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A R Teixeira

Publications and source records attributed to A R Teixeira.

At least 37 records · Page 2Linked to original sources
PubMed1997

Genetic epidemiology of seropositivity for Trypanosoma cruzi infection in rural Goias, Brazil.

Chagas' disease is a zoonotic disease found throughout Latin America. Despite control programs in many of the affected countries, infection with Trypanosoma cruzi continues to be a major public health concern. In Brazil alone, approximately 53 million people live in endemic areas. Research with humans and with animal models indicates that there is variation in susceptibility to infection with T. cruzi. The reasons for this variation are not known although several studies have implicated genetic factors. An indirect immunofluorescence assay was used to assess seropositivity for T. cruzi infection in 716 adults from the municipality of Posse, Goias, Brazil. Detailed genealogic information was gathered at the time of sampling, which allowed assignment of 525 individuals to 146 pedigrees containing between two and 103 individuals; the remaining 191 unrelated individuals were retained as independents in the analysis. Using a maximum likelihood variance decomposition approach, we performed quantitative genetic analyses to determine if genetic factors could partially account for the observed pattern of seropositivity. The maximum likelihood estimate of the heritability of T. cruzi infection was 0.56 +/- 0.27 (mean +/- SE), indicating that genetic factors account for more than half of the observed variation in infection status. An additional 23% of the variation (c2 = 0.23 +/- 0.09) is attributable to the effects of shared environment, as assessed by common household. The results indicate that genetic factors play an important role in determining epidemiologic patterns of T. cruzi infection. Further characterization of these genetic factors may suggest new biologic areas to be targeted by prevention and intervention programs.

Adolescent↗
PubMed1997

Superinfections with genetically characterized Trypanosoma cruzi clones did not aggravate morbidity and mortality in BALB/c mice.

To determine the role of Trypanosoma cruzi superinfections on the outcome of Chagas' disease, groups of BALB/c mice were prime-infected with low virulence clones h1 and h2 and challenged with high virulence clones m3 and m4. All mice injected with the m3 and m4 clones succumbed before or at 16 days postinfection. In contrast, all mice injected with the h1 and h2 clones survived the prime infection and were superinfected with the m3 and m4 clones. Low-level parasitemias were observed in mice after challenge with the virulent clones. The mortality ratios in the superinfected mice were not statistically different from those seen in the mice that received a single T. cruzi injection. The histopathological lesions recorded during the course of the infections showed features in the superinfected mice similar to those seen in the animals receiving a single infection. These data argue that morbidity and mortality in BALB/c mice, infected with T. cruzi clonal lines, are not associated with the frequency of receiving the parasite burden.

Animals↗
PubMed1996

Covalent dimerization of ribulose bisphosphate carboxylase subunits by UV radiation.

The effect of UV radiation (UV-A, UV-B and UV-C) on ribulose bisphosphate carboxylase from a variety of plant species was examined. The exposition of plant leaves or the pure enzyme to UV radiation produced a UV-dependent accumulation of a +5 kDa polypeptide (P65). Different approaches were utilized to elucidate the origin and structure of P65: electrophoretic and fluorographic analyses of 35S-labelled ribulose bisphosphate carboxylase exposed to UV radiation and immunological experiments using antibodies specific for P65, for the large and small subunits of ribulose bisphosphate carboxylase and for high-molecular-mass aggregates of the enzyme. These studies revealed that P65 is a dimer, formed by the covalent, non-disulphide linkage of one small subunit with one large subunit of ribulose bisphosphate carboxylase. For short periods of time (< 1 h), the amount of P65 formed increased with the duration of the exposure to the UV radiation and with the energy of the radiation applied. Prolonged exposure to UV radiation (1-6 h) resulted in the formation of high-molecular-mass aggregates of ribulose bisphosphate carboxylase. Formation of P65 was shown to depend on the native state of the protein, was stimulated by inhibitors of enzyme activity, and was inhibited by activators of enzyme activity. A UV-independent accumulation of P65 was also achieved by the in vitro incubation of plant crude extracts. However, the UV-dependent and the UV-independent formation of P65 seemed to occur by distinct molecular mechanisms. The UV-dependent accumulation of P65 was immunologically detected in all species examined, including Lemna minor, Arum italicum, Brassica oleracea, Triticum aestivum, Zea mays, Pisum sativum and Phaseolus vulgaris, suggesting that it may constitute a universal response to UV radiation, common to all photo-synthetic tissues.

