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Biomedical subjects

V W Fischer

Publications and source records attributed to V W Fischer.

At least 37 records · Page 2Linked to original sources
PubMed1986

Mitigation of an anthracycline-induced cardiomyopathy by pretreatment with razoxane: a quantitative morphological assessment.

A quantitative evaluation of structural modifications was undertaken in the myocardium of daunorubicin (DNR)-treated and razoxane (RZ)-protected mice. BDF1 mice were injected with DNR, 15 mg/kg; a second group of mice was subjected to the same conditions but, in addition, received a pretreatment of RZ, 200 mg/kg. Representative cubes of myocardial tissue were processed for viewing with the electron microscope. Five hundred myocardial cells in each group were examined for the presence of lesions which had been categorized as early, moderate, or advanced. Contrasting the total number of demonstrable lesions in each group revealed a statistically significant reduction of 38% in abnormalities present in RZ-protected mice. By category, RZ-pretreated mice showed a mitigation in the appearance of early and moderate alterations and a striking reduction in the incidence of advanced, irreversible lesions. These results indicate that the cardiomyopathy associated with DNR administration can be ameliorated by pretreatment with RZ; this protective effect is markedly exerted by preventing the development of severe, irreversible lesions in the murine myocardium; the initial, non-transient structural alteration subsequent to DNR-exposure appears to affect the myocardial sarcoplasmic reticulum.

Animals↗
PubMed1986

Thyrotoxic myopathy in mice: accentuation by a creatine transport inhibitor.

To demonstrate the importance of creatine and phosphocreatine in skeletal muscle during periods of metabolic stress, thyrotoxicosis was induced in mice fed the creatine transport inhibitor, beta-guanidinopropionic acid (beta-GPA). Adding 2% of beta-GPA to the diet of normal mice inhibited weight gain and caused a 75% reduction of creatine and phosphocreatine concentrations in skeletal muscle. Addition of 0.25% or 2% of thyroid powder to the diet of normal mice was associated with hyperactivity, cardiomegaly, and a high mortality rate. Superimposing thyrotoxicosis on mice already depleted of creatine and phosphocreatine resulted in degeneration of muscle fibers. These results indicate that high concentrations of creatine and phosphocreatine are essential for the maintenance of muscle integrity during periods of metabolic stress.

Animals↗
PubMed1985

Peripheral nerve axonal dwindling with concomitant myelin sheath hypertrophy in experimentally induced diabetes.

Axons of the peripheral nervous system (PNS) are reduced in caliber in response to the experimental diabetic state. The cause of this reduced axonal size is disputed. Various theories include (a) axonal dwindling, (b) inhibition of growth, and (c) shrinkage due to serum hyperosmolarity. This study was designed to directly address these conflicting theories and to provide additional information on the character of the peripheral neuropathy resulting from an experimentally induced diabetic state. Four weeks, 6 and 12 months after establishing a streptozotocin-induced diabetic condition in rats, a morphometric evaluation of randomly selected cross sections of myelinated nerve fibers in the common peroneal nerve was performed on diabetic and age and weight-matched control animals. A reduction in the cross-sectional area of axons with a concomitant increase in the width of myelin sheaths was detected following 6 months of exposure to the diabetic state. Axons in rats diabetic for 12 months showed smaller cross-sectional areas than those seen in rats diabetic for only 6 months; hence, a dwindling in axonal caliber had occurred during this period. These findings indicate the presence of an axonopathy, associated with a myelin sheath alteration in the common peroneal nerve of the chronically diabetic rat.

Animals↗
PubMed1985

Incorporation of [3H]thymidine into myocardial capillary cells in streptozotocin-diabetic rats.

It was the aim of this study to test the hypothesis that abnormal thickening of capillary basal laminae in the diabetic organism may be due to postulated cycles of capillary cell turnover of increasing frequency. The accelerated cell turnover, it was theorized, may lead to laminar thickening through adhesion of basal laminae synthesized by regenerating cells with residual laminae of previously degenerated capillaries. Nine streptozotocin-diabetic rats and six nondiabetic controls were injected ip with tritiated thymidine, 1.0 microCi/g body weight. Three additional controls, for the purpose of identifying a potentially toxic action of streptozotocin which may affect the incorporation of thymidine into DNA, were treated in an identical manner. One hour postinjection, the animals were sacrificed, the heart was excised and sliced transversely. The tissue slices were fixed in 10% neutral buffered Formalin, dehydrated, and embedded in paraffin. Sections 6 microns thick were dipped in Kodak emulsion and were developed following an exposure of 4 weeks. Examination of the autoradiographs revealed distinctly labeled capillary endothelial cells in the myocardium of nondiabetic controls; labeling of these cells was strikingly reduced in the diabetic rats. These results indicate that proliferative activity of capillary endothelial cells is markedly retarded in the diabetic myocardium and that the reduced labeling can be ascribed genuinely to the diabetic environment. This finding does not provide support for the hypothesis that an accelerated cell turnover may be responsible for basal laminar thickening in the diabetic.

