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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

Salivary concentrations of atrazine reflect free atrazine plasma levels in rats.

The protein binding of atrazine in plasma and its effect on salivary excretion of atrazine was determined in male Sprague-Dawley rats. The degree of protein binding of atrazine was determined at 3 steady-state plasma concentrations, 50, 150, and 250 microg/L, using an ultrafiltration technique. In total, 48 arterial blood samples were collected from 18 rats; 38 of 48 blood samples had their time-matched whole saliva samples. The average protein binding of atrazine ranged from 18% to 37%; however, it was not significantly different across the 3 steady-state plasma concentrations nor among the individual rats. Overall, 26% of atrazine was bound to plasma proteins and not available for transport from blood into saliva. Protein binding of atrazine in plasma was not correlated with total atrazine plasma concentration nor with free atrazine plasma concentration, which indicates that the protein-bound fraction of atrazine is independent of plasma concentration within the range measured in this study (30-400 microg/L). The average saliva/plasma (S/P) concentration ratio of atrazine increased from 0.7 using total atrazine plasma concentration to 0.94 (S/fP) when free atrazine plasma concentrations calculated as 26% of protein binding was used. Salivary concentration was highly correlated with free atrazine plasma concentration. The results suggest that salivary concentration of atrazine not only reflects its total plasma level but accurately measures the portion of atrazine (free atrazine) in plasma, which may be of toxicological significance.

Animals

Occupational exposures and amyotrophic lateral sclerosis. A population-based case-control study.

This population-based case-control study was conducted in three countries in western Washington State to evaluate associations between workplace exposures and the risk of amyotrophic lateral sclerosis (ALS). Cases (n = 174) were all newly diagnosed with ALS by neurologists during 1990-1994, and controls (n = 348), who were matched according to age (+/-5 years) and sex, were identified via random-digit dialing or Medicare enrollment files. Four industrial hygienists blindly assessed detailed lifetime job histories for exposures to metals, solvents, and agricultural chemicals. Case-control comparisons were made for jobs held between 15 years of age and 10 years prior to the cases' dates of diagnosis. After adjustment for age and education, ever exposure to agricultural chemicals was associated with ALS (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.5); this association was observed separately in men (OR = 2.4, 95% CI 1.2-4.8) but not in women (OR = 0.9, 95% CI 0.2-3.8). Among men, the odds ratio for low exposure to agricultural chemicals (below the median level for exposed controls) relative to no exposure was 1.5 (95% CI 0.4-5.3), and for high exposure, it was 2.8 (95% CI 1.3-6.1) (p for trend = 0.03). Similar analyses based on the panel's assessment of exposures to metals and solvents showed no associations. These findings suggest an association between ALS and agricultural chemicals in men.

Adolescent

Characterization of the allergens of the house dust mite Euroglyphus maynei.

BACKGROUND: The house dust mite Euroglyphus maynei inhabits homes in many parts of the world and is the source of many allergens. OBJECTIVE: The purpose of this study was to biochemically and immunologically characterize the major allergens of E. maynei. METHODS: Proteins in an extract of E. maynei were separated into 20 fractions by using preparative isoelectric focusing. Most proteins and allergens were contained in fractions 7 to 17 with pH of 4.8 to 8.0. The fractions were further characterized by nonreducing sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting with the serum of 16 individuals sensitive to E. maynei. RESULTS: Molecular weights and isoelectric points were assigned to 47 IgE-binding proteins in an E. maynei extract, and the frequency of IgE binding to each allergen was determined. Twenty-two of the allergens were recognized by more than 50% of the 16 sera, and all but one of the subjects had IgE that bound to more than 10 allergens (range, 0 to 32). One of the proteins was identified as the allergen Eur m 2. CONCLUSION: E. maynei is the source of at least 47 individual allergens that have been characterized by molecular weight, isoelectric point, and IgE-binding properties.

Allergens

Characterization of lymphocyte subtypes in scabietic skin lesions of naive and sensitized dogs.

We delineated the density of cells expressing CD4, CD8, CD21 and CD45RA antigens in the cellular infiltrates in the epidermis, dermis and follicular epithelium in scabietic skin lesions of naive hosts and sensitized hosts that expressed resistance to scabies infestation. No cells expressing CD21 (B-lymphocytes and follicular dendritic cells) were present in the epidermis and only a few were occasionally present in the dermis during both the first and second infestations. Naive T-cells (CD45RA+) and CD8+ cells (cytotoxic and suppressor T-lymphocytes) were present in varying densities in the infiltrates throughout the epidermis, dermis and follicular epithelium with no apparent differences in density and the rate of appearance between sensitizing and challenge infestations. CD4+ cells were abundant in fluctuating densities in the dermis, epidermis, and follicular epidermis during the sensitizing infestation and these cells became the dominant cell type early during the challenge infestation. The density of CD4+ cells in the infiltrate was much greater during the challenge than during the sensitization infestation. This population of CD4+ cells consisted of both T-helper/inducer cells and neutrophils and the large increase in their numbers during the challenge suggested they played a key role in the successful immune/inflammatory response that resulted in resistance to scabies infestation.

Animals

Correspondence of salivary and plasma concentrations of atrazine in rats under variable salivary flow rate and plasma concentration.

