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Biomedical subjects

R Mickey

Publications and source records attributed to R Mickey.

At least 19 recordsLinked to original sources

Development and characterization of a rapid-onset rodent inhalation model of asbestosis for disease prevention.

A short-term inhalation model of asbestosis was developed in rodents to examine possible preventive approaches to lung disease. Fischer 344 (F344) rats were exposed for 10 and 20 days to National Institute of Environmental Health Sciences (NIEHS) crocidolite asbestos while sham controls were exposed to air only. To determine quantitative biochemical indicators of asbestos-induced lung disease, bronchoalveolar lavage (BAL) fluids were analyzed for lactic dehydrogenase (LDH), alkaline phosphatase, angiotensin-converting enzyme (ACE), and protein. Total and differential cell counts were performed on cell pellets from BAL. Lungs from additional rats were processed for histopathology, measurement of hydroxyproline, and autoradiography after injection of rats with 3H-thymidine. Exposure to asbestos for 10 and 20 days caused increases in LDH, alkaline phosphatase, and protein in BAL. In contrast, ACE was undetectable in BAL fluids from sham or asbestos-exposed rats. At both time periods, the percentages of polymorphonuclear leukocytes (PMNs) and lymphocytes in BAL were increased in asbestos-exposed rats. Total cell numbers in BAL were increased significantly at 20 days in animals inhaling asbestos. Exposure to asbestos for 10 and 20 days caused elevated amounts of hydroxyproline in lung and the development of fibrotic lesions. Asbestos-exposed rats exhibited increased numbers of interstitial cells and airspace epithelial cells incorporating 3H-thymidine, whereas labeled bronchiolar epithelial cells were not elevated significantly. The quantitative changes in asbestos-associated enzyme levels, cell types and protein in BAL, as well as increases in hydroxyproline and morphologic evidence of fibrosis, are useful indices of asbestos-related lung injury which enable preventive and therapeutic approaches to disease.

Administration, Inhalation↗

Inhibition of lung injury, inflammation, and interstitial pulmonary fibrosis by polyethylene glycol-conjugated catalase in a rapid inhalation model of asbestosis.

Several in vitro studies suggest the involvement of active oxygen metabolites in cell damage caused by asbestos. To determine if lung injury, inflammation, and asbestosis could be inhibited in vivo in a rapid-onset, inhalation model of disease, a novel method of chronic administration of antioxidant enzymes was developed. In brief, Fischer 344 rats were treated with polyethylene glycol-conjugated (PEG-) superoxide dismutase or catalase in osmotic pumps over a 10-day (5 days/wk for 2 wk) or 20-day (5 days/wk for 2 wk) period of exposure to crocidolite asbestos. Control rats included sham-exposed animals and those exposed to asbestos but receiving chemically inactivated enzymes. After 10 days of exposure to asbestos, lactic dehydrogenase (LDH), alkaline phosphatase, and total protein in bronchoalveolar lavage (BAL) were measured in one group of rats. Total and differnetial cell counts in BAL also were assessed. After 20 days of exposure, lungs of an additional group of rats were evaluated by histopathology and by measurement of hydroxyproline. Asbestos-associated elevations in LDH, protein, and total cell numbers in BAL were reduced in rats receiving PEG-catalase. Decreases in numbers of alveolar macrophages, polymorphonuclear leukocytes, and lymphocytes occurred in these animals. Exposure to asbestos for 20 days caused significant increases in both the amount of hydroxyproline in lung and the severity and extent of fibrotic lesions as determined by histopathology. These indicators of asbestosis were inhibited in a dosage-dependent fashion in rats receiving PEG-catalase. Use of inactivated PEG-catalase failed to boost serum levels of catalase and did not inhibit asbestos-induced elevation of hydroxyproline in lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term graft survival.

