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Biomedical subjects

J K Dunnick

Publications and source records attributed to J K Dunnick.

At least 55 records · Page 3Linked to original sources
PubMed1987

Comparative inhalation toxicity of nickel subsulfide to F344/N rats and B6C3F1 mice exposed for 12 days.

Groups of F344/N rats and B6C3F1 mice were exposed to aerosols of nickel subsulfide (Ni3S2) 6 hr/day for 12 days not including weekends. Actual exposure concentrations were within 3% of target (target = 10.0, 5.0, 2.5, 1.2, 0.6, and 0.0 mg Ni3S2/m3). Nickel lung burdens of exposed rats and mice increased linearly with exposure concentration. Two male rats and all mice exposed to 10.0 mg Ni3S2/m3 died before the end of the exposures. Exposure to Ni3S2 had no effect on the natural killer cell activity of mouse spleen cells. Lesions in rats and mice related to inhalation of Ni3S2 were found in the nasal epithelium, lung, and bronchial lymph nodes. The most extensive lesions were found in the lung and included necrotizing pneumonia. Emphysema developed in rats exposed to 5.0 or 10.0 mg Ni3S2/m3, while fibrosis developed in mice exposed to 5.0 mg Ni3S2/m3. Degeneration of the respiratory epithelium and atrophy of the olfactory epithelium of the nose occurred in rats exposed to as low as 0.6 mg Ni3S2/m3 and mice exposed to 1.2 mg/m3. Results indicate that inhalation exposure of rats and mice to Ni3S2 aerosol concentrations near the current threshold limit value (TLV) for nickel compounds (1 mg/m3 for Ni metal and roasting fume and dust and 0.1 mg/m3 as Ni for soluble compounds) can produce lesions in the respiratory tract. Atrophy of lymphoid tissues (spleen, thymus, and bronchial lymph nodes) was found in animals of the highest exposure concentration. Degeneration of the testicular germinal epithelium was also observed in mice and rats that survived 5.0 or 10.0 mg/m3 exposure concentrations.

Animals↗
PubMed1986

Reproductive toxicology of methyldopa in male F344/N rats.

Methyldopa, a widely used antihypertensive drug, was administered to male Fischer 344/N rats by gavage 5 days/week for 65 days at dosages of 0, 50, 100, 200, or 400 mg/kg. Decreased body weight was seen in treated animals. After mating to untreated female Fischer 344/N rats on days 57-61, the male rats were necropsied (days 65-67) and reproductive toxicity was measured by sperm count, sperm motility, organ weights, hormone levels and histologic evaluation of the testis. Decreased fertility was seen in males dosed with 200 or 400 mg/kg methyldopa. Decreases were also seen in sperm count, sperm motility, apparent number of late spermatids, and plasma testosterone levels in males in the 200 and 400 mg/kg groups. This alternation of reproductive function in male rats was found to be reversible after a 13-week recovery period without dosing. The marked decrease in circulating testosterone levels following methyldopa treatment at 200 or 400 mg/kg may have contributed to the reproductive toxicity of this drug.

Animals↗
PubMed1986

Lung neoplasms in rodents after chronic administration of dimethyl hydrogen phosphite.

Dimethyl hydrogen phosphite (DMHP), an intermediate in the production of insecticides or herbicides, was administered by p.o. gavage for 2 yr to male Fischer 344/N rats and male and female B6C3F1 mice at doses of 0, 100, or 200 mg/kg and to female Fischer 344/N rats at doses of 0, 50 or 100 mg/kg. Dose related toxicity was seen in the lungs of treated male and female rats. The lung lesions were most prevalent in the high dose male rat group which received a dose twice that given to the high dose female rats. Lung lesions included alveolar epithelial hyperplasia, chemically related pneumonia, alveolar-bronchiolar adenoma, alveolar-bronchiolar carcinoma, and squamous cell carcinoma. DMHP also caused neoplastic and nonneoplastic lesions of the forestomach in male rats; a similar but less pronounced effect was observed in female rats. Nonneoplastic lesions associated with administration of DMHP included mineralization of the cerebellum in male rat and focal calcification of the testis in male mice. Under the conditions of this study, there was clear evidence for carcinogenicity for male rats, equivocal evidence for carcinogenicity in female rats, and no evidence for carcinogenicity in either male or female mice. DMHP caused the highest incidence of lung tumors in the male rat of all chemicals studied to date in the National Cancer Institute-National Toxicology Program Carcinogenesis Testing Program.

Adenoma↗
PubMed1985

Toxicity and carcinogenicity of chlorodibromomethane in Fischer 344/N rats and B6C3F1 mice.

