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Biomedical subjects

D C Wolf

Publications and source records attributed to D C Wolf.

At least 73 records · Page 4Linked to original sources
PubMed1994

Induced cytolethality and regenerative cell proliferation in the livers and kidneys of male B6C3F1 mice given chloroform by gavage.

It has been reported that chloroform administered to male B6C3F1 mice at doses of 138 and 277 mg/kg/day in corn oil by gavage 5 days/week for 2 years resulted in incidences of hepatocellular carcinomas of 36 and 98% relative to an incidence in controls of 6%. Cytotoxicity and regenerative cell proliferation have been implicated in the tumorigenic process for this non-genotoxic compound. Although chloroform is known to be nephrotoxic in the male mouse, no treatment-related increase was observed in the frequency of kidney tumors. To better understand the relationship of these endpoints, this study evaluated chloroform-induced cytotoxicity and cell proliferation in the liver and kidney under conditions of the cancer study. B6C3F1 mice were administered oral doses of 0, 34, 90, 138, or 277 mg/kg/day of chloroform dissolved in corn oil for 4 days or 5 days/week for 3 weeks. Bromo-2'-deoxyuridine (BrdU) was administered via osmotic pumps implanted 3.5 days prior to necropsy to label cells in S-phase. Cell proliferation was evaluated in tissue sections immunohistochemically as the percentage of cells in S-phase (nuclear labeling index; LI). Mice given 34 and 90 mg/kg/day by gavage had mild degenerative changes in centrilobular hepatocytes after 4 days of treatment, which was absent at 3 weeks. Centrilobular necrosis was observed in mice given 138 or 277 mg/kg chloroform for 4 days, with increased severity of necrosis at 3 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Nasal toxicity of chloroform in male F-344 rats and female B6C3F1 mice following a 1-week inhalation exposure.

Chloroform is an important environmental water and air pollutant. Inhalation exposure of female B6C3F1 mice and F-344 rats for 6 hr/day for 7 consecutive days to 0, 1, 3, 10, 30, 100, or 300 ppm of chloroform resulted in concentration-dependent lesions in the nasal passages. Chloroform-induced changes included increased epithelial mucosubstances in the respiratory epithelium of the nasopharyngeal meatus, primarily in the rats. A complex set of responses was seen in specific regions of the ethmoid turbinates, predominantly in the rats. These lesions in the ethmoid region, which involved all of the endo- and ectoturbinates, were most severe peripherally and generally spared the tissue adjacent to the medial airways. These changes were characterized by atrophy of Bowman's glands, increased numbers of vimentin-positive cells in the periosteum, new bone formation, and increased numbers of periosteal cells in S phase as determined by bromodeoxyuridine incorporation. Additional changes were site-specific loss of mucosubstances and loss of immunocytochemical staining of acini and ducts of Bowman's glands for P450-2E1 and pancytokeratin, and loss of P450-2E1 immunostaining of the olfactory epithelium. The only change noted in the mice was increased cell proliferation without the osseous hyperplasia. The no-observed-effect level for these responses ranged from 3 to 100 ppm, with histological changes and induced cell proliferation being the most sensitive parameters. It is proposed that the osseous changes induced by chloroform exposure may be secondary to primary degeneration of adjacent Bowman's glands. The relevance of these changes to human health risks include potential damage to the sense of smell, but such effects would not be expected at the low levels of chloroform commonly encountered in the environment.

Administration, Inhalation↗
PubMed1994

Erythromycin as a prokinetic agent: a prospective, randomized, controlled study of efficacy in nasoenteric tube placement.

OBJECTIVES: Erythromycin, a macrolide antibiotic, has been shown to mimic the effects of the polypeptide motilin in the gastrointestinal tract. To determine whether erythromycin ethylsuccinate elixir would facilitate the transpyloric passage of a standard nasoenteric feeding tube once the tube was placed into the stomach, 20 patients were randomized to receive erythromycin or standard therapy. METHODS: Twenty patients (ages 45-78), mean age 63 yr, all male, had 43-inch nasoenteric tubes placed and were randomized to receive erythromycin ethylsuccinate elixir (400 mg/5 ml per os every 8 h for three doses) through the feeding tube or to receive standard therapy that involved no drug intervention. RESULTS: Three placements resulted in immediate transpyloric passage. This represented 3/21 (14%) with immediate passage. One patient dropped out after initial tube placement. The remaining 17 patients had initial tube placement in the stomach; of these, eight were randomized to receive erythromycin and nine to receive standard therapy. Six of the eight nasoenteric tubes in the erythromycin group achieved transpyloric passage in 1 day. Zero of the nine nasoenteric tubes in the standard therapy group achieved transpyloric passage in 1 day (p = 0.0023, Fisher's exact test). CONCLUSION: This study demonstrates that erythromycin ethylsuccinate elixir improves the success of transpyloric feeding tube passage in 1 day and is superior to the standard therapy, which consists of no drug intervention.

