Disseminated American muco-cutaneous leishmaniasis caused by Leishmania brasiliensis brasiliensis in a patient with AIDS: a case report

The authors report a case of culture-proven disseminated American muco-cutaneous leishmaniasis caused by Leishmania brasiliensis brasiliensis in an HIV positive patient. Lesions began in the oropharynx and nasal mucosa eventually spreading to much of the skin surface. The response to a short course of glucantime therapy was good.

Enhancement of Leishmania amazonensis infection in BCG non-responder mice by BCG-antigen specific vaccine

Different patterns of cutaneous leishmaniasis can be induced when a challenge of alike dose of Leishmania amazonensis amastigotes in various inbred strains was applied. Two strains of mice, the Balb/c and C57 BL/10J, showed exceptional suscepbility, and 10(elevado a sexta potência) amastigotes infective dose lead, to ulcerative progressive lesions with cutaneous metastasis and loss by necrosis of leg on wich the footpad primary lesion occured. Lesions were also progressive but in a lower degree when C3H/HeN and C57BL/6 were infected. Lesions progress slowly in DBA/2 mice presenting lesions wich reach a discreet peack after 12 weeks, do not heal but do not uncerate. DBA/2 mice is, therefore, a good model for immunomodualtion. In attempt to determine the influence of BCG in vaccination schedule using microsomal fraction, DBA/2 became an excellent model, since it is also a non-responder to BCG. Vaccination of DBA/2 mice, receiving the same 10(elevado a sexta potência) BCG viable dose and 10 *g or 50 *g of protein content of microsomal fraction, lead to a progressive disease with time course similar to those observed in susceptible non-vaccinated C57BL/10J mice after 6 months of observation. An enhancement of infection in BCG non-responder mice suggests that use of BCG as immunostimulant in humans could be critical for both vaccination and immunoprophylactic strategies.

Frequent MAGE mutations in human melanoma.

Abstract: Background: Cancer/testis (CT) genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes). Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype. Methodology/Principal Findings: We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1. Significance: These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma.

Increased plasticity of the stiffness of melanoma cells correlates with their acquisition of metastatic properties.

The stiffness of tumor cells varies during cancer progression. In particular, metastatic carcinoma cells analyzed by Atomic Force Microscopy (AFM) appear softer than non-invasive and normal cells. Here we examined by AFM how the stiffness of melanoma cells varies during progression from non-invasive Radial Growth Phase (RGP) to invasive Vertical Growth Phase (VGP) and to metastatic tumors. We show that transformation of melanocytes to RGP and to VGP cells is characterized by decreased cell stiffness. However, further progression to metastatic melanoma is accompanied by increased cell stiffness and the acquisition of higher plasticity by tumor cells, which is manifested by their ability to greatly augment or reduce their stiffness in response to diverse adhesion conditions. We conclude that increased plasticity, rather than decreased stiffness as suggested for other tumor types, is a marker of melanoma malignancy. These findings advise caution about the potential use of AFM for melanoma diagnosis. FROM THE CLINICAL EDITOR: This study investigates the changes to cellular stiffness in metastatic melanoma cells examined via atomic force microscopy. The results demonstrate that increased plasticity is a marker of melanoma malignancy, as opposed to decreased stiffness.

Immunopathology of American cutaneous leishmaniasis

American mucocutaneous leishmaniasis is a granulomatous disease clinically characterized by ulcerated skin lesions that can regress spontaneously. A small percentage of the affected individuals can however develop a severe destruction of the nasal, oral, pharyngeal and/or laryngeal mucous membranes many years after the healing of the primary lesion. The human immune response to the infection and the possible mechanisms underlying the pathogenesis of the disease, determining either the self-healing or the development of chronic and destructive mucosal lesions, are discussed.

Epidemiological aspects of American Cutaneous Leishmaniasis in a periurban area of the metropolitan region of Belo Horizonte, Minas Gerais, Brazil

In order to characterize the epidemiology of American Cutaneous Leishmaniasis (ACL) in a periurban area of the municipality of Sabará in the metropolitan region of Belo Horizonte (MRBH), an area until then considered free of the disease, a cross sectional survey was undertaken in 1990. The survey of the population consisted of 1119 interviews and 881 clinical examinations using Montenegro's skin test (MST). A low prevalence (3.7%) of positive MST was encountered. The disease had been occuring in the area for about 20 years in the form of sporadic cases. The predominant species of sandfly both in domestic areas and nearby areas of secondary vegetation was Lutzomyia whitmani. A canine survey of delayed hypersensitivity to the antigen P10,000 identified only one dog with a positive reaction out of 113 examined. The transmission of ACL in MRBH was confirmed. The occurrence of the disease in women, children and individuals with no contact with forest areas as well as the presence of potential vector species in the domiciliar environment, suggests the transmission of the disease in this environment.

Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts.

We have previously shown that vaccination of HLA-A2 metastatic melanoma patients with the analogue Melan-A(26-35(A27L)) peptide emulsified in a mineral oil induces ex vivo detectable specific CD8 T cells. These are further enhanced when a TLR9 agonist is codelivered in the same vaccine formulation. Interestingly, the same peptide can be efficiently recognized by HLA-DQ6-restricted CD4 T cells. We used HLA-DQ6 multimers to assess the specific CD4 T-cell response in both healthy individuals and melanoma patients. We report that the majority of melanoma patients carry high frequencies of naturally circulating HLA-DQ6-restricted Melan-A-specific CD4 T cells, a high proportion of which express FOXP3 and proliferate poorly in response to the cognate peptide. Upon vaccination, the relative frequency of multimer+ CD4 T cells did not change significantly. In contrast, we found a marked shift to FOXP3-negative CD4 T cells, accompanied by robust CD4 T-cell proliferation upon in vitro stimulation with cognate peptide. A concomitant reduction in TCR diversity was also observed. This is the first report on direct ex vivo identification of antigen-specific FOXP3+ T cells by multimer labeling in cancer patients and on the direct assessment of the impact of peptide vaccination on immunoregulatory T cells.

