HTLV-1 affects the adipogenic differentiation of human mesenchymal stem cells

Financial support: CTC, INCTC, FAPESP, FUNDHERP and CNPq

Epidemiology of HIV/HCV coinfection in patients cared for at the Tropical Medicine Foundation of Amazonas

The association of HIV infection and hepatitis C virus (HCV) infection often occurs because both viruses share the same transmission routes, increasing the possibility of HIV/HCV coinfection. World prevalence greater than 30% of coinfected cases is estimated, and it can reach 90% depending on the transmission route. With the aim of determining the frequency and profile of HIV/HCV coinfected patients, a descriptive analysis was carried out with patients with HIV/AIDS whose serology was positive for hepatitis C virus (HCV), cared for at the Fundação de Medicina Tropical do Amazonas from 2000 to 2007. In the present study, of the 2,653 AIDS cases notified in SINAN, 1,582 patients underwent serology test for hepatitis C, and a frequency of 4.42% (n = 70) of HIV/HCV coinfected patients was identified in the period studied. The most frequent infection route was sexual transmission (84.3%), 68.6% among heterosexual individuals. Most patients were males (72.9%), aged between 25 and 40 years (60.1%), of low income (50% earning up to one minimum wage), and low educational level (80% had completed only middle school). A high percentage of deaths were observed during the study (34.3%). The results indicate a low seroprevalence of HIV/HCV coinfection in this population, in which sexual transmission, characterized by sexual promiscuity among heterosexual individuals, is the major transmission route of the virus rather than the use of injection drugs, as shown in world statistics

CD3e expression in HTLV-1-infected individuals is associated with proviral load and Tax expression

Financial support: FUNDHERP, CTC, INCTC, FAPESP, CNPq and CAPES

Quantitative correlation between transcriptional levels of ER chaperone, peroximal protein and FVIII productivity in human Hek-293 cell line

Hek-293 cell line presents good production platform for recombinant therapeutic proteins, however little is known about the components that contribute to the cellular control of recombinant protein production. In this study, we generated a Hek-293 producing recombinant factor VIII (FVIII) and we evaluated the immunoglobulin-binding protein (BiP) and phytanoil-CoA α-hydroxylase (PAHX) expression levels which are known for diminishing FVIII production. Our analyses showed that the recombinant cell population expresses 3.1 ± 1.4 fold of BIP mRNA (P = 0.0054) and 97.8 ± 0.5 fold of PAHX mRNA (P = 0.0016) compared to nontransduced cells. The amount of these proteins was inversely correlated to the secreted FVIII. In conclusion, BIP and PAHX expression are augmented in human cells producing FVIII and they antagonize the amount of therapeutic factor VIII in the cell culture.This study was supported by the Center for Cell-based Therapy (CTC) and Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP. The authors acknowledge Dr. Garry P. Nolan for contributing with the pBMN-I-GFP vector and David Marco Antonio for statistical support. We thank Fernanda Udinal and Alessandra Almeida for English language support. We also thank Sandra Navarro Bresciani for preparing the figures.This study was supported by the Center for Cellbased Therapy (CTC) and Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP. The authors acknowledge Dr. Garry P. Nolan for contributing with the pBMNIGFP vector and David Marco Antonio for statistical support. We thank Fernanda Udinal and Alessandra Almeida for English language support. We also thank Sandra Navarro Bresciani for preparing the figures

Development of a molecular platform for HTLV confirmatory diagnosis: importance of the internal amplification control

Finnancial Support: CTC/INCTC, FAPESP, FUNDHERP, FINEP

Epidemiological factors related to slow progression of the acquired immune deficiency syndrome (AIDS)