Chromatography↗
PubMed1996

Diversity of Trypanosoma cruzi stocks and clones derived from Chagas disease patients. II. Isozyme and RFLP characterizations.

Isoenzyme and RFLP analyses were carried on freshly isolated Trypanosoma cruzi stocks and subsequent clones derived from patients with chronic Chagas disease. The isoenzymes separated the parasite stocks and clones in two groups: The stock hSLU239 (group I), isolated from a heart disease patient, showed the zymodeme 3 (Z3) profile (M. A. Miles et al., 1977, Transactions of the Royal Society of Tropical Medicine and Hygiene 71, 217-225). The stock mSLU142 (group II), isolated from a digestive disease (megaesophagus) patient, showed the Z2 profile. The parasite clones m1, m2, m3, and m4, derived from mSLU142, and clones h1 and h2, derived from hSLU239, showed isoenzyme profiles similar to those of Z2 and ZA (Miles et al. 1977; J. A. Romanha, 1982, Thesis, Universidade Federal de Minas Gerais). Furthermore, the T. cruzi clones derived from the cardiac disease patient differed from those derived from the megacolon patient in 3 of the 13 enzymes analyzed. RFLP analysis showed polymorphism at the EcoRI and PstI restriction fragments of the DNA sequences coding the glycolytic enzymes ALD, GPI, GAPDH, and PYK and separated the T. cruzi stocks and clones in three groups: I, comprising the stock hSLU239 and clone m4, which was classified as homozygous CC, BB, AA, and AA for the ALD, GPI, PYK, and GAPDH genes, respectively; II, formed by the parasite stock mSLU142 and clones h1 and h2 (derived from hSLU239), which was classified as homozygous AA, AA, CC, and BB for ALD, GPI, PYK, and GAPDH genes, respectively . These findings show that the infection of each Chagas disease patient may be produced by genetically diverse mixed parasite populations.

Animals↗
PubMed1996

Virulence and pathogenicity associated with diversity of Trypanosoma cruzi stocks and clones derived from Chagas' disease patients.

The intraspecific variation that has been described in Trypanosoma cruzi was examined in recent isolates from Chagas' disease patients, using behavioral and molecular markers for characterization of the parasite stocks and derived clones. We used these parasite populations to determine virulence and pathogenicity in vivo. The T.cruzi stocks mSLU142 (megaesophagus) and hSLU239 (heart disease) and the clones h1 and h2 induced very low parasitemias in BALB/c mice, whereas high parasitemias were obtained with clones m1, m2, m3, and m4. Clones m1-m4 also produced heart lesions of higher intensity than those observed in mice infected with the h1 and h2 clones. Furthermore, the heart lesions produced by all of these clones were significantly more intense than those seen in mice infected with either of the T. cruzi parental stocks. In addition, neither the kinetics of growth, doubling time, differentiation in axenic culture, zymodemes, nor DNA restriction length polymorphisms showed correlations with parasitemias and pathogenicity in mice. This study suggests that multiple biochemical and physiological markers are required to enable an association of clinical and pathologic manifestations of the disease with intrinsic characters of the T. cruzi populations.

Animals↗
PubMed1994

Chagas' disease: carcinogenic activity of the antitrypanosomal nitroarenes in mice.