Age Factors↗
PubMed1985

Evaluation of a rat model for assessing interventions to salvage ischaemic myocardium: effects of ibuprofen and verapamil.

Coronary ligated rats were administered intraperitoneal injections of 6.24, 12.52, and 25.00 mg . kg-1 ibuprofen and 5.00 and 10.00 mg . kg-1 verapamil 1 h before ligation, 1 h after ligation, and then every 8 h for 48 h. Ibuprofen at 50.00 mg . kg-1 was administered 1 h before ligation, 1 h after ligation and 5 h after ligation. Infarct size was determined either by weighing the stained excised infarcted area or by measuring the creatine kinase activity from the excised left ventricle. Ibuprofen and verapamil treatment resulted in less myocardial damage after 48 h than placebo treatment but the differences were generally not statistically significant. The reduction in infarct size was greater in the ibuprofen treated animals compared with verapamil treated rats. In addition, there was a lower mortality with ibuprofen treatment than for either verapamil or placebo. This rat model was useful as a screening tool for the initial evolution of therapeutic interventions to reduce myocardial infarct size. It required substantially less time than large animal models and can be used to examine a variety of treatment doses. These experiments also demonstrated the importance of randomisation to treatment and control groups because of the possibility of disproportionate mortality affecting infarct size.

Animals↗
PubMed1984

Pathomorphologic aspects of muscular tissue in diabetes mellitus.

Biopsy specimens from the myocardium were examined in a series of 145 patients who had elected coronary arterial bypass grafting. The patients were divided into three groups; 1) overtly diabetic (OD) patients; 2) chemically diabetic (CD) patients, who demonstrated impaired glucose tolerance only when stressed with a sugar load; and 3) normoglycemic, nondiabetic (ND) patients, who served as a control group. Tissue plugs from the left anterior apical segment of the heart and from the quadriceps femoris in 71 patients, for comparative evaluation, were prepared for ultrastructural examination. Findings were as follows: 1) Myocardial hypertrophy and interstitial fibrosis were twin characteristic abnormalities, seen in all but two of the biopsy specimens; capillary endothelial changes, the third most common abnormality, were present in approximately half of these specimens, regardless of the patients' metabolic status. 2) In patients matched by sex, age, weight, blood pressure, preoperative myocardial ventricular function, and coronary arterial integrity, capillary basal laminar thickening represented a pathomorphologic hallmark, distinguishing structural alterations in the diabetic from those in the normoglycemic patient. 3) Although clear-cut and statistically significant thickening of basal laminae was noticeable in OD patients, a) in the quadriceps markedly increased laminar thickening was present in a number of ND patients, rendering interpretation of this change in skeletal muscle as pathognomonic for diabetes doubtful; and b) within cardiac muscle this increase in laminar width was less than that seen in skeletal muscle, leaving the functional implications of this alteration in doubt. 4) Early but statistically significant increases in capillary basal laminar thickening were observed in the myocardium of CD patients; these patients demonstrated impaired glucose tolerance only when stressed with a sugar load, without exhibiting overt diabetic manifestations. 5) In this group of highly selected patients with epicardial coronary arterial disease, the histopathologic profile of the diabetic myocardium did not include distinctive abnormalities sufficient to warrant the designation of "diabetic cardiomyopathy," indicating that coronary arterial bypass grafting can be recommended for the diabetic patient who requires this procedure.

Adult↗
PubMed1983

Peripheral neuropathy following prolonged exposure to streptozotocin-induced diabetes in rats: a teased nerve fiber study.

An experimental diabetic state was induced in rats by means of an injection of streptozotocin. A histological and histometric evaluation of randomly teased nerve fibers was applied to the common peroneal nerves of both diabetic and age- and weight-matched control rats. A long-term (6-12 months) exposure to the diabetic state was required for the demonstration of the following morphological changes: (1) splitting and notching of myelin sheaths, (2) decrease in the ratio of internodal length/internodal diameter, (3) widening of nodal gaps. This study showed that neurons of smaller caliber are preferentially affected after a prolonged period of the diabetic condition. Neurons of this size are representative of sensory and autonomic components, suggesting that the changes present in this model parallel the derangements of these constituents reported in the human diabetic with adult onset disease.

