Correlation between antigenemia of Paracoccidioides brasiliensis and inhibiting effects of plasma in patients with paracoccidioidomycosis.

Metabolites produced by pathogenic fungi may be involved in the pathogenesis of fungal infections consequently altering the defence mechanisms of the host. In this study the levels of Paracoccidioides brasiliensis antigens detected in the plasma of patients with paracoccidioidomycosis correlated with the suppression index detected by the low mitogenic response of peripheral blood mononuclear cells (PBMC) to phytohaemaglutinin (PHA). This inhibitory effect on lymphoproliferation was observed in the plasma of 58% of the patients, suggesting the presence of inhibitory factors. Plasma samples from paracoccidioidomycosis patients having or not having inhibitory factors showed no significant effect on chromosomes of lymphocytes from healthy individuals. However, these plasmas had a suppressive activity on the blastogenic response of these lymphocytes stimulated with PHA, that was independent of a cytotoxic effect. P. brasiliensis antigens added to the proliferative response of PBMC from healthy individuals stimulated or not stimulated with PHA showed a dose-dependent suppressor effect, reproducing the inhibitory effect of patients' plasma. We suggest that the antigens of P. brasiliensis present in the plasma of patients, even at low concentrations, can play an important role in the reduction of the cellular immune response and in the genesis of the immunoregulatory disturbances observed in paracoccidioidomycosis.

Clinical, cytogenetic and toxicological studies in rural workers exposed to pesticides in Botucatu, São Paulo, Brazil.

Pesticides can cause gene mutations and chromosomal aberrations in exposed individuals. We have investigated 24 workers exposed to pesticides. Clinical examinations and cytogenetic and toxicological tests were performed. Ten non-exposed individuals were used as controls. Toxicological dosages of copper, zinc and manganese (metals found in some pesticides), hepatic enzyme dosage (GOT, GPT, AR) and acetylcholinesterase activity were performed in 16 workers and 8 controls. In the exposed workers, the most relevant clinical symptoms were poor digestion with fullness sensation after meals, irritated eyes, headache and fasciculations. The exposed group showed significantly lower manganese dosage and acetylcholinesterase activity, and significantly higher levels of alkaline phosphatase. Cytogenetic studies showed significantly higher chromosomal aberrations in the exposed group compared to the control group. Although the workers used protection against the pesticide's fog, the results revealed that the workers were contaminated with the pesticides. Therefore, the cytogenetic, toxicological studies with clinical examination are necessary for monitoring workers who are exposed to pesticides in any situation.

Human chromosome aberrations induced in vitro by Paracoccidioides brasiliensis glycoproteic component (GP 43).

The in vitro cytogenetic effects of the 43-kDa molecular mass exocellular glycoproteic component (GP 43) from Paracoccidioides brasiliensis were studied in cultures from human lymphocytes. The sample included 10 healthy, white, non-smoking, non-related males (mean age of 31.3 +/- 8.2 years). Besides the control, three concentrations of GP 43 (0.125, 1.25 and 5 micrograms/ml) were used. In each group, around 1000 cells were examined in search of chromosome aberrations, and 30000 metaphases were analysed for the determination of the Mitotic Index. The authors conclude that GP 43 most probably causes inhibition of the cell cycle and aneugenic and clastogenic effects.

Cycloactive, aneugenic and clastogenic effects of Paracoccidioides brasiliensis exoantigen in human lymphocyte cultures.

The in vitro effect of Paracoccidioides brasiliensis exoantigen on the human lymphocytes cell cycle and chromosomes was studied. Human peripheral blood lymphocyte cultures from ten healthy, white, non-smoking, non-related adult males (mean age 31.3 +/- 8.2 years) were studied. Blood cultures were treated with three exoantigen concentrations (0.25, 2.50 and 10.00 micrograms ml-1). At least 1000 metaphases were analysed at each concentration, for evaluation of numerical and structural chromosome aberrations (CA) and 30,000 for mitotic index (MI). Among the treated cultures, statistically significant differences in the frequencies of MI and CA were not observed. Nevertheless, when compared with control cultures, they all showed a significantly lower frequency of MI and higher frequency of CA. It is suggested that the detected alterations were caused by the exoantigen, its fractions or its metabolites.

Chromosome aberrations in lymphocyte cultures from paracoccidioidomycosis patients.

Blood cell lymphocyte chromosomes from untreated (UT) and clinically-cured (CC) patients with paracoccidioidomycosis and from healthy (control) people (CO) were studied. The frequency of aneuploid cells in the UT patients was higher than in the CC and CO individuals. The frequency of metaphase cells with premature centromere division was significantly higher in the UT than in the CC and CO group. No structural aberration and no statistically significant difference in the frequency of polyploidy was observed in the three groups studied. Our findings are indicative of an aneugenic (aneuploidy-inducing) action of infection by Paracoccidioides brasiliensis.

[The association between glyoxalase I and paracoccidioidomycosis infection]. / Associação entre glioxalase I e paracoccidioidomicose-infecção.

With the purpose to study the genetic susceptibility to paracoccidioidomycosis infection we searched for a possible association between glyoxalase I and the intradermic paracoccidioidin reaction. The phenotype GLO 1 was significantly more frequent among positive reactors.

Autosomal dominant tibial hemimelia-polysyndactyly-triphalangeal thumbs syndrome: report of a Brazilian family.

