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Biomedical subjects

W M Haschek

Publications and source records attributed to W M Haschek.

At least 73 records · Page 4Linked to original sources
PubMed1985

Long-term effects of repeated exposure to 3-methylfuran in hamsters and mice.

Male and female Syrian golden hamsters were exposed for 2 h once a week for 10 consecutive weeks to 344 mumol/l of 3-methylfuran (3MF), an agent known to produce acute Clara-cell necrosis. Ten months later their respiratory function was evaluated. No functional differences were found between control and treated animals, and histopathologic evaluation of the lungs did not reveal any major treatment-related alterations. Male and female BALB/c mice were exposed for 1 h to 26.8 mumol/l of 3MF once weekly for 10 wk. After 2 yr the tumor incidence in exposed animals was not increased when compared to controls. It is concluded that the acute Clara-cell necrosis produced by 3MF at the doses used is of little long-term consequence.

Air Pollutants↗
PubMed1984

Acute inhalation toxicity of 3-methylfuran in the mouse: pathology, cell kinetics, and respiratory rate effects.

The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in male BALB/c mice by morphologic examination of animals killed at varying timepoints following a 1-hr exposure to an initial chamber concentration of 14 to 37 mumol/liter (343 to 906 ppm). In addition, respiratory rate measurements and cell kinetics were used to assess quantitatively pulmonary damage and repair. Necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen 1 day following exposure and was followed by regeneration, which was virtually complete, within 21 days. Cell kinetic studies showed peak bronchiolar cell proliferation at 3 days with a labeling index (LI) of 5.0% compared to 0.4% in controls. An increase in parenchymal cell proliferation was also noted coincident with a mild interstitial pneumonitis. This parenchymal proliferation, peaking at 10 days with an LI of 1.4% compared to 0.2% in controls, consisted primarily of type II epithelial and endothelial cell proliferation indicating possible delayed damage and repair of type I epithelial and endothelial cells. The respiratory rate showed an initial transient increase followed by a more prolonged decrease with eventual return to control levels. 3MF toxicity was also evidenced by a necrotizing suppurative rhinitis, centrilobular hepatic necrosis, lymphocyte necrosis in the thymus and spleen, sialoadenitis, and otitis media.

Air Pollutants↗
PubMed1984

Toxicity-distribution relationships among 3-alkylfurans in the mouse lung.

The present study was designed to investigate the extent to which a homologous series of 3-alkylfurans, 3-methylfuran, 3-ethylfuran, and 3-pentylfuran, may cause lung injury in mice in order to determine whether the chemical properties of these compounds are related to their toxic potential. The pulmonary concentration and pneumotoxicity of these and various other furan derivatives were also measured to determine if a correlation existed between the magnitude of pneumotoxicity produced by these toxins and their concentration in the lung. Along with the 3-alkylfurans, the other furan derivatives investigated were furan, 2-ethylfuran, 2-furamide, and 3-methylthiophene. The absence or presence of lung damage was evaluated by light microscopy. The quantitative index used to assess and rank the compounds as pneumotoxins was the incorporation of [14C]thymidine into DNA. The results obtained with the 3-alkylfurans showed that 3-methylfuran and 3-ethylfuran were toxic to the lung whereas 3-pentylfuran did not produce pneumotoxicity. 2-Ethylfuran, furan, and 2-furamide also caused lung damage but 3-methylthiophene did not. All the compounds, with the exception of furan, reach the lung in comparable concentrations; therefore, there does not seem to be a correlation between pneumotoxicity and concentration of the toxin in the lung. From these studies, it is also apparent that the pneumotoxicity of the 3-alkylfurans extends beyond the methyl group but that the toxicity decreases with increasing chain length.

Animals↗
PubMed1983

Pathology of acute inhalation exposure to 3-methylfuran in the rat and hamster.