The stability of the saliva/plasma (S/P) concentration ratio of atrazine was determined under varying conditions of salivary flow rate and plasma concentration of atrazine in Sprague-Dawley rats. In the salivary flow study, whole saliva samples were collected at different salivary flow rates while the plasma concentration of atrazine was maintained at a steady-state level of approximately 150 micrograms/L. In the plasma level study, whole saliva samples were collected at two steady-state plasma concentrations of atrazine (50 and 250 micrograms/L), while salivary flow rate was maintained at a relatively constant level. In both studies, atrazine concentrations in whole saliva and arterial plasma demonstrated a consistent relationship, but salivary concentrations were always lower than those of arterial plasma. Linear regression analysis demonstrated that the S/P concentration ratio of atrazine was not significantly different for salivary flow rates ranging from 23 to 92 microL/min/kg body weight, and did not vary for atrazine plasma concentrations between 30 and 433 micrograms/L. The S/P concentration ratio of atrazine was relatively constant throughout each experimental period (0.68 +/- 0.1 and 0.70 +/- 0.11 for salivary flow and plasma level studies, respectively) and did not differ significantly between rats. When data from both studies were pooled, salivary concentrations were highly correlated with plasma concentrations (r2 = .94). It is concluded that under these experimental conditions, the stability of the S/P concentration ratio of atrazine is not affected by variations in salivary flow rate or atrazine plasma concentrations. The results from this study support the conclusion that atrazine salivary concentrations can be used to predict plasma levels of atrazine in rats.

Analysis of Variance

Surveillance of nasal and bladder cancer to locate sources of exposure to occupational carcinogens.

OBJECTIVE: To locate sources of occupational exposure to nasal and bladder carcinogens for surveillance follow up in British Columbia, Canada. METHODS: Incident cases of nasal cancer (n = 48), bladder cancer (n = 105), and population based controls (n = 159) matched for sex and age, were interviewed about their jobs, exposures, and smoking histories. Odds ratios (ORs) were calculated for 57 occupational groups with stratified exact methods to control for age, sex, and smoking. RESULTS: Occupational groups at increased risk of nasal cancer included: textile workers (six cases, OR 7.6); miners, drillers, and blasters (six cases, OR 3.5); welders (two cases, OR 3.5); pulp and paper workers (three cases, OR 3.1); and plumbers and pipefitters (two cases, OR 3.0). Nasal cancer ORs were not increased in occupations exposed to wood dust, possibly due to low exposures in local wood industries. Strongly increased risks of bladder cancer were found for sheet metal workers (four cases, OR 5.3), miners (19 cases, OR 4.5), gardeners (six cases, OR 3.7), and hairdressers (three cases, OR 3.2). Among occupations originally considered at risk, the following had increased risks of bladder cancer: painters (four cases, OR 2.8); laundry workers (five cases, OR 2.3); chemical and petroleum workers (15 cases, OR 1.8); machinists (eight cases, OR 1.6); and textile workers (three cases, OR 1.5). CONCLUSIONS: Occupational groups with increased risks and three or more cases with similar duties were selected for surveillance follow up. For nasal cancer, these included textile workers (five were garment makers) and pulp and paper workers (three performed maintenance tasks likely to entail stainless steel welding). For bladder cancer, these included miners (12 worked underground), machinists (five worked in traditional machining), hairdressers (three had applied hair dyes), and laundry workers (three were drycleaners).

Aged

The biological exposure indices: a key component in protecting workers from toxic chemicals.

Biological monitoring of exposure to chemicals in the workplace is an important component of exposure assessment and prevention of adverse health effects. It should be employed in conjunction with ambient air monitoring to provide information on the absorbed dose of a chemical agent and the effect of all routes of exposure. Judgments regarding the acceptable level of a chemical or its metabolite in biological samples are facilitated by comparison to a reference value. The American Conference of Governmental Industrial Hygienists has established a series of recommended reference values called the Biological Exposure Indices (BEI). The history and characteristics of the BEI are reviewed, and their suitability for use by occupational health specialists is examined. A number of challenges and stimuli to the continued development and improvement of these reference values are described, and the impact of recent advances in macromolecular biology is assessed.

Biomarkers

Skin test and radioallergosorbent test characteristics of scabietic patients.

The scabies mite Sarcoptes scabiei and the Dermatophagoides house dust mites (HDM) are related phylogenetically and are the sources of several cross-reactive antigens. The purpose of this study was to investigate the immune response to S. scabiei and HDM in scabietic patients. Skin test sensitivity and serum IgE to both S. scabiei and HDM were determined for patients who had or previously had confirmed ordinary scabies. A retrospective group included nine subjects who had received successful treatment three weeks to one year prior to the study. A prospective group included 16 subjects with active scabies. Allergic histories were obtained, serum was collected, and skin prick tests (SPTs) were performed at enrollment for all and periodically over the next 12 months for the prospective patients. None of the individuals in either group reported a known sensitivity to HDM. Six of the nine retrospective patients were SPT positive to both S. scabiei and HDM and two of these showed circulating IgE specific for these antigens. At diagnosis, 13 of 16 patients with active scabies were SPT positive to S. scabiei and 12 of these were also SPT and/or radioallergosorbent test positive to HDM. Six patients had circulating IgE directed at both S. scabiei and HDM antigens while one subject had IgE to S. scabiei only and another had IgE directed at HDM only. Twelve of the 15 subjects tested also showed IgE and/or IgG binding to one or more bands on Western blots of an S. scabiei-specific protein fraction. This study indicated that approximately half of the patients with active scabies had S. scabiei- and HDM-specific circulating IgE while most patients cured of scabies lacked S. scabiei- and HDM-specific serum IgE. The data also suggested that antibodies to S. scabiei in scabietic patients also recognize HDM; however, some antibodies were directed at scabies-specific antigens.

Adult

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