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Biomedical subjects

R H Gray

Publications and source records attributed to R H Gray.

At least 145 records · Page 8Linked to original sources

The pathogenesis of trimethyltin chloride-induced nephrotoxicity.

In exploratory studies aimed at elucidating CNS effects due to heavy metal toxicity, signs of compromised renal function were seen in rats. The studies reported here describe the sequential steps of the development of nephrotoxicity by trimethyltin chloride (TMT) in rats. Single doses of 12.25 mg/kg TMT administered orally to 150- to 175-g Long-Evans rats elicited overt signs of toxicity including behavioral abnormalities and marked weight loss. Concurrent with the development of these signs, nephrotoxicity was manifested as functional kidney compromise and associated histopathologic evidence of tubular damage. Pathological changes in the kidneys from treated rats were hyaline droplet inclusions, attenuated brush border, basolateral vacuolization, and eosinophilic granular casts in the proximal tubule cells. These lesions were detected as early as 2 days post-treatment and progressed with time in an orderly and sequential fashion. Renal lesions between 5 and 8 days were mild to severe cortical tubular dilatation, hydropic degeneration, and diffuse hyaline droplet deposition in the lower nephron tubules. Medullary edema and exfoliation of degenerated tubular epithelial cells with cast formation followed from 8 to 11 days. The morphological changes were accompanied by marked elevation of blood urea nitrogen, parallel with polyuria at Day 2 and oliguria by Day 14. Behavioral abnormalities as well as weight loss correlated well with the time course and severity of renal dysfunction and progression of morphological changes. A second experiment compared the effects of TMT in rats of different weights. Heavier rats were more sensitive than lighter rats to the nephrotoxic effects of TMT. These effects were independent of recognizable neurotoxic effects of TMT in the hippocampus.

Animals↗

The association between malnutrition and diarrhoea in rural Bangladesh.

The interaction between diarrhoeal disease and nutritional status measured by anthropometry was investigated in approximately 1000 children aged 1 to 4 years during April-December 1976 in a rural area of Bangladesh. Data on diarrhoeal disease were provided by the mothers interviewed at seven-day intervals. Weight and height data were collected bimonthly. Children classified using anthropometric criteria--weight-for-age, height-for-age, and weight-for-height--were prospectively evaluated for incidence and duration of diarrhoea during a short (two-month) period and a long (eight-month) period. Incidence of diarrhoea was not found to be related to nutritional status measured by any of the anthropometric criteria for any of the periods. But duration of diarrhoea was found to be related consistently to nutritional status measured by weight-for-age and weight-for-height. Diarrhoea in the short term affected weight increment in the short term, but not in the long term and did not affect height increment for any of these periods. Diarrhoea in the long term affected both weight increment and height increment in the long term.

Anthropometry↗

Quantitative assessment of trimethyltin induced pathology of the hippocampus.

The pathology induced by trimethyltin in the hippocampus was investigated using a detailed morphometric model. Male Long-Evans rats were dosed with 3 mg/kg trimethyltin chloride (TMT) for three consecutive days and sacrificed at subsequent interim period. Total brain volume was not significantly affected; hippocampus volume decreased within 4 days after completion of dose. Pyramidal cells were more sensitive to the toxic effects of TMT than granule cells, in addition, dorsal pyramidal cells appeared to be more sensitive than ventral pyramidal cells. The dorsal CA4 region appeared to be the most susceptible to cell loss, although the dorsal CA1 region also exhibited significant reductions. The most dramatic reduction in cell numbers occurred between 14 and 28 days post-dose. Cell loss within the CA3c and CA4 but not the CA1 region was preceded by decreased nuclear volume. In addition cellular loss within the dorsal CA1 region appeared to be most pronounced within a well defined rectangular patch of cells immediately adjacent to the CA3-CA1 junction. The data further suggest that TMT is a potent toxicant to the hippocampus. This toxicity is delayed, and selectively affects well defined groups of cells within the structure. Additionally, differences in nuclear pathology suggest that more than one mechanism may be involved in the destruction of these target cell populations.

Animals↗

Postpartum return of ovarian activity in nonbreastfeeding women monitored by urinary assays.