The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in SPF Fischer-derived and CD/CR rats, and golden Syrian hamsters by determination of the 2-week LC50, and by histologic examination of animals killed 1, 3, and 14 days following a 1-hr exposure to 148 and 322 mumole 3MF/liter for CD/CR rats and hamsters, respectively. The Fischer-derived rat was more sensitive to 3MF-induced lethality than the CD/CR rat with an LC50 in the male rat of 81 mumole/liter-1 hr as compared to 222 mumole/liter-1 hr. No sex difference was found. The hamster was relatively resistant with no lethality at 322 mumole 3MF/liter-2 hr. Pulmonary damage was present in both species. In the hamster, selective necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen at 1 day with virtually complete regeneration by 14 days whereas in the rat the bronchiolar epithelial damage was more extensive and was followed by scattered peribronchiolar fibrosis and epithelial mucous metaplasia suggestive of "small airway disease" of man. Relatively selective 3MF-induced necrosis of olfactory epithelium occurred in the nasal mucosa of both species. Resolution of this lesion was seen by 14 days in the hamster. In the rat, however, the necrosis was much more extensive and was followed by partially occlusive fibrosis of the nasal cavity as seen at 14 days. 3MF also induced centrilobular hepatic necrosis in both species. In the rat, lymphocyte necrosis in the thymus and spleen, and esophageal necrosis was also seen.

Acute Disease↗
PubMed1983

Potentiating effects of oxygen in lungs damaged by methylcyclopentadienyl manganese tricarbonyl, cadmium chloride, oleic acid, and antitumor drugs.

The intraperitoneal administration of methylcyclopentadienyl manganese tricarbonyl (MMT) and cyclophosphamide, exposure to an aerosol of cadmium chloride, intravenous administration of oleic acid, and intratracheal instillation of bleomycin to young female BALB/c mice or CD/CR rats result in acute lung injury. Pulmonary morphology and lung collagen content were examined in animals treated with these chemicals alone or in combination with an elevated oxygen concentration (80%) in the inspired air. In mice, the development of fibrosis could be significantly enhanced if animals treated with MMT, cadmium chloride, cyclophosphamide, or bleomycin were exposed to 80% oxygen immediately following exposure to these agents. In rats only cyclophosphamide- and bleomycin-induced acute lung injury was potentiated by hyperoxia, resulting in significant enhancement of lung collagen content. The pathogenesis responsible for this differential species response of pulmonary injury to hyperoxia remains to be investigated.

Animals↗
PubMed1983

Potentiation of butylated hydroxytoluene-induced acute lung damage by oxygen. Cell kinetics and collagen metabolism.

Changes in cell proliferation and in collagen synthesis were studied in young adult male BALB/c mice injected intraperitoneally with 400 mg/kg of butylated hydroxytoluene (BHT) in corn oil or corn oil alone and immediately exposed to 70% oxygen or air for 6 days. Mice received [3H]thymidine either as a single injection 90 min before being killed or as a continual infusion via an osmotic minipump. Autoradiography was done 2 to 14 days after BHT injection, and cell kinetic studies were performed. In a similar experiment, mice were injected intraperitoneally with [3H]proline 3 h before being killed, and type l/type III collagen ratio in newly synthesized lung collagen was determined. We found that exposure to 70% oxygen immediately after the administration of BHT initially delayed the epithelial cell proliferation and the decrease in the percentage of newly synthesized type III collagen that occurred after BHT alone. Once the animals were removed from oxygen there was a compensatory burst of cell proliferation and a precipitous drop in the percentage of newly synthesized type III collagen. The proliferating cell population after removal from oxygen was primarily interstitial and not epithelial. When exposure to oxygen was delayed, cell proliferation was similar to that seen after BHT injection alone.

Animals↗
PubMed1983

Experimental silicosis. II. Long-term effects of intratracheally instilled quartz on collagen metabolism and morphologic characteristics of rat lungs.