1. Long-term graft survival is characterized by failure rates that are essentially constant after about a year or 2. The rate has not varied appreciably among cohorts defined in terms of transplant year. 2. Transplants with an excellent clinical course throughout the first 3 months (about 2-thirds of cadaver-donor first transplants) have substantially better long-term graft survival than those with a less favorable early course. 3. Having an excellent early clinical course did not remove the effects of the several factors related to long-term survival. 4. Use of cyclosporine did not relate to long-term survival. 5. Factors related to short-term graft survival (1 year), generally related to long-term survival and in the same direction. Cyclosporine use was a major exception. 6. The dominant factor for long-term survival was tissue matching as reflected in donor categories: HLA-identical sibling, parent, and cadaver. 7. Black recipients had a decidedly poorer long-term survival than recipients of other races/ethnicities. 8. Transplant center was a dominant factor in long-term graft survival. 9. Multivariable analysis did not materially alter the findings obtained from factors considered separately. This was attributable to the sensitivity associated with small standard errors resulting from the large number of cadaver-donor transplants and the combination of smaller numbers and longer survival of living-related transplants.

Age Factors↗

The polymorphism of HLA antigens in the Chinese.

Remarkable differences were observed in antigen frequencies (AF), gene frequencies (GF) and haplotype frequencies (HF) when 2441 healthy Chinese individuals representing nine different ethnic groups and living in 14 different geographic locations were examined for the genetic distribution of the various HLA Class I and II markers. A sizable number of individuals of each ethnic group within each of the three major categories of the Chinese population, namely, Hans, Mongols, and Southern minorities, have been studied here, providing useful population statistics for applications such as determination of probabilities of paternity, comparisons for HLA and disease associations, and anthropologic studies.

China↗

The head and neck sequelae of cervical intravenous drug abuse.

When peripheral veins sclerose, addicts desperately seek new and more dangerous injection sites. At Howard University Hospital, Washington, DC, a disturbing increase in intravenous head and neck complications has been observed. From 1982 to 1985, 30 patients demonstrating complications resulting from intravenous cervical injections were treated. Computed tomography is emphasized as the most helpful diagnostic modality. Its timely use enables physicians to formulate early diagnosis and precise surgical intervention. A suggested diagnostic and treatment protocol is presented as a guideline in the management of this potentially deadly phenomenon.

Abscess↗

Multivariate analysis of risk factors impacting on immediate and eventual cadaver allograft survival in cyclosporine-treated recipients.

A multivariate analysis dissected the impact of donor procurement variables, immunologic risk factors, and alternate cyclosporine and prednisone induction immunosuppressive regimens on the early and eventual function of 303 consecutive cadaveric renal allografts. Primarily warm, but to a slight extent cold, ischemia time had an adverse impact on allograft function, as did the requirement for vasopressor or diuretic therapy. The occurrence of initial graft non-function adversely affected the probability of three-month graft survival, but did not alter either the longevity of organs, which subsequently recovered function, or patient mortality rate. The major immunologic risk factor was a second or multiple transplant, which was associated with an increased incidence of early graft failure, and impaired renal function in successful transplants. Correlations with HLA-B and DR matching were reflected in the quality of renal function, but not in graft survival rates. Cyclosporine (CsA) administration by continuous intravenous infusion, in order to avert initial elevated mean three-day, serum radioimmunoassay drug levels reduced the incidence of initial graft non-function. High levels were also associated with impaired early and eventual renal function. Rapid posttransplant taper of corticosteroids to 30 mg prednisone by day six was associated with a greater incidence of rejection episodes and early graft failure than a taper that achieved 30 mg prednisone at 60 days. Both the serum creatinine value and the degree of hypertension observed at one month afforded good prognostic indices of eventual graft survival. Therefore, renal allografts in CsA-treated patients were sensitive not only to adverse donor and immunologic risk factors, but also to excessive CsA drug levels in the early postoperative period. These findings suggest an induction immunosuppressive strategy utilizing slightly higher initial doses of steroids for CsA-sparing during the first three days, followed by increased, but judicious, administration of CsA to achieve steroid-sparing by virtue of effective rejection prophylaxis.

Cyclosporins↗

Study of the HLA system in the Haitian population.

The HLA-A and HLA-B phenotypes of 329 unrelated Haitian adults were determined and gene and haplotype frequencies were estimated. A summary of the data is presented together with a brief comparison with American Black, American White, and African Black populations. HLA gene and haplotype frequencies of Haitians are quite similar to those for American Blacks. The frequency of Aw34 appears to be smaller in Haitians than in American and African Blacks. No statistically significant differences were found in the frequencies of B-locus antigens.

