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Biomedical subjects

N Cooke

Publications and source records attributed to N Cooke.

35 records · Page 2Linked to original sources
PubMed1987

Metabolism of uranium in the rat after inhalation of two industrial forms of ore concentrate: the implications for occupational exposure.

Aerosols produced from two commercially available ore concentrates in which the uranium was present essentially in the one as ammonium diuranate (ADU) and in the other as uranium octoxide (U3O8) were administered to rats. The results show that: 1 uranium in the ADU bearing material was cleared rapidly from the lungs, mainly to the blood, such that the retention kinetics were similar to those for a class D (highly transportable) compound as defined by ICRP; 2 uranium in the U3O8 bearing material was removed from the lungs principally by mechanical processes, the retention kinetics in this case being similar to those defined for a class Y (poorly transportable) compound; 3 for both materials the distribution of uranium amongst body tissues and the fraction of the systemic content excreted in urine were similar to those obtained after the injection of soluble hexavalent compounds; 4 for workers potentially exposed to both these materials, urine monitoring and lung radioactivity counting measurements should be used in addition to air sampling procedures for assessing the intake of uranium. 5 intakes of the ADU bearing material should be restricted to those permitted for short-term exposures on the basis of chemical toxicity, whereas those for the U3O8 bearing material should be governed by radiation dose.

Aerosols↗
PubMed1986

Use of gamma-hexachlorocyclohexane (lindane) to determine the ontogeny of metabolism in the developing rat.

The compound lindane (gamma-hexachlorocyclohexane) has been used to study the ontogeny of metabolism in the developing Fischer 344 rat. The distribution and metabolic fate of lindane at 2, 9, 16, and 23 d of age was investigated following subcutaneous administration of lindane at 20 mg/kg containing 0.5 microCi [U-14C]lindane in peanut oil. Groups of 10 pups (5 male and 5 female) were sacrificed at 4-h intervals during the 24-h period following dosing. Adrenals, blood, brain, heart, lung, liver, and kidneys were analyzed for radioactivity. Urine samples were analyzed for radioactivity and metabolites of lindane. There was a significant age-dependent increase in the metabolism of lindane in the rat. High levels of radioactivity in the lung and increased reductive dechlorination suggest that the lung may play a greater role in metabolism of lindane by young rats. Oxidative phase I reactions increased significantly, while anaerobic reductive dechlorination of lindane to 4-chlorophenylmercapturic acid decreased significantly with age. Phase II sulfate and glutathione conjugations decreased significantly and glucuronide conjugation increased significantly with age. Metabolism and excretion of lindane appear to parallel development of the hepatic enzymes involved in phase I and phase II reactions.

Aging↗
PubMed1985

Effects of age and obesity on the metabolism of lindane by black a/a, yellow Avy/a, and pseudoagouti Avy/a phenotypes of (YS x VY) F1 hybrid mice.

Lindane (gamma-hexachlorocyclohexane) has been shown to produce hepatomas in some strains of mice but not in others. Genetic factors and/or altered metabolism may play a role in the susceptibility to lindane-induced hepatomas. This study reports the effect of age and obesity on the comparative metabolism and disposition of lindane in obese yellow Avy/a and in lean pseudoagouti Avy/a and black a/a phenotypes of (YS x VY) F1 hybrid female mice at 8, 17, 30, 56, and 86 wk of age. At 24 h prior to sacrifice the mice were dosed p.o. with 18 mg lindane (containing 55 microCi [U-14C]lindane/kg). Aging altered the biotransformation of lindane such that while the excretion of lindane and its metabolites declined, the proportion of conjugated and polar metabolites increased. Tissue storage was elevated in older animals. In the yellow Avy/a mice, which are known to have a predisposition to the formation of hepatomas, there was accelerated and prolonged growth, reduced metabolite excretion, a greater proportion of conjugated metabolites, and higher dechlorinase activity compared to that of their pseudoagouti Avy/a and black a/a siblings.

Age Factors↗
PubMed1985

Metabolism of some industrial uranium tetrafluorides after deposition in the rat lung.

UNLABELLED: Two commercially produced natural uranium tetrafluorides were administered to rats either by inhalation or direct injection into the lungs. THE RESULTS: show that, for both materials uranium is cleared rapidly from the lungs, much of it to the blood, show that the distribution of uranium amongst body tissues, and the fraction of the systemic content excreted in urine, is similar to that obtained after the administration of U(VI) bicarbonate, show that the transportability of uranium is much greater than in previously reported studies with other preparations of uranium tetrafluoride, suggest that lung radioactivity counting measurements would be of limited value for interpreting human exposures, indicate that for setting exposure limits these tetrafluorides should be considered moderately transportable compounds (ICRP inhalation class W).

Animals↗
PubMed1985

Metabolism of an industrial uranium trioxide dust after deposition in the rat lung.

UNLABELLED: Uranium trioxide, produced industrially, was administered to rats either by inhalation or direct injection of an aqueous suspension into the lungs. THE RESULTS: show that uranium was cleared rapidly from the lungs, mainly to the blood; show that distribution of uranium among body tissues, and the fraction of the systemic content excreted in urine, was similar to that obtained for other transportable hexavalent uranium compounds; suggest that urine monitoring data would be of more value than lung radioactivity counting measurements for assessing occupational human exposure; indicate that for setting exposure limits by inhalation the uranium trioxide should be considered a highly transportable compound. Thus intakes by workers should be restricted to those recommended for short-term exposures and not those based on an annual limit.