Enteral Nutrition↗
PubMed1993

Acute hepatotoxic and nephrotoxic effects of chloroform in male F-344 rats and female B6C3F1 mice.

Previous studies demonstrated that chloroform given by oral gavage in corn oil caused an increased incidence of liver tumors in male and female mice and kidney tumors in male rats, while administration in drinking water resulted in an increased tumor incidence only in the kidneys of the male rats. The tumorigenicity of this nongenotoxic agent has been postulated to be linked with cytolethality and cell proliferation. This study examined the organ-specific toxicity of acute doses of chloroform. Male F-344 rats were given chloroform by gavage in corn oil at the bioassay doses of chloroform of 0 and 180 mg/kg body wt as well as 34 and 477 mg/kg and necropsied 24 hr later. Additional rats were given a single dose of 180 mg chloroform/kg and administered bromodeoxyuridine (BRDU) 2 hr prior to necropsy at 0.5, 1, 2, 4, and 8 days after chloroform treatment. Female B6C3F1 mice were given chloroform by gavage at the bioassay doses of 0, 238, and 477 mg/kg as well as 34 mg/kg and necropsied at 24 hr after treatment. Additional mice were given a single dose of 350 mg chloroform/kg, labeled with BRDU, and necropsied at 0.5, 1, 2, 4, and 8 days after treatment. The kidneys of male rats administered 34, 180, and 477 mg chloroform/kg exhibited mild to severe proximal tubular necrosis in a dose-dependent manner. A 20-fold increase in the labeling index (LI, the percentage of nuclei in S-phase) in the proximal tubule cells was observed 2 days after treatment with the bioassay dose of 180 mg/kg. The livers of male rats exhibited only slight to moderate multifocal centrilobular necrosis at 180 and 477 mg/kg. A 10-fold increase in the LI was observed in the liver of male rats given 477 mg/kg, but no increase was observed at the bioassay dose of 180 mg/kg. In contrast to male rats, female mice developed a dose-dependent centrilobular hepatic necrosis at 238 and 477 mg/kg. No renal lesions were observed in female mice at any dose. A peak increase in LI of 38-fold was observed in hepatocytes in the livers of female mice 2 days after treatment with 350 mg chloroform/kg, with only a 2-fold increase in LI observed in the kidneys. These data indicate that acute chloroform-induced cytolethality leads to increased cell proliferation and that the organ-specific pattern of toxicity is the same as the organ-specific pattern of tumor formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Antibiotic therapy for bacterial enterocolitis: a comprehensive review.

The treatment of bacterial enterocolitis is a major health care issue throughout the world. Many cases of diarrhea due to invasive bacterial pathogens can be managed by oral rehydration, only. Nonetheless, antibiotics play an invaluable role in the management of patients suffering from severe diarrhea or extraintestinal symptoms. This article reviews the literature supporting current recommendations for antibiotic therapy.

Anti-Infective Agents↗
PubMed1992

P-glycoprotein transports corticosterone and is photoaffinity-labeled by the steroid.

Multi-drug-resistant cells overproduce a 130-180-kDa integral membrane phosphoglycoprotein known as P-glycoprotein which acts as an energy-dependent drug efflux pump. While P-glycoprotein has been shown to transport hydrophobic anti-tumor drugs out of multi-drug-resistant cells in tissue culture, its endogenous substrates remain unknown. This report shows that 3H-corticosterone can specifically photoaffinity label P-glycoprotein. Furthermore, corticosterone is effluxed from multi-drug-resistant cells by P-glycoprotein. These data suggest that corticosterone may be an endogenous substrate for P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Predisposition to renal cell carcinoma due to alteration of a cancer susceptibility gene.

A single germ line gene mutation at a tumor susceptibility locus in a rodent model of hereditary human renal cancer caused a 70-fold increase in susceptibility to chemical carcinogenesis. A carcinogen that targeted both renal epithelial and mesenchymal cells caused an increase in tumors of epithelial origin in susceptible animals; the number of carcinogen-induced mesenchymal tumors was unaffected by the presence of the mutation at the susceptibility locus. Thus, this mutation defines a genetic locus for susceptibility to carcinogen-induced tumors and modulation of carcinogen susceptibility by this locus exhibits cell-type specificity.

Animals↗
PubMed1992

Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome.

