating the use of ecotoxicity testing methods to assess mixed aerosol ecological impacts. Selection of test methods for ecoepidemiology begins with the identification of the data required to meet defined environmental quality objectives. The data requirements are then matched with appropriate test methods, and testing results are related to important ecological effects resulting from aerosol exposure. The critical element of test system selection is to ensure that toxicity testing results relate to important ecological effects. The procedures developed for identifying test methods to assess mixed aerosols are also applicable to a range of environmental contaminants regulated by air, water, and solid waste regulations.

Aerosols↗
PubMed1985

Antagonism of N-methyl-D-aspartate-induced transmitter release in the rat striatum by phencyclidine-like drugs and its relationship to turning behavior.

Representatives from several chemical classes known to share behavioral properties with phencyclidine [(1-phenylcyclohexyl)piperidine] (PCP) have been shown to antagonize the excitatory effects of N-methylaspartate on spinal neurons selectively. This study compared the abilities of several of these PCP-like drugs to inhibit N-methyl-D-aspartate (NMDA)-stimulated efflux of acetylcholine in rat striatum. PCP completely inhibited this parameter with an IC50 value of 68 nM. The IC50 values (nanomolar) found for the other drugs tested were as follows: etoxadrol (98), (-)-cyclazocine (120), N-allylnormetazocine (or SKF 10047) (940), ketamine (1600) and ethylketocyclazocine (8300). Morphine had no effect at concentrations as high as 30,000 nM. In addition, 100 nM dexoxadrol, 1-[1-(napthyl)cyclohexyl]piperidine HCl (m-amino PCP) and (-)-cyclazocine inhibited NMDA-induced acetylcholine release by about 50%, whereas the same concentration of their enantiomers (or a structural analog in the case of m-amino-PCP) produced no significant effect. It was also found that 10 mg/kg of dexoxadrol, m-amino-PCP and (-)-cyclazocine induced significant ipsilateral turning in rats with unilateral destruction of the substantia nigra, whereas 10 mg/kg of levoxadrol, 1-[1-(m-nitrophenyl)cyclohexyl]piperidine HCL (m-nitro-PCP) and (+)-cyclazocine produced no such similar effect. In spite of the ability of several dopaminergic antagonists to block turning produced by (+/-)-cyclazocine, we concluded, based on our previously reported studies of the dopaminergic properties of these drugs, that turning is the result of nondopaminergic properties of the PCP-like drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1984

Phencyclidine-induced inhibition of striatal acetylcholine release: comparisons with mu, kappa, and sigma opiate agonists.

The effects of phencyclidine (PCP) on ACh release were compared to those of morphine, ethylketocyclazocine (EKC), and N-allylnormetazocine (SKF10047) in a superfused striatal slice preparation. The (+)-isomer of the prototypic sigma opiate agonist, SKF10047, and the prototypic kappa opiate agonist, EKC, had essentially the same pharmacological profile as did PCP. That is, they each inhibited ACh release in a concentration dependent manner (with EKC being the most potent) and this effect was antagonized by 0.1 microM naloxone. Since morphine was without effect on ACh release, it is unlikely that these drugs inhibit ACh release by acting at mu receptors. In addition, we observed that the inhibitory effect of PCP, (+) SKF10047, and EKC on ACh release was reversed by 0.1 microM haloperidol. Given that PCP has been shown to stimulate basal DA release in this preparation, it is possible that PCP, EKC and (+) SKF10047 inhibit ACh release indirectly by stimulating DA release. The naloxone-induced blockade of the effect of PCP and these benzomorphans is discussed in relation to the effects of naloxone on other systems known to influence ACh release.

Acetylcholine↗
PubMed1984

Heat-induced temperature sensitivity of outgrowing Bacillus cereus spores.