The carcinogenic activity of antitrypanosomal 2-nitroimidazole, 5-nitroimidazole and 5-nitrofuran derivatives was assessed in female Swiss mice of the same age group. A statistically significantly higher incidence of growths was seen in mice into which 2-nitro had been injected than in mice receiving 5-nitro derivatives intraperitoneally. A histologic type of lymphoblastic lymphoma that invades lymph nodes, spleen, liver, lungs and lymphatic tissue elsewhere was frequently found in nitroarene-treated mice. Further, it is shown that the potency of the drug, rather than the duration of its administration, was usually associated with the growth of lymphomas. The 2-nitro derivative which induced the highest incidence of lymphomas significantly decreased the survival of treated mice; this probably occurred because it undergoes enzymatic reduction of the nitro group more efficiently than the 5-nitro compounds used. The differences of incidence of lymphomas in mice receiving any of these nitroarenes and in control mice that received daily injections of 0.15 M saline were statistically significant (alpha = 0.05). The indiscriminate use of these nitroarenes to treat Trypanosoma cruzi infections in man could therefore induce a significant number of lymphomas.

Animals↗
PubMed1994

Possible integration of Trypanosoma cruzi kDNA minicircles into the host cell genome by infection.

Infection with Trypanosoma cruzi is known to induce the division of peritoneal macrophages in BALB/c mice. We have demonstrated, by cytogenetic analysis, that accessory DNA elements are associated with the metaphase macrophage chromosomes of such infected macrophages. The identification of these accessory DNA elements with T. cruzi DNA is strongly supported by the association of 3H-label with some chromatids in macrophages previously infected with T. cruzi which had been labelled with 3H-methyl-thymidine. The karyotyping consistently showed preferential associations of T. cruzi DNA with chromosomes 3, 6 and 11. A conclusive demonstration of the parasite origin of the integrated DNA came from fluorescein in situ hybridization studies using specific parasite DNAs as probes. In order to determine the identity of the inserted DNA and to investigate the nature of the integration mechanism, Southern blot analyses were performed on DNA extracted from both uninfected and infected (but parasite-free) macrophages. Hybridizations of BamHI, EcoRI and TaqI digests of DNA from T. cruzi-infected host cells all revealed the presence of a 1.7-kb DNA fragment when probed with kDNA. The covalent association of kDNA with that of the host was confirmed by the fact that AluI and Hinf-I digests of DNA from infected host cells produced a number of bands, in a size range of 0.8-3.6 kb, which hybridized with kDNA minicircles. None of these bands was found in DNA purified from cell-free preparations of the parasite and thus it must be concluded that they represent insertion fragments between parasite and host cell DNA. These results strongly suggest that kDNA minicircles from T. cruzi have been integrated into the genome of the host cell following infection.

Animals↗
PubMed1992

Sulfur starvation in Lemna leads to degradation of ribulose-bisphosphate carboxylase without plant death.

Little is known about the degradation of the most abundant protein in nature, ribulose-bisphosphate carboxylase (RuBP carboxylase, EC 4.1.1.39), probably reflecting the fact that no stress situation has been identified capable of causing extensive RuBP carboxylase degradation without causing the death of the plant. We have subjected plants of Lemna minor L. to a variety of stress situations, nutritive deficiencies in particular, and have found a single condition--sulfur starvation--that caused almost complete degradation of RuBP carboxylase without causing plant death. Moreover, the enzyme was preferentially degraded under these conditions. However, when the plants were deprived of calcium, no RuBP carboxylase degradation was observed. Instead, the enzyme was oxidized and polymerized into high molecular mass aggregates. On the other hand, RuBP carboxylase shows an extreme stability when Lemna is deprived of some macronutrients (e.g. nitrogen, phosphorus, potassium, and magnesium) probably reflecting that this plant had to evolve in a way to cope with frequent shortages of such elements. The implications of these data for the role of RuBP carboxylase as a leaf storage protein are discussed.

Calcium↗
PubMed1990

Malignant, non-Hodgkin's lymphomas in Trypanosoma cruzi-infected rabbits treated with nitroarenes.

