New therapeutic approaches for protecting hematopoietic stem cells in aplastic anemia

Aplastic anemia (AA) is an immune-mediated and life-threatening form of acquired bone marrow failure (BMF), characterized by development and expansion of self-reactive T cells. These T cells cause continuous destruction of hematopoietic stem cells (HSCs), progenitors, and mature blood cells, leading to severe and if left untreated fatal marrow hypoplasia and pancytopenia. Standard treatment options for patients with AA include: (1) immunosuppressive therapy (IST) with anti-thymocyte globulin and cyclosporine A which targets self-reactive T cells, or (2) matched sibling or unrelated BM transplant (BMT). The IST treatment is often not effective due to poor response to therapy or disease relapse after IST. Also, BMT is not an option for many patients due to their age, comorbidities, and the lack of histocompatible donor. This necessitates development and testing of novel approaches to reduce severity of AA and to efficiently treat patients with refractory and relapsed AA. Immune-mediated AA was reproduced in animals, including mouse lymphocyte infusion models, which are used to study further etiology and pathophysiology of AA and test new drugs and approaches in treating and managing AA. In these mouse models the immune correlates and pathologic features of AA are strikingly similar to features of severe human AA. In this article we (a) briefly review standard and developing approaches for treating AA and (b) describe development and testing of novel treatment approach with a potential to safely reduce BM hypoplasia and significantly decrease the loss of HSCs in mouse lymphocyte infusion model of AA

Diabetes Risk in Older Mexican Americans: Effects of Language Acculturation, Generation and Socioeconomic Status

The effect of language acculturation, socioeconomic status (SES), and immigrant generation on development of diabetes among Mexican Americans was evaluated in the Hispanic Established Population for the Epidemiologic Study of the Elderly (HEPESE). HEPESE is a longitudinal cohort study of 3,050 non-institutionalized Mexican Americans aged 65 years at baseline (1993-1994) from 5 Southwestern states. Diabetes incidence was ascertained in 4 follow-up surveys to 2004-05 by respondent self-reported physician-diagnosis of diabetes, high blood glucose, or sugar in the urine. Language of interview, immigrant generation, gender, age, education, family history of diabetes, smoking status, alcohol use, health insurance type and self-reported height and weight were assessed. High socioeconomic status (SES) was defined by high school graduation and non-Medicaid insurance. Cox's proportional hazards models were fit to evaluate the effects of language acculturation, generation and SES on incident diabetes. 845 of 3,050 (27.7%) Mexican Americans had diabetes at baseline and were younger, more educated, and more likely to have health insurance than those without diabetes. Risk of developing diabetes increased for Spanish-speaking respondents with low SES from 1st to 3rd generation (HR = 1.76, 95% CI = 1.02-3.03) and from 2nd to 3rd generation (HR = 2.15, 95% CI = 1.20-3.84). Among English-speaking, high SES participants, generation had a protective effect on developing diabetes: HR = 0.45 (95% CI = 0.22-0.91) when comparing 3rd versus 1st generation. The effect of language acculturation and immigrant generation on incident diabetes is moderated by SES status in HEPESE participants