Inactivation of Bacillus cereus spores during cooling (10 degrees C/h) from 90 degrees C occurred in two phases. One phase occurred during cooling from 90 to 80 degrees C; the second occurred during cooling from 46 to 38 degrees C. In contrast, no inactivation occurred when spores were cooled from a maximum temperature of 80 degrees C. Inactivation of spores at a constant temperature of 45 degrees C was induced by initial heat treatments from 80 to 90 degrees C. The higher temperatures accelerated the rate of inactivation. Germination of spores was required for 45 degrees C inactivation to occur; however, faster germination was not the cause of accelerated inactivation of spores receiving higher initial heat treatments. Repair of possible injury was not observed in Trypticase soy broth (BBL Microbiology Systems), peptone, beef extract, starch, or L-alanine at 30 or 35 degrees C. Microscopic evaluation of spores outgrowing at 45 degrees C revealed that when inactivation occurred, outgrowth halted at the swelling stage. Inhibition of protein synthesis by chloramphenicol at the optimum temperature also stopped outgrowth at swelling; thus protein synthesis may play a role in the 45 degree C inactivation mechanism.

Bacillus cereus↗
PubMed1984

Hantaan-like viruses from domestic rats captured in the United States.

Recent observations that Rattus rodents in Asia harbor Hantaan (HTN)-like viruses associated with hemorrhagic fever with renal syndrome led us to investigate the possibility that similar viruses might be present in the United States. Wharf rats were captured at major port cities, their sera were examined for HTN antibody by immunofluorescent antibody (IFA) assay and tissues from selected antibody-positive rats were examined for HTN antigen. Rats positive for both antibody and antigen to HTN virus were found in Philadelphia, PA and Houston, TX. Infected rats were found clustered in discrete foci where a significant proportion was antibody and antigen positive. Viruses isolated from lung tissues of Rattus norvegicus captured at Philadelphia and Houston were grown in cell culture and shown to be closely related to each other and to the 76-118 strain of HTN virus by IFA, but clearly distinct from HTN by plaque reduction neutralization tests. The isolates appear to be variants of the same new virus, for which the name Girard Point virus is proposed.

Animals↗
PubMed1984

A comparison between classes of drugs having phencyclidine-like behavioral properties on dopamine efflux in vitro and dopamine metabolism in vivo.

Phencyclidine [(l-phenylcyclohexyl) piperidine] (PCP) is known to increase the basal efflux of striatal dopamine (DA) in vitro and to enhance haloperidol (HAL)-induced striatal DA metabolism in vivo. This study compared these activities of PCP to several representatives of the arylcyloalkylamine, benzomorphan and substituted dioxolane classes whose behavioral similarities to PCP have been well studied. The affinity of these drugs for the PCP/sigma opiate receptor also was estimated by determining the concentration of these drugs required to inhibit the specific binding of 10 nM [3H]PCP to rat cortical membranes by 50%. Of the arylcycloalkylamines tested on the basal efflux of [3H]DA, we found the rank-order effectiveness to be as follows: PCP greater than 1-[l-(napthyl)cyclohexyl]piperidine HCl (m-amino-PCP) greater than ketamine greater than or equal to 1-[l-(m-nitrophenyl)cyclohexyl]piperidine HCl (m-nitro-PCP) greater than N-ethyl-l-phencyclohexylamine (PCE). However, in vivo we found that PCP, m-amino-PCP and PCE significantly elevated HAL-induced DA metabolism, whereas ketamine and m-nitro-PCP were without effect. Although each of the benzomorphans tested [N-allylnormetazocine (NANM) and ethylketocyclazocine (EKC)] slightly enhanced the basal efflux of [3H]DA from striatal slices, concentrations of 10 to 30 microM were required to elicit the same magnitude of [3H]DA release caused by 3 microM PCP. Quantitatively similar responses were produced by the substituted dioxolanes tested (etoxadrol, dexoxadrol and levoxadrol). Neither (+)-NANM, (-)-NANM, (+/-)-NANM, etoxadrol nor dexoxadrol had any effect on HAL-induced DA metabolism. On the other hand, both levoxadrol and EKC significantly decreased the ratio of HVA/DA after HAL administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Detection and enumeration of injured bacterial spores in processed foods.