Chlorodibromomethane, a trihalomethane found in water supplies after chlorination, was administered by gavage in corn oil to male and female Fischer 344/N rats and B6C3F1 mice in toxicity studies of 13 weeks and 2 years duration. Doses used in the 13-week study were 0, 15, 30, 60, 125, and 250 mg/kg in rats and mice. At 250 mg/kg, hepatic and renal toxicity was produced in male and female rats and male mice, and mortality was increased in male and female rats. In the chronic study, male and female rats were administered the chemical at 0, 40, and 80 mg/kg. No adverse effects on survival in treated rats were observed. Male rats receiving 80 mg/kg had reduced body weight gains relative to controls. Fatty change and cytoplasmic changes were seen in the liver of treated male and female rats. The male and female mice in the chronic study received doses of 0, 50, and 100 mg/kg of chemical. A dosing accident rendered the number of low-dose male mice inadequate for statistical analysis. High-dose male mice had reduced survival relative to controls. Survival was similar in dosed and control female mice. Dosed male and high-dose female mice had reduced body weight relative to controls. Non-neoplastic hepatic lesions were seen in treated male mice (necrosis and hepatocytomegaly) and in treated female mice (calcification and fatty change); nephrosis was seen in treated male mice. The incidence of hepatocellular adenoma and carcinoma (combined) was increased in treated female mice, but only marginally so in treated male mice. Chlorodibromomethane, like chloroform, is toxic to liver and kidneys, and like chloroform induces hepatocellular tumors in mice.

Adenoma↗
PubMed1984

Reproductive toxicity of dimethyl methyl phosphonate (DMMP) in the male Fischer 344 rat.

Dimethyl methyl phosphonate (DMMP) has been considered for use by the U.S. Armed Forces as a nerve gas simulant in a variety of experimental situations to simulate the physical properties of nerve gases, but not the neurotoxic properties. Dimethyl methyl phosphonate is also used as a flame retardant for urethane foams and polyester resins. This study was conducted to determine the reproductive toxicity of DMMP after subchronic dosing. DMMP was administered to male Fischer 344 rats by gavage 5 days/week for 90 days at dosages of 0, 250, 500, 1000, and 2000 mg/kg, and all animals survived this dosing schedule. At Day 84, the rats were mated to untreated female Fischer 344 rats. There was a dose-related decrease in sperm count, sperm motility, and the male fertility index. The male fertility index was 70, 75, 60, 40, and 0% in the 0, 250, 500, 1000, and 2000 mg/kg dose groups. DMMP acted as a dominant lethal mutagen as demonstrated by an increase in the number of resorptions with increasing doses of the drug. The percentage of resorptions in the control group was 6.1% and increased to 14.9, 37.8, and 79.1% in the 250, 500, and 1000 mg/kg groups, respectively. The testes of the male rats were examined histologically to determine the relationship between reproductive function and pathologic abnormalities. DMMP altered reproductive function at all dose levels, while histologic abnormalities of the testis were seen only in the high-dose group. Changes in the testes of the high-dose animals were characterized by lack of spermatogenesis or by degeneration, vacuolization, and necrosis of cells in the spermatogenic tubules. Histopathologic abnormalities of the kidney were seen in some animals from each of the dosed groups and microscopic changes of the prostate were seen in some of the high-dose animals.

Animals↗
PubMed1984

Chemical characterization of psoralens used in the National Toxicology Program research projects.

Chemical analyses of 4 psoralen derivatives were performed with the use of various techniques, including thin-layer chromatography, gas chromatography, infrared and nuclear magnetic resonance spectroscopy. 8-Methoxypsoralen, 5-methoxypsoralen, 3-carbethoxypsoralen, and 5-methylisopsoralen were determined to be 99, 93, 97, and 99% pure, respectively. A 7% contaminant in the 5-methoxypsoralen sample was identified as a dimethoxypsoralen isomer. These psoralens are being used in research projects sponsored by the National Toxicology Program.

5-Methoxypsoralen↗
PubMed1984

Subchronic toxicity in rats administered oral 8-methoxypsoralen.

Scientists at the National Toxicology Program are studying the toxicologic properties of 8-methoxypsoralen (8-MOP) with and without 320-400 nm UV (UVA). The combination of psoralen and UVA is a promising treatment for psoriasis. In this study, 8-MOP was administered to male and female Fischer 344 rats without subsequent UVA exposure for the determination of toxic effects of the psoralen alone. The drug (in corn oil) was administered by gavage 5 days/week for 90 days at doses of 0, 25, 50, 100, 200, and 400 mg/kg. The effects of toxicity were seen primarily in the 200- and 400-mg/kg dose groups, which included mortality, decreased body weight gain, and dose-related increases in liver:body ratios. On histopathology, target organ toxicity was seen in the liver, testes, and adrenals. In this study, relatively high doses of 8-MOP were tolerated in comparison to the dose of psoralen used in combination therapy clinically.