Aerosols↗
PubMed1985

Rheumatoid arthritis and chronic bronchial suppuration.

Twenty-two patients with rheumatoid arthritis and severe chronic bronchial suppuration are described. In 11 patients the respiratory symptoms appeared after the onset of arthritis at an unusually late age. We discuss causes for the disease association, in particular the possibility that disease modifying drugs in rheumatoid arthritis may predispose to the development of chronic bronchial suppuration; such a possibility requires prospective investigation.

Adult↗
PubMed1983

Expression of the prolactin gene in human decidua-chorion.

Messenger RNA (mRNA) purified from human decidua-chorion hybridizes with a 32P-cDNA probe for human prolactin. In contrast, mRNA from human trophoblast and amnion does not hybridize to prolactin cDNA. The migration position on agarose gels of prolactin-specific mRNA from human decidua-chorion is similar to that for mRNA from ovine pituitary, suggesting a similar sized mRNA coding for prolactin in these different tissues and species. These data demonstrate unambiguously that the prolactin gene is expressed in human decidua-chorion, confirming previous immunochemical reports of prolactin production by this tissue in culture.

Amnion↗
PubMed1981

Gold lung.

A rare syndrome of acute pulmonary damage due to gold therapy is described. It appears to be an entity separate from the usually reported side-effects of gold. It has a good prognosis, responding to the cessation of gold and to corticosteroid therapy. Apart from this syndrome of acute pulmonary damage, there is, as yet, no convincing evidence to incriminate gold as a cause of other pulmonary manifestations which have been attributed to rheumatoid arthritis.

Adrenal Cortex Hormones↗
PubMed1980

Juvenile dermatomyositis: a clinical and immunologic study.

Twenty-one children were diagnosed as having juvenile dermatomyositis on the basis of the strict criteria of Bohan and Peter. In addition to the typical skin and muscle changes, abnormalities of esophageal motility (eight of 19), pulmonary function (14 of 17), ECG (10 of 20), and gastrointestinal absorption of D-xylose (two of eight) with active disease were observed. Clinical signs of other collagen vascular disease appeared in five children. Serologic evaluation demonstrated that ANA and rheumatoid factor were transiently positive in six; one child developed a persistently positive rheumatoid factor after four years of disease inactivity. Antibody to ENA was negative in all, but antibody to PM-1 antigen was present in four of 18. Six had a low C3 or C4; evidence of immune complexes was demonstrated by Clq or Raji binding in eight with active disease. One child was IgA deficient. The HLA-B8 antigen was present in 72% of the Caucasian children as compared with the expected incidence of 21%. Therefore, classical dermatomyositis in children has more systemic involvement then previously appreciated, may be related to the presence of circulating immune complexes, and appears to be under immunogenetic control.

Adolescent↗
PubMed1978

Antacid-induced osteomalacia and nephrolithiasis.

A 36-year-old woman suffered from bone pain, muscle weakness, and renal stones after prolonged ingestion of antacids for esophageal reflux. Investigation disclosed hypophosphatemia, hypercalciuria, and osteomalacia by bone biopsy. All symptoms and abnormal laboratory findings reversed with a regimen of oral phosphate supplementation and cessation of antacid intake.

Adult↗
PubMed1977

Hypercalcemic hyperparathyroidism in hypophosphatemic rickets.

A 25-year-old white woman with sporadic hypophosphatemic rickets presented with a 7 year history of chronic mild hypercalcemia, osteitis fibrosa cystic and hypercalcemic nephropathy. Serum immunoreactive parathyroid hormone was elevated by greater than 100-fold and a 3.5 g parathyroid tumor was found at operation. Survey of the literature reveals that of 9 previous cases in which hypercalcemic hyperparathyroidism occurred in association with hypophosphatemic rickets, only two had classical x-linked familial hypophosphatemic rickets. It appears more than likely that this unusual combination of skeletal diseases represents the chance occurrence of primary hyperparathyroidism in patients with underlying x-linked familial hypophosphatemic rickets rather than a complication of phosphate therapy.

Adolescent↗
PubMedDate not supplied

Chlorobenzene-impaired lindane metabolism and the effect of pretreatment with chlorobenzene, lindane, or chlorobenzene plus lindane.

The storage and metabolism of lindane (gamma-HCH) was studied in the female rat after the administration of a hepatotoxic dose of chlorobenzene. Impaired lindane metabolism was observed following a challenge dose of 1.12 g chlorobenzene/kg. The data indicated that a hepatotoxic dose of chlorobenzene (CB) selectively impaired certain pathways, such as dehydrochlorination and the direct hydroxylation of lindane, to a greater extent than others, such as the dehydrogenation and dechlorination of lindane. Pretreatment with a subtoxic level of chlorobenzene produced: (1) significant increases in the dehydrogenation of lindane, (2) significant increase in the excretion of conjugated metabolites, (3) significant increases in the excretion of metabolites derived from the dehydrogenation of lindane through hexachlorocylohexene, gamma-HCCH, (4) significant improvement in the excretion of metabolites derived from CB-impaired dehydrochlorination of lindane as well as from the CB-impaired hydroxylation of lindane, and (5) significant reduction in the level of unaltered lindane stored in the adipose tissue. Repeated pretreatment with a subtoxic level of chlorobenzene offered significant protection against the reduction in lindane metabolism produced by the single hepatotoxic dose of chlorobenzene. Pretreatment with gamma-HCH alone was not as effective against the hepatotoxic effect of CB on lindane metabolism.

Animals↗