Search PubMed⌕ Search

Biomedical subjects

H Witschi

Publications and source records attributed to H Witschi.

At least 91 records · Page 5Linked to original sources
PubMed1983

Disintegration of lung peroxisomes during differentiation of type II cells to type I cells in butylated hydroxytoluene-administered mice.

Ultrastructural and cytochemical changes in peroxisomes of Type II alveolar cells were investigated in butylated hydroxytoluene (BHT)-administered mouse lungs. Male mice were given a single injection of BHT (400 mg/kg, ip) and sacrificed 1 to 7 days later. By means of tracheal infusion, lungs were fixed with a 2% glutaraldehyde or half-strength Karnovsky solution. Type I epithelium was selectively destroyed by BHT and was replaced by cuboidal Type II cells. Type II cells proliferated and some became squamous, extended their cytoplasm, and might differentiate into Type I cells (Hirai, Witschi, and Côté (1977) Exp. Mol. Pathol. 27, 295-308). Peroxisomes, Type II cell constituents, were clustered around and continuous with endoplasmic reticulum. The shape of the peroxisomes became indistinct after Type I cell injury by BHT. Also the density of the matrix was reduced in proportion to the reduction in the peroxidatic activity of catalase. These changes were accompanied by a decrease in the number of peroxisomes. New pinocytotic vesicles, one of the Type I cell characteristics, were generated at the apical and basal cell surfaces. Therefore, these cells had characteristics intermediate between Type I and Type II cells. These findings may indicate further evidence of the origin of Type I cells from Type II cells.

Animals↗
PubMed1983

The effect of ethanol on the absorption, accumulation and biotransformation of xenobiotics by the isolated perfused rabbit lung.

The effects of acutely administered ethanol on absorption, accumulation and biotransformation of several model compounds were examined in the isolated perfused lung (IPL). To determine pulmonary accumulation imipramine and paraquat were studied. To determine the effect of ethanol on the absorption of substances from the airways into the blood sulfanilic acid was used as an example of a relatively lipid soluble compound while mannitol was chosen as a non-lipid soluble compound. Aldrin was chosen to demonstrate the effects of circulating ethanol on pulmonary biotransformation. The results obtained with imipramine and paraquat indicate that after a 60-min perfusion period 93% and 20% of the original amount added are respectively lost from the blood perfusate. Ethanol at an initial concentration of 300 mg/100 ml has no apparent effect either on the rate or the quantities accumulated by the lungs. When sulfanilic or mannitol were administered into the airways both compounds appeared in the perfusate and ethanol had no effect on this absorption. Finally we obtained evidence that aldrin is converted to dieldrin by the IPL but that the quantities metabolized are not modified by the presence of ethanol.

Absorption↗
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↗
PubMed1981

The effect of indomethacin, prednisolone and cis-4-hydroxyproline on pulmonary fibrosis produced by butylated hydroxytoluene and oxygen.

The purpose of this study was to examine whether development of pulmonary fibrosis in mice could be influenced by indomethacin, prednisolone or a proline analog. Pulmonary fibrosis was produced in mice treated with butylated hydroxytoluene (BHT) 400 mg/kg and immediately exposed to 80% oxygen for 3 days. This treatment regimen resulted in 47% mortality. Surviving mice exhibited significant accumulations of pulmonary collagen as evidenced by increases in total lung hydroxyproline levels. The administration of indomethacin (4 mg/kg/day) on days 1-6 after BHT decreased mortality to 14% and diminished the accumulation of collagen in lung tissue. Indomethacin also enhanced survival when administered on days 1-3 after BHT/O2 but had no effect on lung collagen levels. Treatment with indomethacin on days 4-6 after BHT had no beneficial effect. The administration of prednisolone (60 mg/kg/day) on days 1-3, 1-6, or 4-6 after BHT decreased mortality but had no effect on accumulation of lung collagen. Cis-4-hydroxyproline (400 mg/kg/day) also had no effect on pulmonary fibrosis but did enhance survival when given on days 1-3 after BHT. Administering prednisolone (60 mg/kg/day) on days 1-6 after BHT to mice left in room air produced significantly more pulmonary fibrosis than in BHT-treated mice given saline. These data support the use of the BHT/O2 model of pulmonary fibrosis for screening potential antifibrotic agents. The possibility that corticosteroid treatment may enhance pulmonary fibrosis in a damaged lung is also demonstrated.

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↗
PubMed1979

The influence of hyperoxia on the acute toxicity of paraquat and diquat.

Hyperoxia has been shown to enhance the toxicity of the herbicide paraquat. Experiments were conducted to learn more about the effects of oxygen following acute poisoning with paraquat as well as the structurally related herbicide, diquat. Rats were injected intravenously with various doses of diquat or paraquat and placed into an atmosphere of either 100% oxygen or room air. The time required for 50% lethality (LT50) of both diquat and paraquat was greatly diminished by hyperoxia and was dependent upon the herbicide dosage. Rats treated with 40 or 80 mg/kg diquat and exposed to 100% oxygen had a shorter LT50 than those treated similarly with paraquat. A dose of 20 mg/kg was equitoxic in 100% oxygen while rats treated with 5 or 10 mg/kg diquat had a longer LT50 than rats treated with the same dose of paraquat. All animals exhibited severe respiratory distress terminally. The plasma concentrations and tissue distribution of either herbicide at 20 mg/kg were the same in oxygen and air exposed animals. When oxygen concentrations were varied between 100% and 60% rats treated with 20 mg/kg diquat or paraquat exhibited increasing but equal LT50's. In 40% oxygen diquat treated rats died more rapidly than paraquat treated rats. These data demonstrate a toxic interaction between hyperoxia and diquat as well as paraquat.

Animals↗
PubMed1978

Toxicity of butylated hydroxytoluene in mouse following oral administration.

Male Swiss--Webster mice were given 400 mg/kg of butylated hydroxytoluene ([methyl-14C]toluene) by stomach tube. Radioactivity was measured in plasma, lung, liver and kidney from 0.5 h to 10 days later. Radioactivity associated with butylated hydroxytoluene (BHT) or its metabolites was highest in plasma and all tissues examined between 1 and 12 h after administration. After 24 h, less than 1% of the administered dose remained in the lung, kidney or liver. One day after BHT, DNA synthesis in lung increased and, on days 3, 4 and 5, was 6--8 times as high as in controls. DNA content of the lungs almost doubled. Synthesis and net increase of pulmonary DNA were dose-dependent. If BHT was given orally following injection of one single dose of urethane, adenoma formation in lung was enhanced. It is concluded that BHT, given by stomach tube and in doses higher than 100 mg/kg, produces extensive cell proliferation in mouse lung and acts as a promoting agent in adenoma development.

Adenoma↗
PubMed1977

In vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung.

Intravenous injection of rats with 156 mumol/kg of paraquat or 140 mumol/kg of diquat produced, within 60 min, a sharp drop in the ratios of NADPH to NADP in lung. The effect persisted for a time period of at least 24 h. Exposure to 100% oxygen enhanced the toxicity of both compounds without substantially amplifying changes in the NADPH/NADP ratio. Lungs retained the capability to synthesize adenine nucleotides de novo. Electron microscopic studies showed that both paraquat and diquat damage type I alveolar cells, but only paraquat produces type II cell lesions. Although bipyridylium herbicides produce acute oxidation of NADPH in vivo, there seems not to exist a straightforward relationship between this event and cell damage.

Animals↗