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EV Pavlova SZ Wang J Archer N Dekker JMFG Aerts S Karlsson TM Cox 《The Journal of pathology》2013,231(1):88-97
Multiple myeloma and B cell lymphoma are leading causes of death in Gaucher's disease but the nature of the stimulus driving the often noted clonal expansion of immunoglobulin‐secreting B cells and cognate lymphoid malignancy is unknown. We investigated the long‐term development of B cell malignancies in an authentic model of non‐neuronopathic Gaucher's disease in mice: selective deficiency of β‐glucocerebrosidase in haematopoietic cells [Gbatm1Karl/tm1KarlTg(Mx1‐cre)1Cgn/0, with excision of exons 9–11 of the murine GBA1 gene, is induced by poly[I:C]. Mice with Gaucher's disease showed visceral storage of β‐glucosylceramide and greatly elevated plasma β‐glucosylsphingosine [median 57.9 (range 19.8–159) nm; n = 39] compared with control mice from the same strain [median 0.56 (range 0.04–1.38) nm; n = 29] (p < 0.0001). Sporadic fatal B cell lymphomas developed in 11 of 21 GD mice (6–24 months) but only two of eight control animals developed tumours by age 24 months. Unexpectedly, most mice with overt lymphoma had absent or few Gaucher cells but local inflammatory macrophages were present. Eleven of 39 of Gaucher mice developed monoclonal gammopathy, but in the control group only one animal of 25 had clonal immunoglobulin abnormalities. Seven of 10 of the B cell lymphomas were found to secrete a monoclonal paraprotein and the lymphomas stained intensely for pan‐B cell markers; reactive T lymphocytes were also present in tumour tissue. In the Gaucher mouse strain, it was notable that, as in patients with this disease, CD138+ plasma cells frequently surrounded splenic macrophages engorged with glycosphingolipid. Our strain of mice, with inducible deficiency of β‐glucocerebrosidase in haematopoietic cells and a high frequency of sporadic lethal B cell malignancies, faithfully recapitulates human Gaucher's disease: it serves as a tractable model to investigate the putative role of bioactive sphingolipids in the control of B cell proliferation and the pathogenesis of myelomatosis—the most prevalent human cancer associated with this disorder. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
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Pileggi Antonello Klein Dagmar Fotino Carmen Bravo-Egaña Valia Rosero Samuel Doni Marco Podetta Michele Ricordi Camillo Molano R. Damaris Pastori Ricardo L. 《Immunologic research》2013,57(1-3):185-196
Immunologic Research - The ultimate goal of diabetes therapy is the restoration of physiologic metabolic control. For type 1 diabetes, research efforts are focused on the prevention or early... 相似文献
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Luis Rosero Bixby 《Pan American journal of public health》2004,15(2):94-103
OBJECTIVE: To assess the impact of health sector reform in Costa Rica on that country's child and adult mortality rates and on the people's access to primary health care. METHODS: Health sector reform was initiated in Costa Rica in 1995 in some districts, but in others reforms were adopted later. This made it possible to perform a time series analysis, using a quasi-experimental study design, in which observations were made annually from 1985 through 2001 for each of the 420 districts that existed in Costa Rica in 1984. The time series were divided into three periods that allowed all districts to be grouped into three categories (pioneer, intermediate, and late) according to the year when they first implemented health sector reform: 1995-1996; 1997-2000; and 2001 or after, respectively. For each of these periods, mortality rates were broken down by cause (communicable, socially-determined, or chronic disease), sex, and age group. The status of the reform process in a particular district was described by two indicators: (1) the presence or absence of health sector reform during a given period and, wherever such reforms had been adopted, (2) the number of years that had transpired since their adoption. Eight variables were used to control for confounders. Vital statistics and demographic data were obtained from the National Institute for Statistics and Census' [Centro Nacional de Estadística y Censos] electronic database. Poisson multiple regression analysis with fixed effects was used to estimate the impact of reform on child and adult mortality from different causes. Assessment of the population's access to primary care before and after the reform was based on the percentage of people who lived within a 4 km radius of a health facility that offered patient visiting hours two or more days a week. This information came from a previous study that used census data from 2000 and geographic information systems to map health care facilities throughout the country. RESULTS: Multiple regression showed that the reform was associated with an overall 8% reduction in deaths among children and with a 2% reduction in deaths among adults, both statistically significant. Also noted were a 14% reduction in deaths from communicable diseases or from conditions brought on by the presence of infectious processes, a 0% reduction in deaths from socially-determined causes, and a 2% reduction in deaths from chronic diseases. An estimated 120 child lives and 350 adult lives were saved by the reform in 2001 alone. Also, the percentage of people without equitable access to primary health services dropped by 15% between 1994 and 2000 in areas where health sector reform was implemented in 1995-1996, whereas areas that had not yet initiated health sector reform in 2000 experienced only a 3% reduction. CONCLUSION: Health sector reform significantly reduced mortality in Costa Rica and put an end to a decade of stagnation, as shown by certain health indicators, such as life expectancy. Equity in access to primary care improved considerably, perhaps because the first reforms were implemented in less developed areas of the country. 相似文献
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陈仕珠 《世界华人消化杂志》2006,14(27):2718-2721
乙型肝炎病毒(HBV)疫苗问世近30 a以来,成效巨大,但因各种因素影响,不同群体和不同个体乙肝(HB)免疫的重点或迫切性及免疫效果始终存在差异,即存在HBV疫苗接种群体化甚至个体化问题.因此,在实际操作中需注意根据不同年龄、不同人群甚至不同个体选择不同接种方案和不同剂量;对高危等人群应采用快速接种方案,并监测其抗-HBs水平,必要时加强免疫或应用佐剂.对HBsAg阳性母亲的子女等应加大接种剂量和/或接种4针.HBV疫苗与某些其他疫苗联合或同时接种为一省时简便的方法,效果肯定. 相似文献
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L. E. Bautista J. P. Casas V. M. Herrera J. J. Miranda P. Perel R. Pichardo A. González J. R. Sanchez C. Ferreccio X. Aguilera E. Silva M. Oróstegui L. F. Gómez J. A. Chirinos J. Medina-Lezama C. M. Pérez E. Suárez A. P. Ortiz L. Rosero N. Schapochnik Z. Ortiz D. Ferrante 《Obesity reviews》2009,10(3):364-370
Current, high-quality data are needed to evaluate the health impact of the epidemic of obesity in Latin America. The Latin American Consortium of Studies of Obesity (LASO) has been established, with the objectives of (i) Accurately estimating the prevalence of obesity and its distribution by sociodemographic characteristics; (ii) Identifying ethnic, socioeconomic and behavioural determinants of obesity; (iii) Estimating the association between various anthropometric indicators or obesity and major cardiovascular risk factors and (iv) Quantifying the validity of standard definitions of the various indexes of obesity in Latin American population. To achieve these objectives, LASO makes use of individual data from existing studies. To date, the LASO consortium includes data from 11 studies from eight countries (Argentina, Chile, Colombia, Costa Rica, Dominican Republic, Peru, Puerto Rico and Venezuela), including a total of 32 462 subjects. This article describes the overall organization of LASO, the individual studies involved and the overall strategy for data analysis. LASO will foster the development of collaborative obesity research among Latin American investigators. More important, results from LASO will be instrumental to inform health policies aiming to curtail the epidemic of obesity in the region. 相似文献