Horácio Friedman

Differences in HLA class II alleles of isolated South American Indian populations from Brazil and Argentina

We have studied the HLA class II alleles in 277 South American Indians, which included Argentinian tribes from the Gran Chaco: Toba (n = 135), Toba-Pilaga (n = 19), Mataco-Wichi (n = 49), and Xavantes, a tribe from Central Brazil (n = 74). In the Brazilian tribe, only four DR groups were found: DRB1*1602 (gf = 0.303), DRB1*04 including DRB1*0404 (gf = 0.070) and DRB1*0407 (gf = 0.077), DRB1*0802 (gf = 0.265), and DRB1*1402 (gf = 0.303). The HLA class II allele frequencies were similar among the different Argentinian tribes, and 90% of DRB1 alleles belonged to three families: DRB1*04 (including DRB1*0403, DRB1*0404, DRB1*0407, DRB1*0411, and DRB1*0417), DRB1*0802, and DRB1*14 (including DRB1*1402 and DRB1*1406). At the DPB1 locus, we found only seven alleles, the most frequent being DPB1*0402. Comparison of HLA class II alleles with those of North American Indians that we have previously studied shows that the frequency of some HLA class II alleles in Brazilian Xavantes resembles that of North American Indians more than that of the Argentinian Indian tribes. The allele DRB1*0417 was found exclusively in this population.

HLA antigens and risk for development of pemphigus foliaceus (fogo selvagem) in endemic areas of Brazil

Endemic pemphigus foliaceus (EPF), is an autoimmune disease associated with production of IgG antibodies against epidermal antigens. We have tested 38 patients and 50 control subjects living in endemic areas to investigate whether HLA genes are associated with host factors that determine whether or not exposed individuals will develop this disease. A variant of HLA-DR1, an antigen common in Blacks (DRB1*0102), was found to be the main susceptibility factor (relative risk=7.3, P<0.0002). Two amino acids, in positions 85 and 86 of DRB1, distinguish DRB1*0102 from DRB1*0101. These residues appear to be involved in the formation of a functional epitope that causes T cell recognition and determines disease susceptibility. Moreover, subjects having DQw2 did not develop the disease, while the frequency of DQw2 in controls was 22% (RR=0.04, P<0.006). Thus HLA genes appear to play a crucial role in the response to an environmental factor which in this setting frequently leads to the development of autoimmune disease. An HLA-DQ allele, DQw2, appears to be associated with factors that prevent the development of the disease in exposed individuals.

Endemic pemphigus foliaceus (fogo selvagem) in Native Americans from Brazil

BACKGROUND Fogo selvagem (FS) is an autoimmune disease that is endemic in certain regions of Brazil and appears to be precipitated by an environmental factor. OBJECTIVE Our purpose was to confirm the occurrence and prevalence of FS in a population of Xavante Indians living in an endemic region of central Brazil. METHODS Clinical, anthropologic, and immunologic studies were carried out in patients and in normal inhabitants of the Pimentel Barbosa Indian Reservation, Mato Grosso, Brazil. RESULTS FS was identified and confirmed in 10 patients from a patient pool of 295 with various skin diseases. The Xavante settlement has a total population of 746. Anti-desmoglein 1 autoantibodies were detected in all patients with FS and were absent from more than 300 serum samples collected from randomly selected unaffected persons. CONCLUSION FS is strongly linked to outdoor activities and is largely restricted to immunogenetically predisposed persons. FS appears to have been endemic in certain regions of South America for several centuries.

Melanoma cutâneo: características clínicas, epidemiológicas e histopatológicas no Hospital Universitário de Brasília entre janeiro de 1994 e abril de 1999

BACKGROUND: The incidence of cutaneous melanoma has increased at a rate of approximately 4 to 6% annually. This neoplasm occurs preferably in the female gender, between 30 and 79 years old and among Caucasian persons. The most common histopathological form is the extensive superficial one, and its location varies according to gender. OBJECTIVES: The objective of this study was to evaluate the clinical, epidemiological and histopathological characteristics of primary cutaneous melanoma, at the University Hospital of Brasilia, during a period of five years. MATERIAL AND METHODS: A review was conducted of the data registry concerning primary cutaneous melanoma cases, in the University Hospital of Brasilia, diagnosed and treated between January 1994 and April 1999, with a total of 32 cases. The patients were analyzed, characterizing the tumor distribution according to gender, age, skin color, topography, symptomatology, histopathological type, Clark level, Breslow index and presence of metastasis. Data was analyzed by simple statistics and by Chi-square (c2). RESULTS: A predominance was observed of lesions in the limbs, corresponding to sixteen patients (50.0%). There was the primary nodular form in nine (45%) patients, and seventeen (58.6%) patients did not have any complaint. According to the presence or absence of metastasis and Clark level, it was found that the patients with a level of invasion up to the subcutaneous layer (Clark V) presented a relative risk of 2.94 (1.24<CI<6.99). CONCLUSIONS: The clinical, epidemiological and histopathological profile of the patients with primary cutaneous melanoma at the University Hospital of Brasilia, between January 1994 and April 1999, comprised of elderly females (from 61 to 80 years old), Caucasians, whose tumor was located predominantly in the limbs, the nodular type was the most frequent, and the patients did not present symptoms at the time of diagnosis.

