Isolation and characterization of a spontaneous lymphocytic leukemia (L-76) in the strain 2 guinea pig.
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Biomedical subjects
Publications and source records attributed to V W Fischer.
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The present study presents evidence for a third hypocholesterolemic drug, zuclomiphene, being able to induce an experimental myotonic condition. Other drugs used singly or in combination were AY-9944, Triparanol and 20, 25-diazacholesterol. It has also been demonstrated for the first time that experimental myotonia can be induced in developing rats as well as adults. Developing rats received the initial intraperitoneal injections of drug at 5 days of age and were examined at 50 days of age. Adult rats were treated for 5 weeks. Two injections were given per week. Positive electromyography findings were observed in the developing and adult animals receiving 20, 25-diazacholesterol and zuclomiphene. The electromyography data of the other regimens of treatment were equivocal with regard to myotonia. Histological, histochemical, and electron microscopic examination of the muscle demonstrated no important changes. estimation of sterol composition showed that desmosterol was a major sterol in muscle after 20, 25-diazacholesterol or zuclomiphene treatment, thus furthering the concept that it is desmosterol in the muscle membrane, and not the drug, that is responsible for the myotonic condition.
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Allergic bronchopulmonary aspergillosis (ABA) in man is featured by the presence of IgE skin sensitizing and IgG precipitating antibodies against Aspergillus fumigatus (AF). An animal model of this disease was created. 2 monkeys immunized with AF produced IgG-precipitating antibody. Normal human serum was infused into both immunized and unimmunized monkeys and allergic human serum containing a high titer of IgE against AF was infused into another pair of immunized and unimmunized monkeys. All monkeys then received an aerosol of AF. Lung biopsies were obtained and light microscopic, immunofluorescent and electron microscopic studies were performed. Only the monkey with precipitating antibody to AF who received human allergic serum showed changes which included an interstitial cellular infiltrate containing large numbers of eosinophils, edema of the intra-alveolar spaces, thickening of the alveolar septa, intracellular and interstitial deposits of IgG and IgM and proliferation of collagen fibrils. No evidence of vasculitis was observed. This primate model of ABA should enhance our understanding of the inflammatory response and the immunologic processes in this disease.
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Developing rats were injected intraperitoneally twice weekly with a combination of three hypocholesterolemic agents: Zuclomiphene (formerly called trans-clomiphene; dosage, 30 mg/kg body weight), Triparanol (30 mg/kg body weight) and AY-9944 (3 mg/kg body weight). Treatment was initiated at 4 days of age. Biochemical and electron microscopic examination was conducted on animals sacrificed at 20 days of age. Cytoplasmic inclusion bodies were not seen in the CNS. Isolated edematous changes were seen in myelinated axons. Analysis of the sterol content of the brain and spinal cords of drug-treated animals indicated the presence of abnormal concentrations of five sterols, desmosterol, 5alpha-cholesta-7,24-dien-3beta-ol, zymosterol (5alpha-cholesta-8,24-dien-3beta-ol), 7-dehydrocholesterol (cholesta-5,7-dien-3beta-ol) and 7-dehydrodesmosterol (cholesta-5,7,24-trien-3beta-ol). Zymosterol and 5alpha-cholesta 7,24-dien-3beta-ol were minor constituents (5--7% and 1--1.5% of total sterol, respectively). The 7-dehydrosterols represented approximately one-half (44--52%) of the total CNS sterol.
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Morphologic and histochemical characteristics of selected portions of normal arteries from two species known to differ in susceptibility to vascular disease were examined. Arteries were classified as predominantly elastic, muscular or complex. Species differences in the structural organization of the abdominal aortic segment were observed. Arterial mucopoly-saccharides were stained more intensely in the tunica intima and media of chicken vessels than within those of the rat, and tended to be most concentrated in proximity of the internal elastic membrane. Histochemical procedures for the demonstration of enzymatic activity revealed inter-and intraspecies variations in vascular metabolism. Pronounced differences in reaction intensity for hydroxybutyrate dehydrogenase and malic enzyme, affecting chicken and rat coronary arteries, were noted. In contrast, theses vessels displayed only minimal activity for acid phosphatase. Marked endothelial deposition of alkaline phosphatase reaction products in the arteries of the chicken was demonstrated, while this enzyme's activity in the vessels of the rat was restricted to the tunica adventitia. The implications of these structural and histochemical factors with regard to vascular susceptibility to disease were discussed.
Developing rats were injected intraperitoneally twice weekly with a combination of two hypocholesterolemic agents: trans-clomiphene 50 mg per kg body weight, and AY-9944, 5 mg per kg body weight. Treatment was initiated at 5 days of age. Biochemical and electron microscopic examination was carried out on animals sacrificed at 20 days of age. Only rarely were cytoplasmic inclusion bodies seen in the CNS. Biochemical analysis of the brain and spinal cords of treated animals indicated the abnormal accumulation of three sterols, zymosterol (5alpha-cholesta-8,24-dien-3beta-ol), 7-dehydrocholesterol (cholesta-5,7-dien-3beta-ol) and 7-dehydrodesmosterol (cholesta-5,7,24-trien-3beta-ol). The 7-dehydrosterols constituted from 56--66% of the total CNS sterol component. Zymosterol was a relatively minor (2.4--5.0%) component.
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