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Biomedical subjects

M L Wilson

Publications and source records attributed to M L Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1983

Differing degrees of susceptibility to experimental allergic encephalomyelitis among inbred strains of hamsters.

Susceptibility to experimental allergic encephalomyelitis was examined in five highly inbred strains of hamsters. The frequency of disease was reproducible within a given strain, but differed remarkably from strain to strain. Two strains--Bio 15.16 and Bio 87.20--appeared to share similar major histocompatibility genes. Despite genetic similarities, susceptibility to acute paralytic EAE was remarkably different in the two strains. Strain 15.16 hamsters consistently developed acute paralysis 10-21 days after sensitization with heterologous nervous tissue and immunologic adjuvants. Strain 87.20 hamsters never developed disease acutely. Protection from EAE was not absolute, however, for some animals developed histopathologic evidence of EAE. Using alternative methods to induce EAE did not alter susceptibility in 87.20 hamsters. Genetic analysis of offspring of susceptible 15.16 and resistant 87.20 hamsters suggested that a single autosomal gene, unrelated to the major histocompatibility locus, accounted for differences in EAE susceptibility in these two strains. This gene had a more profound influence on clinical patterns of EAE than on histopathologic markers of disease.

Animals↗
PubMed1982

Fluorinated ligands as nuclear magnetic resonance probes of active-site nonequivalence in abortive ternary complexes of horse liver alcohol dehydrogenase.

The interactions of the dimeric horse liver alcohol dehydrogenase (LADH) with ligands in two nonreactive ternary complexes have been examined by using nuclear magnetic resonance and fluorescence techniques. One complex contains the enzyme, NADH, and the abortive alcohol substrate p-(trifluoromethyl) benzyl alcohol. The trifluoromethyl group allows the bound environment and bound to free exchange kinetics of this alcohol to be examined by using 19F NMR. Binding isotherms of the coenzyme and the abortive substrate were examined by using fluorescence. Similar measurements were made with the enzyme, NADH, and the aldehyde analogue p-(trifluoromethyl) benzamide. For both complexes there was no evidence of cooperative equilibrium binding of any ligand. Careful measurements of the exchange kinetics of the fluorinated alcohol or amide when binding to the enzyme NADH complex using NMR techniques showed that a single lifetime describes the exchange of ligands from both subunits of the protein. These results appear to rule out any site-site interactions in this system and support the notion that the observed biphasic kinetics observed in transient reactions of LADH with NAD and alcohols is a property of a single site in this system.

Alcohol Dehydrogenase↗
PubMed1975

Phase I study of ftorafur, an analog of 5-fluorouracil.

Ftorafur, a furanyl analog of 5-fluorouracil (5-FU), is reported to be five to six times less toxic and possibly more effective in cancer of the breast and colon than 5-FU. The drug was synthesized, formulated, and utilized in toxicologic studies, and then in 24 patients with advanced incurable malignancies. When Ftorafur is given by intravenous push, it results in immediate flushing, dizziness, nausea, retching, and in some cases transient hypotension. These immediate side effects are largely eliminated by administering the drug slowly by infusion. In patients, 60 mg/kg of Ftorafur given i.v. daily for up to 10 days resulted in mild toxicity. However, 80 mg/kg given i.v. daily for 7 days resulted in severe toxicity, with nausea, vomiting, stomatitis, leukopenia, and thrombocytopenia. These studies confirm those of the Russian investigators as to toxicity and dosage, even with a different method of administration more convenient for therapy. Phase II studies are presently being carried out to compare the effectiveness of Ftorafur and 5-FU.

Adult↗
PubMedDate not supplied

A fatal case of Crimean-Congo haemorrhagic fever in Mauritania: virological and serological evidence suggesting epidemic transmission.

Crimean-Congo haemorrhagic fever (CCHF), a tick-borne viral zoonosis, is focally endemic throughout parts of Eurasia, the Middle East and Africa. In sub-saharan West Africa only 2 previous cases, both non-fatal, have been reported. We documented a fatal human case of CCHF in south-western Mauritania during May 1988 by demonstrating CCHF virus-specific class M antibodies and by isolating CCHF virus. Five of 7 other patients simultaneously in hospital with haemorrhagic fever symptoms also exhibited elevated immunoglobulin (Ig) G. Healthy family members and contacts of these patients showed an IgG prevalence of 36%; similarly 29% of their sheep also had antibodies. A serosurvey of 1219 sheep from 14 widely dispersed sites throughout southern Mauritania demonstrated IgG prevalences ranging from 4.9% to 43.6%. IgM was found in many herds. These observations demonstrate that CCHF virus is enzootic in southern Mauritania, and suggest a recent period of intense transmission in parts of the region.

