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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 361 records · Page 20Linked to original sources

The modulation of inflammatory response in the peritoneal cavity through stimulation of the pleural cavity: an experimental study in the rat.

To establish whether local inhibition of emigration or a centrally acting mechanism is responsible for the diminished response to a second inflammatory stimulus, three groups of young adult male Sprague-Dawley rats received in intrapleural injections of glycogen followed 4 h later by intra-peritoneal Beef Heart Infusion/protease Peptone. Two, 4 and 8 h after the second injection cell counts were made on both the pleural and peritoneal effusions. Circulating PMNs were also monitored using tail vein blood. The prior injection of glycogen intrapleurally significantly suppressed the subsequent accumulation of peritoneal PMNs in response to the second stimulus. The mechanism of this suppression is discussed.

Animals↗

Trace metal determinations in blood obtained in evacuated collection tubes.

Using atomic absorption spectrophotometry, we determined levels of iron, copper and zinc in serum or plasma samples collected in acid-washed containers and in commercially available evacuated tubes including one model equipped with rubber stoppers prepared by a process which reduces zinc contamination of the rubber. Serum or plasma from all evacuated tubes yielded iron and copper values which were comparable to those from serum obtained in acid-washed glass. Zinc values were higher from all evacuated tubes than from acid-washed glassware. Values obtained from samples collected in the specially-prepared tubes were 10% higher than values obtained from samples collected in acid-washed glassware. Thus, the specially-prepared evacuated tubes may only be useful in large-scale clinical screening studies. Traditional blood collection methods for zinc determination should be used when accuracy is required.

Blood Specimen Collection↗

Hereditary hypoceruloplasminemia.

Serum ceruloplasmin values of less than 21.0 mg/100 ml in males or less than 23.0 mg/100 ml in females were observed in 14 out of 156 otherwise healthy members of a pedigree. The hypoceruloplasminemia segregated in a fashion suggesting that the affected individuals are heterozygous for a mutant gene that results in hypoceruloplasminemia. This mutant gene could be a Wilson's disease gene, but excessive copper loading was absent. It is suggested that hereditary hypoceruloplasminemia may be a benign entity distinct from Wilson's disease.

Adolescent↗

Experimental chemotherapy of histoplasmosis in nude mice.

Nude (nu/nu) mice were infected with Histoplasma capsulatum and treated with varying doses of 3 drug regimens: oral ambruticin, intraperitoneal amphotericin B, and amphotericin B plus oral rifampin. Therapy with amphotericin B alone was the most effective regimen. High-dose ambruticin (50 mg/kg of body weight every 8 hours) led to significantly prolonged survival compared to that of untreated control animals, but no long-term cures. Addition of rifampin produced no benefit and might actually have decreased the efficacy of amphotericin B; this combination may be deleterious in a setting of immunodeficiency.

Administration, Oral↗

Light microscope and electron microscope alkaline phosphatase cytochemistry of rat bone marrow leukocytes.

An enzyme cytochemical method yielding an osmiophilic reaction product, visible at both the light and electron microscope levels, has been applied to the study of alkaline phosphatase in rat bone marrow cells. The enzyme is present in both eosinophils and, in much smaller amounts, in neutrophils. In both cases it is present on the plasma membrane, and in eosinophils intracellular aggregations of reaction product are also seen. The specific granules in both cell types fail to react and the enzyme is first detectable at the promyelocyte stage. Thus the enzyme is demonstrable before specific granule formation begins in the neutrophil, indicating that they are not a significant site of alkaline phosphatase activity in the rat.

Alkaline Phosphatase↗

CT scans in Menkes disease.

The clinical courses and serial computerized tomography (CT) scans of four patients with Menkes disease are described. Although the initial clinical presentations were similar, head growth and serial CT scans showed striking individual differences. The CT scans varied from showing no abnormalities early in the disease to showing diffuse cortical atrophy, subdural accumulation of fluid, or multifocal areas of ischemic infarction. The pathologic findings in one patient showed only cerebral and cerebellar atrophy, whereas the findings in another patient showed areas of ischemic infarction, probably secondary to abnormal vessels. Menkes disease should be suspected in male infants with psychomotor deterioration and seizures, or when trauma is suspected from subdural hematoma and multiple fractures.