Use of 2-nitroimidazole, 5-nitrofuran and 5-nitroimidazole compounds in T. cruzi-infected rabbits resulted in a reduction in duration of parasitaemia in comparison with untreated, infected rabbits. The chronic myocarditis associated with Chagas' disease was not, however, prevented in nitroarene-treated rabbits; lymphocytic infiltrates associated with cardiac cell lysis, in the absence of parasites in situ, were present in both treated and untreated rabbits. The carcinogenic effect of each trypanocidal nitroarene used in this study was also assessed. Administration of nitroarenes to rabbits resulted in the appearance of solid tumours in 37.8 per cent of animals that received drug therapy. Untreated, control rabbits in this series did not show tumour growth. Furthermore, malignant, mixed-cell type, non-Hodgkin's lymphomas were seen in 32.4 per cent of the treated rabbits. It seems that a direct relationship could be present between the presence of the nitro group, the trypanocidal cytotoxicity and the prevalence of tumours. Benznidazole cleared up parasitaemias in the shortest time and was associated with 41.6 per cent of lymphoma growths, whereas MK-436 required twice as much time to clear blood parasites, and showed lymphomas in 25 per cent of experimental rabbits. The demonstration of a high prevalence of malignant tumours in addition to the chronic myocarditis of Chagas' disease in nitroarene-treated rabbits is important since indiscriminate use of such compounds currently used to treat T. cruzi infections in man could increase the risk of lymphoma.

Animals↗
PubMed1990

Chagas' disease: lymphoma growth in rabbits treated with Benznidazole.

Administration of the trypanocidal drug, Benznidazole (N-benzyl-2-nitro-imidazoleacetamide) to Trypanosoma cruzi-infected rabbits did not arrest the destructive Chagas' heart myocarditis. A typical feature of lymphocytic infiltrates associated with non-parasitized heart cell lysis was present in both treated and untreated groups of rabbits. Benznidazole-treated rabbits had their survival time shortened, probably as a consequence of Chagas' heart disease and of the development of lymphomas. The survival time of untreated T. cruzi-infected rabbits was 765 +/- 639 days and those treated with Benznidazole in the chronic phase of infection survived for 392 +/- 571 days. Malignant, non-Hodgkin's lymphomas were present in 38% of the rabbits that received the nitroarene therapy. Testicular atrophy was observed in 2 out of 10 nitroarene-treated rabbits. Benznidazole administration caused severe cell-mediated immunosuppression in T. cruzi-infected and BCG-immunized rabbits. Specific antibodies against the parasite and an unrelated antigen were detected in high levels, regardless of the nitroarene administration.

Animals↗
PubMed1990

Chagas' disease. Immunotoxin inhibition of Trypanosoma cruzi release from infected host cells in vitro.

Virulent tissue culture-derived Trypanosoma cruzi trypomastigotes were readily killed by immune IgG-ricin A chain conjugates (ITR) in vitro. Forty micrograms of ITR immobilized 10(6) trypomastigotes after 48 hours of incubation at 37 degrees C. ITR showed antibody specificity and 125I-labeled anti-T. cruzi IgG bound to parasitized host cells 9-fold more than to nonparasitized host cells. The degree of specificity was evaluated further in experiments in which 10 micrograms of ITR showed 78% inhibition of [3H]thymidine incorporation by T. cruzi. In contrast, nonimmune IgG-ricin A chain conjugate neither immobilized nor inhibited [3H]thymidine incorporation by the parasite. Furthermore, 20 micrograms of ITR significantly inhibited T. cruzi trypomastigote release from infected host cells and thus prevented reinfection of other cells in vitro.

Animals↗
PubMed1989

Autoimmunity in Chagas' disease: specific inhibition of reactivity of CD4+ T cells against myosin in mice chronically infected with Trypanosoma cruzi.

In this study, we assessed the proliferative response of T cells from mice chronically infected with Trypanosoma cruzi to actin, myosin, or T. cruzi soluble antigen (SA). We report here that CD4+ T cells from mice chronically infected with T. cruzi proliferated in response to myosin but not to actin, whereas cells from naive mice did not proliferate against any of the antigens tested. Antisera raised against myosin- or SA-activated T cells specifically inhibited respectively, the myosin or SA in vitro proliferative response, whereas the response to unrelated antigen remained unimpaired. Sera from chronically infected mice failed to show any significant inhibitory activity. The above findings suggest that autoreactive and T. cruzi-reactive T cells belong to different, perhaps nonoverlapping, compartments of the immune cell repertoire of mice chronically infected with T. cruzi. The failure of infected mice to trigger the suppressive mechanisms described here might be the primary immune defect leading to breakdown of self-tolerance and unopposed, perhaps tissue-damaging, autoimmunity in experimental Chagas' disease.