Adolescent↗
PubMedDate not supplied

Fecal leukocytes in stool specimens submitted for Clostridium difficile toxin assay.

To determine their diagnostic utility, fecal leukocytes were sought by methylene blue stain in 502 consecutive stool specimens submitted for Clostridium difficile toxin assay. In addition, the stability of fecal leukocytes was assessed by daily examination of 23 stool specimens stored at 4 degrees C and room temperature. The sensitivity, specificity, and positive and negative predictive values of fecal leukocytes in predicting C. difficile toxin assay results were 28%, 92%, 27%, and 93%, respectively. At 4 degrees C, fecal leukocytes retained morphology for a minimum of 3 days. Leukocytes survived as long in stool specimens containing either C. difficile toxin or an enteric pathogen as they did in stool specimens with neither finding. We conclude that testing stool specimens for fecal leukocytes is not useful for predicting the presence of C. difficile toxin, because 72% of stool specimens positive for C. difficile toxin are negative for fecal leukocytes despite their stability.

Adolescent↗
PubMedDate not supplied

Transmission of Crimean-Congo haemorrhagic fever virus from experimentally infected sheep to Hyalomma truncatum ticks.

Crimean-Congo haemorrhagic fever (CCHF) virus was inoculated into West African sheep that were simultaneously infested with adult Hyalomma truncatum ticks. Certain sheep developed a viraemia and antibodies, indicating virus infection and replication; however, the length and magnitude of the viraemia and serological responses corresponded to the animals' immunological status. Tick attachment and feeding was not influenced by sheep infection. CCHF virus infection was acquired by 11-33% of female and 0-60% of male ticks. Infection in the ticks did not influence their feeding success, as judged by weight at drop-off, and the weight of eggs produced by infected and non-infected ticks was similar. Transovarial transmission of CCHF virus was demonstrated in 2 of 12 (17%) egg batches from infected female ticks, but in none of 19 egg batches from ticks that tested negative for CCHF virus. Our results suggest that under certain ecological conditions, sheep may serve to amplify CCHF virus in nature through horizontal transmission and that the maintenance cycle also may be influenced by transovarial transmission to the next generation of ticks.

Animals↗
PubMedDate not supplied

Crimean-Congo haemorrhagic fever virus replication in adult Hyalomma truncatum and Amblyomma variegatum ticks.

The kinetics of the replication of the Crimean-Congo haemorrhagic fever virus (CCHFV) was studied in intra-anally inoculated adult Hyalomma truncatum and Amblyomma variegatum ticks. The virus was re-isolated by suckling mouse inoculation and revealed by antigen capture with ground ticks and indirect immunofluorescence of haemolymph. The virus was detected in ticks in the first hours post-inoculation (p.i.) and its replication was observed from 36 h p.i. onwards. Virus titre reached a maximum within 3-5 days then decreased slowly to a level of at 2 log LD50/ml for several months until the end of observations. Several specific, non-identified factors seem to favour CCHFV replication in H. truncatum. Long-term virus persistence seems to occur in CCHFV-infected adult ticks.

Animals↗
PubMedDate not supplied

Host-passage-induced phenotypic changes in crimean-congo haemorrhagic fever virus.

Changes in virulence of Crimean-Congo haemorrhagic fever (CCHF) virus toward intracerebrally inoculated suckling mice (SM) were studied in relation to different host-passage histories. Two CCHF virus strains, one isolated from a human and the other from a tick, were passaged through various vertebrate and tick hosts and then reisolated and tested for their virulence toward SM. In various experiments, SM were inoculated with 12 different viral suspensions, each having a specific passage history. Survival curves of SM, which may reflect differences in viral strain characters, were established using an actuarial life table; differences were evaluated with the log-rank test. Regardless of the origin of the strain, CCHF viruses exhibited pathogenicity when passaged among SM. However, virulence, as measured by the proportion of deaths in SM, was altered following passage through another vertebrate host or tick. The final host seems to have a major influence on virulence. Because CCHF virus strains appear to vary little in their antigenic characters, it is hypothesized that hosts can induce phenotypic changes that modulate viral virulence.

Animals↗