Brain↗

Early colonisation of a local inflammatory lesion and its relationship to changes in systemic leucocyte availability: a study of turpentine-induced lesions in the rat.

The changes in both peripheral blood leucocyte counts and lesion inflammatory cells have been measured at intervals up to 24 hr following the subcutaneous injection of turpentine in rats. The lesion PMNL changes were characterised by a sharp rise between 0 and 6 hr and a less-rapid fall between 6 and 24 hr. The half-life of lesion PMNL's, as determined by tritiated thymidine labelling between 12 and 24 hr after turpentine injections, was 13 hr and there was a significant correlation between blood and lesion PMNL counts throughout the experimental period. A dependence of the lesion PMNL population on the availability of these cells is thus suggested. Mononuclear cells, which were predominantly monocyte-derived, showed a sharp rise between 6 and 12 hr, plateauing thereafter. These changes were not associated with significant alterations in blood monocyte counts. Although significant changes in blood lymphocyte counts were observed, these were not reflected in the local inflammatory lesion.

Animals↗

A comparison using quantitative enzyme cytochemistry between leucocyte alkaline phosphatase levels in the bone marrow and blood of the rat.

Leucocyte alkaline phosphatase (LAP) levels have been compared in neutrophil polymorphs in bone marrow and blood in the rat, using a quantitative enzyme cytochemical technique. It has been shown that LAP levels are higher in bone marrow than blood, both in normal animals and those with experimentally-induced local inflammatory lesions. In the latter group both marrow and blood LAP levels were higher than in controls; blood levels rose because of the outpouring of cells with moderately high LAP levels into the blood and marrow levels rose because only cells with very high LAP levels remained. The inverse relationship between neutrophil age and alkaline phosphatase content, previously demonstrated in the peripheral blood of the rat, has also been shown to exist in the bone marrow.

Alkaline Phosphatase↗

Differential leucocyte counts: a comparison of results using light and electron microscopy.

A method is described for handling leucocytes from an inflammatory peritoneal exudate prior to electron microscopy, which allows differential counts from ultra-thin sections to be made. The results of counts from ultrathin sections, viewed on the electron microscope, are compared with samples from the same cell populations prepared on a cytocentrifuge and counted by light microscopy. The results from several cell populations of widely different compositions show clearly that with suitable care taken over preparation and orientation, ultrathin sections can yield comparable differential counts to those obtained by standard light microscope procedures. Possible sources of error are discussed and the advantages of ultrastructural counting assessed. The method has a wide application wherever accurate differential counts are required from cell suspensions processed for electron microscopy.

Ascitic Fluid↗

Genetic control of murine resistance to Toxoplasma gondii.

The genetics of murine susceptibility to Toxoplasma gondii was investigated in inbred mice and their F1 and F2 offspring. Among four strains of congenic mice of the B10 background, those with H-2a/a and H-2b/b genotypes were more susceptible than were those with H-2d/d and H-2k/k genotypes. Breeding studies utilizing three of these strains demonstrated linkage between the H-2a allele and greater susceptibility. These data suggest the existence of an H-2-linked gene affecting susceptibility to T. gondii. In challenge of recombinant inbred mice derived from C57Bl/6J (high susceptibility) and BALB/c (low susceptibility) strains, lines BE, BJ, and BK were more susceptible than lines BD, BG, BH, and BI. These data are consistent with the existence of a second disease susceptibility gene linked to the H-13 locus. F1 offspring of the C57B1/6J X B10.D2 mice were significantly less susceptible than either parent. This phenotypic complementary suggests the presence of more than one genetic mechanism of resistance to T. gondii. From these combined data, we conclude that (i) susceptibility to T. gondii in mice is affected by at least two genes, (ii) one of the genes is linked to the H-2 and one to the H-13 locus, and (iii) more than a single mechanism of resistance must be considered to explain the observed genetic controls of susceptibility.