Adjuvants, Immunologic↗
PubMed1989

Trypanosoma cruzi: endocytosis and degradation of specific antibodies by parasite forms.

Specific human IgG antibodies bound to a Trypanosoma cruzi envelope were internalized by antigen receptor-mediated endocytosis. Ferritin conjugated antibodies and horseradish peroxidase (HRP) conjugated IgG were found inside parasite cytoplasmic vesicles. Nonspecific IgG that did not bind to the external membrane was not internalized by the parasite. The ratio of 3H-protein A labeled: specific IgG internalization by parasites in the exponential growth phase (95% epimastigotes) was much smaller than that of parasites in the late stationary growth phase (38% trypomastigotes). Antibodies bound to the latter parasite forms almost disappeared from their outer membranes after 12 hr incubation at 27 degrees C. Results of experiments in which membrane bound antibodies were removed by an excess of pronase showed that only small amounts of radiolabeled IgG were found inside the parasites. The fate of immunoglobulins that vanished from external membrane receptors and did not accumulate inside the cells was explained by experiments in which the supernatants of IgG-3H-protein A labeled parasites were precipitated with trichloroacetic acid (TCA). In these, membrane-bound antibodies were taken in and degraded by the parasites as increased amounts of free radiolabel appeared in the supernatants as functions of incubation time and parasite stage.

Animals↗
PubMed1989

Effect of immunotoxins against Trypanosoma cruzi.

Immunotoxins were constructed with IgG antibodies against Trypanosoma cruzi surface antigens by hybridization with abrin (ITA) and ricin (ITR) A chains. The biological activity of the hybrid macromolecules was tested on the parasite forms. Motility of parasite forms was lost in vitro after incubation with ITR. In general, killing of the parasite with ITR was more efficient than with ITA. Inhibition of protein synthesis after incubation with either ITR or ITA, measured by 3H-leucine incorporation, confirmed the parasite immobilization experiments. The lethal effect was potentiated when the immunotoxins were used in the presence of 2.5 mM ammonium chloride. T. cruzi antibodies specific to cell surface antigens are excellent drug carriers that can be delivered to the target cell. However, ITR and ITA did not reduce parasitemia or increase survival of mice infected with T. cruzi.

Abrin↗
PubMed1983

Chagas' disease: a clinical, parasitological, immunological, and pathological study in rabbits.

Thirty-four rabbits were experimentally infected with trypomastigotes of either the Ernestina or the Albuquerque strains of Trypanosoma cruzi. These animals showed patent parasitemias, as demonstrated by xenodiagnosis, in the acute phases of the infections. Typical chagoma signs developed in two rabbits 1 week after parasite inoculation in the skin, although the acute phase of Chagas' disease in the rabbit model was usually asymptomatic. In the 6th month of infection the parasitemias became negative and the infections remained subpatent, as indicated by the persistence of positive serologic tests and of delayed-type skin reactions elicited in Chagas' rabbits against a microsomal T. cruzi antigen. This latent infection continued asymptomatically, in the absence of electrocardiographic (ECG) alterations. However, ECG changes consistent with enlargement and overload of cardiac chambers, alterations of ventricular repolarization, S-T changes and bundle-branch blocks were frequently recorded later in the chronic phase of Chagas' disease. The pathological manifestations of these ECG alterations were confirmed at the autopsy of each experimental rabbit. Congestive heart failure and pulmonary thromboemboli related to chronic myocarditis of Chagas' disease were frequent causes of death. Megacolon was seen in two rabbits inoculated with the Ernestina strain of the parasite. The relatively limited duration of detectable parasitemia even when xenodiagnosis is used, the lack of correlation between parasitemia and severity of pathological manifestations, and the fact that all infected animals showed histopathological evidence of myocarditis, destructive inflammatory lesions characterized by mononuclear infiltrates in skeletal muscles, as well as cutaneous delayed hypersensitivity to T. cruzi antigens, are notable observations in this animal model of the human disease.

Animals↗