We report on 3 persons in a 3-generation Brazilian family affected with complex limb defects. The spectrum of limb anomalies ranged from isolated toe syndactyly to severe bilateral tibial aplasia. Radioulnar synostosis was present in 2 of the 3 patients. Clinical and genetic aspects are discussed.

[In vitro behavior of macrophages of healthy subjects and Hansen patients against Mycobacterium leprae]. / Comportamento in vitro frente ao Mycobacterium leprae dos macrófagos de pessoas sadias e de pacientes com hanseníase.

The in vitro phagocytic capacity of human macrophages facing M. leprae was analysed in a selected sample of healthy and hanseniasis patients (Virchowian and tuberculoid) individuals. Families where at least one of the spouses presented Hansen's disease were selected and 176 white people were studied. The analysis of the macrophages' behavior was performed by reading the slides in the 5th, 10th, 15th, 20th and 30th days after inoculation of M. leprae. The classification is discussed. The results showed a high variability. The main conclusions reached are: (a) people differ in their capacity to lyse M. leprae, as measured by their macrophages' behavior in vitro; (b) the results obtained give support to Beiguelman's theory of the lysis threshold.

[Familial analysis of the in vitro behavior of human macrophages against Mycobacterium leprae]. / Análise familial do comportamento in vitro dos macrófagos humanos frente ao Mycobacterium leprae.

The lysogenic capacity of human macrophages facing M. leprae in vitro may be dependent on an important genetic component. Although the family aggregation of the trait is demonstrated, this is a necessary but not sufficient condition to prove genetic influence. The data do not fit some simple genetic models (autosomal dominant or incompletely dominant gene; dominant or recessive sex-linked gene). The results obtained are consistent with the hypothesis that the macrophages' lysogenic capacity is mainly due to a major gene with variable expressivity. This hypothesis may be too simple to account for the whole variability detected and therefore must be considered just as a working hypothesis.

Epidemiology and genetics of endemic goiter. I. Epidemiological aspects.

This study dealt with approximately 2,000 children and their parents living in a hyperendemic goiter area in Central Brazil, which is bounded by the jungle to the north and by a large plain to the south. The determination of goiter was made according to the methods and classification adopted by WHO. Conspicuous forms of goiter were found in 41% of the children examined. Multiple linear regression analysis showed an increase with age in the frequency of goiter in both sexes. Although data from the literature show that Mulattoes and Negroes have statistically higher frequencies of goiter than do Whites, our multiple linear regression analysis revealed no evidence for an effect of race on the endemism. There was no significant association with socioeconomic level. The presence of goiter in parents was shown to be statistically associated with its occurrence in the children.

Comportamento in vitro frente ao Mycobacterium leprae dos macrofagos de pessoas sadias e de pacientes com hanseniase. / In vitro behavior facing Mycobacterium leprae of macrophages of healthy subjects and of patients with Hansen's disease

A capacidade fagocitica in vitro dos macrofagos humanos frente ao M. leprae foi analisada em uma amostra selecionada de individuos sadios e hansenianos (virchowianos e tuberculoides). Foram estudadas 176 pessoas caucasoides, pertencentes a familias em que pelo menos um dos conjuges era hanseniano. A analise do comportamento dos macrofagos foi realizada atraves de leituras das laminas no 5o.,10o.,15o.,20o.e 30o. dias apos a inoculacao do M. leprae Os resultados mostraram uma alta variabilidade. Discute-se a classificacao adotada e conclui-se que: (a) os individuos se distribuem ao longo de uma escala de valores no concernente a capacidade de lise dos seus macrofagos em relacao ao M.leprae fagocitado; (b) os resultados obtidos dao suporte a "teoria do limiar de lise" de Beiguelman

Analise familial do comportamento in vitro dos macrofagos humanos frente ao Mycobacterium leprae. / Familial nalysis of the in vitro behavior of human macrophages facing Mycobacterium leprae

A analise genetica do comportamento dos macrofagos face ao M. leprae foi discutida, confrontando-se os resultados obtidos com as indicacoes que favorecem a hipotese de ser a capacidade lisogenica dos macrofagos frente ao M. leprae dependente de um componente genetico importante. Foi demonstrada a existencia de familiaridade do carater, mas os dados nao se conformam com alguns modelos geneticos simples (gene autossomico, dominante ou incompletamente dominante; e gene ligado ao sexo, dominante ou recessivo). Os dados nao contrariam a hipotese de a capacidade lisogenica dos macrofagos ser condicionada por um gene principal, autossomico e recessivo, com expressividade variavel, mas essa hipotese, por ser muito simplista para explicar a variabilidade existente na capacidade de lise dos diferentes individuos, deve ser considerada com reservas

Endemic goitre in whites and negroes: racial or social effect?

A sample of 2688 individuals, about half of them showing endemic goitre, has been studied in a hyper-endemic area of the state of Mato Grosso, Brazil. The codified data were processed in computers. Analyses through contrasts among multinominal proportions showed Negroes and Mulattoes with higher frequencies of goitre than Whites, thus agreeing with results from the literature. A number of multiple regression models, including 21 independent variables, showed no evidence of any intrinsic racial effect on the occurrence of goitre. The authors conclude that the higher prevalence of goitre among Malattoes and Negroes probably reflects the influence of their poorer socio-economic conditions. Although genetic factors are generally assumed to play some role in the development of goitre, it is to environmental causes that the most important role is ascribed.