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Biomedical subjects

K M Johnson

Publications and source records attributed to K M Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1987

Standardization of a plaque assay for Lassa virus.

The plaque reduction neutralization test (PRNT) has been used routinely in serological studies with such arenaviruses as Junin, Machupo, and Parana. However, difficulties have been encountered in using the PRNT for LCM virus, while conflicting views have been expressed about the reliability and efficacy of the test with Lassa virus. We have therefore investigated and evaluated the plaque assay for Lassa virus. In addition, the suitability of the PRNT for determining the potency of a serum and its efficacy in passive immunization for the treatment of Lassa fever was also investigated. The Lassa virus plaque assay satisfied the criteria proposed by Cooper [1961] for determining satisfactory plaque technique. Lassa virus plaques appear within 3 days of inoculating Vero cell cultures. By day 5, the plaques are clearly defined, discrete, and measure 1.5 to 2.0 mm. In the plaque reduction neutralization test, the use of native non-inactivated serum was required for a reliable and reproducible determination of serum antibody titer. The potency and suitability of a serum for Lassa fever serotherapy was determined by the use of a constant serum-varying virus (CS-VV) and/or a constant virus-varying serum (CV-VS) PRN technique.

Animals↗
PubMed1987

A prospective study of the epidemiology and ecology of Lassa fever.

In studies of Lassa fever in Sierra Leone, the prevalence of human antibody to Lassa virus ranged from 8% to 52%. Mastomys natalensis, the reservoir of Lassa virus, constituted 50%-60% of the rodents captured in houses but only 10%-20% of those captured in surrounding agriculture and bush areas (chi 2 = 90.2, P less than 10(-6), df = 1), a finding suggesting that houses are the most-important location for transmission of Lassa virus. Viral infection of Mastomys from houses ranged from 0% to 80%. The incidence of seroconversions in susceptible persons ranged from 5% to 22% per year; the ratio of illness to infection ranged from 9% to 26%, and the proportion of febrile illness associated with seroconversion was 5%-14%. Eightfold rises in titer of antibody occurred in 1%-18% of the antibody-positive population, a result suggesting reinfection. We estimate the ratio of fatalities to infection to be 1%-2%, a rate lower than estimates based on hospitalized cases. The high incidence of Lassa fever makes it a major problem in West Africa.

Adolescent↗
PubMed1987

A case-control study of the clinical diagnosis and course of Lassa fever.

A prospective case-control study of Lassa fever was established in Sierra Leone to measure the frequency and case-fatality ratio of Lassa fever among febrile hospital admissions and to better delineate the clinical diagnosis and course of this disease. Lassa fever was responsible for 10%-16% of all adult medical admissions and for approximately 30% of adult deaths in the two hospitals studied. The case-fatality ratio for 441 hospitalized patients was 16.5%. We found the best predictor of Lassa fever to be the combination of fever, pharyngitis, retrosternal pain, and proteinuria (predictive value together, .81); of outcome, the best predictor was the combination of fever, sore throat, and vomiting (relative risk of death, 5.5). Complications included mucosal bleeding (17%), bilateral or unilateral eighth-nerve deafness (4%), and pleural (3%) or pericardial (2%) effusion. Lassa fever is endemic in this area and is a more-common cause of hospital admission and death than has previously been described; this disease must be considered when diagnosing febrile illness in West Africa.

Adolescent↗
PubMed1987

Clinical virology of Lassa fever in hospitalized patients.

We measured levels of virus in sequential specimens from 137 patients with Lassa fever. The probability of fatal disease increased significantly with the level of viremia measured either on admission or during the course of illness. The odds ratio of death in patients with viremia greater than 10 TCID50/ml was 3.7 (90% confidence interval, 1.9-7.2). The same ratio in patients with viremia greater than 10 TCID50/ml and with levels of aspartate aminotransferase greater than or equal to 150 IU/liter was 21.5 (95% confidence interval, 5.2-99.0). Virus was found in throat cultures from 39% of viremic patients, compared with 14% of nonviremic patients (P less than .002); however, the level of virus was usually less than or equal to TCID50/ml. Fewer than 3% of patients were viruric during acute illness, and virus was isolated from three of three samples of cerebrospinal fluid. On admission, 53% of patients had IgG antibodies, and 67% had IgM antibodies. Recovery was not associated with the presence of either IgG or IgM. Virus was isolated from greater than 100 serum specimens that also contained high titers of IgG. Clinical Lassa fever was shown to be a disseminated systemic, primary viral infection, with an outcome highly associated with viremia but not with development of antibody.