Administration, Oral↗
PubMed1981

Herpes simplex encephalitis: vidarabine therapy and diagnostic problems.

To learn more about the treatment of herpes simplex encephalitis with vidarabine, we conducted an uncontrolled study of 132 patients referred to 22 hospitals because of suspected disease. All had a brain biopsy and were started on vidarabine, but only 75 were diagnosed by isolation of virus from a brain-biopsy specimen. Cumulative mortality in the latter group was 39 per cent at one year. Other than therapy, levels of consciousness and age were the major variables that influenced outcome. Of 23 patients under 30 years of age who were lethargic at the initiation of therapy, two died and 16 returned to normal. Of 26 patients over 30 years of age who were lethargic at the outset, nine died and 10 returned to normal. Semicoma and coma were associated with worse outcomes, especially in older patients. Our data suggest that outcome is improved with treatment; they provide more support for the use of brain biopsy to diagnose the infection and indicate a need for better therapy.

Adolescent↗
PubMed1977

Studies of radiopharmaceutical-enclosing lipid-protein vesicles formed from native plasma components.

Vesicles 500-600 A in diameter were formed by sonicating diluted samples of rat and mouse plasma. An average preparation of these vesicles formed from 1 ml of plasma contained 7.5 mg of plasma lipid and 7.3 mg of plasma protein. Plasma vesicles could be made to enclose such radiopharmaceuticals as 99mTcO4-, and the vesicles were found to be impermeable to this anion. We have studied the in vivo distribution patterns of 99mTc after intravenous injection into the rat or mouse of pertechnetate-plasma vesicles formed from rat or mouse plasma, and we find that the radioactivity remains primarily within the circulation even at 60 min after injection. In contrast, vesicles formed from artificial lipids are rapidly removed by the liver and spleen. Formation of vesicles from native plasma constituents offers a means of carrying drugs and radiopharmaceuticals in vivo in packages that have a low risk of being either toxic or antigenic.

Animals↗
PubMed1976

Alteration of mammalian cells by interaction with artificial lipid vesicles.

Artificial lipid vesicles interact with a variety of mammalian cells, including blood cells, spleen cells, and tumor cells, and during this interaction components can be transferred from the vesicle to the cell and from the cell to the vesicle. Transfer of intravesicular material is observed when artificial lipid vesicles carrying an intravesicular marker, 99mTc (as TcO4- ion), are incubated with mammalian cells. When vesicles prepared with [14C] phospholipid are incubated with mammalian cells, the labeled lipid is also transferable to mammalian cells. Conversely, if the mammalian cell surface is radiolabeled (with 125I), the cell marker is in part transferable to the vesicles. Thus, interaction of mammalian cells with vesicles alters the characteristics of the cell in several ways. There is a loss of some cell surface components, a gain of vesicle lipid components, and an acquisition of intravesicular contents. Such alteration may affect the biological behavior of the cell in vivo. Thus, the in vivo distribution in the mouse of isologous red blood cells is altered after interaction with vesicles; the liver and spleen remove large proportions of such cells in comparison to control erythrocytes labeled with 51Cr. The behavior of vesicle survivors from a cell interaction is also altered. Upon reexposure of such vesicles to a fresh population of cells, the intravesicular marker is no longer transferable to cells; and upon injection of such vesicles into mice, the liver accumulation of vesicular label is reduced as compared with that of nonincubated vesicles.

Animals↗
PubMed1976

Vesicle interactions with antibody and peptide hormone: role of vesicle composition.

Artificial lipid vesicles (artificial membranes) were shown to bind human 125I-antithyroglobulin (anti-Tg) and human 125I-thyrotropin. Vesicles made with gangliosides bound more antibody and hormone than vesicles lacking them. These gangliosides contained a variety of carbohydrates including glucose, galactose, N-acetyl-galactosamine, and sialic acid. The in vivo stability of antibody-vesicle complexes was a function of vesicle composition: vesicles were most stable when formed from phosphatidylcholine, cholesterol, and gangliosides. Anti-Tg-vesicle complexes bind to thyroglobulin, indicating that at least some of the antibody associated with the vesicle still retains ability to bind to its specific antigen. The addition of a specific antibody or hormone to artificial lipid vesicles may serve as a mechanism to confer specificity to the vesicle in vivo.

Antibodies↗