Assays of first morning urine samples for pregnanediol-3 alpha-glucuronide (PdG), estradiol-17 beta-glucuronide (E2G), and LH were used to monitor endocrine function in 16 regularly cycling women and 22 postpartum nonbreastfeeding women. Twice weekly blood samples were also obtained from the postpartum group. Ovulation was inferred by a significant rise in LH and PdG, and reversal of the E2G to PdG ratio. Luteal phase PdG excretion was measured by the peak of smoothed PdG levels and the area under the smoothed luteal phase PdG curve. The lower limits of normal established in 16 cycling women were a peak luteal phase PdG of 4 micrograms/ml and an area under the PdG curve of 20 micrograms/ml. In the postpartum women, 32% of first cycles were anovulatory, and among ovulatory cycles, 73% had abnormally low luteal phase PdG excretion or short luteal phases. In second and subsequent cycles, 15% were anovulatory and 26% had luteal phase abnormalities. There was a progressive increase in luteal PdG excretion from the first to third cycles. The mean delay before first ovulation was 45.2 days, and no woman ovulated before 25 days after delivery. The correlations between blood and urinary hormone levels were 0.78 for PdG, 0.65 for E2G, and 0.55 for LH. We conclude that assays of daily early morning urine samples provide reliable information on ovulation and luteal phase adequacy, and that there is gradual recovery of pituitary ovarian function after parturition.

Adult↗

Growth and differentiation of primary rat keratinocytes on synthetic membranes.

The attachment, proliferation, and differentiation of primary cultures of keratinocytes isolated from murine epidermis were monitored after purified cell suspensions were seeded and incubated in vitro on various synthetic membranes. Concomitant studies of the effects of attachment factors added to synthetic membranes before use as substrata for keratinocytes were also done. The study demonstrated that a synthetic membrane composed of nylon was superior to other membranes and to plastic control culture vessels in supporting the growth of murine keratinocytes. Although laminin enhanced initial attachment and proliferation of cells on nylon membranes, the untreated substratum was more effective for extended incubation. Stratification and differentiation of these keratinocytes on the nylon substratum was enhanced by raising confluent cultures (7 d) to the air-medium interface so that they were in contact with medium only from the bottom. Cultures raised for 14 d produced many morphologic markers of the epidermis and closely resembled the architecture of this tissue in situ.

Animals↗

Designing new substance abuse treatment services for a competitive environment.

A multivariate analysis of the relationships between service attributes and physician perceptions was conducted as an approach to marketing substance abuse treatment services. The results of this attribute-perceptive-preference study indicate: the physician(s) on staff attribute makes the greatest contribution to perceived quality and efficiency; easy referral admission makes the largest contribution to accessibility perceptions; and providing feedback produces the greatest contribution to perceived continuity. The JCAH attributes neither adds to nor subtracts from the perceptions of any of the four perceptual attributes. Other findings indicate that perceived efficiency produces the greatest contribution to overall consumer preference. Quality perceptions make the second largest contribution to overall preference, followed by continuity and accessibility perceptions.

Community Mental Health Centers↗

Effects of sulfuric acid mist inhalation on mucous clearance and on airway fluids of rats and guinea pigs.

The responses of guinea pigs and rats to inhaled sulfuric acid aerosols were compared to define species differences and to determine the small-animal model most relevant to human exposures. Rats were exposed for 6 h to 1, 10, and 100 mg H2SO4/m3. Guinea pigs were exposed for 6 h to 1, 10, and 27 mg H2SO4/m3. Tracheal mucous clearance of guinea pigs was slowed 1 d after exposures to 1 mg H2SO4/m3. A tendency toward faster clearance was observed at high concentrations of H2SO4 for both guinea pigs and rats (statistically significant only for the rats). The speeding of mucous clearance was correlated with increases in airway sialic acid and also with the appearance of excess tracheal secretions, detected using scanning electron microscopy in both rats and guinea pigs. The responses of guinea pigs to sulfuric acid exposures were more similar to those reported for humans than were those of rats.

Aerosols↗

Retinoids alter the direction of differentiation in primary cultures of cutaneous keratinocytes.

