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Biomedical subjects

J C Seely

Publications and source records attributed to J C Seely.

16 recordsLinked to original sources
PubMed1995

Potentiation of carbon tetrachloride hepatotoxicity by inhaled methanol: time course of injury and recovery.

Increases in the use of methanol (MeOH) as a transportation fuel would result in greater potential for inhalation exposure. Because oral exposure to MeOH potentiates the hepatotoxicity of carbon tetrachloride (CCl4), we examined the ability of inhaled MeOH to potentiate CCl4 hepatotoxicity and the time course of injury and recovery. Adult male F-344 rats were exposed to 0 or to 10,000 ppm MeOH by inhalation for 6 h and gavaged with 0.075 ml CCl4/kg 24 h later. Hepatotoxicity was assessed 0.5, 1, 1.5, 2, 3, 7, 15, 30, and 61 d after CCl4 exposure. For CCl4 alone, hepatotoxicity was most severe at 0.5 and 1 d, when minimal centrilobular hepatocellular necrosis and predominately mild centrilobular hepatocellular vacuolar degeneration occurred. By d 3, the livers from the CCl4 rats were histologically normal. For MeOH+CCl4, peak severity of hepatic injury was at 1 and 1.5 d, when moderate centrilobular necrosis and moderate/marked centrilobular degeneration occurred. MeOH+CCl4 resulted in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that were increased, relative to CCl4 alone, 171- and 113-fold, respectively, on d 1, and 166- and 140-fold, respectively, on d 1.5. Significant serum elevations in MeOH+CCl4 rats, relative to CCl4 alone rats, were present until d 7 and d 15 for AST and ALT, respectively. By d 3 and d 7, degeneration and necrosis, respectively, due to MeOH+CCl4 were essentially resolved. On d 7, the MeOH+CCl4 hepatic injury consisted mainly of chronic inflammation and centrilobular fibrosis. By d 30, the livers of MeOH+CCl4 rats were histologically normal. These data demonstrate that inhaled MeOH potentiates the hepatotoxicity of orally ingested CCl4, increasing the severity of CCl4 hepatotoxicity as well as the time required for recovery.

Administration, Inhalation↗
PubMed1992

Comparison of open and blind histopathologic evaluation of hepatic lesions.

This paper explores the controversy among scientists on whether microscopic evaluation of tissue slides should be done in an open or blind fashion. Definitions are given and discussed that provide a better focus to the problem. An experiment was conducted in which hepatocellular degeneration and necrosis in rats were assessed both openly and blindly. The results indicate that 'simple bias' is present when the slides are read openly. Valid comparisons among treatment groups are possible in the presence of simple bias, provided appropriate control groups have been incorporated into the experimental design.

Animals↗
PubMed1991

Acute sarcocystosis-like disease in a dog.

Two of 8 littermate Rottweiler dogs developed persistent diarrhea at 6.5 weeks of age. Dog 1 was euthanatized at 14 weeks of age and had hepatitis characterized by necrosis and mixed leukocyte infiltrations in association with a previously unrecognized Sarcocystis-like protozoon. The organism was free in the hepatocyte cytoplasm without a parasitophorous vacuole, had divided by schizogony, and stained with anti-Sarcocystis serum, but did not stain with anti-Toxoplasma gondii or anti-Neospora caninum serum in an immunohistochemical test. Dog 2 was euthanatized at 10 weeks of age. This dog had large necrotic, hemorrhagic mesenteric lymph nodes. Numerous T gondii tachyzoites were observed in association with these lesions. The organism divided by endodyogeny and stained specifically with anti-T gondii serum.

Acute Disease↗
PubMed1991

Reproductive toxicity of boric acid in Swiss (CD-1) mice: assessment using the continuous breeding protocol.

The potential reproductive toxicity of boric acid (BORA) in CD-1 mice (Swiss) was evaluated using the Reproductive Assessment by Continuous Breeding (RACB) Protocol. BORA was administered in the feed for 27 weeks to male and female Swiss (CD-1) mice at concentrations of 0, 1000, 4500, or 9000 ppm. Estimated doses, based on feed consumption and body weight, averaged 152, 636, and 1262 mg/kg body wt during Week 1 for males for 1000, 4500, and 9000 ppm, respectively. During 14 weeks of cohabitation, fertility of F0 mice was partially reduced at 4500 ppm and totally eliminated at 9000 ppm. No litters, dead or alive, were produced by 9000 ppm cohabited pairs. Among the litters born at 4500 ppm, live litter size and body weight were significantly reduced. A crossover mating trial of control and 4500 ppm groups confirmed the male as the affected sex, with fertility rates and the mating index significantly lower in the 4500 male x 0 ppm female group. At necropsy, after 27 weeks of BORA exposure, dose-related changes were present in F0 males for reduced body and reproductive organ weights, increased incidence of abnormal sperm, decreased sperm concentration and motility, and seminiferous tubule degeneration. In the 4500 ppm females, dietary BORA for 27 weeks caused significantly decreased weights of kidney/adrenals and livers; kidney/adrenal weight was also reduced in 4500 ppm males. The last litters of the control and 1000 ppm females, born in the 14-week breeding phase, were reared to 74 days of age and then mated in nonsibling pairs within treatment groups. These F1 mice had normal fertility, but the adjusted mean body weight of F2 pups was decreased. These data establish the reproductive toxicity of BORA in CD-1 mice and demonstrate that the male is the most sensitive sex.

