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Biomedical subjects

M S Morgan

Publications and source records attributed to M S Morgan.

At least 19 recordsLinked to original sources

Characterization of antigen presenting cells and T-cells in progressing scabietic skin lesions.

Experimentally infested dogs expressed successful adaptive immunity and self-cured of scabies after previously having scabies that required treatment to cure. A biphasic increase and decrease of CD1a+ Langerhans cells (LCs) in the epidermis of hosts infested the first time (sensitized) and infested a second time (challenged) suggested that these cells were actively involved in the hosts' early immune response to scabies. In contrast, in the dermis CD1a+ cell densities during both infestations increased to a single peak that followed the first peak of these cells in the epidermis. In addition, there was an influx of T-lymphocytes (CD3 epsilon + cells) and CD11c+ cells into the dermis following the first peak of LCs in the epidermis. The influx of T-lymphocytes in the dermis coincided with the peak density of CD1a+ cells in the dermis and epidermis during the second infestation. In both the epidermis and dermis, MHC Class II+ cell density profiles were similar to that of CD1a during the first infestation and then exhibited single peaks during the second infestation. The increases in CD1a+, CD3 epsilon + (T-lymphocytes), CD11c+, and MHC Class II+ cell responses in the dermis occurred earlier and were more intense in the challenge infestation compared with the first infestation. These data indicate that T-lymphocytes (CD3 epsilon +), CD11c+, MHC Class II+, and CD1a+ cells in the dermis played a major role in the successful immune response to scabies mites.

Animals

Interindividual differences in 2H8-toluene toxicokinetics assessed by semiempirical physiologically based model.

Recent applications of physiologically band toxicokinetic (PBTK) models have used animal to human scaling, the hypothetical average man, and Monte Carlo techniques to estimate human exposure to toxicants. Our study built a PBTK model suitable for person-specific dosimetry. Individual measurements of age, ventilation rate, blood/air partition coefficient, body weight, and adipose tissue fraction were made on 26 male subjects exposed to 50 ppm 2H8-toluene and 50 ppm toluene for 2 hr at rest, with collection of venous blood samples for 120 hr postexposure. Fitted lung metabolism was a novel feature of the PBTK model, used to explain a systemic clearance of 2H8-toluene well in excess of hepatic blood flow. A 10-fold interindividual range in venous concentrations was found. Subject-specific modeling explained 91% of the observed data variability, compared to 53% using literature values for model parameters. Body weight, adipose tissue fraction, and blood/air partition coefficient were correlated with terminal half-life, steady-state volume of distribution, and terminal volume of distribution. Lung metabolism was correlated with systemic clearance and terminal half-life. Interindividual differences in lung metabolism resulted in divergent predicted fractions of 2H8-toluene in the body at 2 and 100 hr. An increased adipose fraction led to lower blood concentrations up to 8 hr postexposure, and simulations showed that at 98 hr, adipose tissue contained 97-99% of 2H8-toluene in the body. Use of subject-specific model parameters greatly improved model fit and demonstrated interindividual differences in toxicokinetics.

Absorption

The development of protective immunity in canine scabies.

Seven of eight dogs that had been previously infested with Sarcoptes scabiei var. canis and then cured, expressed protective immunity when experimentally reinfested with scabies. All seven dogs that expressed resistance were spontaneously cleared of scabies by 64 days after they were experimentally reinfested. Five of the eight dogs were free of scabies by 24 days. The sequential changes in the inflammatory/immune cellular infiltrate in the scabietic lesions of each dog were determined during the sensitizing infestation, cure and the subsequent experimental reinfestation (challenge). During the initial infestation and in the subsequent challenge reinfestation, dogs developed mixed cellular infiltrates in their scabietic lesions that contained mononuclear cells, neutrophils, plasma cells and mast cells. Reinfestation induced more rapid increases in the densities of these cells than had occurred during the sensitizing infestation. Mononuclear and mast cells were the most numerous infiltrating cells during the sensitizing phase. During the challenge phase the most numerous infiltrating cells were mononuclear cells and neutrophils. The sensitizing and challenge infestations induced circulating scabies-specific antibody responses, but the response was more rapid during the reinfestation challenge. Both the cell-mediated response in the skin and the circulating antibody response waned in parallel with clearing of the mites following reinfestation.

Animals

Cross-allergenicity of the house dust mites Euroglyphus maynei and Blomia tropicalis.