Injury of bacterial spores is manifested in ways similar to those for vegetative cells, i.e. altered nutritional requirements, increased sensitivity to inhibitors and modified optimum temperatures. However, injury in spores may involve activation, germination and/or outgrowth systems, in addition to the vegetative growth processes. Food processes in the form of heat, acid, inhibitors, preservatives, low water activity and combinations of these factors can stress spores. Consequently, detection and enumeration methods designed to recover bacterial spores from processed foods must always consider the requirements of injured spores. Injury to germination systems has been circumvented through the addition of non-nutritive agents, such as lysozyme, to recovery media, or by incubation at an alternative temperature which favours a secondary germination system. A shift in temperature has also permitted repair of damaged outgrowth systems. Addition of materials such as starch and charcoal can reduce the sensitivity of injured spores to some inhibitors. Our current research on hypochlorite injury of Cl. botulinum, differing injury responses for B. cereus in rice and TSB, and injury of B. cereus earlier in the heating process at 85 degrees C than at 90 degrees C indicate a need for more information on the injury of spores in processed foods.

Bacteria↗
PubMed1983

Effects of phencyclidine on the release and synthesis of newly formed dopamine.

The effect of phencyclidine (PCP) on the release and synthesis of [3H]-dopamine ( [3H]-DA) newly synthesized from [3,5-3H]-L-tyrosine was studied under both basal and potassium-stimulated conditions in slices from the rat striatum. Phencyclidine (3-100 microM) stimulated the release of [3H]-DA during superfusion with low level potassium (4.5 mM) buffer, but had no effect on the release of [3H]-DA elicited by superfusion with buffer containing 40 mM potassium. On the other hand, phencyclidine had no effect (except at 100 microm) on the spontaneous release of [3H]-H2O (formed as a result of the hydroxylation of [3,5-3H]-L-tyrosine), but inhibited the increase in formation of [3H]-H2O normally associated with potassium-induced depolarization. These data are discussed in relation to results obtained with phencyclidine on other in vitro and in vivo models of dopaminergic function.

Animals↗
PubMed1983

Antigenic analysis of strains of Ebola virus: identification of two Ebola virus serotypes.

A sensitive radioimmunoassay has been adapted for Ebola virus antigens and antibodies to them. It uses 125I-labeled staphylococcal protein A and a specially designed filter manifold. The assay is applicable to the sera of humans and to a wide range of animal sera. Virus isolates from two discrete outbreaks of Ebola hemorrhagic fever that occurred in 1976 were shown by this assay to be antigenically distinct. This lack of identity was further confirmed by cross-absorbing antisera to each isolate with antigens of the heterologous virus strain. The advantages of this assay include the use of noninfectious antigens, the requirement for only small quantities of serum, the capability of screening large numbers of sera, the speed of execution, and the objectivity of end point determination.

Animals↗
PubMed1983

Evidence for two subtypes of Ebola virus based on oligonucleotide mapping of RNA.

Ebola viruses isolated during outbreaks of acute hemorrhagic fever in Africa from 1976 to 1979 were examined by T1 oligonucleotide mapping of virion RNA. Two Ebola virus subtypes distinguishable by their oligonucleotide patterns were involved in the outbreaks of the disease during this three-year period. The first type was isolated in Zaire in 1976 and again in 1977; the second type caused outbreaks in Sudan in 1976 and again in 1979. Oligonucleotide patterns of the two groups of Ebola viruses (Zaire and Sudan) were remarkably similar within the group but differed between groups by approximately 60 oligonucleotides. We can conclude from this study (1) that the outbreaks of hemorrhagic fever which occurred concurrently in 1976 in Zaire and Sudan were caused by viruses that are genetically distinct; (2) that compared with other RNA viruses there was an unusually high genetic stability among viruses within Zaire and Sudan over two- and three-year periods, respectively; and (3) that the two genetic subtypes probably evolved from a common ancestor since they share common oligonucleotides.

Democratic Republic of the Congo↗
PubMed1983

An arenavirus isolated from wild-caught rodents (Pramys species) in the Central African Republic.

