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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 343 records · Page 19Linked to original sources

Hepatic cytochrome P-450 and microsomal heme oxygenase in copper-deficient rats.

Copper deficient and control rats were pair-fed from weaning a milk-based diet. Each animal received 25 mg of iron parenterally. After 6 weeks of dietary manipulations the animals were killed. As expected, rats fed the copper-deficient diet were anemic. Copper-dependent enzyme activities and copper content of plasma and liver confirmed that copper deficiency was present in these rats. Hepatic microsomal cytochrome P-450 specific contents were similar in control and copper-deficient animals in the uninduced state and following induction of cytochrome P-450 by treatment with phenobarbital. However, microsomal heme oxygenase was increased in copper-deficient animals compared with controls whether they were treated with phenobarbital or not. No differences were observed in splenic microsomal heme oxygenase between dietary groups. These studies suggest that hepatic heme catabolism is enhanced in copper deficiency. The explanation for this enhancement may be related to increased hepatic iron accumulation in copper-deficient animals or to the associated defect of selenium metabolism in copper deficiency.

Animals↗

Cloning restriction fragments that promote expression of a gene in Bacillus subtilis.

Plasmid pPL603 (3.1 megadaltons) specifies neomycin resistance in Bacillus subtilis and contains a structural gene for chloramphenicol acetyltransferase. Cells harboring the plasmid cannot grow on solid media containing 10 microgram of chloramphenicol per ml. Cloning EcoRI (or EcoRI)-generated fragments of deoxyribonucleic acid from several sources into the single EcoRI site in plasmid pPL603, with subsequent selection of transformants of media containing 10 micrograms of chloramphenicol per ml, permits the identification of restriction fragments that promote expression of the chloramphenicol acetyltransferase gene.

Acetyltransferases↗

Delayed auditory brainstem responses in diabetes mellitus.

Diabetic patients have longer interpeak latencies in the brainstem auditory evoked responses than age-matched controls. The delay is not related to clinical hearing loss or blood glucose level at time of testing. Since waves I and II are normal in latency, the conduction velocity of the eighth nerve is not involved. The delay occurs between waves II and V, which would reflect altered transmission times in auditory brainstem and midbrain structures, and suggests the presence of a central neuropathy in patients with diabetes.

Adult↗

Adoptive transfer of immunity to Histoplasma capsulatum in athymic nude mice.

Studies of adoptive transfer of resistance to Histoplasma capsulatum were performed with athymic nude (nu/nu) recipients and heterozygous (nu/+) donor mice. This model has the benefit of employing a recipient mouse (nu/nu) which cannot be immunized actively against H. capsulatum. Nu/nu mice were protected against H. capsulatum by whole spleen cells, fractioned T lymphocytes, and macrophages from immunized nu/+ donor mice. Similar cell populations from nonimmune nu/+ mice were not protective. Treatment with gold sodium thiomalate, an inhibitor of macrophage function, increased susceptibility to H. capsulatum in nu/+ and nu/nu mice. Adoptive transfer of immunity to H. capsulatum is multifactorial and depends on both T lymphocytes and macrophages.

Animals↗

The effect of intrauterine gonadectomy on fetal and neonatal gonadotrophin secretion in the lamb.

In Exp. 1, sheep fetuses (2 male and 3 female) were gonadectomized between Days 70 and 120 of gestation and their blood LH and FSH levels were compared to those of control animals (4 male, 6 female) at regular times during the first year after birth. In Exp. 2, fetuses (3 male and 5 female) were gonadectomized between Days 50 and 60 of gestation and gonadotrophin levels at Day 90 of gestation were compared to those of control fetuses of the same age. In neither study did the blood LH and FSH levels differ significantly between gonadectomized and intact lambs of either sex in utero or in the first week of life. However, by 2 weeks of age in the males and by 5 weeks of age in the females, gonadotrophin levels were higher in the gonadectomized than in the intact animals and this difference persisted throughout the first year of life. These results imply that fetal and neonatal gonadotrophin levels are suppressed by maternal and placental steroids in the sheep, and not by fetal gonadal hormones.

Aging↗

Osteoclast formation in response to intraperitoneal injection of 1 alpha-hydroxycholecalciferol in mice.

In order to assess osteoclast formation in response to 1 alpha-hydroxycholecalciferol, osteoclast counts per cm of bone surface were performed on paraffin sections of femurs of male CBA mice killed at daily intervals up to 5 days. All animals received daily intraperitoneal injections of 1 alpha-hydroxycholecalciferol up to the time of death. Peak osteoclast formation occurred during the third day, by the end of which maximum numbers of osteoclasts were achieved (11.9 +/- 0.9 osteoclast cm-1) compared to controls (3.5 +/- 0.6 osteoclast cm-1), this increase being highly significant (p less than 0.01). Although the osteoclast population was most dense at the metaphyseal plate in both experimental and control groups, osteoclast counts in this region only doubled whereas overall osteoclast counts more than tripled. The number of nuclei per osteoclast did not significantly alter following four daily injections of 1 alpha-hydroxycholecalciferol.

Animals↗

Formation of osteoclasts from blood monocytes during 1 alpha-OH Vit D-stimulated bone resorption in mice.

In order to investigate a monocyte origin for osteoclasts, tritiated thymidine labelled blood monocytes, harvested from the blood of donor mice, were injected intravenously into syngeneic recipient animals in which osteoclast formation was being stimulated by concomitant intraperitoneal injections of 1 alpha-hydroxycholecalciferol. Labelled osteoclasts were found in autoradiographs prepared from the femurs of recipient mice, demonstrating for the first time that, during hormonally stimulated osteoclast formation, blood monocytes form one source of osteoclasts.