Animals↗
PubMed1982

The effect of inorganic lead on heptic biochemical and ultrastructural changes produced by phenobarbital.

Lead acetate (105 mumol/kg, i.p.) decreased rat hepatic cytochrome P-450 to 57% and 63% of control values when measured 24 and 48 h after lead administration, respectively. A large increase in urinary delta-aminolevulinic acid (U-ALA) was observed after lead treatment, indicating a depression of heme synthesis. In addition, lead treatment produced dilated cisternae of the smooth endoplasmic reticulum (SER). Phenobarbital (100 mg/kg, i.p.) produced an induction of cytochrome P-450, proliferation of the SER, and did not alter U-ALA content. Simultaneous lead and phenobarbital treatment produced a delayed but robust induction of cytochrome P-450, only a moderate rise in U-ALA, and a reduced proliferation of the SER of hepatocytes. Therefore, phenobarbital, an inducer of heme synthetic enzymes, is apparently capable of reversing lead-induced inhibition of heme synthesis as measured by hepatic cytochrome P-450 induction and U-ALA content.

Aminolevulinic Acid↗
PubMed1982

Mitigating effects of ICRF-159 (razoxane) on a daunomycin-induced cardiomyopathy in mice.

In an attempt to induce in mice the cardiomyopathy associated with daunomycin treatment and to ameliorate this disorder by a protective pretreatment with ICRF-159 (razoxane), young male BDF 1 mice were injected with daunomycin, 6 mg/kg, in multiple doses. A second group of mice were pretreated by injection with razoxane, 200 mg/kg, 24 hours before each daunomycin administration. Within three weeks of the third daunomycin injection one half of the unprotected mice were moribund and were sacrificed. Mice pretreated with razoxane survived the length of the experiment without exhibiting any disabilities. Myocardial tissue of all mice was processed for light and electron microscopic examination. The myocardial ultrastructure of daunomycin-toxic mice showed foci of incipient changes, characterized by sarcoplasmic translucency, vacuolation of membrane-limited components, degeneration of mitochondria and lysosomal aggregates. Evaluation of mice pretreated with razoxane either failed to reveal ultrastructural alterations or demonstrated only minimal changes in the myocardium.

Animals↗
PubMed1982

Quadriceps and myocardial capillary basal laminae. Their comparison in diabetic patients.

Quadriceps and myocardial biopsy specimens were obtained from 24 patients undergoing elective coronary arterial bypass grafting. Patients were divided into those with chemical diabetes (CD) (with incidentally discovered elevated glucose levels when stressed), overt diabetes (OD) (who required insulin support), and euglycemic nondiabetics (ND). Specimens from the quadriceps femoris and left anterior apical segment of the heart were examined ultrastructurally, with particular attention to the evaluation of capillary basal laminar thickness, using morphometric techniques. Results indicate (1) an increased, though statistically insignificant, thickening of capillary basal laminae in the quadriceps of CD and OD patients, in contrast with statistically significant laminar thickening in the diabetic myocardium; (2) early, mild laminar thickening in quadriceps and myocardium of the asymptomatic CD group; and (3) two characteristic patterns of basal laminar contours, homogeneous and lamellated, the latter being seen prominently in the quadriceps of diabetic patients in frequent association with pericapillary edema. These findings support the concept that basal laminar thickening in the diabetic is associated with deranged carbohydrate metabolism.

Adult↗
PubMed1981

Progressive neuropathologic lesions in vitamin E-deficient rhesus monkeys.

A consistent group of progressive central and peripheral nervous system lesions developed in seven rhesus monkeys maintained on a vitamin E-deficient diet for 30 to 33 months. These lesions were absent from vitamin E-supplemented monkeys. The principal neuropathologic alteration was loss of sensory axons in the posterior columns, sensory roots, and peripheral nerves. Morphologic and morphometric studies indicated that the distal segments of the axons were affected most severely and large-caliber myelinated fibers are selectively involved. Swollen, dystrophic axons (spheroids) occurred infrequently. Degeneration and phagocytosis of small numbers of neuronal perikarya were observed in the dorsal root ganglia and the anterior horns. The number of affected neurons was not proportional to the number of affected axons. Accumulation of lipopigment was evident in neuronal perikarya and CNS endothelial cells. The nervous system lesion were usually accompanied by a chronic necrotizing myopathy. The neuropathologic lesions in vitamin E-deficient monkeys are compared with those in vitamin E-deficient rats and in humans with low serum vitamin E concentrations. A similar type of sensory axonopathy is associated with chronic deficiency of vitamin E in these three species.