Adult↗
PubMed1987

Wilms tumor occurring as a botryoid renal pelvicalyceal mass.

Wilms tumor usually occurs as an abdominal mass arising from the renal parenchyma. A case was encountered in which the neoplasm filled the pelvicalyceal system of an 8-year-old boy as a botryoid mass, with minimal parenchymal involvement. The radiologic manifestations, pathologic features, and surgical implications are discussed.

Child↗
PubMed1987

Phencyclidine selectively inhibits N-methyl-D-aspartate-induced hippocampal [3H]norepinephrine release.

We have reported previously that phencyclidine (PCP) antagonizes N-methyl-D-aspartate (NMDA)-induced release of dopamine and acetylcholine from slices of rat striatum and nucleus accumbens. In the present experiments, we examined the effect of PCP on NMDA and kainic acid (KA)-induced release of [3H]norepinephrine (NE) from superfused rat hippocampal slices. NMDA and KA stimulated the efflux of NE with EC50 values of 192 and 245 microM, respectively. The presence of 1.2 mM MgCl2 in the buffer abolished NMDA-induced release but had little effect on KA-induced release. PCP inhibited the release of [3H]NE induced by 100 microM NMDA with an IC50 of 46 nM, but had no effect on the release of NE stimulated by 300 microM KA. 2-Aminophosphonovalerate antagonized NMDA-induced release, producing a parallel shift to the right in the concentration-response curve. However, PCP shifted the concentration-response curve to the right in a nonparallel fashion. Drugs with PCP-like properties, such as dexoxadrol and cyclazocine, inhibited NMDA-induced release, whereas related drugs such as levoxadrol, ethylketocyclazocine and morphine, which are not PCP-like, had no effect. These data suggest that PCP is a potent, selective, noncompetitive inhibitor of amino acid-induced [3H]NE release and that this action of PCP is mediated through the PCP/sigma receptor.

2-Amino-5-phosphonovalerate↗
PubMed1986

Lassa fever. Effective therapy with ribavirin.

In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and Lassa virus-convalescent plasma for the treatment of Lassa fever. A serum aspartate aminotransferase level greater than or equal to 150 IU per liter at the time of hospital admission was associated with a case-fatality rate of 55 percent (33 of 60). Patients with the same risk factor who were treated for 10 days with intravenous ribavirin, begun within the first 6 days after the onset of fever, had a case-fatality rate of 5 percent (1 of 20) (P = 0.0002 by Fisher's exact test). Patients whose treatment began seven or more days after the onset of fever had a case-fatality rate of 26 percent (11 of 43) (P = 0.01). Viremia with levels greater than or equal to 10(3.6) TCID50 per milliliter on admission was associated with a case-fatality rate of 76 percent (35 of 46). Patients with this risk factor who were treated with intravenous ribavirin within the first six days after onset of fever had a case-fatality rate of 9 percent (1 of 11) (P = 0.006), whereas those treated after seven days or more of illness had a fatality rate of 47 percent (9 of 19) (P = 0.035). Oral ribavirin was also effective in patients at high risk of death. Lassa-convalescent plasma did not significantly reduce mortality in any of the high-risk groups. We conclude that ribavirin is effective in the treatment of Lassa fever and that it should be used at any point in the illness, as well as for postexposure prophylaxis.

Administration, Oral↗
PubMed1986

Lassa fever in children in Sierra Leone, West Africa.