Animals↗
PubMed1991

Assessment of the hepatotoxicity of acute and short-term exposure to inhaled p-xylene in F-344 rats.

Due to the ubiquitous presence of p-xylene in air and the existing uncertainty regarding its hepatotoxic potential, we examined the effect of acute and short-term exposure to inhaled p-xylene on the liver. Male F-344 rats were exposed to 0 or to 1600 ppm p-xylene, 6 h/d, for 1 or 3 d. Exposure to inhaled p-xylene caused no histopathological evidence of hepatic damage and had little or no effect on the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ornithine carbamyl transferase, alkaline phosphatase, and total bilirubin. Exposure to p-xylene for 1 or 3 d resulted in an increase in relative liver weight on d 1 post-exposure. The concentration of hepatic cytochrome P-450 was increased by both p-xylene exposure regimens on d 1 postexposure and had returned to control levels by d 3 following the single p-xylene exposure and by d 2 following the 3-d exposure. These observations provide consistent evidence that acute and short-term exposure to 1600 ppm p-xylene by inhalation did not produce overt hepatotoxicity but resulted in a significant increase in the concentration of hepatic cytochrome P-450, the principal enzyme system involved in the metabolic biotransformation of xenobiotics.

Administration, Inhalation↗
PubMed1990

Assessment of hepatic indicators of subchronic carbon tetrachloride injury and recovery in rats.

To determine the course of hepatic recovery from subchronic oral administration of carbon tetrachloride (CCl4), male F-344 rats were gavaged with 0, 20, or 40 mg CCl4/kg, 5 days/week, for 12 weeks. Exposure to CCl4 caused dosage-dependent increases in relative liver weight and the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and cholesterol as well as a dosage-dependent decrease in hepatic cytochrome P450. Centrilobular hepatocellular vacuolar degeneration, necrosis, and cirrhosis occurred at both 20 and 40 mg/kg, with dosage-dependent severity. Reversibility of these reported effects varied with parameter. By Day 8 postexposure, necrosis had disappeared and all serum indicators and cytochrome P450 had returned to control levels. By Day 15 postexposure, the severity of the vacuolar degeneration had decreased. Reversibility of cirrhosis was dosage dependent; complete recovery occurred in the low- but not the high-dose group by Day 15. The disappearance of the increase in relative liver weight was also dependent on dosage; the low- but not the high-dose group had returned to the control level by Day 22. In an attempt to measure persistent hepatic damage, liver uptake relative to the spleen was determined for a sulfur colloid labeled with technetium-99m and for tritiated 2-deoxyglucose. Neither method consistently measured hepatic damage in cirrhotic livers due, in part, to the high degree of variability in the tracer uptake data.

Animals↗
PubMed1989

Characterization of the mammalian toxicity of the crystal polypeptides of Bacillus thuringiensis subsp. israelensis.

Solubilized crystal polypeptide preparations of Bacillus thuringiensis subsp. israelensis (BTI) were fractionated by immunoaffinity chromatography using a bound monoclonal antibody formed against the 28K crystal polypeptide. The 28K polypeptide was confirmed to be hemolytic and to possess low mosquitocidal activity against Aedes aegypti larvae. By comparison, the 28K polypeptide was more potent than the solubilized BTI crystals in male Swiss Webster mice, as the LD50 values were (p less than 0.05) 0.77 and 2.33 mg protein/kg body wt, respectively. Acute administration of the 28K polypeptide (mg/kg, ip) produced severe hypothermia and bradycardia in the mouse. No evidence for cooperativity between the 28K and other crystal polypeptides was observed. Preliminary histological examination of the mouse hearts exposed to the 28K polypeptide did not reveal any specific lesion, suggesting that the deficient cardiac performance might be a secondary physiological response. Gross pathological examination of mice as well as Sprague-Dawley rats acutely treated with equivalent doses of solubilized BTI crystal preparations revealed focal to segmental reddened and edematous areas within the small intestine. Histopathology indicated that the major lesion was in the jejunum. Contrary to expectations from in vitro hemolysis assays, cytolysis of mouse red and white blood cells was not detectable after in vivo exposure to the BTI solubilized proteins. The present results indicate that the 28K polypeptide is the mammalian toxic component of BTI crystals.

Aedes↗
PubMed1986

Generalized nodular dermatofibrosis and renal cystadenocarcinomas in a German shepherd dog.