We isolated nine arenavirus strains from blood and/or tissues of Praomys sp. rodents wild-caught in derived savannah and forest gallery areas of the Central African Republic (CAR). Convalescent serum from either humans or animals infected by Lassa, Mozambique, or lymphocytic choriomeningitis virus cross-reacted with the strains from the CAR. However, monoclonal antibodies to these three viruses gave a profile against the CAR strains suggesting major antigenic differences between each of them and the CAR virus. These data along with the fact that other African arenaviruses have been recovered from Mastomys natalensis and not Praomys suggest that this virus is significantly different from the others.

Africa, Central↗
PubMed1983

Mastomys (rodentia: muridae) species distinguished by hemoglobin pattern differences.

Hemoglobin electrophoresis patterns were found to be reliable markers for distinguishing two species of Mastomys in Sierra Leone having 32 and 38 chromosomes. All 32-chromosome animals exhibited a single hemoglobin pattern, whereas those with 38-chromosomes had four distinguishable patterns. Both karyotypes were present throughout Sierra Leone. The 38-chromosome species was more prevalent in the Guinea savanna zone to the north, while the 32-chromosome species was most dominant in human-modified high forest areas of the eastern and southern parts of the country. In almost all situations the 32-chromosome species was more common in houses than in bush habitats; the reverse was true for Mastomys having 38 chromosomes. Analysis of hemoglobin patterns thus becomes useful for species identification, and is necessary to understand the roles of the different Mastomys forms as reservoirs of human diseases, such as Lassa fever in West Africa.

Animals↗
PubMed1983

Case-control study of Mastomys natalensis and humans in Lassa virus-infected households in Sierra Leone.

Lassa virus infection and antibodies were studied in households where Lassa fever cases occurred, and compared to those in nearest neighbor houses and "far" houses located across the village from case houses. Seventy-nine percent of all rodents caught in the houses were Mastomys, the natural reservoir of Lassa virus. Rodent infection was not randomly distributed, but rather focal. Thirty-nine percent of the Mastomys in case houses were viremic, compared to 3.7% in control houses. Human antibody prevalence in case houses was 30%, compared to 20% in non-case houses (P less than 0.05, chi-square test, df = 2). Neither seroconversions nor antibody prevalence rates were associated with household size or number of persons per room. Trapping of rodents in half of the case and control houses resulted in a Mastomys reduction ranging from 2.2- to 3.3-fold. This reduction failed to significantly reduce the seroconversion rate to Lassa virus in the people of trapped houses compared to those in untrapped ones. More complete trapping will be needed in order to better evaluate this procedure as a means of interruption of Lassa virus transmission in endemic villages.

Animals↗
PubMed1983

Phencyclidine: behavioral and biochemical evidence supporting a role for dopamine.

Pharmacological studies of phencyclidine (PCP)-induced behaviors such as stereotypy and turning suggest that PCP is an indirectly acting dopamine (DA) agonist with some anticholinergic potential. In vitro studies show that PCP is a potent, competitive inhibitor of monoamine uptake. PCP has also been shown to stimulate synaptosomal striatal tyrosine hydroxylase activity via a release of DA (which normally inhibits this enzyme). The mechanism by which PCP releases DA is unknown, but is similar to that of methylphenidate and distinct from that of amphetamine. In vivo studies also show similarities between PCP and the nonamphetamine class of stimulants. For example, PCP and amfonelic acid, but not amphetamine, potentiate haloperidol-induced DA metabolism. This effect can be blocked by baclofen, which suggests a dependence on nigrostriatal impulse flow. Other studies suggest that PCP releases a pool of DA that is in rapid equilibrium with the vesicular compartment, thereby activating a feedback mechanism (probably transsynaptic) that inhibits the synthesis of DA. Despite the similarities between PCP and nonamphetamine stimulants, there are both behavioral and biochemical anomalies that caution against the strict classification of PCP as a nonamphetamine stimulant.

Animals↗