Animals↗

Histoplasma capsulatum infection in nude mice.

Congenitally athymic nude (nu/nu) mice, when injected intraperitoneally with Histoplasma capsulatum, developed a rapidly fatal disseminated infection characterized by heavy parasitization of reticuloendothelial tissues. In contrast, their heterozygous (nu/X) littermates, which possessed a functioning thymus, developed only a low-grade infection which was apparently self-limited and rarely fatal. Transplantation of thymic tissue into nu/nu mice diminished greatly the severity of infection and reduced mortality by about 50%. These studies emphasize the importance of cell-mediated immunity in host defense against histoplasmosis and suggest that the nude mouse may be a valuable model for the study of this chronic intracellular infection.

Animals↗

Ultrastructural localization of alkaline phosphatase in rat eosinophil leucocytes.

The ultrastructural localization of alkaline phosphatase in eosinophil leucocytes, obtained from experimentally-induced peritoneal exudates in rats, has been studied using an osmiophilic technique with 2-naphthylthiolphosphoryl dichloride as substrate, fast Blue BBN as diazonium salt and postosmication with 1% aqueous osmium tetroxide. With this method identical incubation procedures could be used for both light and electron microscope examination. Eosinophils were the only cells which contained alkaline phosphatase. The enzyme was predominantly associated with the outer surface of the plasma membrane, being present in much lower concentrations in cytoplasmic cisternae. Eosinophil granules only rarely showed reaction product. The plasma membrane location of alkaline phosphatase in eosinophil leucocytes is identical to that recently demonstrated in the human neutrophil.

Alkaline Phosphatase↗

Families of young, hearing-impaired children: the impact of diagnosis.

In 1976--77 there were 15 families with young hearing-impaired children, living in Kingston or within a radius of 50 miles, who participated in a study, funded by the Atkinson Charitable Foundation, to evaluate the impact which the diagnosis of deafness made upon them and their families. The sample was too small for sophisticated statistical analysis, but certain indications are provided by the research. The age at which the children were diagnosed was remarkably late and physicians and other involved professionals were felt to be uncomfortable in facing the parents whose children had hearing losses. Parents willingly admitted their need for more guidance at the time of diagnosis but had, in many cases, become somewhat complacent in their responses to their children and their needs. A strong source of support at the preschool stage was felt to be the home-visiting teacher service provided by the Ministry of Education. A need for more in-home guidance was felt by most parents when their children reached school age. Similarly, a need was expressed for a locally based correspondence course.

Attitude↗

Support services in schools for the hearing- impaired in Canada.

A questionnaire was sent to the principals of 20 schools for the hearing-impaired across Canada seeking data on the types and numbers of professional support staff utilized by them. In addition the schools were asked to express opinions regarding the additional number of professionals in various disciplines that should be employed. The most commonly employed professionals were audiologists and the least common otolaryngologists. The greatest need was said to be for a vast increase in the number of speech therapists available, although among them the schools employed less than the equivalent of one such full-time person.

Audiology↗

Reduction in inflammatory response by prior injection of a different agent at the same site: an experimental study in the rat.

Glycogen, producing a weak PMN response, and BHI/PP, which induces a strong response, have been injected both separately and sequentially into the peritoneal cavity of the rat. It was found that the first stimulus, glycogen, had a modifying effect on the response to the second stimulus, which was reduced. Changes in the number of PMNs in the peritoneal cavity were found to correspond to PMN count changes in the blood, which were monitored simultaneously. This suggests the possibility that the number of PMNs in an exudate is dependent on blood PMN numbers. The point at which the modifying mechanism has its effect remains to be demonstrated, and an assessment of the importance of the changes in blood counts is crucial in locating the point at which the two stimuli interact.

Animals↗