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Biomedical subjects

M Sadigursky

Publications and source records attributed to M Sadigursky.

At least 19 recordsLinked to original sources
PubMed1991

Experimental chemotherapy of Trypanosoma cruzi infection: persistence of parasite antigens and positive serology in parasitologically cured mice.

Mice infected with Trypanosoma cruzi, but parasitologically cured after specific chemotherapy, continued to exhibit positive indirect immunofluorescence serological tests 3-6 months after the therapy. Treatment of trypanosome antigens with monospecific antisera produced in rabbits, and examination by immunoelectron-microscopy following peroxidase labelling disclosed the presence of membrane deposits in cell processes in the spleens of the mice. Similar deposits were observed in the external membranes of T. cruzi amastigotes in the spleens of acutely infected mice, but not in normal control mice. No reaction occurred in tissues not previously treated with the monospecific anti-T. cruzi serum. Positive cells in treated and cured mice, as well as in the not cured or untreated control mice, were located in germinal centres of the splenic white pulp and presented long and branching cytoplasmic processes, which are indicative of dendritic cells of the lymphoid follicles of the spleen.

Animals↗
PubMed1989

Development of metacyclic Leishmania promastigotes is associated with the increasing expression of GP65, the major surface antigen.

Using immunofluorescence techniques and flow microfluorometry analysis, we have demonstrated that the binding of a monoclonal antibody (VD5/25) produced against GP65, the major surface antigen of Leishmania braziliensis, increased on the surface of stationary-phase promastigotes from all the New World Leishmania species causing mucocutaneous or cutaneous disease as compared with the log-phase parasites. In addition, a sequential development of Leishmania amazonensis promastigotes from a non-infective to an infective stage was demonstrated. Indeed, promastigotes in the stationary phase (days 6-7) were found to be far more infective than those in the logarithmic phase of growth (day 3) both in vitro for mouse peritoneal macrophages and in vivo for BALB/c mice. The intracellular survival and multiplication of L. amazonensis were significantly inhibited when infective promastigotes were treated with the VD5/25 monoclonal antibody. The increasing expression of GP65 on the promastigote surface may thus contribute to Leishmania infectivity. This seems to represent a characteristic mechanism applicable to all New World Leishmania species studied.

Animals↗
PubMed1989

Association of elevated anti-sarcolemma, anti-idiotype antibody levels with the clinical and pathologic expression of chronic Chagas myocarditis.

Antibody F(ab')2 fragments derived from the sera of four patients with histology-proven chronic Chagas myocarditis [cF(ab')2]-complexed antibody F(ab')2 fragments of children with acute Trypanosoma cruzi infection [aF(ab')2] in significantly higher molar ratios than those measured with F(ab')2 antibody fragments of normal subjects [nF(ab')2] from nonendemic areas (p less than 0.05). Anti-idiotype [cF(ab')2 X aF(ab')2] immune-complex formation was significantly blunted by preabsorption of cF(ab')2 with porcine heart atria sarcolemma (PAMs) immobilized on sepharose beads (inhibition, mean, 78.1 +/- 2.4%, n = 4). cF(ab')2 X nF(ab')2] immune-complex formation was also inhibited by pretreatment of cF(ab')2 with PAMs (inhibition, mean, 48.7 +/- 7.5%, n = 4). The sera of three groups of subjects from a geographic zone endemic for T. cruzi infection in the northeast of Brazil were assayed for free and immune-complexed IgG anti-acute T. cruzi infection F(ab')2. The indexed levels of free IgG anti-idiotype antibody activity and levels of IgG anti-idiotype immune complexes (IC') were markedly elevated in hospitalized patients with severe, decompensated chronic Chagas myocarditis (n = 23), and their IC' indexes were significantly higher than those measured in asymptomatic seropositive subjects from a nearby endemic village of the northeast of Brazil (Moniz Ferreira, n = 92, p less than 0.001) and in healthy seronegative villagers (n = 84, p less than 0.001). There exists a strong correlation between elevated IgG anti-sarcolemma, anti-idiotype activity levels and the clinical and pathologic expression of chronic Chagas myocarditis.

Adult↗
PubMed1988

Complementary surface epitopes, myotropic adhesion and active grip in Trypanosoma cruzi-host cell recognition.

Plasma membranes with complementary surface epitopes and with essentially the same orientation as tissue infective metacyclic trypomastigotes and epimastigotes of Trypanosoma cruzi adhere to L6 myoblast host cells preferentially to smooth muscle and epithelial cells as a function of time, surface area and concentration in saturation phenomena at 4 and 37 degrees C. The initial adhesion rates are partially calcium ion dependent and, at saturation, they are also dependent on high energy phosphorylated intermediates, exerting an active grip on adherent parasite membranes. These phenomena are consistent with the existence of parasite attachment molecules on the external surface of the plasma membrane and complementary host cell receptor structures with the capacity to bind them.

