Accelerated programmed cell death (apoptosis) in erythroid precursors of patients with severe beta-thalassemia (Cooley's anemia) [see comments]

The profound and life-threatening anemia in patients with Cooley's anemia is ascribed primarily to intramedullary hemolysis (ineffective erythropoiesis), the cause of which is obscure. Based on prior morphologic data showing nuclear abnormalities, we hypothesized that accelerated apoptosis could occur in these erythroid precursors. The highly successful bone marrow (BM) transplantation program for patients with Cooley's anemia provided us with a unique opportunity to test this hypothesis. We obtained pretransplantation BM aspiration samples from patients undergoing BM transplantation in Pesaro, Italy and from their allogeneic donors. The erythroid precursors were isolated using ficoll sedimentation and then panning selecting fro CD45- cells. Cytospin and Giemsa staining showed that the separation provided greater than 90% erythroblasts. Five million of these erythroblasts were lysed and their DNA was isolated. There were obvious ladder patterns of DNA breakdown products in beta-thalassemia major samples, with less occurring in beta- thalassemia trait. Normal individuals showed only a slight smear of breakdown of DNA. These results indicate there is enhanced apoptosis in the erythroblasts in the BMs of Cooley's anemia patients. This finding might partially explain why most of these erythroblasts never survive to become mature erythrocytes.     

Epigenetic Changes in Bone Marrow Progenitor Cells Influence the Inflammatory Phenotype and Alter Wound Healing in Type 2 Diabetes

Classically activated (M1) macrophages are known to play a role in the development of chronic inflammation associated with impaired wound healing in type 2 diabetes (T2D); however, the mechanism responsible for the dominant proinflammatory (M1) macrophage phenotype in T2D wounds is unknown. Since epigenetic enzymes can direct macrophage phenotypes, we assessed the role of histone methylation in bone marrow (BM) stem/progenitor cells in the programming of macrophages toward a proinflammatory phenotype. We have found that a repressive histone methylation mark, H3K27me3, is decreased at the promoter of the IL-12 gene in BM progenitors and this epigenetic signature is passed down to wound macrophages in a murine model of glucose intolerance (diet-induced obese). These epigenetically “preprogrammed” macrophages result in poised macrophages in peripheral tissue and negatively impact wound repair. We found that in diabetic conditions the H3K27 demethylase Jmjd3 drives IL-12 production in macrophages and that IL-12 production can be modulated by inhibiting Jmjd3. Using human T2D tissue and murine models, we have identified a previously unrecognized mechanism by which macrophages are programmed toward a proinflammatory phenotype, establishing a pattern of unrestrained inflammation associated with nonhealing wounds. Hence, histone demethylase inhibitor–based therapy may represent a novel treatment option for diabetic wounds.     

创伤性膈肌破裂的诊断与治疗

1　临床资料　我院 1985 / 1997共收治创伤性膈肌破裂 2 6例 ,平均年龄 32 .5 (9～ 5 8)岁 ,其中穿透性膈肌破裂 3例 ,闭合性膈肌破裂 2 3例 .合并颅脑损伤 3例 ,肋骨骨折 11例 ,肺裂伤 2例 ,肝破裂 1例 ,脾破裂 15例 ,胃肠破裂 3例 ,骨盆骨折 5例 ,四肢骨折 7例 .临床表现除合并伤的症状和体征外 ,伴休克 7例 ,呼吸困难 2 1例 ,胸痛 2 1例 ,腹痛 18例 ,板状腹15例 .2　诊断与手术　术前确诊 2 1例 ,剖胸探查发现 1例 ,剖腹探查发现 4例 .胸穿 13例 ,阳性 11例 ;腹穿 18例 ,阳性 14例 .X线检查 2 2例 ,发现膈下游离气体 2例 ,胸内胃肠影 6…     

神经网络用于环丙胺类衍生物的构效关系研究

将神经网络应用于定量构效关系研究。用改进的反传算法探讨了单胺氧化酶抑制剂N-(苯氧乙基)环丙胺取代衍生物的生物活性与取代基电子效应σ、疏水作用π、空间效应Es等参数之间的定量关系。给出了精密拟合和准确预测(最大误差均小于10%),优于经典的多元线性回归及逐步回归方法。作为一种有效的计量化学新方法,神经网络有良好的预测能力和非线性处理功能,从而可望在QSAR研究中发挥重要作用。     

It takes two: the influence of dance partners on the perceived enjoyment and benefits during participation in partnered ballroom dance classes for people with Parkinson’s

Purpose: To explore the views of people with Parkinson’s and their dance partners on the influence and issues surrounding dancing with an able-bodied dance partner during partnered ball room dance classes.

Methods: In depth, semi-structured interviews explored purposively selected participants’ experiences and views about dance classes. Fourteen people with Parkinson’s and their dance partners (six spouses, two friends/relatives, five volunteers) were interviewed within a month of completing the 10-week dance class program. Data were analyzed thematically.

Results: Generally, those partnered with a spouse or an experienced dancer, or when dance couples were able to develop good rapport, gained greater enjoyment and sense of achievement from dance classes in comparison to couples who did not enjoy dancing together or had clashing approaches to dance. Managing and negotiating who would “lead” in a dance was challenging for dance couples particularly among male people with Parkinson’s.

Conclusions: People with Parkinson’s experience of the dance classes were influenced by the relationship and compatibility with their dance partner. Dance partnerships may impact on recruitment, enjoyment, outcome and continued participation in dance classes. Potential effects of partnerships should be analyzed and reported in studies evaluating the outcomes of dance classes.

• Implications for rehabilitation

• We recommend that health professionals consider involving spouses in Parkinson’s dance classes as this may improve recruitment, adherence, enjoyment and overall outcome of the dance classes.

• If volunteers are needed, aim to recruit those who already have good dancing ability, convey a love of dancing and have the sensitivity and social skills to interact positively with the person with Parkinson’s.

• Consider dance partnership issues when advertising and promoting dance classes.

• Address partnership issues through open communication and by changing partners if the dance partnership is not working well.

     

Investigation of the relative infectivity and pathogenicity of different hepatitis C virus genotypes in hemophiliacs

To assess the relative infectivity and pathogenicity of variants of hepatitis C virus (HCV) genotypes, the distribution of genotypes in hemophilic patients who had been treated with nonvirally inactivated factor concentrates or cryoprecipitates prepared from local blood donors was compared with those found in the respective blood donor populations. Genotype frequencies differed markedly in the four countries investigated (Scotland, Hungary, South Africa, and Thailand) but in each, the HCV genotype distributions in hemophiliacs and blood donors were similar. In addition, HCV genotypes in recipients of commercially manufactured concentrates were similar to those found in the US general population. These findings provide no evidence that HCV genotypes differ significantly from each other in replication rate, transmissibility, or infectivity.