BACKGROUND: The domestic mites Euroglyphus maynei and Blomia tropicalis frequently co-inhabit homes in subtropical/tropical regions around the world. Both species are the source of substances that cause allergic reactions in patients. OBJECTIVE: The purpose of this study was to examine the immunologic cross-reactivity between E. maynei and B. tropicalis. METHODS: Sera of 19 mite-sensitive patients who were skin test positive to B. tropicalis and/or RAST positive to E. maynei were used to probe immunoblots or crossed radioimmunoelectrophoresis (CRIE) gels. RESULTS: Western blotting showed that individual sera had IgE that bound to 0 to 17 and 2 to 15 proteins in E. maynei and B. tropicalis extracts, respectively. Corresponding IgE-binding proteins of 105, 75, 57, 18, and 14 kD were detected in both E. maynei and B. tropicalis extracts. The majority of IgE-binding proteins did not show corresponding bands in both extracts. Heterologous CRIE showed IgE binding to six of the nine E. maynei antigens precipitated by anti-B. tropicalis serum with individual sera recognizing 0 to 4 of the six allergens. In the reciprocal reaction, 10 of the 12 proteins of B. tropicalis that were precipitated by anti-E. maynei serum bound IgE with individual sera binding to 0 to 5 proteins. CONCLUSION: This study indicated that E. maynei and B. tropicalis are the source of both species-specific and cross-reactive allergens, but most allergens in each extract were species-specific.

Adult

Immunologic cross-reactivity among various strains of Sarcoptes scabiei.

Varieties of Sarcoptes scabiei from different hosts are highly host specific but they are morphologically indistinguishable. The purpose of this study was to investigate the immunologic cross-reactivity among several varieties of scabies mites using serum from a human scabies patient and from several other species of infested hosts. Homologous and heterologous crossed-immunoelectrophoretic (CIE) analysis of extracts prepared from var. canis (dog) and var. suis (pig) mites yielded very similar antigen profiles. Serum from a human patient infested with var. hominis had circulating IgE that bound to antigens present in extracts prepared from each animal mite variety. Antigen homology was further confirmed by fused peaks on tandem CIE. Additionally, sodium dodecyl sulfate polyacrylamide gel electrophoresis/immunoblot analysis showed that the 2 extracts contained proteins that bound antibody in serum from a var. suis-infested pig, a var. canis-infested dog, var. canis-infested rabbits, and a var. hominis-infested human. The results of this study clearly indicate that different varieties of scabies mites, though host specific, introduce some immunologically cross-reactive molecules into the host. However, each serum from the 4 scabies-infested hosts also contained antibody that was specific for proteins in extract from only 1 variety of mite. These data indicated that each variety of scabies introduced some unique molecules into the host, each strain produced some similar molecules, or both, but different hosts responded immunologically to different sets of these.

Aged

Intraoperative blood transfusion is a major risk factor for coronary artery bypass grafting in women.

BACKGROUND: Women have been found to have greater mortality from coronary artery bypass grafting than men. Uncertainty exists regarding the causes of the differences in outcomes between men and women after coronary artery bypass grafting. METHODS: From a database of 2,569 patients having coronary bypass grafting we have determined factors that contribute to poorer outcomes in women compared with men. RESULTS: Women were found to have greater mortality, postoperative bleeding, and postoperative pulmonary failure than men (p < 0.05). There was no significant difference between men and women in postoperative renal failure, postoperative infection, postoperative stroke, or intraaortic balloon pump (p = not significant). Patient factors other than sex accounted for all the significant predictors (stepwise logistic regression) of mortality, postoperative bleeding, postoperative renal failure, postoperative pulmonary failure, postoperative stroke, need for intraaortic balloon pump, and postoperative infection (p < 0.05). Poorer outcomes in women are associated with greater need for transfusion during operation. Diabetes is predictive of renal failure and stroke. CONCLUSIONS: Mortality and morbidity is less in men despite their higher preoperative creatinine level, greater incidence of reoperation, lower ejection fraction, and more common atherosclerosis of the ascending aorta.

Bacterial Infections

Perceptions of a medical microbiology service: a survey of laboratory users.