The effects of vitamin A on the morphological expression of differentiation were studied in cell cultures of cutaneous keratinocytes from the newborn rat. The cells were first cultivated in a medium containing 0.11 mM calcium until a confluent monolayer had been formed. Stratification and terminal differentiation were then triggered by raising the calcium concentration of the medium to 1.96 mM ('normal' culture). The rise in the concentration of calcium was coupled with the addition of retinol (RL) of retinoic acid (RAC) to the medium to produce an excess of vitamin A (high-retinoid culture). Delipidized serum was used to produce a deficiency of vitamin A (low-retinoid culture). The tissue organization and the ultrastructure of the keratinocytes in the stratified culture were the same as those seen in conventional cultures and skin explants. These stratified cultures expressed the morphological features of the epidermis of intact skin. The addition of RL or RAC to the medium enhanced features characteristic of the secretory epithelium, such as the formation of an extensive endoplasmic reticulum, an enlargement of the Golgi zone, and an increase in the number of vacuoles. At the same time, the addition of retinoids diminished features characteristic of the terminal differentiation of the stratified squamous epithelium, such as stratification and keratinization. Deficiency of vitamin A in the medium resulted in a culture with many differentiated layers. The differentiated cells of the low-retinoid cultures contained densely packed tonofilaments and synthesized products that reacted with the monoclonal antibody AE2 that is specific for keratin peptides which are markers of epidermal differentiation. In the cell culture system that is presented here, an excess of retinoids redirected epithelial differentiation from a stratifying and keratinizing epithelium towards a secretory epithelium. This system is a useful tool for elucidating the mechanisms responsible for the effect of vitamin A on the differentiation of epithelial cells.

Animals↗

Contraceptive usage during lactation: analysis of 1973 and 1976 National Survey of Family Growth: I. Age and race.

Data from the National Survey of Family Growth are analyzed to estimate the prevalence of contraceptive use during lactation. Approximately 20 per cent of lactating women were sexually active and did not use a method in months two through six, postpartum. Among method users, the largest proportion chose barrier methods but 14 per cent used oral contraceptives in the early postpartum period. Between 1973 and 1976 there was an increase in the percentage of women who utilized a contraceptive method during lactation and a decrease in the per cent using oral contraceptives.

Adolescent↗

Chemical and toxicological aspects of coal liquefaction and other complex mixtures.

Chemists, biologists, and ecologists at Battelle's Pacific Northwest Laboratories are developing a data base to aid engineers in the safe design of coal liquefaction process options. Objectives of this effort have been to identify and evaluate long-term health and environmental issues, evaluate options to permit environmentally acceptable design, and assess risk to man and the environment from deployment of a large-scale coal liquefaction industry. Chemically complex materials produced by various coal liquefaction processes, and under various stages of process design and operating conditions, have been screened for potential health and environmental effects. Biologically active materials have been fractionated and rescreened. Chemical constituents of biologically active fractions have been identified, and the environmental fate of problematic agents is currently being determined. This approach, linking engineering and life sciences research, is also relevant to the development of other energy technologies and industries that produce chemically complex materials. Results indicate that full-boiling-range coal-derived liquids are generally more active than shale oil and petroleum crudes in biological and ecological test systems. Several biologically active agents have been identified, including primary aromatic amines (PAA), polynuclear aromatic hydrocarbons (PAH), and phenols. Some components of coal-derived materials are taken up by biota and metabolized. Hydrotreating, a refining or upgrading process, reduces PAA, PAH, and phenol content, as well as mutagenicity, carcinogenicity, and toxicity of coal liquids. Selective distillation restricts PAA and PAH content, as well as mutagenicity and carcinogenicity to high-boiling-range coal liquids. Other process conditions (i.e., extraction severity, catalyst age, etc.) and environmental factors influence chemical characteristics and biological activity of coal-derived materials. Eliminating toxic input of coal liquids to ecological test systems results in partial system recovery. Recent findings indicate that biological responses to a particular chemical agent vary, depending on whether that material is presented to the organism or environment as a pure compound or in a complex mixture. Thus, results of studies with pure compounds cannot be used alone to predict effects of complex mixtures. The research approach described here provides guidance to solve environmental problems before regulatory agencies require limitations or facility construction is completed, and costs of process changes are higher.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Aged gametes, adverse pregnancy outcomes and natural family planning. An epidemiologic review.

Unconfirmed epidemiologic studies suggest a possible increased risk of birth defects associated with Natural Family Planning (NFP) use, and an increased incidence of spontaneous abortion or frequency of chromosomal abnormalities in abortuses associated with conceptions outside the most "fertile period". The risk is approximately two- to four-fold, but the evidence is by no means conclusive. The implication for NFP depends on the frequency of method failures in user populations, but is not likely to constitute a major hazard. Further research could utilize a data bank of NFP charts.

Abortion, Spontaneous↗