A Czechoslovakian teenager with Hb E-β∘-thalassemia [IVS-I-1 (G → A)] complicated by the presence of an α-globin gene triplication

Summary We have examined the molecular basis of three inherited hemoglobin (Hb) disorders present in a Czechoslovakian girl with a severe, transfusion-dependent, hemolytic anemia. She is heterozygous for Hb E (on a genetic background specific for Czechoslovakian families), heterozygous for the -thalassemia (thal) allele IVS-I-1 (G A), and heterozygous for an -globin gene triplication. The combination of these three undesirable traits results in a severe chain imbalance that is the basis of the serious hemolytic disorder observed in this teenager.This study was supported in part by USPHS Research Grant HLB-41544. This is contribution 1282 from the Department of Cell and Molecular Biology at the Medical College of Georgia in Augusta     

The Effect and Side Effect of Hydroxyurea Therapy on Patients With β-Thalassemia: A Systematic Review to December 2012

Hydroxyurea (HU) is being used for patients with transfusion-dependent β-thalassemia major (β-TM) as well as non transfusion-dependent β-TM. As controversy exists regarding efficacy and safety of HU, we searched the published literature on efficacy, effectiveness and toxicity of HU in patients with β-TM. The research sources we used were: Medline, SID, PubMed, Scopus, Request, Web of Knowledge, Springer, Ovid, Cochrane searched up to October 2012. Using search terms sensitive to studies of clinical trials combined with searches on terms related to thalassemia and HU. We selected studies on randomized trials, quasi experimental trials (before and after design), case reports (with 1–5 cases), side effect studies in patients with β-TM, studies related to the mechanism of action and toxicity when used in patients with other hemoglobinopathies. We researched studies in English and Persian. Eligible articles were reviewed by two independent reviewers. Patient’s characteristics, duration of trial, outcome and side effects were extracted. The main outcomes were synthesized under a random-effects model. Heterogeneity was assessed using the Q statistic, Tau² and I². Subgroup analyses were performed and the statistics data (STATA) software used. More than 500 articles were reviewed. No randomized clinical trial was found. Seventeen trials with before and after designs were found, 16 case reports (1–5 cases), 19 articles for mechanism of action and 16 studies for side effects were published from 1969 to October 2012. Hemoglobin levels after treatment showed modest but significant increase in non transfusion-dependent β-TM (p?p?相似文献   

Tolerogenic dendritic cells induce antigen-specific hyporesponsiveness in insulin- and glutamic acid decarboxylase 65-autoreactive T lymphocytes from type 1 diabetic patients

Tolerogenic dendritic cells (tDC) constitute a promising therapy for autoimmune diseases, since they can anergize T lymphocytes recognizing self-antigens. Patients with type 1 diabetes mellitus (T1D) have autoreactive T cells against pancreatic islet antigens (insulin, glutamic acid decarboxylase 65 -GAD65-). We aimed to determine the ability of tDC derived from T1D patients to inactivate their insulin- and GAD65-reactive T cells. CD14 + monocytes and CD4 + CD45RA- effector/memory lymphocytes were isolated from 25 patients. Monocyte-derived DC were generated in the absence (control, cDC) or presence of IL-10 and TGF-β1 (tDC), and loaded with insulin or GAD65. DC were cultured with T lymphocytes (primary culture), and cell proliferation and cytokine secretion were determined. These lymphocytes were rechallenged with insulin-, GAD65- or candidin-pulsed cDC (secondary culture) to assess whether tDC rendered T cells hyporesponsive to further stimulation. In the primary cultures, tDC induced significant lower lymphocyte proliferation and IL-2 and IFN-γ secretion than cDC; in contrast, tDC induced higher IL-10 production. Lymphocytes from 60% of patients proliferated specifically against insulin or GAD65 (group 1), whereas 40% did not (group 2). Most patients from group 1 had controlled glycemia. The secondary cultures showed tolerance induction to insulin or GAD65 in 14 and 10 patients, respectively. A high percentage of these patients (70–80%) belonged to group 1. Importantly, tDC induced antigen-specific T-cell hyporesponsiveness, since the responses against unrelated antigens were unaffected. These results suggest that tDC therapy against multiple antigens might be useful in a subset of T1D patients.     

Associations between Dietary Patterns and Cardiometabolic Risk Factors—A Longitudinal Analysis among High-Risk Individuals for Diabetes in Kerala,India

The association between dietary patterns and cardiometabolic risk factors is not well understood among adults in India, particularly among those at high risk for diabetes. For this study, we analyzed the data of 1007 participants (age 30–60 years) from baseline and year one and two follow-ups from the Kerala Diabetes Prevention Program using multi-level mixed effects modelling. Dietary intake was measured using a quantitative food frequency questionnaire, and dietary patterns were identified using principal component analysis. Two dietary patterns were identified: a “snack-fruit” pattern (highly loaded with fats and oils, snacks, and fruits) and a “rice-meat-refined wheat” pattern (highly loaded with meat, rice, and refined wheat). The “snack-fruit” pattern was associated with increased triglycerides (mg/dL) (β = 6.76, 95% CI 2.63–10.89), while the “rice-meat-refined wheat” pattern was associated with elevated Hb1Ac (percentage) (β = 0.04, 95% CI 0.01, 0.07) and central obesity (OR 1.16, 95% CI 1.01, 1.34). These findings may help inform designing dietary interventions for the prevention of diabetes and improving cardiometabolic risk factors in high-diabetes-risk individuals in the Indian setting.     

急性有机磷农药中毒患者血细胞数Hb和CRP浓度的变化及意义

目的　探讨急性有机磷农药中毒患者血细胞数、血红蛋白和C -反应蛋白浓度的变化及临床意义。方法　把35例中毒患者分为轻、中和重度中毒 3组 ,在入院 1、3、7d分别采集静脉血 4mL ,作红细胞 (RBC)、血红蛋白 (Hb)、白细胞(WBC)、中性粒细胞 (N)、血小板 (PLT)及C -反应蛋白 (CRP)浓度检测。并与对照组进行对比分析。结果　各中毒组第 1日检测上述各项指标均有不同程度的升高 ,且中毒越重 ,升高越显著 ;中毒第 3日 ,各中毒组RBC数和Hb浓度均明显下降 ,随中毒的严重程度而下降更显著。PLT数则随中毒程度而明显升高 ,中、重度中毒组与对照组比较差异显著 (P <0 .0 1或P <0 .0 0 1) ;WBC、N和CRP浓度随中毒的程度而显示不同的变化 ,中度中毒组较中毒第 1日有所下降 ,而重度中毒组则呈现出上升趋势 ;中毒第 7日 ,中度中毒组除PLT和N仍显示升高外 ,其余各项均基本恢复正常 ;重度中毒组除RBC和Hb较第 3日更进一步降低外 ,其余各项呈上升趋势 ,与对照组比较差异显著 (P <0 .0 1或P <0 .0 0 1)。结论　对急性有机磷农药中毒患者动态观察血细胞数、Hb和CRP浓度的变化 ,对判定中毒程度和了解病情变化有重要临床意义。