AIM: To ascertain the perception of laboratory users regarding the quality of the medical microbiology services in a district general hospital. METHODS: Detailed questionnaires were circulated to all clinicians in the locality, with headings covering the quality of medical advice provided, the availability of information on specimen collection, format of request forms, specimen transport arrangements, turnaround times, the quality and need for interpretative advice, and the overall impression of the quality of the services provided. RESULTS: Two hundred and thirty five replies were received, giving a response rate of 69%. Transportation of specimens and communication of reports were identified as priority areas for improvement. The overall quality of the service was perceived as satisfactory, although areas were identified where substantial improvements could be made, some at little or no cost to the laboratory. CONCLUSIONS: The survey focused clinicians' attention on the service, raised the profile of the laboratory, and resulted in improved communications and a better understanding of customer needs. Overall, the exercise was felt to be extremely useful, and worthwhile repeating to gauge the effect of the changes instituted as a result.

Forecasting

Resistance and immune response in scabies-infested hosts immunized with Dermatophagoides mites.

Seventy-one percent of rabbits immunized with a mixed (50:50) Dermatophagoides farinae and D. pteronyssinus house dust mite extract were resistant to infestation by Sarcoptes scabiei var. canis. The resistance was evidenced by a marked reduction in parasite load. All immunized hosts developed similar immunogen-specific antibody titers that were independent of the levels of scabies infestation that developed when the hosts were infested with scabies. Resistant hosts exhibited significantly lower scabies-specific immunoglobulin titers and produced antibody to fewer scabies antigens than did nonresistant hosts. All infested hosts (resistant and nonresistant) showed a cellular infiltrate in the scabietic lesions that was composed of neutrophils, plasma cells, macrophages, and mononuclear cells. Resistant hosts were characterized by fewer plasma cells in the infiltrate than were observed for non-resistant hosts. Resistant hosts exhibited a gradual increase in the number of infiltrating neutrophils, followed by a decrease that correlated with a decrease in the mite burden. Nonresistant hosts exhibited an early rapid increase, a decrease, and then a gradual increase in the concentration of neutrophils as the mite load increased. These results clearly showed that D. farinae/D. pteronyssinus antigens/epitopes can sensitize the hosts to scabies mites and induce protective immunity. The lower circulating antibody levels and generally stronger inflammatory cell-mediated response of resistant hosts compared with nonresistant hosts suggested that the mechanism by which immunization with Dermatophagoides mites induces immunity to scabies mites involved a down-regulated T helper cell type 2 (Th2) response with reduced antibody production but an up-regulated and stronger Th1 (inflammatory cell-mediated) response to scabies.

Animals

Some effects of sarcoptic mange on dogs.

Sequential changes in pathology were examined for scabies-infested dogs to determine the effects of infestation with Sarcoptes scabiei var. canis. During 8 wk of infestation with S. scabiei, the progression of the disease was evaluated weekly by skin scrape, clinical examination, and blood analyses. At 8 wk, selected organs were microscopically examined for histopathology. All infested dogs developed an advanced level of scabies infestation by 8 wk. Of the 36 blood parameters evaluated, only values for erythrocyte sedimentation rate (ESR) deviated significantly from the normal ranges for dogs. However, infested dogs had significantly (P < 0.01) lower average hemoglobin and hematocrit concentrations after 8 wk of infestation compared to their values prior to infestation or to the values for the control dogs. Red blood cell levels for infested dogs dropped significantly (P < 0.01) from preinfestation concentrations by week 8. Conversely, by 8 wk total white blood cell and neutrophil concentrations were significantly (P < 0.01) greater than uninfested controls. Also, whereas average eosinophil concentrations were not statistically different for infested dogs compared to controls, some individual infested dogs exhibited eosinophilia at 4-8 wk of infestation. The ESRs for infested dogs were significantly (P < 0.01) greater at week 6 and 8 than for experimental dogs prior to infestation or control dogs. All parameters except neutrophils had returned to preinfestation levels by 2 wk after treatment for scabies. Neutrophil concentrations were no longer significantly different by 4 wk posttreatment. There were no significant differences in serum enzyme, biochemical and electrolyte concentrations between infested and control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

English plantain and psyllium: lack of cross-allergenicity by crossed immunoelectrophoresis.