A systematic study of Lassa fever in febrile children was undertaken over a four-year period, from August 1977 to August 1981, in the Eastern Province of Sierra Leone, West Africa. 479 patients were studied; of these, 245 had adequate specimens to confirm or exclude the laboratory diagnosis of Lassa fever. 51 cases of Lassa fever were identified (21% of patients from whom diagnosis was possible). Virus was isolated from 23 patients. All children had fever; cough and vomiting were present in over 60% of cases studied. The five to nine-year age group had the highest prevalence rate (41% of cases). Seasonal clustering occurred in April, May, and August. A significantly higher proportion of females than males had Lassa fever, a finding which remains to be explained. It is concluded that Lassa fever is a disease of significant concern in the paediatric age group.

Adolescent↗
PubMed1986

Lassa virus hepatitis: a study of fatal Lassa fever in humans.

In order to explore the significance of a previous observation that the most important pathologic changes in fatal Lassa fever are hepatic, we have studied postmortem liver biopsies from 19 patients with fatal Lassa fever. We observed a vigorous macrophage response to cellular damage, but we found no evidence of lymphocyte infiltration in infected hepatic tissues. Using semi-quantitative estimates of liver cell damage, we found a wide range in the severity and progression of Lassa virus hepatitis in our fatal cases. We have classified for descriptive purposes three general nosopoeitic phases: active hepatocellular injury (less than 20% necrosis), continued damage and early recovery, and mitotic activity representing hepatic recovery. We conclude that the liver goes through cellular injury, necrosis and regeneration and any or all may be present at death. In no instance was the degree of hepatic damage sufficient to implicate hepatic failure, and all three phases were represented among our cases. We conclude that the hepatitis of Lassa fever in humans is not the primary cause of death.

Hepatitis, Viral, Human↗
PubMed1986

Modulation of brain NMDA receptors: common mechanism of sigma/PCP receptors and their exogenous and endogenous ligands.

Quantitative autoradiographic distribution patterns of sigma/PCP and NMDA receptors show striking similarities but not in all brain areas. We have identified an endogenous ligand of brain PCP receptors which noncompetitively antagonizes NMDA-induced neurotransmitter release from brain slices. These data support the concept that the sigma/PCP receptor ligands may exert their unique behavioral effects by indirect modulation of NMDA-mediated transmission.

Acetylcholine↗
PubMed1986

Characterization of the inhibition of excitatory amino acid-induced neurotransmitter release in the rat striatum by phencyclidine-like drugs.

In the present study, the authors found that, in Mg++-free buffer, N-methyl-D-aspartate (NMDA) was able to evoke the Ca++-dependent and tetrodotoxin-sensitive release of striatal acetylcholine (ACh), presumably via interaction with receptors on cholinergic interneurons. In Mg++-free buffer containing pargyline, NMDA also evoked a Ca++-dependent and tetrodotoxin-sensitive release of striatal [3H]dopamine (DA). Phencyclidine (PCP) and physiological concentrations of Mg++ (1.2 mM) also inhibited ACh release evoked by L-glutamate, L-aspartate and DL-homocysteate, but not ACh release evoked by the glutamate analogs quisqualate and kainate, suggesting that PCP is selective for the magnesium-sensitive, NMDA-preferring glutamate-aspartate receptor subtype. Comparison of PCP inhibition of NMDA-stimulated ACh and DA release with that produced by the competitive NMDA antagonist 2-amino-5-phosphonovalerate indicates that PCP is probably not altering release by a direct action on the NMDA recognition site. The ability of 2-amino-5-phosphonovalerate, but not PCP, to prevent desensitization of NMDA-induced ACh release is consistent with this interpretation. Binding studies did, however, reveal a reduction in the apparent affinity of the PCP binding site by high concentrations of NMDA. This may suggest an allosteric link between the PCP-sigma receptor and the NMDA-type glutamate-aspartate receptor. The receptors mediating excitatory amino acid-induced DA release were somewhat less selective than those on cholinergic neurons in their sensitivity to both Mg++ and PCP. Structure-activity-relationship studies suggested that the inhibition off ACh and DA release evoked by NMDA involves biding to the PCP-sigma receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Striatal synaptosomal dopamine synthesis: evidence against direct regulation by an autoreceptor mechanism.

