Intervento

Track meet on May 4, 1972.https://scholarworks.moreheadstate.edu/historic_images_1930_1965/3865/thumbnail.jp

Mapeamento da variabilidade genética espontânea das cepas vacinais B19 E RB51 contra Brucella abortus, comercializadas no Brasil.

A brucelose é uma zoonose causada por bactérias intracelulares do gênero Brucella, que infectam humanos, animais domésticos e silvestres. Esta doença apresenta grande impacto econômico, devido à ocorrência de distúrbios reprodutivos nos animais. A prevenção contra infecções causadas por Brucella abortus em bovinos é feita por meio da administração das cepas vacinais B19 e RB51 de B. abortus. Existem relatos de que estas vacinas podem causar aborto às fêmeas vacinadas. Devido a isso, a vacinação de fêmeas jovens é preconizada. Entretanto, há diversos relatos na literatura de persistência da B19 no úbere, proporcionando a eliminação da bactéria pelo leite. Portanto, toda a ocorrência de aborto em animais vacinados, seja por B19 ou por RB51, merece um estudo aprofundado sobre a sua causa. Técnicas moleculares capazes de diferenciar cepas vacinais de cepas selvagens têm sido descritas. O gene ery, ligado ao catabolismo do eritritol, foi caracterizado como um importante marcador nessa diferenciação, por apresentar uma deleção espontânea de 702 pares de base na cepa B19. Como esta cepa é comercializada por diferentes empresas, estudos descreveram que algumas destas cepas comercializadas na Índia não apresentam essa deleção. No Brasil, não há registro sobre a origem das amostras B19 e RB51 utilizadas na confecção das vacinas comerciais, logo um estudo no sentido da verificação de possíveis mutações em relação à amostra padrão se faz necessário, devido a estas poderem reverter a sua virulência. Objetiva-se com este estudo caracterizar genotipicamente as cepas vacinais B19 e RB51 comercializadas no Brasil contra a brucelose bovina. A metodologia utilizada será a genotipagem de genes marcadores de virulência destas cepas vacinais, através da amplificação, sequenciamento e análises in silico das sequências obtidas. Os resultados obtidos permitirão a identificação do genótipo de todas as vacinas comerciais B19 e RB51 utilizadas para a imunização de bovinos no Brasil

Genetic and Clinical Features of Multiple Endocrine Neoplasia Types 1 and 2

Multiple endocrine neoplasia (MEN) are clinical inherited syndromes affecting different endocrine glands. Three different patterns of MEN syndromes can occur (MEN 1, MEN 2A, and MEN 2B). MEN syndromes are very rare, affect all ages and both sexes are equally affected. MEN 1 is characterized by the neoplastic transformation of the parathyroid glands, pancreatic islets, anterior pituitary, and gastrointestinal tract. Heterozygous MEN 1 germline mutations have been detected in about 70–80% of patients with MEN 1. The mutations are scattered throughout the entire genomic sequence of the gene. MEN 1 patients are characterized by variable clinical features, thus suggesting the lack of a genotype-phenotype correlation. Therapeutical approaches are different according to the different endocrinopathies. The prognosis is generally good if adequate treatment is provided. In MEN 2 syndromes, the medullary thyroid cancer (MTC) is almost invariably present and can be associated with pheochromocytoma (PHEO) and/or multiple adenomatosis of parathyroid glands with hyperparathyroidism (PHPT). The different combination of the endocrine neoplasia gives origin to 3 syndromes: MEN 2A, MEN 2B, and FMTC. The clinical course of MTC varies considerably in the three syndromes. It is very aggressive in MEN 2B, almost indolent in the majority of patients with FMTC and with variable degrees of aggressiveness in patients with MEN 2A. Activating germline point mutations of the RET protooncogene are present in 98% of MEN 2 families. A strong genotype-phenotype correlation has been observed and a specific RET mutation may be responsible for a more or less aggressive clinical course. The treatment of choice for primary MTC is total thyroidectomy with central neck lymph nodes dissection. Nevertheless, 30% of MTC patients, especially in MEN 2B and 2A, are not cured by surgery. Recently, developed molecular therapeutics that target the RET pathway have shown very promising activity in clinical trials of patients with advanced MTC. MEN 2 prognosis is strictly dependent on the MTC aggressiveness and thus on the success of the initial treatment

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

Purpose: RAS mutations represent common driver alterations in thyroid cancer. They can be found in benign, low-risk and malignant thyroid tumors with follicular architecture, which are often diagnosed as indeterminate nodules on preoperative cytology. Therefore, the detection of RAS mutations in preoperative setting has a suboptimal predictive value for malignancy. In this study, we investigated differentially expressed microRNA (miRNA) in benign and malignant thyroid tumors with follicular architecture carrying mutations in RAS genes. Methods: Total RNA was purified from 60 RAS-mutant follicular-patterned thyroid tumors, including follicular adenoma (FA), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), papillary and follicular thyroid carcinoma cases (PTC, FTC); 22 RAS-negative FAs were used as controls. The expression analysis of 798 miRNAs was performed by digital counting (nCounter nanoString platform). Results: Comparing RAS-mutant and RAS-negative FAs, 12 miRNAs showed significant deregulation, which was likely related to the oncogenic effects of RAS mutations. Twenty-two miRNAs were differentially expressed in RAS-mutant benign versus malignant tumors. Considering the tumor type, 24 miRNAs were deregulated in PTC, 19 in NIFTP, and seven in FTC and compared to FA group; among these, miR-146b-5p, miR-144-3p, and miR-451a showed consistent deregulation in all the comparisons with the highest fold change. Conclusions: The miRNA expression analysis of follicular-patterned thyroid tumors demonstrated that RAS mutations influences miRNA profile in benign tumors. In addition, several miRNAs showed a histotype-specific deregulation and could discriminate between RAS-mutant benign and RAS-mutant malignant thyroid lesions, thus deserving further investigation as potential diagnostic markers