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Biomedical subjects

M Wittner

Publications and source records attributed to M Wittner.

At least 145 records · Page 8Linked to original sources
PubMed1984

Alteration of the pattern of beta-adrenergic desensitization in cultured L6E9 muscle cells infected with Trypanosoma cruzi.

L6E9 myoblasts infected with Trypanosoma cruzi undergo desensitization to beta-adrenergic catecholamines in a manner distinct from uninfected control myoblasts. Following incubation of intact cells with isoproterenol for 2 h, homogenates prepared from differentiated, high density uninfected L6E9 cells retain isoproterenol-dependent adenylate cyclase activity. In addition, previous exposure to isoproterenol is accompanied by a decrease in the number of beta-adrenergic receptors. Homogenates of high density L6E9 cells infected with T. cruzi retain their adenylate cyclase responsivity to isoproterenol but demonstrate a marked decrease in beta-adrenergic receptors. Following desensitization infected cell homogenates lose their responsiveness to isoproterenol and demonstrate a more marked decrease in beta-receptors. There does not appear to be any effect of T. cruzi infection on affinity of beta-adrenergic agonists for the beta-receptor or on changes in agonist affinity associated with desensitization. Infection of low density undifferentiated cells results in no apparent change in adenylate cyclase activity or in beta-receptors. Their behavior in the setting of desensitization--decreased whole cell cyclic AMP, decreased adenylate cyclase, unchanged beta-receptors--is also not affected by infection. The pattern of desensitization to beta-adrenergic agonists in high density infected cells shares several properties with the pattern of desensitization in low density uninfected cells, suggesting that infection may be associated with part of the more primitive cellular response pattern.

Adenylyl Cyclases↗
PubMed1983

Inhibition of muscle differentiation by trypanosoma cruzi.

L6E9 rat myoblasts were infected in tissue culture with the myotropic Brazil strain of Trypanosoma cruzi. The effect of parasite infection on the ability of myoblasts to differentiate into myotubes was studied. Both morphological and biochemical differentiation were found to be profoundly affected by parasitic infection in a dose-related fashion. Evidence is presented to suggest that infected myoblasts can no longer differentiate. Differentiation, once underway, seemed unaffected by the parasitic infection; biochemical markers of differentiation remained intact.

Actins↗
PubMed1983

Alterations in acetylcholine receptors in experimental chagas' disease.

Acetylcholine (ACH) receptors were studied to determine whether these receptors are affected during infections due to Trypanosoma cruzi in resistant and susceptible mice. Nicotinic ACH receptors were measured by the binding of [125I] alpha-bungarotoxin in skeletal muscle and brain tissues of two susceptible mouse strains (A/J and C3H) infected with the Brazil strain of T. cruzi. In skeletal muscle and brain tissues there were significant increases in alpha-bungarotoxin binding late but not early in infection. Infected resistant mice studied at 30 and 90 days after challenge showed no increase in alpha-bungarotoxin binding. Muscarinic ACH receptors were measured using [3H]quinuclidinyl benzilate. There were no significant changes in numbers of muscarinic ACH receptors in hearts and brains of infected mice. Pathologic studies revealed marked necrosis and many pseudocysts in skeletal muscle of C3H and A/J strain mice. Clinical denervation hypersensitivity occurs in Chagas' disease and is associated with an increase in ACH receptors. Our findings may provide a cellular basis for denervation hypersensitivity in Chagas' disease.

Animals↗
PubMed1983

Cellular responses in human strongyloidiasis.

Peripheral lymphocytes from 16 patients with chronic uncomplicated strongyloidiasis and 15 non-infected controls were stimulated in vitro with Strongyloides stercoralis larval antigens, other non-parasite antigens and the T cell mitogen phytohemagglutinin (PHA). In the presence of autologous plasma the patients' responses to Strongyloides antigens were similar to those of controls. When lymphocytes from nine patients were cultured in the presence of normal human serum, responses to parasite antigens were enhanced, while responses to other antigens and to PHA were unaffected. Lymphoproliferative responses to PHA were significantly lower in the patients' group than in the controls. These findings suggest that in chronic strongyloidiasis, in addition to a depression of T cell activity, factors are present in the patients' serum that inhibit parasite-specific cellular responses in vitro.

Cells, Cultured↗
PubMed1983

Specific allergic sensitization to Strongyloides antigens in human strongyloidiasis.