Regulation of the rate-limiting step in dopamine (DA) synthesis was estimated in striatal synaptosomes by measuring the rate of hydroxylation of L-4-[3H]phenylalanine, a substrate of tyrosine hydroxylase (TH). DA inhibited hydroxylation with an IC50 of 0.2 microM. The concentration-response curve of DA-induced inhibition was not affected by the presence of 1 microM chlorpromazine, a phenothiazine DA antagonist. Sulpiride and haloperidol, DA antagonists of the benzamide and butyrophenone classes respectively, also failed to alter the inhibition of substrate hydroxylation by 1 microM DA, even at concentrations up to 10 microM. In contrast, a parallel 15 fold shift to the right in the concentration-response curve of DA-induced inhibition of hydroxylation was obtained when 10 microM nomifensine, a competitive DA uptake inhibitor, was added. Even in the presence of nomifensine, 1 microM chlorpromazine had no effect on the DA concentration-response curve. The addition of DMPH4, an artificial cofactor for TH, completely blocked DA-induced inhibition of enzymatic activity. These data suggest that direct autoreceptor control of synaptosomal TH activity does not exist in vitro, and that DA-induced inhibition of TH occurs subsequent to reuptake via classical feedback inhibition, presumably by competitive displacement of the necessary endogenous cofactor.

Animals↗
PubMed1985

False-positive reporting of Down syndrome on Ohio and New York birth certificates.

Although correction for underreporting of congenital malformations on birth certificates is included in most studies, inaccuracy of reporting has not been widely examined. Two separate investigations were conducted on the inaccuracy of Down syndrome (DS) reporting on birth certificates; ie, false-positive cases in which an individual coded as DS did not in fact have DS. In Ohio, 824 individuals were coded as DS on their birth certificate during 1970-1981. Of these, a definitive determination as to whether or not they had DS was made on 778 by using cytogenetic data, medical records, the state's birth defects registry, school records, and by questioning physicians. Fifty-seven false-positives were found, indicating a 7.8% level of coding inaccuracy for all races and 6.9% for whites only. Nine of these arose from miscodings during data processing; 48 were misdiagnosed as DS. This can be contrasted with false-negatives also studied in Ohio, where 66.1% of DS cases were not reported on the birth certificate. No statistical differences were observed between false-positives and true DS in the distribution of sexes, in population size of county of birth, or in year of birth (although there was a declining false-positive rate over the 12 year period). The percentage of DS false-positives, however, was significantly higher for younger maternal ages (greater than or equal to 30 years) than older ones (greater than or equal to 30 years) and for nonwhites compared to whites. Further, there was a strong negative correlation between the percentage of false-positives and the degree of certainty expressed in reporting DS on the birth certificate.

Adolescent↗
PubMed1985

Effects of phencyclidine (PCP)-like drugs on turning behavior, 3H-dopamine uptake, and 3H-PCP binding.

In this study representatives from three chemical classes which are known to produce a phencyclidine (PCP)-like discriminative stimulus cue in rats were tested for their ability to inhibit synaptosomal uptake of 3H-dopamine (3H-DA) and to compete for a binding site labeled with 3H-PCP. Although there was a good correlation between these two in vitro activities within the arylcycloalkylamine class (PCP, N-ethyl-phenylcyclohexylamine (PCE), and ketamine) it did not hold when representatives from the benzomorphans, N-allynormetazocine (NANM), cyclazocine (CYCL), and ethylketocyclazocine (EKC), or a substituted dioxolane (etoxadrol) were included. At some dose each of these drugs with the exception of EKC also produced ipsilateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra. This effect was also not well correlated with inhibition of 3H-DA uptake. However, a significant correlation was found to exist between turning behavior and affinity for the putative PCP/sigma receptor. The possibility that a non-dopaminergic mechanism involving the PCP/sigma receptor underlies the ability of these agents to induce turning behavior is discussed.

Animals↗