Adult↗

Theophylline administration in children with asthma: optimal pulmonary function and possible tolerance to chronic administration.

This study was performed to assess the need of obtaining serum theophylline (T) levels between 10--20 micrograms/ml to achieve maximum reversibility of airway obstruction in chronic childhood asthma. Twenty-seven children with daily asthma (ages 9--16 years mean 11.7) were studied to determine the serum T levels required to obtain optimal pulmonary function tests as measured by FEV1 and FEF25--75. Two parallel groups were created. Group 1 (13 subjects) received rapid release (RR) anhydrous T. Group 2 (14 subjects) received sustained release (SR) anhydrous T. The groups were identical in age, weight, height and PFT: p = values greater than or equal to .21 (t test for equivalent means). During initial titration maximal PFT's were obtained in Group 1 subjects with mean T level of 7.1 micrograms/ml and in Group 2 subjects with mean T level of 8.5 micrograms/ml. The PFT responses and theophylline dose responses of each group were not significantly different from each other. After two months of continuous high dose (10--20 micrograms/ml) therapy each subject was again titrated for dose response of PFT with serum T levels. PFT's were not significantly different from the acute studies. After continuous high dose theophylline therapy serum T levels needed (mean 11.5 micrograms/ml) to obtain the maximal PFT response were significantly higher than during the initial titration (mean 7.1 to 8.5 micrograms/ml). Maximal PFT's in many asthmatic children do not require serum T greater than or equal to 10 micrograms/ml in an acute dosage. The continuous use of high dose theophylline may lead to tolerance, thus requiring a higher theophylline dose and subsequent serum level to obtain maximal PFT.

Adolescent↗

Cytomegalovirus infections associated with leukocyte transfusions.

Patients randomized to receive or not to receive prophylactic leukocyte transfusions were evaluated prospectively for serologic, histologic, and cultural evidence of cytomegalovirus infection. Recipients of prophylactic leukocyte transfusions and control subjects were similar with regard to age, sex, underlying disease, immunosuppressive therapy, and number of other transfusions. The recipients of prophylactic leukocyte transfusions (mean, 23.1) had significantly more cytomegalovirus infections (19 of 31 versus seven of 27, p = 0.01) than did control patients receiving no leukocytes or only therapeutic leukocyte transfusions (mean, 3.8). Twenty-seven of 66 donors of leukocytes were seropositive for cytomegalovirus complement-fixation antibody, but cytomegalovirus was not isolated from any of 62 leukocyte transfusions cultured for virus. These results are consistent with the hypothesis that latent cytomegalovirus may be present in leukocytes of blood donors with previous cytomegalovirus infection and after transfusion may be activated to produce active cytomegalovirus infection.

Adolescent↗

Antigenic specificities detected on papainized human granulocytes by microgranulocytotoxicity.

A reliable and routine identification of human granulocyte antigens is possible with an improved microgranulocytotoxicity assay. Freshly isolated, papainized granulocytes, an extended incubation period, and alcohol to prevent the adherence of cells are important factors enhancing cellular reactivity. Absorption studies indicate an absence of B-lymphocyte alloantigens on granulocytes. Five tentative granulocyte specificities were defined with granulocytotoxic non-HLA alloantisera. Sib-pair studies suggest the independent chromosomal segregation of the granulocyte and HLA antigen systems.

B-Lymphocytes↗

Immune function and survival in a long-lived mouse strain subjected to undernutrition.

Functional immune changes were monitored in populations of the long-lived C57BL/6J strain of mice which were subjected to dietary restriction from time of weaning or subjected to such restriction both before and after weaning, along with the appropriate control populations. Responses to T and B cell mitogens (PHA, Con-A, pokeweed, bacterial lipopolysaccharide, and PPD), to injected sheep red blood cells, and measurement of skin allograft rejection rates were followed. Early in life, restricted mice appear immunosuppressed, as judged by all these parameters. Skin allograft rejection remained suppressed until relatively late in life. Other responses tended to reverse from the earlier pattern; by mid-life restricted mice responded better than controls. Dietary restriction profoundly affects the immune system. Mice on such regimes display anatomic and certain immune functional changes which suggest that the immune system may mature less rapidly and stay "younger" longer than in the controls. Furthermore, dietary restriction results in prolongation of life span.

Animals↗