Lip biopsy in connective tissue diseases: A review and study of seventy cases

The labial salivary glands from seventy patients with systemic lupus erythematosus (twenty cases), systemic progressive sclerosis (twenty-two cases), rheumatoid arthritis (twenty-three cases), and Sjögrens syndrome (five cases) and from fifty subjects without connective tissue diseases were studied by means of light and fluorescence microscopy. The availability of the lip biopsy as a diagnostic tool is stressed, but a differential diagnosis between the different connective tissue diseases was not achieved. Yet some of the latter disclosed peculiar lesions. The role of the inflammatory and degenerative components, as well as the pathogenesis of the lesions, is discussed.

The profile of fogo selvagem (endemic pemphigus foliaceus) at the University Hospital of Brasilia–Brazil. Epidemiological and clinical considerations

Background  Endemic pemphigus foliaceus (EPF) or fogo selvagem (FS) is an endemic autoimmune disease, characterized by flaccid bullae induced by IgG4 subclass antibodies. The authors demonstrate the epidemiological and clinical status of patients who have been followed at the University Hospital of Brasília (HUB) for more than 15 years.

Pentavalent antimonial nephrotoxicity in the rat

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sbv (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.

Imunofluorescência indireta no pênfigo foliáceo endêmico. contribuição para sua padronização

The aim of the present research was to standardize the indirect immunofluorescence reaction for Endemic Pemphigus Foliaceus (Fogo Selvagem). We found that fresh human skin was the ideal substrate and could proceed from foreskin, head, neck, or anterior abdominal wall. PBS pre-washing of the skin preceding the incubation with the serum should be avoided since the antigenicity might be diminished. TAS-calcium pre-serves the Pemphigus antigenic properties of the skin and shall be preferred as the diluent for the sera. Albumin-coated slides are useful because they increase the adherence of the skin sections. The conjugate appropriate dilution is convenientely determined by the radial immunodiffusion test (Ouchterlony method). So far as the correlation between the antibody titer and the clinical activity is concerned, we concluded that a titer of 160 or more was of bad prognosis, since it was associated with the generalized form of the disease or with cases of the localized form refractory to the usual therapy. Nevertheless, this assumption needs confirmation by further studies involving an appropriate clinical approach.O proposito da presente investigacao foi padronizar a reacao de imunofluorescencia indireta para Penfigo Foliaceo Endemico (Fogo Selvagem). Verificamos que a pele humana normal e o substrato ideal e que pode proceder de prepucio, cabeca, pescoco ou da parede abdominal anterior. A lavagem previa da pele precedendo a incubacao com o soro deve ser evitada pois a antigenicidade pode ser diminuida. O TAS-calcio preserva as propriedades antigenicas da pele e deve ser preferido como diluente para os soros. Lâminas cobertas com albumina sao uteis porque aumentam a aderencia dos cortes de pele. A diluicao apropriada do conjugado e convenientemente determinada pelo teste de imunodifusao radial (metodo de Ouch-terlony). Com referencia a correlacao entre titulo de anticorpos e atividade clinica, concluimos que um titulo igual ou maior do que 160 era de mau prognostico pois estava associado a forma generalizada da doenca ou a casos de forma localizada refratarios a terapeutica usual. Contudo, esta obervacao requer confirmacao atraves de estudos que envolvam uma abordagem clinica apropriada.The aim of the present research was to standardize the indirect immunofluorescence reaction for Endemic Pemphigus Foliaceus (Fogo Selvagem). We found that fresh human skin was the ideal substrate and could proceed from foreskin, head, neck, or anterior abdominal wall. PBS pre-washing of the skin preceding the incubation with the serum should be avoided since the antigenicity might be diminished. TAS-calcium preserves the Pemphigus antigenic properties of the skin and shall be preferred as the diluent for the sera. Albumin-coated slides are useful because they increase the adherence of the skin sections. The conjugate appropriate dilution is convenientely determined by the radial immunodiffusion test (Ouchterlony method). So far as the correlation between the antibody titer and the clinical activity is concerned, we concluded that a titer of 160 or more was of bad prognosis, since it was associated with the generalized form of the disease or with cases of the localized form refractory to the usual therapy. Nevertheless, this assumption needs confirmation by further studies involving an appropriate clinical approach.

A síndrome do respirador bucal como fator de risco para queilite actínica

A sindrome do respirador bucal e caracterizada por alteracoes anatomicas que acarretam disturbios respiratorios induzindo as criancas afetadas a utilizarem a via bucal para respirar. Entre as alteracoes anatomicas que esses pacientes apresentam, esta a tipica facies adenoidiana, caracterizando um individuo sempre com a boca aberta. Tais alteracoes anatomicas conferem ao labio inferior posicao mais propensa a acao dos raios ultravioleta e das alteracoes actinicas decorrentes dessa exposicao mais frequente. Os autores relatam o caso clinico de uma crianca de 11 anos com sindrome do respirador bucal e alteracoes labiais intensas de queilite actinica. Defendem a ideia de que a sindrome do respirador bucal poderia ser um fator de risco a mais para o aparecimento da queilite actinica.

Pênfigo foliáceo endêmico (fogo-selvagem) no grupo indígena Xavánte, Mato Grosso, Brasil

Foi realizado inquerito soro-epidemiologico atraves de testes de imunofluorescencia indireta e imunoprecipitacao visando determinar a prevalencia do penfigo foliaceo endemico (PFE) na populacao indigena Xavante do Brasil Central. Do total de 163 amostras de soro testadas, 5 (3,1%) foram positivas a imunofluorescencia. Todos os soros positivos procediam de individuos com sintomas clinicos da doenca. Nao foram observadas diferencas do PFE entre os Xavante e a populacao em geral sob o ponto de vista imunologico, ja que se verificou uma predominância da IgG4 entre os anticorpos nos pacientes indigenas.