Animals↗
PubMed1987

Induced tolerance to Schistosoma mansoni antigens modulates periovular granuloma.

Immunological tolerance to Schistosoma mansoni antigens induced by oral exposure of neonatal and adult mice to adult worm, soluble egg and polysaccharide antigens conducted to modulated periovular granuloma of infected mice. However the tolerance do not interfere in the infection. The estimative population and subpopulation of lymphocytes in the spleen of tolerized (not infected) animals do not differ from normal animals but Lyt 2.2 reactive lymphocytes to Schistosoma antigens was demonstrated in the tolerized animals.

Administration, Oral↗
PubMed1987

Specific immunization of mice against Leishmania mexicana amazonensis using solubilized promastigotes.

Successful immunization of highly susceptible BALB/c mice against progressive infection by Leishmania mexicana amazonensis, using whole solubilized promastigotes was achieved. The best immunization schedule consisted of three weekly injections of 5 X 10(7) parasite equivalents. Intravenous was superior to intraperitoneal or subcutaneous immunization. Protection persisted for up to 2 months after immunization, and beneficial effects could be observed in long-term follow-up (24 weeks after infection). Immunized mice exhibited marked reduction in primary lesion size, as well as reduction of the number of parasites in the spleen, and developed less metastases. High titres of specific anti-L. m. amazonensis IgG antibodies resulted from immunization, but titres did not correlate with protection. Groups with widely differing pre-infection antibody titres were equally protected, and similar antibody titres resulted in different levels of protection. Immunization alone did not induce significant serum interferon-gamma levels and specific delayed-type hypersensitivity (DTH) reactions, but resulted in the persistence of positive (DTH) reactions after infection, at a time when infected control animals had suppressed responses. Resistance to leishmaniasis appears to depend on cell mediated immune mechanisms, and the possibility of immunization with a solubilized antigen without adjuvant is intriguing and opens new perspectives in this area.

Animals↗
PubMed1987

Enhancement of chronic Trypanosoma cruzi myocarditis in dogs treated with low doses of cyclophosphamide.

An enhancement of chronic myocarditis was obtained in dogs chronically infected with Trypanosoma cruzi protozoa soon after they were submitted to treatment with low doses of cyclophosphamide (50 mg/sq m bs three times a week for 3 weeks). Such treatment did not cause immunodepression. Myocarditis varied in intensity, but was quite severe and diffuse in some animals, with focal fibrinoid, coagulative, and lytic necrosis and invasion of disintegrating myocardial fibers by the mononuclear inflammatory cells. Untreated infected controls exhibited mild focal myocarditis, usually represented by accumulation of lymphocytes in the interstitial connective tissue. It is suggested that the administration of low doses of cyclophosphamide interfered with the immunologic suppressor network that is thought to maintain the chronic indeterminate (or latent) phase of T cruzi infection.

Animals↗
PubMed1987

[Recurrent polychondritis (report of a case)].

A case of relapsing polychondritis with atrophic lesions in nose and ears and conjunctivitis is presented. The patient was treated with dapsone during 18 months with remission of the acute breaks.

Atrophy↗
PubMed1986

A new liquid medium without blood and serum for culture of hemoflagellates.

A liquid medium without blood or serum was developed for cultivation of hemoflagellates. To a basic LIT medium containing liver infusion broth and tryptose, a mixture of RPMI 1640 and Medium 199 was added. This combination permitted high parasite yields useful for biochemical and immunological studies.

Animals↗
PubMed1986

Electrocardiographic changes in experimental chronic murine Chagas' disease.

An electrocardiographic study was performed on 26 AKR and 32 A/J inbred mice and on 100 Swiss outbred mice, chronically infected with different strains of T. cruzi, characterized as Types I, II and III. The incidence of electrocardiographic alterations in AKR mice was of 87.0%, 80.0% and 83.3% respectively for infection with the Type I, Type II and Type III strains of T. cruzi. In A/J mice the incidence of electrocardiographic alterations was 100% in the infection with the Type I and Type III strains and 26.1% with the Type II strain of T. cruzi. In Swiss mice the electrocardiographic alterations occurred in 53.5% of the mice infected with the Type II strain and in 71.4% of those infected with the Type III strain of T. cruzi. The most frequent electrocardiographic alterations in chronically infected mice, independently of mouse or T. cruzi strain, were first degree AV block, intraventricular conduction abnormalities, sinus tachycardia and bradycardia. The predominant alterations caused by each of the T. cruzi strains varied according to mouse strain. In A/J mice, the electrocardiographic alterations were more frequent in those animals infected with Type I and III strains of T. cruzi and in Swiss mice the alterations were more frequent in those infected with the Type III strain. The results presented in this study demonstrate that the murine model is suitable for electrocardiographic studies related to the heart lesions that occur in Chagas' disease.