A rodent model of hereditary cancer in which a single gene mutation predisposes rats to bilateral multicentric renal cell carcinoma (RCC) is described. This rat hereditary cancer syndrome shares certain similarities with von Hippel-Lindau disease (VHLD). In addition to the early development of renal epithelial tumors with morphologic similarity to human RCC, rats which bear the RCC gene are predisposed to the development of secondary primary cancers later in life. Splenic vascular proliferative lesions, including hemangiosarcoma, were seen in 23% of 14-month-old rats of both sexes that had renal tumors. At fourteen months of age, 62% of female rats with renal cell tumors had sarcomas of the lower reproductive tract of probable smooth muscle origin. Non-carrier siblings of affected animals did not have renal, reproductive, or splenic neoplasia. The finding of a specific constellation of familial neoplasms, including multicentric bilateral renal cell carcinoma, in this autosomal dominant disorder of rats suggests that this syndrome is analogous to human VHLD. In addition to its usefulness for studies of the biochemical and molecular mechanisms of renal carcinogenesis, this animal model will provide a unique tool to investigate how cancer susceptibility genes interact with environmental risk factors such as chemical carcinogens.

Animals↗
PubMed1992

Experimental renal papillary necrosis in the Mongolian gerbil (Meriones unguiculatus).

Sequential light microscopic and ultrastructural examination of kidneys from male and light microscopic examination of female Mongolian gerbils given 250 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight ip were performed. In addition, male Mongolian gerbils were treated with both BEA and ip injections of either water, dimethyl sulfoxide, piperonyl butoxide, or reserpine. Light microscopic renal lesions in male Mongolian gerbils progressed from congestion of the vasa recta of the proximal inner medulla at 6 hr post-treatment to total renal papillary necrosis (RPN) at 24 hr post-treatment. There was no sex difference in sensitivity to BEA. Ultrastructural alterations in male gerbils were restricted to the vasa recta. Vascular lesions of endothelial swelling and pericapillary edema in the vasa recta of the proximal inner medulla was observed 2 hr post-treatment and progressed to occlusion by platelets adherent to exposed basement membranes at 6 hr post-treatment. Diuresis induced by injections of saline and injections of dimethyl sulfoxide or piperonyl butoxide did not affect the development of BEA-induced RPN. Reserpine slowed the development of BEA-induced RPN by its vasodilatory effect on the renal vasculature, not by blocking the endothelial toxicity of BEA. RPN induced by BEA in the Mongolian gerbil is apparently an ischemic necrosis of the inner medulla that develops secondary to endothelial damage of the vasa recta.

Animals↗
PubMed1992

Early sequential ultrastructural renal alterations induced by 2-bromoethylamine hydrobromide in the Swiss ICR mouse.

Thirty-two male Swiss ICR mice were injected intraperitoneally with 300 mg 2-bromoethylamine hydrobromide/kg body weight, anesthetized, and perfused with glutaraldehyde-paraformaldehyde solution at 5, 15, 30, 60, 90, 120, 150, and 180 minutes after treatment. Eight control mice were injected intraperitoneally with sterile diluent, and one was perfused at each of the same time periods as the treated mice. Proximal tubule epithelial alterations progressed over time from increased secondary lysosome and myeloid body formation to cellular and mitochondrial swelling and eventually cell necrosis. The glomerular, peritubular, and vasa recta capillaries had endothelial cell swelling and desquamation and platelet aggregation. Bromoethylamine nephrotoxicosis in the male Swiss ICR mouse is an ischemic necrosis of the proximal tubules and papilla initiated by endothelial cell damage and makes an excellent model of chemically induced damage to endothelial cells and tubular necrosis.

Animals↗
PubMed1991

Effects of reserpine and L-cysteine and glutathione depletion on 2-bromoethylamine hydrobromide-induced tubular necrosis in Swiss ICR mice.

Female Swiss ICR mice were injected ip with 100 or 300 mg 2-bromoethylamine hydrobromide (BEA)/kg body weight. Male Swiss ICR mice were subjected to water deprivation, or treated with 5% dextrose in water, dimethylsulphoxide, piperonyl butoxide, SKF-525A, sodium phenobarbital, beta-naphthoflavone, probenecid, reserpine, diethyl maleate, buthionine sulphoximine or L-cysteine. Urine collected sequentially from male Swiss ICR mice given 300 mg BEA/kg body weight was analysed for glucose, protein, pH and specific gravity. Female mice were less sensitive to BEA than were male mice. Diuresis, antidiuresis, treatment with cytochrome P-450 inducers and inhibitors, and the antioxidant dimethyl-sulphoxide had no effect on the incidence or severity of tubular necrosis (TN) induced by BEA. Probenecid and L-cysteine decreased the severity, but they had no effect on the incidence of TN. Glutathione depletion by diethyl maleate and inhibition of glutathione synthesis by buthionine sulphoximine decreased the dose of BEA necessary to cause TN; buthionine sulphoximine was more effective than diethyl maleate. Reserpine decreased both the incidence and severity of TN. Glycosuria, aciduria and decreased urinary specific gravity occurred before morphological changes were seen under the microscope, indicating that the functional changes precede the morphological changes. These data indicate that glutathione is important in protecting against BEA-induced TN, that BEA or a metabolite is concentrated in the tubule epithelium by way of anion transport, and that vasoconstriction contributes to the development of BEA-induced TN.

