[Use of spatial analysis tools in the epidemiological surveillance of American visceral leishmaniasis, Araçatuba, São Paulo, Brazil, 1998-1999]. / Utilização de ferramentas de análise espacial na vigilância epidemiológica de leishmaniose visceral americana - Araçatuba, São Paulo, Brasil, 1998-1999.

The control of American visceral leishmaniasis (AVL) is based on combating the vector and eliminating the domestic reservoir of the focus area - defined as 200 meters around human or canine cases. This paper discusses the use of spatial analysis techniques in the epidemiological surveillance of AVL in Araçatuba, São Paulo State, in order to propose a model for territorial epidemiological surveillance, reformulating current control strategies. The results showed that AVL transmission was not homogeneous; human cases were more frequent in areas with higher canine prevalence rates. Vector dispersion appeared to be restricted to a few houses, although it was not possible to model the vector density. In order to study the vector distribution and correlated covariates, a field study based on house sampling is being conducted. The results will aid the development of new spatial analysis tools and possibly redefine protocols and routines for the control of this endemic disease in urban areas.

A link between apoptosis and degree of phosphorylation of high mobility group A1a protein in leukemic cells.

Nuclear phosphoprotein HMGA1a, high mobility group A1a, (previously HMGI) has been investigated during apoptosis. A change in the degree of phosphorylation of HMGA1a has been observed during apoptosis induced in four leukemic cell lines (HL60, K562, NB4, and U937) by drugs (etoposide, camptothecin) or herpes simplex virus type-1. Both hyper-phosphorylation and de-phosphorylation of HMGA1a have been ascertained by liquid chromatography-mass spectrometry. Hyper-phosphorylation (at least five phosphate groups/HMGA1a molecule) occurs at the early apoptotic stages and is probably related to HMGA1a displacement from DNA and chromatin release from the nuclear scaffold. De-phosphorylation (one phosphate or no phosphate groups/HMGA1a molecule) accompanies the later formation of highly condensed chromatin in the apoptotic bodies. We report for the first time a direct link between the degree of phosphorylation of HMGA1a protein and apoptosis according to a process that involves the entire amount of HMGA1a present in the cells and, consequently, whole chromatin. At the same time we report that variously phosphorylated forms of HMGA1a protein are also mono-methylated.

In vitro and in vivo effects of 2'-deoxycoformycin (Pentostatin) on tumour cells from human gammadelta+ T-cell malignancies.

Hepatosplenic gammadelta+ T-cell lymphoma represents a rare neoplasm of post-thymic phenotype, characterized by an aggressive clinical course and a poor response to conventional chemotherapy. In the present study, we have examined the cytotoxic effects of the purine analogue 2'-deoxycoformycin (dCF) on cultured mononuclear cells and purified gammadelta+ tumour cells from bone marrow or peripheral blood of four patients with hepatosplenic gammadelta+ T-cell lymphoma. At a concentration of 10 microM, dCF, in the presence of 2'-deoxyadenosine (dAdo), displayed an early and selective cytotoxic effect on gammadelta+ tumour T cells. After 48 h of in vitro exposure to dCF, the absolute number of viable CD3+/gammadelta+ tumour T cells was reduced by more than 90% in all samples with respect to control cultures, with absolute counts of viable CD3+/alphabeta+ lymphocytes being reduced only by 6-40% of the initial cell input. Analysis of cultures after 5 d of exposure to dCF plus dAdo revealed the persistence of normal CD3+/alphabeta+ T cells, which accounted, however, for only 20-25% of the initial cell input. Accordingly, the combination of dCF (10-100 microM) plus dAdo was able to induce a dose-dependent inhibition of clonogenic growth and [3H]-thymidine incorporation in purified CD3+/CD4-/CD8- gammadelta+ tumour cells. We also report that one patient with hepatosplenic gammadelta+ T-cell lymphoma in terminal leukaemic phase showed a striking haematological response to single-agent dCF given as fourth-line treatment. In particular, the selective clearance of gammadelta+ tumour T cells in peripheral blood and bone marrow was observed starting after the second course of treatment. Our results suggest that dCF may represent a potentially active drug for the management of this aggressive form of T-cell lymphoma.

Kinetic characterization of bovine lung low-molecular-weight protein tyrosine phosphatase.

Protein tyrosine phosphatase is an important class of enzymes that plays an essential role in the cellular proliferation, differentiation, and oncogenesis. In this paper we report characterization of a low-molecular-weight protein tyrosine phosphatase purified from bovine lung. The enzyme activity was essentially independent of metal ions and sensitive to sulfhydryl reagents. Both vanadate and inorganic phosphate are competitive inhibitors, with Ki values of 0.38 microM and 0.28 mM, respectively. Besides p-nitrophenyl phosphate, the enzyme was also able to efficiently hydrolyze tyrosine phosphate, beta-naphthyl phosphate, and flavine mononucleotide.

Hodgkin's disease: a disorder of dysregulated cellular cross-talk.

Hodgkin's disease (HD) is a peculiar type of human malignant lymphoma characterized by a very low frequency of tumor cells, the so called Hodgkin and Reed-Sternberg (H-RS) cells, embedded in a hyperplastic background of non-neoplastic (reactive) cells recruited and activated by H-RS cells-derived cytokines. H-RS cells can be functionally regarded as antigen-presenting cells (APC) able to elicit an intense, but anergic and ineffective, T-cell mediated immune response along with a hyperplastic inflammatory reaction which involves several cell types including T- and B-cells, neutrophils, eosinophils, plasma cells, fibroblasts and stromal cells. In tissues involved by HD, malignant H-RS cells and their reactive neighboring cells are able to cross-talk via a complex network of cytokine- and cell contact-dependent interactions. As a result of such interactions, mediated by specific surface receptors and adhesion molecules on both tumor and non-neoplastic cells, H-RS cells may receive several proliferative and anti-apoptotic signals favoring the cellular expansion and tumor cell survival in HD. The ineffective T-cell immune response elicited by the abnormal APC function of H-RS cells may further contribute to the biologic and clinical progression of HD. Innovative therapeutic strategies aimed at blocking the pathways of dysregulated cellular cross-talk among H-RS cells and bystander reactive cell populations might be beneficial in the treatment of HD patients.