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M F Kanz

Publications and source records attributed to M F Kanz.

23 records · Page 2Linked to original sources

Potentiation of 1,1-dichloroethylene hepatotoxicity: comparative effects of hyperthyroidism and fasting.

The responses of fed, fasted, and hyperthyroid (T4) Sprague-Dawley male rats to 50 mg 1,1-dichloroethylene (1,1-DCE)/kg were compared. Hyperthyroid rats received three sc injections of thyroxine (100 micrograms/100 g) at 48-hr intervals; all other rats were sham-injected. 1,1-DCE was given po in mineral oil 24 hr after the last T4 dose; controls received only mineral oil. Animals were killed at 2, 4, and 8 hr. Liver GSH contents were lowered about 55% by both fasting and T4 while GSH transferase activities were lowered about 20% by fasting and 35% by T4. Only T4 pretreatment lowered alcohol dehydrogenase activities. Liver injury (i.e., serum glutamate pyruvate transaminase, histology) after 1,1-DCE was minimal in fed rats, moderate in fasted rats, and intermediate in T4 rats. Fasted rats showed a more pronounced depletion of liver GSH after 1,1-DCE than T4 rats and only in fasted rats did the toxicant decrease activities of the detoxification enzymes. Hypoglycemia after 1,1-DCE occurred in fed rats, but more rapidly in T4 rats. In contrast, fasted rats unexpectedly became hyperglycemic after the toxicant. Patterns of body temperature change after the toxicant, which might be due to its metabolites, were dissimilar. Hypothermia was not observed in fed rats, was only transiently evident in T4 rats, but occurred rapidly within 1 hr in fasted rats and steadily became more severe. The dissimilar patterns of liver enzyme and body temperature and serum glucose change after the toxicant in the three groups are indicative of different pathways of injury potentiation by fasting and hyperthyroidism.

Alcohol Dehydrogenase↗

Asbestos bodies in children's lungs. An association with sudden infant death syndrome and bronchopulmonary dysplasia.

Lungs from 46 autopsied children (age range, 1 to 27 months) were examined for asbestos bodies using a bleach-digestion extraction technique. Ten (21.7%) of 46 children had asbestos bodies in their lungs. Of these ten children, seven were diagnosed with sudden infant death syndrome, and three were diagnosed with bronchopulmonary dysplasia. Thus, 46.6% of children with sudden infant death syndrome and 42.8% of children with bronchopulmonary dysplasia had asbestos bodies. Impaired lung-clearing mechanisms due to either abnormal lung physiology or reorganization of pulmonary architecture may be significant in the formation of asbestos bodies. Additionally, children with asbestos bodies may have been exposed to higher ambient levels of asbestos and other pollutants.

Asbestosis↗

Early effects of 1,1-dichloroethylene on canalicular and plasma membranes: ultrastructure and stereology.

The pathogenesis of 1,1-dichloroethylene (1,1-DCE)-induced hepatotoxicity was investigated in fasted male rats by identifying the earliest morphological alterations in organelles. In situ perfusion-fixed liver tissue was examined by light and electron microscopy at 1, 2, or 3 hr after oral administration of 25, 50, and 100 mg 1,1-DCE/kg in mineral oil. The earliest morphological alterations, which occurred within 1 to 2 hr after 1,1-DCE administration, were dilation of bile canaliculi with an increase in the number of microvilli or membrane fragments in canaliculi and the formation of canalicular diverticuli in centrolobular hepatocytes. Subsequently, microvilli on sinusoidal surfaces were disrupted or lost. Membrane whorls were frequently found in bile canaliculi, the space of Disse, and between the lateral membranes of hepatocytes at early times. As injury progressed, centrolobular hepatocytes retracted from endothelial cells and sinusoidal plasma membranes invaginated to form cytoplasmic vacuoles. Stereological analysis of centrolobular hepatocytes at the 25 mg/kg dose showed a significant increase in canalicular volume density by 3 hr and no detectable alteration in mitochondrial volume density. These results indicate that changes in canalicular shape and microvilli configuration are the earliest morphological alterations following 1-DCE ingestion.

Animals↗

1,1-Dichloroethylene: an apoptotic hepatotoxin?

Within 2 hr after 1,1-dichloroethylene administration, the following phenomena occur in livers of fasted rats: dilation and disruption of bile canaliculi, plasma membrane invagination and loss of microvilli, cytoplasmic vacuolation, and loss of density in mitochondrial matrices. Early, selective loss of enzyme activities was localized by histochemical staining to bile canalicular, and inner and outer mitochondrial membranes. Biliary permeability to inulin increased, a change suggestive of the breakdown of junctions between hepatocytes. Endoplasmic reticulum and lysosomes appeared spared. In addition, scattered, individual hepatocytes exhibited changes characteristic of apoptosis by 2 hr: chromatin aggregation and margination, nucleolar coarse granulation and enlargement, rounded blebs and proturberances on cell surfaces, and the separation of these cells from surrounding parenchyma. In contrast, evidence of plasma membrane leakiness to K+, Ca2+ and soluble cytoplasmic enzymes was not detected until after 2 hr. Based on these observations, we propose that 1,1-dichloroethylene may initiate apoptosis-like cell degradation in selected parenchymal cells prior to or coincident with centrolobular necrosis.

Animals↗

Two cannula method for parenteral infusion and serial blood sampling in the freely moving rat.

Materials and techniques are described for positioning and exteriorizing two chronic venous cannulas in the rat. A cannula for fluid infusion is placed in the inferior vena cava via the femoral vein and exteriorized on the tail, whereas a cannula for blood withdrawal is placed in the superior vena cava and exteriorized in the scapular region. Grooming behavior and range of motion are not impeded since the cannula used for chronic infusion is shielded by a light-weight tail cover instead of a torso harness. Application of this method can minimize numbers of rats used in total parenteral nutrition (TPN) studies as demonstrated by our feasibility study in which serum parameters of liver function were serially monitored in toxin-treated rats infused with nutrient mixtures.

Animals↗