Animals↗

Suppression of cryptococcosis and histoplasmosis by ketoconazole in athymic nude mice.

Congenitally athymic nude (nu/nu) mice are more susceptible to disseminated cryptococcosis and histoplasmosis than their heterozygous (nu/ + ) thymus-bearing litter-mates. The therapeutic efficacy of ketoconazole, an orally absorbable antifungal agent, was evaluated in nu/nu and nu/ + mice infected intraperitoneally with Cryptococcus neoformans and Histoplasma capsulatum. Two- to five-week courses of ketoconazole significantly prolonged the survival of nu/nu mice infected with either fungus in dose-dependent fashion, but death eventually followed discontinuance of therapy. More significant protection was seen in nu/ + mice infected with C. neoformans, and markedly lower fungal counts in organs, with some negative cultures, were seen in ketoconazole-treated nu/ + mice infected with H. capsulatum. These studies indicate that ketoconazole is effective against both fungi, although results of treatment are much better in the immunologically intact nu/ + host.

Animals↗

Clinical studies of a large family with Wilson's disease.

We have identified 11 individuals with Wilson's disease, members of five sibships within a larger family which was traced through seven generations. Of 206 other family members evaluated for Wilson's disease, none had abnormally low serum ceruloplasmin or copper levels and none had Wilson's disease. There were two documented instances of consanguinity, associated with two of the five affected sibships and four of the 11 affected individuals. The patterns of occurrence of Wilson's disease within the family is consistent with the hypothesis that the disorder is transmitted as an autosomal recessive characteristic. It is likely that the apparently high frequency of disease within the family can be explained solely by the founder effect.

Ceruloplasmin↗

Alkaline phosphatase as a marker of maturity in human neutrophils. Studies in normals dosed with aetiocholanolone and prednisolone.

Changes in the level of neutrophil alkaline phosphatase (NAP) in a population of peripheral blood neutrophils were determined in healthy subjects dosed with either aetiocholanolone (Aetio, 4 mg/m2 im) or prednisolone sodium succinate (Pred, 30 mg/m2 iv). Before dosing the mean NAP score, as measured by a modified Gomori azo-dye method, was 109 and 118 in the Aetio and Pred groups, respectively. Fifteen hours after injection the NAP score in the Aetio group had risen to 187 concomitant with the appearance of large numbers of juvenile (band) and mature neutrophils. Twenty-four hours after dosing, the NAP score increased to 213 with still further concentrations of juvenile cells, while the numbers of mature neutrophils returned to approximately baseline values. Five hours after injection, in subjects given Pred, the NAP score had fallen to 108 concomitant with a marked increase in the numbers of mature neutrophils. These data in normals dosed with either Aetio or Pred appear to substantiate a 'first-in, first-out' cellular progression with initial release of the oldest of the mature bone marrow reserve neutrophils containing less (relative to juvenile forms) NAP activity. These data also indicate that NAP activity is inversely related to cellular age and may support previous findings in the rat that enzyme levels are higher in bone marrow relative to peripheral blood.

Alkaline Phosphatase↗

Incubation in mallards (Anas platyrhynchos): changes in plasma levels of prolactin and luteinizing hormone.

The concentrations of prolactin and LH were measured in the plasma of male and female mallards (Anas platyrhynchos) during the breeding season. The concentration of prolactin in the female birds was low before and during egg-laying, increased threefold (P less than 0.001) during incubation and returned to basal levels immediately after the young were hatched. The drakes, which do not participate in incubation in this species, had fairly low prolactin levels throughout the breeding period; levels being slightly higher during the incubation phase than at other times but still much lower (P less than 0.001) than in the incubating females. Concentrations of LH in the females were high during egg-laying but declined at the onset of incubation. In the drakes levels of LH remained high for much longer and did not appear to decline at a fixed time relative to the reproductive cycle of the female birds. These observations support the view that prolactin is associated with incubation in birds, though the data do not permit a conclusion as to whether an increase in prolactin secretion causes incubation behaviour or is stimulated by it.

Animals↗

Pathologic rupture of the spleen in non-Hodgkin's lymphoma.

Pathologic rupture of the spleen was the signal event in the onset of diffuse histiocytic lymphoma in a young woman. The diagnosis of lymphoma was established only after one month of observation. In a review of clinical features of ten patients with pathologic rupture of the spleen due to lymphoma, spleen size was variable, and in four of ten patients a diagnosis of lymphoma had not been suspected previously. In addition to the patient described herein, only two of those previously described survived splenic rupture.

Adult↗

An epidemiological study of speech and hearing disorders.

The research described in this report began on January 1, 1976, and continued for three and a half years. The object was to examine the prevalence of communication disorders in southeastern Ontario in order to make recommendations for the planning of future facilities and services. The study is, to the best of the writers' knowledge, the largest of its kind ever undertaken; it involved more than 5,000 subjects over 18 months of age, each assessed in a one-to-one situation. The research consisted of the following stages, which often overlapped in order to achieve the goals of the study as rapidly and as effectively as possible: -- A review of literature. -- Data collection on known cases of communication disorders in 1975. -- Testing speech and hearing in almost 5,500 people. -- Making recommendations for the future provision of services.

Adolescent↗

Basic audiological and related services in the north -- the role of a native technician.

Over an 18 month period a native technician in the James Bay area was selected, trained, and supervised in the execution of certain audiological functions including record keeping, basic testing, hearing aid "trouble shooting", taking of impressions for moulds, and follow-up. The evidence indicates that this is an effective program which can supplement the occasional services of otolaryngologists and audiologists in the James Bay area. In particular, language barriers are overcome, there is continuity of care, and there is some indication of cost benefit. Recommendations are made for the continuance and possible expansion of this type of service.

Audiology↗