Generalized, nodular dermatofibrosis with coexisting bilateral renal cystadenocarcinomas was diagnosed in a 6-year-old male German Shepherd Dog. Approximately 3 years earlier, the dog had been examined because of lameness attributable to 2 nodular growths between the third and fourth digits of the right front limb. Biopsy revealed dense collagenous dermal fibrosis, often in a nodular arrangement. As the disease progressed, attempts to alleviate the discomfort and lameness caused by the nodular growths were performed by surgical excision. During this period, other nodular growths that developed apparently did not bother the dog. Because of the long and protracted clinical progression of the disease and poor prognosis for successful treatment, the dog was euthanatized. At necropsy, multiple multicentric nodules were found in the skin and subcutis, with most located on the limbs. The nodules were well-circumscribed and hard. Epithelial ulceration and inflammation were confined to nodules on the feet. Small foci of collagenous proliferation were found along fascial planes. In addition, cystic neoplasms were in both kidneys. The microscopic diagnosis was generalized nodular dermatofibrosis, with bilateral renal cystadenocarcinomas.

Animals↗
PubMed1980

Lymphosarcoma associated with virus-like intranuclear inclusions in a California king snake (Colubridae: Lampropeltis).

A laboratory-bred and laboratory-reared male California king snake was submitted for clinical evaluation, and a mass was palpated caudal to the stomach and within the abdominal cavity. The snake was anesthetized and the mass was excised. A constricted atonic section of adjacent small intestine was removed and the ends were subsequently reanastomosed. The snake died 2 days post surgery; after histopathologic examination of all major organs (except muscle and brain), lymphosarcoma was diagnosed. Lymphocytes, approximately 70% of which contained small to large eosinophilic intranuclear inclusions, had infiltrated all major organs. By electron microscopic examination these inclusions were found to be large electron-dense granular structures. Aggregates of circular structures that measured 50 nm were seen in the cytoplasm of several cells.

Abdominal Neoplasms↗
PubMed1979

Heart failure associated with unusual hepatic inclusions in a Deckert's rat snake.

A juvenile Deckert's rat snake, Elaphe obsoleta deckerti, was presented with a circumferential enlargement of the body in the region of the heart. The heart was enlarged approximately twice normal size. Focal mineralized lesions were present in the tunica media of the right aorta and the right atrioventricular valve. The normal sinusoid architecture of the liver was disrupted with deeply eosinophilic to lightly basophilic granules of variable size in the cytoplasm and light eosinophilic intranuclear inclusions. Similar appearing intracytoplasmic granules were seen in the glomeruli and kidney tubules.

Animals↗
PubMed1978

Leiomyosarcoma of the canine urinary bladder, with metastases.

An enlarged nodular mass, assumed to be the prostate gland because of location and consistency, was palpated in the pelvic region of a 10-year-old German Shepherd Dog. Castration was performed as a therapeutic procedure after an estrogenic hormone failed to reduce the size of the mass. A tumor identified histologically as a seminoma was in the right testicle. The dog died 1 month after castration, and generalized metastatic neoplasia was observed at necropsy. The mass that involved the neck of the bladder and the metastases were identified as leiomyosarcoma.

Animals↗
PubMedDate not supplied

Toxicity of bromodichloromethane in female rats and mice after repeated oral dosing.

The carcinogenic water disinfection byproduct, bromodichloromethane (BDCM), produces renal and hepatic toxicity in rodents in acute and subchronic studies. In the present investigation, female rats and mice (n = 6) were dosed daily for 5 consecutive days with BDCM (dissolved in an aqueous, 10% Emulphor solution) by gavage. Rats received 75, 150 and 300 mg BDCM/kg body weight/day and mice received 75 and 150 mg BDCM/kg body weight/day. Two rats in the 300 mg/kg/day treatment group died on day 5. On day 6, the animals were sacrificed and serum samples were taken for analysis of indicators of hepatic and renal toxicity. Livers and kidneys were excised and samples taken for histopathological evaluation. Portions of the livers were also utilized to produce microsomes for analysis of cytochrome P450 enzyme activities and total P450 content. Total hepatic cytochrome P450 was decreased in rats dosed with 150 and 300 mg BDCM/kg body weight/day, but was not significantly affected in BDCM-treated mice. Serum lactate (LDH) and sorbitol (SDH) dehydrogenase, aspartate aminotransferase (AST), creatinine and blood urea nitrogen were increased above those of controls in rats dosed with 300 mg BDCM/kg/day. These data suggested that hepatic and renal damage had occurred in this treatment group. This was confirmed by histopathological analyses which revealed that lesions occurred in both hepatic and renal tissues from rats dosed with 150 and 300 mg BDCM/kg/day. The hepatic lesions were centrilobular and primarily consisted of vacuolar degeneration. The hepatotoxicity indicators alanine aminotransferase (ALT) and SDH were increased in mice dosed with 150 mg BDCM/kg/day. However, no histopathological lesions were observed in these animals. This study shows that BDCM is both hepatotoxic and nephrotoxic to female rats after repeated dosing, but is only weakly hepatotoxic to female mice at the administered doses. Also, reduced activities of hepatic cytochrome P450 were observed in rats, but not mice. These species differences in toxicity and xenobiotic metabolizing enzyme inhibition caused by BDCM suggest that an understanding of the mechanism of toxicity of this compound will be critical when extrapolating rodent toxicity data to humans for this environmental pollutant.

Administration, Oral↗