Com o objetivo de identificação de fatores envolvidos na progressão lenta para aids, realizou-se estudo transversal para avaliação de dados epidemiológicos de indivíduos infectados pelo Vírus da Imunodeficiência Humana tipo 1 (HIV-1), atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP. Foram selecionados pacientes, conforme critérios definidos, constituindo duas populações: população 1, composta por lentos progressores (P1), que possuía anticorpos anti-HIV há mais de oito anos e com ocorrência de menos de duas doenças oportunistas no último ano, e a população 2 (P2), pacientes rápidos progressores, com diagnóstico de infecção pelo HIV e doença manifesta a menos de dois anos e com mais de duas doenças oportunistas, diagnosticadas no último ano. Todos os indivíduos foram submetidos a questionário, contendo dados demográficos, profissão, ocorrência de outras doenças sexualmente transmissíveis, forma de contágio, data de diagnóstico e hábitos. O período do estudo foi de março de 1998 a outubro de 1999. Obtivemos na P1: doze homens e quatro mulheres, idade média 30,7 anos, forma de contágio predominantemente sangüínea, tempo de progressão da doença 10,5 anos; P2: 12 homens e 4 mulheres; idade média 34,8 anos, forma de contágio predominantemente sexual, tempo de progressão da doença de 1,5 anos. Tabagismo foi o principal vício em ambas as populações. Quando interrogados sobre a causa do bom estado de saúde, os indivíduos da P1 responderam estar ela relacionada à fé e ao uso adequado das medicações. Os pacientes da P2 não foram interrogados sobre a causa de seu estado de saúde. Quanto à prática sexual, nove pacientes da P1 mantinham relações, sendo cinco sem uso regular do preservativo. Na P2, apenas um paciente utilizava preservativo. Dois pacientes da P1 e um da P2 revelaram ter apresentado DST, Sífilis e Papiloma Vírus Humano. Em vista do reduzido número de pacientes, não foi possível estabelecer associação entre as variáveis estudadas e os padrões de progressão da doença. Os dados sobre hábitos não parecem contribuir para o padrão de desenvolvimento da doença. O estudo oferece um perfil epidemiológico dessas populações de pacientes.To determine the factors involved in slow progression to aids, a transverse study was conducted for the evaluation of the epidemiological data of individuals infected with type 1 human immunodeficiency virus seen at the University Hospital of the Faculty of Medicine of Ribeirão Preto-USP. Patients were choosed in conformity some judgment, establish two populations: population 1, consisting of slow progressors (P1), had been carrying HIV antibodies for more than 8 years, with the occurrence of less than 2 opportunistic diseases in the last year, and population 2 (P2), consisting of rapid progressors, had a diagnosis of HIV infection and overt disease detected less than 2 years before and more than 2 opportunistic diseases diagnosed during the last year. All patients responded to a questionnaire concerning demographic data, profession, occurrence of other sexually transmissible diseases, form of contagion, date of diagnosis, and habits. The study was conducted from March 1998 to October 1999. We obtain in the P1: 12 men and 4 women, mean age 30.7 years, predominant form of contagion: blood route, time of disease progression 10.5 years; P2 12 men and 4 women; mean age 34,8 years, predominant form of contagion: sexual, time of disease progression 1.5 years. Tabagisme was the principal vice in about populations. When asked about motivation yours good health, the subjects of P1 answered to be relationed the faith and medications use. The patients of the P2 did not answer about yours health state. Whatever the sexual custom, 9 patients of the P1 had sexual relations, five without regular use of condom. In the P2 only um patient used condom. Two patients of the P1 and one of P2 declared to have STD, syphilis and Human Papiloma Virus (HPV). Because there are reduces number of patients it’s impossible to make asociation between the variables studies and mesures of the disease progression. The dates about habits don’t contribute for the disease development. The study offers an epidemiological profile of these patient populations

Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis

<p>Abstract</p> <p>Background</p> <p>Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and <it>PRV1 </it>gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34⁺hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, <it>PRV1 </it>overexpression, and clinical and laboratory parameters.</p> <p>Results</p> <p>By real time PCR assay, we observed that <it>A1, MCL1, BIK and BID</it>, as well as <it>A1, BCLW </it>and <it>BAK </it>gene expression were increased in ET and PMF CD34⁺cells respectively, while pro-apoptotic <it>BAX </it>and anti-apoptotic <it>BCL2 </it>mRNA levels were found to be lower in ET and PMF CD34⁺cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes <it>A1, BCL2, BCL-X_L</it>and <it>BCLW</it>. In contrast, pro-apoptotic <it>BID </it>and <it>BIM_EL</it>expression were downregulated in ET leukocytes. Increased BCL-X_Lprotein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and <it>BAX, BIK and BAD </it>gene expression and between <it>A1, BAX </it>and <it>BIK </it>and <it>PRV1 </it>gene expression. A negative correlation between <it>PRV1 </it>gene expression and platelet count was observed, as well as a positive correlation between <it>PRV1 </it>gene expression and splenomegaly.</p> <p>Conclusions</p> <p>Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, <it>PRV1 </it>and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.</p