BACKGROUND: English plantain (Plantago lanceolata) weed pollen and psyllium (Plantago ovata) husk dust are inhalant allergens. Because of the phylogenetic relationship between these plant species, cross-allergenicity has been a concern. OBJECTIVE: The purpose of this study was to investigate the possible cross-allergenicity of plantain and psyllium. METHODS: Homologous and heterologous crossed immunoelectrophoresis (CIE) were performed using a commercial English plantain pollen extract and an extract of psyllium seed embryo. Crossed radioimmunoelectrophoresis (CRIE) was performed using sera from subjects who were RAST positive only to plantain (group A), RAST positive only to psyllium (group B), RAST positive to both plantain and psyllium (group C), or RAST negative to both (group D). RESULTS: All of the group A plantain subjects showed IgE binding to at least one of the six plantain allergens in homologous plantain CRIEs while only one of the sera from the group B subjects reacted very weakly to these plantain allergens. In homologous psyllium CRIE, all group B subjects showed pronounced IgE binding to 2 to 7 of the seven psyllium allergens. Several of the plantain subjects demonstrated only very weak binding to psyllium allergens. Heterologous CRIEs demonstrated little relevant IgE binding. CONCLUSIONS: These results indicate that there is little cross-allergenicity between psyllium husk and English plantain pollen.

Allergens

Effects of sulfur dioxide exposure on African-American and Caucasian asthmatics.

There is concern that air pollution may be causing increases in asthma morbidity and mortality, especially among African-Americans. It is possible that there may be ethnic differences in susceptibility. To evaluate this speculation, a comparative pilot study of respiratory function in 10 African American and 12 Caucasian methacholine positive asthmatic males was conducted. Subjects were exposed to pure air or 1 ppm SO2 while breathing inside a polycarbonate head dome, for 10 min of rest and 10 min of exercise. Baseline and postexposure pulmonary function measurements were recorded, and nasal lavage fluid samples were collected and processed for epithelial and white blood counts. Although significant increases were seen in total respiratory resistance following SO2 exposure in both groups (P = 0.04), no ethic-based difference in response was seen. No significant differences were found in pulmonary or nasal measurements after exposure to SO2 between African-American and Caucasian subjects. No significant changes in epithelial or white blood cell count were found either when data were analyzed from the entire group or separately from the two subject groups. Even though there were no significant group changes, some individuals were particularly responsive to SO2. Three Caucasian and 5 African-American subjects showed greater than 20% increases in total respiratory resistance.

Adult

Sarcoptes scabiei: the circulating antibody response and induced immunity to scabies.

Scabies is an important parasitic disease that continues to persist throughout the world despite the availability of acaricides to control it. The immune response mechanism to scabies and the possible development of a vaccine for control of scabies was investigated. This study demonstrated that hosts infested with scabies develop immunity (resistance) to reinfestation. All hosts developed scabies-specific elevated circulating antibody titers during scabies infestations that followed the classical pattern for primary and secondary infestations. Parallel elevated levels of complement C3 were also observed. The hosts that exhibited acquired immunity after their first infestations had antibody and complement levels during challenge infestations lower than those of the hosts that showed no immunity when reinfested. Induction of immunity coupled with generally elevated antibody levels for both immune and nonimmune hosts suggested that resistance to reinfestation was associated with a cell-mediated response. These data also suggested that vaccination with specific scabies tissue containing the relevant antigens or recombinant relevant antigens could enhance the cell-mediated response to protect the hosts against natural infestations.

Animals

Sarcoptes scabiei: histopathological changes associated with acquisition and expression of host immunity to scabies.

The sequential changes in the histology in scabietic lesions were investigated for hosts (rabbits) during sensitization and reinfestation with Sarcoptes scabiei. Experimentally infested naive hosts developed heavy scabies infestations but 65% of the hosts showed induced immunity (resistance) to reinfestation. All hosts (naive, immune, and susceptible) exhibited an initial cell infiltrate in scabietic lesions that consisted predominantly of neutrophils and a few macrophages. This was followed by a dense plasma cell infiltrate. Upon reinfestation the progression of neutrophil infiltration was faster and the response was greater in hosts who acquired immunity than those in the susceptible hosts.

Animals

Serum antibody profiles of Sarcoptes scabiei infested or immunized rabbits.

The circulating antibody profiles of rabbits infected or immunized with Sarcoptes scabiei var. canis were compared. Crossed immuno-electrophoretic analysis showed that infested hosts produced serum antibody to 12 proteins (antigens) in an extract made from sarcoptic mite bodies. In contrast, rabbits immunized with an extract made from mite bodies produced antibody to 20 Sarcoptes proteins (antigens). SDS-PAGE/immunoblot analysis revealed that serum from immunized rabbits contained antibodies that bound strongly to proteins of 25 and 39-52 kD that were only barely visualized by antibodies in serum from infested rabbits.

Animals