Animals↗
PubMed1986

Leishmania mexicana amazonensis infections in 'resistant' inbred mice following removal of the draining lymph node.

Highly resistant (C57BL/10) and intermediately resistant (DBA/2) mice were infected subcutaneously with Leishmania mexicana amazonensis in a hind footpad subsequent to removal of the draining popliteal node. These mice developed greatly exacerbated Leishmania infections as compared to sham-operated controls or to mice infected in the contralateral footpad. The majority of mice in which the draining lymph nodes were removed prior to infection developed metastases, lost their delayed hypersensitivity responses to Leishmania, and some died. Significantly fewer metastases and no deaths were observed in the control groups. The results emphasize the importance of lymphatic control of Leishmania m. amazonensis infection in relatively resistant mouse strains.

Animals↗
PubMed1985

Primary muscle disease: definition of a 25-kDa polypeptide myopathic specific chagas antigen.

The sera from patients with primary heart and skeletal muscle diseases, hospitalized patients without intrinsic muscle disease from an area endemic for Trypanosoma cruzi infections, and normal subjects (N = 693) were studied for the presence of immunoglobulin G (IgG) antisarcolemma activity using serologic methods. The prevalence of elevated serum IgG antisarcolemma activity from patients with chronic Chagas' cardiomyopathy, idiopathic cardiomyopathy, polymyositis, and Duchenne muscular dystrophy was 58.9 +/- 10.4% (N = 101) (P less than 0.001 when compared to normal subjects). Two of twelve (16.7%) patients with acute T. cruzi infection and parasitemia developed elevated antisarcolemma titers, and 9/46 (19.6%) patients with chronic T. cruzi infection without evidence of cardiomyopathy yielded high antisarcolemma titers. On the other hand, patients with chronic T. cruzi infection with advanced cardiomyopathy yielded high antisarcolemma titers in 35/74 (47.3%) (P less than 0.001 when compared to normal subjects). Radioimmunoprecipitation showed a circulating antibody to a 25-kDa T. cruzi polypeptide (P25) in 16/17 (94.1%) patients with advanced cardiomyopathy and T. cruzi infection. No such antibody was shown in 12 asymptomatic subjects with chronic T. cruzi infection.

Antibodies↗
PubMed1985

Infectivity of Leishmania promastigotes is associated with surface antigenic expression.

Differentiation between a non-infective and an infective Leishmania promastigote population was demonstrated. Promastigotes in the stationary phase (day 5) were found to be highly infective in vitro to BALB/c mouse peritoneal macrophages, compared with those of the logarithmic phase (day 3). The infective promastigotes showed surface antigenic determinants different from non-infective ones. Polyclonal anti-3 day and anti-5 day antibodies were bound specifically to the surface of corresponding promastigotes in both SRIA and IFAT; no strong cross-reactions were observed otherwise. Also, polyclonal anti-5 day but not anti-3 day antibodies recognized efficiently the antigenic molecules on the surface of late stage (day 7) sandfly promastigotes. This clearly indicates the appearance of new antigenic molecules on the surface of infective promastigote forms. Intracellular multiplication of Leishmania was significantly inhibited by anti-5 day antibodies compared with anti-3 day antibodies. The presence of new surface molecules on late stage promastigotes may contribute to Leishmania infectivity.

Animals↗
PubMed1985

Subspecies-specific surface antigens of promastigotes of the Leishmania donovani complex.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns of proteins and externally exposed labeled surface constituents were analyzed in promastigotes of three etiological agents of kala azar (Leishmania donovani, HS70 strain from India; L. chagasi, Imperatriz strain from Brazil; L. infantum, ITMPA K263 strain from Morocco and MO strain from France). Coomassie blue-stained gels showed similar protein patterns for L. donovani and L. chagasi and a more distinct one for L. infantum. Surface radioiodination with two different methods, lactoperoxidase and IODO-GEN, gave identical autoradiographic patterns for each parasite. Four major labeled proteins with apparent Mr values of 65,000, 60,000, 50,000, and 26,000 were detected in both L. chagasi and L. donovani. However, the radioiodinated polypeptide pattern of L. infantum only showed two major bands with an apparent Mr of 62,000 and a doublet of 26,000 to 23,000. Immunoprecipitation of detergent extracts of labeled promastigote subspecies with immune sera from rabbits immunized with either L. chagasi or L. infantum and from patients and mice infected with these two parasites, as well as with a monoclonal antibody against the surface of L. donovani promastigotes, demonstrated that the surface antigenic expression of L. infantum is different from that noticed in the two other subspecies, which are similar. Immunofluorescence experiments with some of these antibodies confirmed these results. The present findings should be considered in taxonomic and immunological studies in visceral leishmaniasis.

Animals↗