Rats received intratracheal instillations of 50 mg of silica (quartz, 0.5 mu particles). One, 2, 4, 5, 6, 9, and 12 months later, the lungs were evaluated histologically and by various biochemical measurements. The lung content of protein, proline, and hydroxyproline (collagen) were quantitated, as were the synthesis rates of lung collagen and the total lung protein (evaluated with lung minces in vitro. The ratio of newly synthesized and of total lung Type I to Type III collagen was also determined. These experiments were performed in parallel on rats free of chronic respiratory disease and a strain of conventional animals. The authors conclude that 1) the excess collagen deposited in granulomas and/or silicotic nodules as part of the fibrotic response of the lung is similar to normal lung collagen with respect to relative ratios of Types I and III present, in contrast to the response of the lung to oxidant pneumotoxins; 2) the response of the lung to silica continues for at least 1 year; 3) there are essentially no differences in the response of chronic respiratory disease-free Sprague-Dawley and conventional Wistar rats to intratracheally instilled silica. Both strains of rats develop silica-containing granulomas, mature silicotic nodules, and areas of alveolar lipoproteinosis associated with interstitial pneumonitis. Even 1 year after instillation of silica areas of granulomas, silicotic nodules and alveolar lipoproteinosis may be observed in most of the lungs studied; ie, these responses are not mutually exclusive.

Animals↗
PubMed1982

Myocardial necrosis secondary to neural lesions in domestic animals.

Focal myocardial necrosis secondary to neural lesions was diagnosed in 2 dogs and 1 horse. In each case, the neural lesions were traumatic in origin. Spinal cord injury was evident in 1 dog; brain damage was evident in the other dog and presumably in the horse. Retrospective analysis of necropsy material showed that many species were affected, without apparent age or sex predisposition. Central nervous system injury resulting from trauma, infection or space-occupying lesions was associated with acute myocardial necrosis in all cases. The myocardial necrosis was rarely fatal; however, it did cause cardiac arrhythmias.

Animals↗
PubMed1982

Nonciliated bronchiolar epithelial (Clara) cell necrosis induced by organometallic carbonyl compounds.

The administration of transition metal organometallic compounds such as manganese, chromium, and iron carbonyls by the i.p. route, and nickel by inhalation (mice) or intravenously (rats), resulted in selective necrosis of the nonciliated bronchiolar epithelial (Clara) cells and variable pulmonary parenchymal damage in BALB/c mice and Fischer-derived rats within 24 h of administration. The pulmonary toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT), a representative of this group of compounds, was enhanced by pretreatment with piperonyl butoxide (PB), an inhibitor of the mixed-function oxidase system. This finding suggests that Clara cell necrosis can result from direct toxicity and that the specificity of toxic agents for Clara cells may not be related solely to the presence of the mixed-function oxidase system.

Animals↗
PubMed1982

Long-term morphologic and biochemical features of experimentally induced lung fibrosis in the mouse.

Mice were injected with 400 mg. per kg. of butylated hydroxytoluene (BHT) and exposed to an atmosphere of 70 per cent oxygen for 6 days. Control groups were animals treated with BHT alone or injected with vehicle and kept for 6 days in either O2 or air. Animals were killed at various time intervals after BHT treatment, and the lung changes were evaluated with biochemical and morphologic techniques. In animals exposed to BHT + O2, there was initially a diffuse interstitial pneumonitis, increased levels of interstitial collagen, and a decreased ratio of type III to type I collagen. With time the inflammatory component subsided, and degenerative changes primarily consisting of dilation of terminal airways and of alveoli became apparent. Elevated levels of lung hydroxyproline persisted until the termination of the study at 1 year, although ratios of type III to type I collagen returned to normal. In animals treated with BHT alone, collagen accumulation and morphologic changes were similar, although much less severe. It is concluded that potentiation of acute lung injury by oxygen produces long-lasting morphologic and biochemical alterations in lung parenchyma.

Animals↗
PubMed1982

Experimental silicosis. I. Acute effects of intratracheally instilled quartz on collagen metabolism and morphologic characteristics of rat lungs.