Animals↗
PubMed1991

Occupational and industrial toxin exposures and the gastrointestinal tract. Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee.

The subcommittee on Gastrointestinal Toxicology of the Patient Care Committee of the American College of Gastroenterology has reviewed potential effects of exposures to occupational and industrial hazards on the gastrointestinal tract, liver and pancreas. This review is presented to 1) share clinical data concerning gastrointestinal toxicology, 2) emphasize the paucity of available information to the practicing clinician, and 3) stimulate basic research interest in this field.

Digestive System Diseases↗
PubMed1990

Usefulness and limitations of laboratory and hepatic imaging studies in iron-storage disease.

Liver biopsy with measurement of hepatic iron concentration is the most certain procedure for evaluation of iron-storage disease, although use of computed tomography and magnetic resonance imaging procedures recently have been proposed as alternative, noninvasive methods for estimating the degree of iron overload. The results of these imaging procedures were compared with those of other noninvasive techniques and liver biopsies in 48 patients. Final diagnoses, based on synthesis of clinical and laboratory data, included (a) primary hemochromatosis (n = 25; 19 homozygous, 6 heterozygous); (b) secondary hemochromatosis (n = 7); (c) alcoholic liver disease (n = 11); (d) chronic active hepatitis (n = 3); and (e) other (n = 2). Serum ferritin and computed tomography or magnetic resonance scanning had 100% sensitivity in detecting hepatic iron overload more than fivefold above the upper limit of normal (greater than 10.7 mumol Fe/100 mg dry liver) but did not detect lesser degrees of iron overload reliably, including those found in 6 of 13 patients with untreated homozygous primary hemochromatosis and 3 of 7 with secondary hemochromatosis. Computed tomography and magnetic resonance imaging were more specific than ferritin (64% and 92% vs. 21%) in the detection of iron excess, more than five times the upper limit of normal. Among magnetic resonance imaging measures, the ratio of the second echo signal intensities of liver to paraspinous muscle was the most sensitive and most specific for detection of this degree of iron overload. The degree of correlation between hepatic iron concentration and results of noninvasive laboratory or imaging studies were insufficient to permit prediction of hepatic iron content by noninvasive studies alone. It is concluded that computed tomography or magnetic resonance scanning as currently usually used is not cost-effective in routine evaluation of iron overload, although these imaging procedures may play a role in patients in whom liver biopsy is contraindicated. Because of their low cost and ready availability, serum ferritin and transferrin saturation tests remain the preferred screening studies for iron overload. Liver biopsy with quantitative iron measurement remains the study of choice for the definitive diagnosis of hemochromatosis.

Biopsy↗
PubMed1990

Acute cortical tubular necrosis in the Swiss ICR mouse induced by 2-bromoethylamine hydrobromide.

Dose-response and sequential studies of 2-bromoethylamine hydrobromide (BEA) nephrotoxicosis were carried out using Swiss ICR mice. For the dose-response study, 150 male mice, 30 per group, were injected intraperitoneally (ip) with 100, 200, 300, 400 or 500 mg BEA/kg and ten from each group were killed 1, 3 or 5 days after treatment. For the sequential study, 80 male mice were injected ip with 300 mg BEA/kg and ten were killed at 0.5, 1, 2, 3, 6, 12 or 18 hr, or 10 days after treatment. Control mice (10-15) in both studies were given 0.15 ml of 0.9% NaCl solution injected ip and were killed after 1, 3 or 5 days in the former study and after 18 hr of 10 days in the latter study. Mortality and the extent of the renal lesions were dose dependent. The percentage of mice with tubular necrosis varied from 0 in mice given 100 mg BEA/kg to 100 in mice given 400 mg BEA/kg. The percentage of mice with renal papillary necrosis was also dose dependent and varied from 0 in the 100 mg/kg group to 72 in the 400 mg/kg group. Degeneration of proximal tubules was detected 2 hr after treatment. Three hours after treatment, grossly, the renal cortex was diffusely pale and, microscopically, there was marked acute tubular necrosis. Epithelial cells lining the cortical tubules were regenerating 3 days after treatment. By 10 days after treatment cortical interstitial fibrosis was marked with many tubules lined by regenerating epithelium and many tubules were dilated. BEA-induced nephrotoxicosis in the mouse was primarily an acute cortical tubular necrosis.

