Cell and humoral immunity in endemic pemphigus foliaceus

Foram avaliados dezesseis doentes portadores de pênfigo foliáceo endêmico, dez com a forma localizada da doença (Grupo G1) e seis com a forma disseminada (Grupo G2), com os objetivos de correlacionar o quadro clínico e laboratorial desses pacientes com o perfil imunológico dos mesmos, e verificar a relação dos títulos dos anticorpos antiepiderme circulantes, identificados pela imunofluorescência indireta, com intensidade da lesão e com a evolução das lesões em tratamento. Foram realizados: hemograma completo, quantificação de subpopulação de células mononucleares por anticorpos monoclonais e estudo da transformação blástica de linfócitos e quantificação de anticorpos circulantes por meio da reação de imunofluorescência indireta. Observou-se leucocitose principalmente no grupo G2, diminuição dos valores relativos das subpopulações de linfócitos CD3+ e CD4+ e tendência à diminuição dos valores relativos da subpopulação CD8+ nos doentes (Grupos G1 e G2). Os índices de transformação blástica de linfócitos frente à fitohemaglutinina revelaram níveis mais elevados nos doentes (Grupos G1 + G2), que nos controles. A reação de imunofluorescência indireta foi positiva em 100% dos doentes do grupo G2 e em 80% do grupo G1 A mediana dos valores dos títulos foi maior no grupo G2, quando comparado com o grupo G1. A análise global dos resultados permite concluir que a imunidade celular está preservada, e que existe uma relação entre os títulos de anticorpos obtidos à reação de imunofluorescência indireta e extensão da lesão cutânea.

Cell death evaluation in benzo[a]pyrene-transformed human breast epithelial cells after microcell-mediated transfer of chromosomes 11 and 17

The incidence of apoptosis and nuclear instability, including the incidence of catastrophic death, were investigated in benzo[a]pyrene (BP)-transformed human breast epithelial cells (BP1-E cell line) after microcell-mediated transfer of chromosomes 11 and 17. Since the introduction of normal chromosomes 11 and 17 into tumorigenic human breast BP1-E cells reverts some of these cells' characteristics (especially those affected by microsatellite instabilities and loss of heterozygosity) those of parental non-transformed MCF-10F cells, it was expected that the cell death rates would also be affected by this treatment. The transfer of the mentioned chromosomes, especially chromosome 17, to tumorigenic BP1-E cells increased the apoptotic ratios and decreased the nuclear instability ratios, thus showing that the microsatellite instability and loss of heterozygosity induced by BP in these chromosomes of MCF-10F cells affect the control of cell death mechanisms. (C) 2003 Elsevier B.V. All rights reserved.

Purine nucleoside phosphorylase: A potential target for the development of drugs to treat T-cell- and apicomplexan parasite-mediated diseases

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and thus drugs that inhibit human PNP activity have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Besides, the purine salvage pathway is the only possible way for apicomplexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites an attractive target for drug development against diseases such as malaria. Hence, a number of research groups have made efforts to elucidate the mechanism of action of PNP based on structural and kinetic studies. It is conceivable that the mechanism may be different for PNPs from diverse sources, and influenced by the oligomeric state of the enzyme in solution. Furthermore, distinct transition state structures can make possible the rational design of specific inhibitors for human and apicomplexan enzymes. Here, we review the current status of these research efforts to elucidate the mechanism of PNP-catalyzed chemical reaction, focusing on the mammalian and Plamodium falciparum enzymes, targets for drug development against, respectively, T-Cell and Apicomplexan parasites-mediated diseases.

Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)