Reaginic antibodies to antigens from the human parasite Strongyloides stercoralis were studied by histamine release from basophils in 15 patients with chronic uncomplicated strongyloidiasis and in 12 controls (six North Americans with no evidence of parasitic diseases, two patients with Schistosoma mansoni, two with hookworm, one with Ascaris lumbricoides, and one with Onchocerca volvulus). All of the patients had antibodies to the somatic larval antigens, and 14 of 15 patients also had antibodies to the excretory/secretory products of S. stercoralis larvae. None of the controls had a positive response to any of the antigens tested. These findings indicate that patients with chronic strongyloidiasis have parasite-specific IgE antibodies and that S. stercoralis larval allergens may have a potential role in the immunodiagnosis of strongyloidiasis.

Antigens↗
PubMed1983

Diagnosis of giardiasis by two methods. Immunofluorescence and enzyme-linked immunosorbent assay.

Antibody response in giardiasis was measured by indirect fluorescent antibody (IFA) and enzyme-linked immunosorbent assays (ELISA) on serum samples of 125 patients. Twenty-nine of these patients had symptomatic giardiasis; 30 were asymptomatic (carriers); 40 had other parasitic infections; 16 had inflammatory bowel diseases; ten were normal subjects. It was found that those patients with symptomatic giardiasis had higher IFA titers compared with all patients who did not have giardiasis and patients who had asymptomatic giardiasis. Serum samples with titers of 1:64 or greater in Giardia IFA were absorbed with Giardia and other parasite antigens. Only absorption with Giardia caused the titers to fall significantly. The ELISA technique was less specific than the IFA technique. Giardiasis elicits a specific host antibody response that may be used as an adjunct in its diagnosis.

Antibodies↗
PubMed1982

The effect of adenosine analogues on the in vitro growth of Trypanosoma cruzi.

Trypanosoma cruzi (Brazil strain) was maintained in liver infusion tryptose and medium supplemented with 5 or 10% foetal calf serum at 27 degrees C on a rotating shaker platform. 85 to 95% of the organisms under these conditions are epimastigotes and the medium supported logarithmic growth for up to 24 hours. The effect of S-isobutyl adenosine and Sinefungin against cultured T. cruzi epimastigotes was studied: growth rate was slowed by both in a dose-dependent fashion; 500 micrometer Sinefungin caused complete inhibition which was irreversible after 24-hour exposure but the effect of S-isobutyl adenosine (100 micrometer) was reversible. Motility and morphology appeared to be unaffected.

Adenosine↗
PubMed1982

Infection of organotypic cultures of spinal cord and dorsal root ganglia with Trypanosoma cruzi.

Although the involvement of the nervous system in Chagas' disease is well described, the mechanism of the neuronal destruction is unclear. Immunologic, toxic mechanisms and direct invasion have been advocated. Organotypic cultures of spinal cord and dorsal root ganglion derived from Swiss outbred mice were infected with the Brazil strain of Trypanosoma cruzi. Light microscopic and ultrastructural studies were performed at regular intervals. It was found that trypomastigotes were rapidly taken up by glial and other supporting cells. Neurons were rarely parasitized and demyelination was not evident. Loss of several cytoskeletal components was seen. Dendrites were swollen and axons lost their normal filamentous structures but synaptic membranes remained intact. Mitochondrial swelling was evident even in nonparasitized neurons from infected cultures. By 7-10 days of infection the majority of neurons lost their typical morphology and were eventually destroyed by mechanisms other than direct parasite invasion. Organotypic cultures exposed to T. cruzi-conditioned medium exhibited no change in morphology. Since neurons were found only rarely to be parasitized, it is suggested that neuronal destruction is an indirect result of the parasitism of supporting cells such as glial cells and macrophages.

Animals↗
PubMed1982

Successful chemotherapy of transfusion babesiosis.

We describe babesiosis transmitted by transfusion. The infected blood donor was identified and a minimum period of infectivity of the donor's blood was established. We report a new modality for chemotherapy consisting of quinine plus clindamycin, and a new endemic focus for this zoonosis on Fire Island, New York. There are insufficient data to establish a reasonably safe period after which visitors and residents of Babesia-endemic foci can become blood donors. Screening of such persons by a rapid serologic test, such as the ELISA or immunofluorescent antibody tests, is suggested.

Adult↗
PubMed1981

Taxol, a microtubule stabilizing agent, blocks the replication of Trypanosoma cruzi.

Taxol, an experimental antitumor agent and stabilizer of microtubules, inhibits in vitro replication of the human pathogenic hemoflagellate Trypanosoma cruzi. Micromolar concentrations of the drug prevent the completion of cell division in these organisms but allow the multiplication of cell organelles such as the nucleus, kinetoplast, and flagellum. The result is the formation of motile organisms that have extra organelles but cannot fully replicate. Division proceeds to a relatively fixed locus on the long axis of the organism, suggesting the presence of a specific affected structure or function at this site. It is postulated that taxol produces these effects by stabilizing a portion of the microtubular cytoskeleton of T. cruzi.

Alkaloids↗