Acute Kidney Injury↗
PubMed1989

Choline may be an essential nutrient in malnourished patients with cirrhosis.

Elemental diets designed for nutritional support in protein-calorie malnutrition are often deficient in choline, a nonessential nutrient. Previously, malnourished patients on these diets were found to be at risk of developing plasma choline deficiency. We have now estimated the prevalence of this deficiency by determining fasting plasma levels of choline among cirrhotic and noncirrhotic malnourished male subjects maintained on regular hospital mixed food or elemental parenteral and enteral formulas. Plasma choline concentrations (microM, average +/- SD) were as follows: (i) mixed foods, 11.3 +/- 4.3 for cirrhotic (n = 22) and 9.3 +/- 2.4 for noncirrhotic (n = 12) patients; (ii) parenteral formula, 5.3 +/- 1.6 for cirrhotic (n = 5) and 8.6 +/- 5.2 for noncirrhotic (n = 16) subjects; and (iii) enteral formula, 6.1 +/- 1.2 for cirrhotic (n = 5) and 11.7 +/- 1.9 for noncirrhotic (n = 4) subjects. The level for healthy normal subjects eating mixed foods was 12.0 +/- 2.2. The prevalence of plasma choline deficiency, i.e., plasma levels greater than or equal to 2 SD below the normal average, was as follows: parenteral formula, all cirrhotic and 10 of 16 noncirrhotic subjects; enteral formula, all cirrhotic and none of the noncirrhotic subjects. The reversibility of choline deficiency was examined in a longitudinal study of three phases involving 10 patients--5 with alcoholic cirrhosis (all on enteral formula); 5 noncirrhotic (1 on enteral and 4 on parenteral formula). During phase 1 (3-day equilibration period; ad libitum regular hospital diet), plasma choline levels were within the normal range for all subjects. During phase 2 (2 wk, choline depletion phase, elemental formulas), choline levels were subnormal in all cirrhotic subjects (5.1 +/- 2.0 microM) on enteral formula and all noncirrhotic patients on parenteral formula (5.9 +/- 1.3 microM). During phase 3 (2 wk, choline repletion phase, elemental formula + 6 g choline/day), the levels normalized in all patients (cirrhotic 11.4 +/- 3.1 microM and noncirrhotic 11.9 +/- 3.2 microM). Analyses of abdominal computed tomographic scans and plasma liver chemistries in the cirrhotic subjects during the three phases suggested a correlation between plasma choline deficiency and hepatic steatosis and abnormal liver enzyme levels in some patients. Therefore, choline may be an essential nutrient in malnourished cirrhotic patients and its deficiency may be associated with adverse hepatic effects.

Adult↗
PubMed1989

Bacterial sorption of heavy metals.

Four bacteria, Bacillus cereus, B. subtilis, Escherichia coli, and Pseudomonas aeruginosa, were examined for the ability to remove Ag+, Cd2+, Cu2+, and La3+ from solution by batch equilibration methods. Cd and Cu sorption over the concentration range 0.001 to 1 mM was described by Freundlich isotherms. At 1 mM concentrations of both Cd2+ and Cu2+, P. aeruginosa and B. cereus were the most and least efficient at metal removal, respectively. Freundlich K constants indicated that E. coli was most efficient at Cd2+ removal and B. subtilis removed the most Cu2+. Removal of Ag+ from solution by bacteria was very efficient; an average of 89% of the total Ag+ was removed from the 1 mM solution, while only 12, 29, and 27% of the total Cd2+, Cu2+, and La3+, respectively, were sorbed from 1 mM solutions. Electron microscopy indicated that La3+ accumulated at the cell surface as needlelike, crystalline precipitates. Silver precipitated as discrete colloidal aggregates at the cell surface and occasionally in the cytoplasm. Neither Cd2+ nor Cu2+ provided enough electron scattering to identify the location of sorption. The affinity series for bacterial removal of these metals decreased in the order Ag greater than La greater than Cu greater than Cd. The results indicate that bacterial cells are capable of binding large quantities of different metals. Adsorption equations may be useful for describing bacterium-metal interactions with metals such as Cd and Cu; however, this approach may not be adequate when precipitation of metals occurs.

Adsorption↗