RESUMO
PURPOSE: Recruit and sequence breast cancer subjects in Guatemalan and US Hispanic populations. Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer. METHODS: We used targeted gene sequencing to identify pathogenic variants in 19 familial breast cancer susceptibility genes in DNA from unselected Hispanic breast cancer cases in the US and Guatemala. Recruitment across the US was achieved through community-based strategies. In addition, we obtained patients receiving cancer treatment at major hospitals in Texas and Guatemala. RESULTS: We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2, and ATM. In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic variants (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (p < 0.001). CONCLUSION: Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women.
Assuntos
Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Hispânico ou Latino , Neoplasias de Mama Triplo Negativas , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Guatemala/epidemiologia , Hispânico ou Latino/genética , Hispânico ou Latino/estatística & dados numéricos , Seleção de Pacientes , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/etnologia , Neoplasias de Mama Triplo Negativas/epidemiologia , Estados Unidos/epidemiologia , Texas/epidemiologiaRESUMO
This study documented the parasite faunas of the spiral valves of blue sharks Prionace glauca (L. 1758) and common thresher sharks Alopias vulpinus (Bonnaterre, 1788) caught in the California Current Large Marine Ecosystem (CCLME) north of the Mexican border. The spiral valves of 18 blue and 19 thresher sharks caught in the CCLME from 2009 to 2013 were examined for parasites. Seven parasite taxa were found in blue sharks and nine in threshers. The tetraphyllidean cestode Anthobothrium sp. (78% prevalence) was the most common parasite in blue sharks, and the phyllobothriid cestode Paraorygmatobothrium sp. (90% prevalence) was the most common in threshers. An adult nematode of the genus Piscicapillaria was found in threshers for the first time and may be a new species. Adult individuals of Hysterothylacium sp. were found in both shark species. The adult acanthocephalan Rhadinorhynchus cololabis and remains of the parasitic copepod Pennella sp. - both parasites of Pacific saury, Cololabis saira - were found in the intestines of threshers, indicating recent feeding on saury. This study paves the way for a more comprehensive examination, including more samples and a wider variety of shark species, to provide a greater understanding of shark feeding behaviour and possibly provide information on shark population biology.
Assuntos
Comportamento Alimentar , Doenças dos Peixes/parasitologia , Doenças Parasitárias em Animais/parasitologia , Tubarões/fisiologia , Tubarões/parasitologia , Animais , Ecossistema , México , Parasitos/classificação , Parasitos/isolamento & purificaçãoRESUMO
Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from â¼ 35 to â¼ 1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin.
Assuntos
Tecido Adiposo/metabolismo , Insulina/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Células 3T3-L1 , Adulto , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Glucose/metabolismo , Humanos , Insulina/sangue , Masculino , Camundongos , Pessoa de Meia-Idade , Estresse Oxidativo , Processamento de Proteína Pós-Traducional , Ubiquitinação , Resposta a Proteínas não Dobradas/genéticaRESUMO
This article summarizes the points of view of professionals from different nationalities, working in diverse organizations and dealing with concepts and activities related to health promotion effectiveness evaluation. This collection of views came from a panel presentation and dialogue held during the First Brazilian Seminar on Effectiveness in Health Promotion. Four professionals working in evaluation and health promotion--two from the United States, one from French Canada and another representing an international professional organization--facilitated by one Brazilian and one Puerto Rican moderator, had an informal dialogue with the audience. Four questions about how these professionals perceive evaluation in health promotion were asked to initiate the dialogue. The panelists deliberated five aspects of health promotion evaluation, asking: "how", "how much", "what for", "with whom" and "why". Professionals working in developing countries (in this case, Brazil) and those dealing with indigenous communities (in developed countries) tended to put more emphasis on "what for?", "with whom?" and "why?" regarding initiatives to evaluate effectiveness of health promotion. Questions associated with "how?" and "how much?" were more often mentioned by professionals working for international or governmental agencies. A 90-minute dialogue among panelists with a clearly Brazilian bias, was not sufficient to produce conclusions on the predominant character of international evaluation efforts of effectiveness. Nevertheless, this debate framed the five aspects of evaluation into a value perspective. The questions, "what for?", "with whom?", "why?", "how?" and "how much?" are linked to a political or technical presumptions that could be orchestrated in evaluations of health promotion effectiveness.
Assuntos
Promoção da Saúde , Política , Avaliação de Programas e Projetos de Saúde , Brasil , Países em Desenvolvimento , Saúde Global , Humanos , Marketing SocialRESUMO
Cytochrome p450s (cyp450s) are a family of structurally related proteins, with diverse functions, including steroid synthesis and breakdown of toxins. This paper reports the full-length sequence of a novel cyp450 gene, the first to be isolated from the tropical freshwater snail Biomphalaria glabrata, an important intermediate host of Schistosoma mansoni. The nucleotide sequence is 2291 bp with a predicted amino acid sequence of 584aa. The sequence demonstrates conserved cyp450 structural motifs, but is sufficiently different from previously reported cyp450 sequences to be given a new classification, CYP320A1. Initially identified as down-regulated in partially resistant snails in response to S. mansoni infection, amplification of this gene using RT-PCR in both totally resistant or susceptible snail lines when exposed to infection, and all tissues examined, suggests ubiquitous expression. Characterization of the first cyp450 from B. glabrata is significant in understanding the evolution of these metabolically important proteins.
Assuntos
Biomphalaria/genética , Sistema Enzimático do Citocromo P-450/genética , Sequência de Aminoácidos , Animais , Biomphalaria/parasitologia , Interações Hospedeiro-Parasita/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Schistosoma mansoni , Análise de Sequência de DNARESUMO
Cytochrome p450s (cyp450s) are a family of structurally related proteins, with diverse functions, including steroid synthesis and breakdown of toxins. This paper reports the full-length sequence of a novel cyp450 gene, the first to be isolated from the tropical freshwater snail Biomphalaria glabrata, an important intermediate host of Schistosoma mansoni. The nucleotide sequence is 2291 bp with a predicted amino acid sequence of 584aa. The sequence demonstrates conserved cyp450 structural motifs, but is sufficiently different from previously reported cyp450 sequences to be given a new classification, CYP320A1. Initially identified as down-regulated in partially resistant snails in response to S. mansoni infection, amplification of this gene using RT-PCR in both totally resistant or susceptible snail lines when exposed to infection, and all tissues examined, suggests ubiquitous expression. Characterization of the first cyp450 from B. glabrata is significant in understanding the evolution of these metabolically important proteins.