Modulação pelo haplótipo Bantu da resposta ao uso de hidroxiureia em anemia falciforme

Pós-graduação em Genética - IBILCE

Caracterização molecular das infecções pelos poliomavírus humanos JC e BK em pacientes renais crônicos candidatos a transplante renal no Estado do Acre

O presente trabalho investigou a ocorrência de infecção pelos poliomavírus JCV e BKV na população de pacientes com doença renal crônica, no Estado do Acre e em um grupo controle de indivíduos sem doença renal. Foram examinadas 100 amostras de urina do grupo de Pacientes e 99 amostras de urina do grupo Controle. Após a extração do DNA, a PCR foi usada para a amplificação de 173pb do gene que codifica o antígeno-T de ambos os vírus. A diferenciação entre as infecções por JCV e por BKV foi realizada por meio da digestão enzimática do produto amplificado, usando-se endonuclease de restrição. Esse estudo não identificou a presença do BKV nas amostras de urina do grupo de Pacientes e do grupo Controle. O JCV foi identificado em 11,1% (11/99) dos indivíduos do grupo Controle e em 4% (4/100) dos indivíduos do grupo de Pacientes. Foi encontrada diferença estatisticamente significante entre os grupos de Pacientes e Controle quanto à média de Uréia (p < 0,001), onde a média no grupo de Pacientes foi significantemente maior do que a média no grupo Controle. Estes resultados sugerem que os elevados níveis de uréia excretada na urina, a baixa celularidade urinária, a diminuição do “washout” (limpeza) da bexiga e o tempo para a análise das amostras, justifiquem a baixa prevalência de infecção encontrada no grupo de pacientes renais crônicos; pois esses fatores podem diminuir a quantidade de vírus na urina ou podem atuar como inibidores da PCR. Esse estudo sugere a necessidade de aumentar a sensibilidade dos testes para a identificação desses vírus.

Prevalência da infecção pelos Polyomavirus JC e BK em pacientes com Doença Renal Crônica e transplantados

O presente estudo teve como objetivo realizar a investigação molecular da infecção pelos Poliomavírus JC e BK em pacientes com Doença Renal Crônica (DRC) terminal, transplantados e em indivíduos sem DRC. Foram testadas 295 amostras de urina, que após a extração de DNA, foram submetidas à amplificação de um fragmento de 173 pb do gene do antígeno-T de Polyomavirus por meio da PCR seguida pela análise de RFLP, utilizando a endonuclease de restrição BamHI, na qual foi detectado 17,6% (52/295) de infecção por Polyomavirus, sendo 3,9% (4/102) nos pacientes com DRC, 30,5% (18/59) nos pacientes transplantados e 22,4% (30/134) nos assintomáticos. A prevalência da infecção pelo BKV foi de 88,9% (16/18) nos transplantados e de 10,0% (3/30) nos assintomáticos, não sendo detectada a infecção pelo BKV em pacientes com DRC. A prevalência de infecção pelo JCV foi de 3,9% (4/102) nos pacientes com DRC, de 11,1% (2/16) no transplantados e de 90,0% (27/30) nos assintomáticos. O risco de infecção por BKV foi determinada ser 72 vezes maior em pacientes transplantados do que em assintomáticos. A baixa frequência de infecção encontrada entre os pacientes com DRC pode estar relacionada ao fato de que esses pacientes apresentam uma elevada taxa de excreção de uréia na urina, assim como, baixo volume e densidade urinária, podem ser outros dois fatores contribuintes para a ausência de amplificação por estarem associados à baixa carga viral presente. De acordo com estes resultados, sugere-se que a investigação da infecção por Polyomavirus deve ser realizada, rotineiramente, nos pacientes pré e póstransplante, assim como nos doadores de órgãos, uma vez que a infecção por BKV tem sido associada com rejeição de enxerto em transplante de rins.

Type 2 Diabetes Elicits Lower Nitric Oxide, Bradykinin Concentration and Kallikrein Activity Together with Higher DesArg(9)-BK and Reduced Post-Exercise Hypotension Compared to Non-Diabetic Condition

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

BK virus associated meningoencephalitis in an AIDS patient treated with HAART

A severely immune-suppressed AIDS patient was suspected of suffering from BK virus (BKV) meningoencephalitis, after being studied for common causes of neurological complications of co-infectious origin. Polymerase chain reaction (PCR) and sequence analysis of cerebrospinal fluid and brain samples, confirmed the presence of BKV. His clinical condition improved along with the regression of brain lesions, after modifications on his antiretroviral regime. Five months after discharge, the patient was readmitted because of frequent headaches, and a marked inflammatory reaction was evidenced by a new magnetic resonance imaging (MRI). The symptoms paralleled a rising CD4+ lymphocyte count, and immune reconstitution syndrome was suspected. This is the first non-postmortem report of BKV meningoencephalitis in an AIDS patient, showing clinical and radiographic improvement solely under HAART.