Animals↗
PubMed1981

Skin tests in a primate model of allergic bronchopulmonary aspergillosis.

We have previously reported producing a primate model of allergic bronchopulmonary aspergillosis in which monkey precipitating IgG and transfused human IgE antibodies against Aspergillus fumigatus (AF) combined with aerosolized AF to produce an inflammatory response in the lung. In this study we attempt to demonstrate similar changes in the skin. Immunized and unimmunized monkeys with and without IgG precipitating antibody to AF were injected at multiple sites intradermally with normal human serum or human serum rich in IgE against AF. 1 day later each site was injected with AF. Serial skin biopsies were taken at intervals of 15 min, 1, 2, 6, 12, 24, and 48 h and light microscopic, immunofluorescent, and electron microscopic studies were performed. The most profound changes were associated with simian antibody (IgG) and human antibody (IgE) directed against AF and consisted or perivascular and interstitial neutrophilic infiltration at 2 h, eosinophils at 6 h, and mononuclear cells at 24 h. Immunofluorescent staining for fibrin-fibrinogen, IgM, and C3 was present and diapedesis of cells to extra-vascular dermal areas was evident. The skin appear to mirror the inflammatory changes seen in the lung in this primate model of allergic bronchopulmonary aspergillosis and should afford a useful model for further studies.

Animals↗
PubMed1980

The biochemical and morphological response of hydrolytic enzymes in the developing brain to hypocholesterolemic agents.

Administration of hypocholesterolemic agents to developing rats has been found to selectively induce brain hydrolases. Certain regimes also caused an appreciable increase in total brain protein content. The hypocholesterolemic agents AY-9944 and zuclomiphene were tested individually and in combination. A fourth type of treatment utilized the above drugs in combination with Triparanol. Whenever AY-9944 was used, singly or in combination with other compounds, the beta-glucuronidase activity of developing brain was increased. Acid phosphatase and total brain protein were increased in animals treated with AY-9944 plus zuclomiphene or AY-9944 plus zuclomiphene and Triparanol. Neither AY-9944 nor zuclomiphene alone significantly affected brain total protein or acid phosphatase. Electron microscopic examination of tissue specifically reacted for acid phsophatase demonstrated that the increased enzyme activity was localized in cells in the perivascular spaces. Alkaline phosphatase and N-acetyl-beta-glucosaminidase, two other hydrolytic enzymes assayed, seemed to be much less influenced by the drug treatments.

Acetylglucosaminidase↗
PubMed1979

Ultrastructural integrity of human ventricular myocardium following cardioplegic arrest.

The appearance of the ventricular myocardium in 6 patients electing coronary bypass operation was evaluated by electron microscope before and after aortic cross-clamping. Bypassing protocol included the induction of hypothermic cardioplegia by intermittent aortic root perfusion, with potassium chloride added to cold blood serving as the cardioplegic agent. Cross-clamp intervals ranged from 66 to 125 minutes. Ultrastructural alterations following bypass manipulations, and distinct from those observed before cross-clamping, were limited to the presence of extensive myocardiocytic pooling of glycogen. Scrutiny of the intramyocardial capillary bed following perfusion with the cardioplegic solution revealed no abnormalities attributable to, or intensified by, the bypass maneuver. These findings indicate that hypothermic potassium cardioplegia, as specified, is not injurious to human myocardial ultrastructure.

Adult↗
PubMed1979

Capillary basal laminar thichness in diabetic human myocardium.

Biopsied myocardial tissue was obtained from 24 patients electing coronary arterial bypass surgery who were divided into three groups: chemical diabetics (CD) with normal fasting blood sugar levels and incidentally encountered elevated glucose levels after sugar loading; overt diabetics (OD) requiring insulin treatment; and euglycemic, nondiabetic patients (ND) serving as a control group. Specimens from the left anterior apical segment of the heart were processed for ultrastructural examination, with special emphasis on determining capillary basal laminar thickness with the aid of morphometric techniques. Results of this study indicate that (1) a statistically significant increase in basal laminar thickness is evident in myocardial tissue of OD patients; (2) incipient alterations in laminar width are demonstrable in the CD group; (3) the predominant morphologic abnormalities, which we have examined in the parenchymal tissue of the biopsied hearts, namely myocardial hypertrophy and interstitial fibrosis, are present to a comparable degree in all three groups of patients; and (4) the average thickness of basal laminae around myocardial capillaries tends to be narrower compared with measurements reported in other tissue compartments.

Adult↗