Inflammatory cutaneous reaction induced by the lectin of Dioclea grandiflora (Mart. )

The lectin from Dioclea grandiflora (Mart.) that selectively binds glucose and mannose, when subcutaneously injected in mouse induces an inflammatory cutaneous reaction whose histological analysis reveals an hemorrhagic ulceration with exudative reaction accompanied by an influx of polymorphonuclear leukocytes and giant cells. The presence of lymphocytes and plasma cells in the lesion was insignificant. In order to characterize the in vivo action of inflammatory factors generated by this lesion, distinct lines of mice were used: high and low antibody responder mice; the genetically selected mice to the acute phase of inflammatory reaction; lines of mice deficient in C5, a protein of the complement system. It is shown that the lectin of D. grandiflora acts as an inflammatory agent probably promoting exocytosis and release of mediators.

HTLV-I associated cutaneous T-cell lymphoma: report of a case with atypical clinical presentation

A case of a 20-years-old black man from Salvador, Bahia with HTLV-I associated T cell lymphoma is presented. In spite of the absence of splenomegaly and leukemia, the patient had a marked cephalic tumoral infiltrationassociated with axillary tumors in a pattern not yet described in adult T cell lymphoma. Peripheral blood involvement was observed later on in the course of thedisease. The patient underwent chemotherapy but died seven monts after diagnosis.

Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis.

Radiotherapy is a widely used treatment option in cancer. However, recent evidence suggests that doses of ionizing radiation (IR) delivered inside the tumor target volume, during fractionated radiotherapy, can promote tumor invasion and metastasis. Furthermore, the tissues that surround the tumor area are also exposed to low doses of IR that are lower than those delivered inside the tumor mass, because external radiotherapy is delivered to the tumor through multiple radiation beams, in order to prevent damage of organs at risk. The biological effects of these low doses of IR on the healthy tissue surrounding the tumor area, and in particular on the vasculature remain largely to be determined. We found that doses of IR lower or equal to 0.8 Gy enhance endothelial cell migration without impinging on cell proliferation or survival. Moreover, we show that low-dose IR induces a rapid phosphorylation of several endothelial cell proteins, including the Vascular Endothelial Growth Factor (VEGF) Receptor-2 and induces VEGF production in hypoxia mimicking conditions. By activating the VEGF Receptor-2, low-dose IR enhances endothelial cell migration and prevents endothelial cell death promoted by an anti-angiogenic drug, bevacizumab. In addition, we observed that low-dose IR accelerates embryonic angiogenic sprouting during zebrafish development and promotes adult angiogenesis during zebrafish fin regeneration and in the murine Matrigel assay. Using murine experimental models of leukemia and orthotopic breast cancer, we show that low-dose IR promotes tumor growth and metastasis and that these effects were prevented by the administration of a VEGF receptor-tyrosine kinase inhibitor immediately before IR exposure. These findings demonstrate a new mechanism to the understanding of the potential pro-metastatic effect of IR and may provide a new rationale basis to the improvement of current radiotherapy protocols.

Ecoepidemiological aspects of american cutaneous leishmaniasis in the state of São Paulo, Brazil

The aim of this study is to review some of the ecoepidemiological aspects of american cutaneous leishmaniasis (ACL) in the state of São Paulo, Brazil. During the first half of this century ACL occured in São Paulo, predominantly on the bank of the Tietê river, where there were railroad constructions and there was inevitable contact between and forested areas. Man's activities resulted in a drastic reduction of the forested regions of the state and molded the present landscape found in São Paulo, which brought a gradual change in the epidemiology of ACL during this century. Currently ACL can be considered as an endemic disease. Nowadays, ACL is found in different regions of São Paulo state, and is no longer limited to the bank of the Tietê river. The disease occurs in all age groups and sexes. Lack of knowledge about wild reservoir hosts of Leishmania (V.) braziliensis has simulated speculation about the possible role played by domestic animals (dogs and equines). Man's activities also favoured Lutzomyia intermedia a sandfly species which can clearly thrive in changed environments L. (V.) braziliensis continues to be transmitted, even after decades of forest destruction in São Paulo.

American cutaneous leishmaniasis in Pernambuco, Brazil: eco-epidemiological aspects in "Zona da Mata" region

American cutaneous leishmaniasis (ACL) has been increasing in Pernambuco, thus becoming an important problem for Public Health. The incindence is predominant in the region called "Zona da Mata", in the east of this state. This region corresponds geographically to the primitive area of the Atlantic forest. In order to characterize the eco-epidemiology expression of ACL in this region, two localities situated in the municipalities of Amaraji e Cortes have been selected by the criterion of higher incindence of human cases. Five stocks of patients were characterized and identified on the basis of enzyme profiles as a new variant of Leishmania (V.) braziliensis. A survey of wild and domestic animals was carried out by means of a parasitological and serological diagnosis. Through the analysis of the spleen and liver imprints, were detected amastigotes compatible with Leishmania in five Nectomys s. squamipes, five Bolomys l. pixuna, two Rattus r. alexandrinus and one Rattus r. frugivorus. For two years we carried out monthly sandflies captures using CDC light traps as well as manual captures. Lutzomyia whitmani was predominant, which accounted for 97.4 por cento of the total. These data indicate a strong evidence on the vector and the potential reservoirs of L. braziliensis in this region.