High prevalence of the simultaneous excretion of polyomaviruses JC and BK in the urine of HIV-infected patients without neurological symptoms in São Paulo, Brazil

OBJECTIVE: To evaluate the prevalence of the urinary excretion of BKV and JCV in HIV-infected patients without neurological symptoms. METHODS: Urine samples from HIV-infected patients without neurological symptoms were tested for JC virus and BK virus by PCR. Samples were screened for the presence of polyomavirus with sets of primers complementary to the early region of JCV and BKV genome (AgT). The presence of JC virus or BK virus were confirmed by two other PCR assays using sets of primers complementary to the VP1 gene of each virus. Analysis of the data was performed by the Kruskal-Wallis test for numerical data and Pearson or Yates for categorical variables. RESULTS: A total of 75 patients were included in the study. The overall prevalence of polyomavirus DNA urinary shedding was 67/75 (89.3%). Only BKV DNA was detected in 14/75 (18.7%) urine samples, and only JCV DNA was detected in 11/75 (14.7%) samples. Both BKV and JCV DNA were present in 42/75 (56.0%) samples. CONCLUSION: In this study we found high rates of excretion of JCV, BKV, and simultaneous excretion in HIV+ patients. Also these results differ from the others available on the literature.

Studio prospettico sul significato clinico e prognostico delle infezioni da virus BK e virus JC nel trapianto di rene

Le infezioni post trapianto sono una complicanza frequente, tra queste l'infezione da Polyomavirus rappresenta una patologia molto frequente e causa di perdita del graft. Sono stati studiati 70 pazienti portatori di trapianto renale per valutare l'incidenza dell'infezione e la sua prognosi e la risposta alla terapia

Die Bantu-Philosophie von Tempels aus afrikanischer Perspektive

The study presents Placide Temples’ way towards the “Philosophie bantoue” and the repercussion of the latter in the African discourse. Three decisive aspects are investigated: first the prehistory, i.e., the socio-political, scientific and religious contexts, which prepared him and put him in an estate to discover that Africans do have a Philosophy, second his purposefulness and his singularity, and finally the history of its reception and the reactions by the African scholars and sages.

Comments on the review by Kathrin Tiewa

The review of the book Matrix nominal Phrases in Kiswahili Bantu (2009), Rüdiger Köppe Verlag, in Afrikanistik online is lucid and welcome. We appreciate it very much. There are, however, a few inexactitudes that need to be corrected.

Mandombe

Mandombe, one of the most recent modern African scripts, was originally designed to write the Bantu languages of the Congos, and eventually all languages on the continent. Its symbols are made of simple and composite geometrical forms which predate the script. It is apparently the only African script which has gained some social success without any political support.

Die Bantu-Stämme Süd-Afrikas : eine ethnologisch-mythologische Studie

Leipzig, Univ., Diss. 1890

The JC and BK human polyoma viruses appear to be recent introductions to some South American Indian tribes: There is no serological evidence of cross-reactivity with the simian polyoma virus SV40

In an effort to understand the unusual cytogenetic damage earlier encountered in the Yanomama Indians, plasma samples from 425 Amerindians representing 14 tribes have been tested for hemagglutination inhibition antibodies to the human JC polyoma virus and from 369 Amerinds from 13 tribes for hemagglutination inhibition antibodies to the human BK polyoma virus. There is for both viruses highly significant heterogeneity between tribes for the prevalence of serum antibody titers ≥1/40, the pattern of infection suggesting that these two viruses only relatively recently have been introduced into some of these tribes. Some of these samples, from populations with no known exposure to the simian polyoma virus SV40, also were tested for antibodies to this virus by using an immunospot assay. In contrast to the findings of Brown et al. (Brown, P., Tsai, T. & Gajdusek, D. C. (1975) Am. J. Epidemiol. 102, 331–340), none of the samples was found to possess antibodies to SV40. In addition, no significant titers to SV40 were found in a sample of 97 Japanese adults, many of whom had been found to exhibit elevated titers to the JC and BK viruses. This study thus suggests that these human sera contain significant antibody titers to the human polyoma viruses JC and BK but do not appear to contain either cross-reactive antibodies to SV40 or primary antibodies resulting from SV40 infection.

Ca2+-binding activity of a COOH-terminal fragment of the Drosophila BK channel involved in Ca2+-dependent activation

Mutational and biophysical analysis suggests that an intracellular COOH-terminal domain of the large conductance Ca2+-activated K+ channel (BK channel) contains Ca2+-binding site(s) that are allosterically coupled to channel opening. However the structural basis of Ca2+ binding to BK channels is unknown. To pursue this question, we overexpressed the COOH-terminal 280 residues of the Drosophila slowpoke BK channel (Dslo-C280) as a FLAG- and His6-tagged protein in Escherichia coli. We purified Dslo-C280 in soluble form and used a 45Ca2+-overlay protein blot assay to detect Ca2+ binding. Dslo-C280 exhibits specific binding of 45Ca2+ in comparison with various control proteins and known EF-hand Ca2+-binding proteins. A mutation (D5N5) of Dslo-C280, in which five consecutive Asp residues of the “Ca-bowl” motif are changed to Asn, reduces 45Ca2+-binding activity by 56%. By electrophysiological assay, the corresponding D5N5 mutant of the Drosophila BK channel expressed in HEK293 cells exhibits lower Ca2+ sensitivity for activation and a shift of ≈+80 mV in the midpoint voltage for activation. This effect is associated with a decrease in the Hill coefficient (N) for activation by Ca2+ and a reduction in apparent Ca2+ affinity, suggesting the loss of one Ca2+-binding site per monomer. These results demonstrate a functional correlation between Ca2+ binding to a specific region of the BK protein and Ca2+-dependent activation, thus providing a biochemical approach to study this process.