Rats were intratracheally instilled with 50 mg of silica as quartz (0.5-mu particles) at day 0. One and 2 weeks later, lungs were evaluated histologically and by a variety of biochemical measurements. Protein, proline, and hydroxyproline content (as an index of total lung collagen) were quantitated, as were the lung collagen synthesis rate and the total lung protein biosynthesis rate (evaluated with lung minces in vitro). The ratio of newly synthesized Type I/Type III collagen was determined, as was the same ratio for total lung collagen. These experiments were performed in parallel on chronic respiratory disease-free rats and in a strain of conventional animals. The authors conclude that 1) changes in lung structure and composition can be appreciated as early as 1 week, the earliest time point studied, after intratracheal instillation of 50 mg of quartz; 2) observed morphologic changes during the first 2 weeks are consistent with biochemical changes; 3) there are essentially no differences in the response of chronic respiratory disease-free Sprague-Dawley and conventional Wistar rats to intratracheally instilled silica. Both strains of rats developed silica-containing granulomas, which ultimately developed into silicotic nodules, as well as areas of alveolar lipoproteinosis associated with interstitial pneumonitis.

Animals↗
PubMed1981

Primary renal cell carcinoma in two horses.

Of 2 horses with renal cell carcinoma, 1 had massive ascites but no other signs of urinary tract disease; the other had hematuria. In both horses, the tumors were palpable as large perirenal masses. The tumor mass of horse 1 almost completely replaced the left kidney, and there were tumor implants on the serosa of abdominal organs. The right kidney of horse 2 was compressed peripherally by the tumor, which completely filled the renal pelvis. The prevalence of renal cell carcinoma in horses and dogs necropsied at the New York State College of Veterinary Medicine between 1953 and 1976 was similar, and these 2 species had a higher prevalence than cattle, cats, or swine.

Adenocarcinoma↗
PubMed1981

Potentiation of diffuse lung damage by oxygen: determining variables.

The antioxidant, butylated hydroxytoluene (BHT), caused diffuse necrosis of type I alveolar cells in mouse lung followed by proliferation of type II epithelial cells. Exposure to oxygen during the phase of epithelial cell division led to the development of diffuse interstitial fibrosis. The extent of the fibrotic changes, as quantitated by measuring total lung hydroxyproline, was dependent upon both oxygen concentration in the inspired air and length of exposure. Fibrotic changes were seen in animals exposed after 400 mg/kg of BHT for 6 days to 50% oxygen or more, 3 days to 60% oxygen or more, or 2 days to 70% oxygen or more, but not if exposure was limited to 24 h only. Minimal fibrosis developed in animals exposed for 6 days to 80% oxygen alone. Additional factors determining the severity of fibrotic changes were the extent of the initial lung lesion caused by BHT and the time interval between BHT administration and the beginning of oxygen exposure. Potentiation of lung fibrosis was also observed in animals treated with methylcyclopentadienyl manganese tricarbonyl and 70% oxygen. We conclude that oxygen can severely aggravate lung damage caused by bloodborne agents, and that the severity of the resulting lesion is determined by many variables.

Animals↗
PubMed1981

Epithelial-mesenchymal associations of cells in human pulmonary fibrosis and in BHT-oxygen-induced fibrosis in mice.

It was reported earlier that in the lungs of individuals with idiopathic pulmonary fibrosis, many cells lining small air spaces have intimate associations with underlying interstitial cells. The present study confirms and extends these previous observations by describing changes seen in a different patient group. Light microscopy of lung biopsy tissue showed thickened alveolar walls with infiltrates of mixed inflammatory cells. There were undefined associations between interstitial cells and cuboidal and attenuated epithelial cells lining smaller air spaces. Electron microscopy demonstrated that cytoplasmic processes from the lining cells protruded through discontinuities in underlying basement membranes, and that intimate connections between lining cells and interstitial cells frequently were present. In addition, some of the cells lining air spaces had few microvilli, rare pinocytotic vesicles, and did not lie on basement membranes. These cells were mesenchymal-like in appearance and were clearly associated with interstitial cells and connective tissue. Similar pulmonary lesions were observed in mice that received a single intraperitoneal injection of butylated hydroxytoluene and were exposed subsequently to 70% oxygen for 6 days. Our findings suggest that communication between a regenerating epithelium and the underlying mesenchyme is an integral step for ongoing alveolar repair.

Animals↗