Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis

We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena.     

Recombinant rat stem cell factor synergizes with recombinant human granulocyte colony-stimulating factor in vivo in mice to mobilize peripheral blood progenitor cells that have enhanced repopulating potential

Splenectomized mice treated for 7 days with pegylated recombinant rat stem cell factor (rrSCF-PEG) showed a dose-dependent increase in peripheral blood progenitor cells (PBPC) that have enhanced in vivo repopulating potential. A dose of rrSCF-PEG at 25 micrograms/kg/d for 7 days produced no significant increase in PBPC. However, when this dose of rrSCF-PEG was combined with an optimal dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 200 micrograms/kg/d), a synergistic increase in PBPC was observed. Compared with treatment with rhG-CSF alone, the combination of rrSCF-PEG plus rhG-CSF resulted in a synergistic increase in peripheral white blood cells, in the incidence and absolute numbers of PBPC, and in the incidence and absolute numbers of circulating cells with in vivo repopulating potential. These data suggest that low doses of SCF, which would have minimal, if any, effects in vivo, can synergize with optimal doses of rhG-CSF to enhance the mobilization of PBPC stimulated by rhG-CSF alone.     

The effects of vitamin D binding protein-macrophage activating factor and colony-stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats

Osteopetrosis is a heterogeneous group of bone disorders characterized by the failure of osteoclasts to resorb bone and by several immunological defects including macrophage dysfunction. Two compounds, colony-stimulating factor-1 (CSF-1) and vitamin D-binding protein- macrophage activating factor (DBP-MAF) were used in the present study to evaluate their effects on the peritoneal population of cells and on cells within the bone marrow microenvironment in normal and incisors absent (ia) osteopetrotic rats. Previous studies in this laboratory have demonstrated that administration of DBP-MAF to newborn ia animals results in a substantial increase in bone marrow cavity size due to upregulated osteoclast function. To study the effects of these compounds on the macrophage/osteoclast precursors, DBP-MAF, CSF-1, and the combination of these compounds were given to newborn ia and normal littermate animals. Both the normal and mutant phenotypes responded similarly when treated with these compounds. Rats exhibited a profound shift toward the macrophage lineage from the neutrophil lineage when compared with vehicle-treated control animals after treatment with these compounds. In the in vivo peritoneal lavage study, animals received injections of CSF-1, DBP-MAF or DBP-MAF/CSF-1 over a 4-week period. The various types of cells in the peritoneal cavity were then enumerated. The in vitro study consisted of cells isolated from the bone marrow microenvironment and cultured on feeder layers of CSF-1, DBP-MAF, or DBP-MAF/CSF-1 for colony enumeration. The increase in macrophage numbers at the expense of neutrophil numbers could be seen in both the in vivo and in vitro experiments. The macrophage/osteoclast and neutrophil lineages have a common precursor, the granulocyte/macrophage colony-forming cell (GM-CFC). With the addition of CSF-1, the GM-CFC precursor may be induced into the macrophage/osteoclast lineage rather than the granulocyte lineage. This increased pool of cells in the macrophage/osteoclast lineage can be functionally upregulated with the subsequent addition of DBP-MAF to perform the activities of phagocytosis and bone resorption. The in vitro data also showed that DBP-MAF did not support colony development as in CSF-1 or the combination treatment. The recruitment and activation of cells into the macrophage/ osteoclast lineage may help to correct the bone and immune defects found in diseases demonstrating a significant lack of myeloid cells, as well as neutrophilia disorders and the disease, osteopetrosis.     

Prague women's drinking before and after the 'velvet revolution' of 1989: a longitudinal study

Results are presented of a follow-up study in which a representative sample of 608 Prague women aged 20–49 years in 1987 at first interview was re-interviewed in 1992 3 years after the revolution that ended the 41 years of the Communist era in Czechoslovakia. The average yearly consumption of alcohol in the followed-up female sample increased between 1987–92 from a reported 3.6 litres to 4.8 litres. The percentage of heavier drinkers (with average daily consumption of over 20 g alcohol) increased from 7.2% to 14.0%. The women expressed increased tolerance of drunkenness in their attitudes to drinking. The consumption increase was mainly due to increased drinking frequency of spirits and to increased quantity of beer consumed per occasion. The consumption increase was largest in women working as free-lance and the newly emerging self-employed women; economically inactive women did not increase their consumption. Women who reported a positive impact of the socio-political changes on their personal lives and an expansion of social contacts also reported larger than average consumption increases. A coincidence of stressful, possibly self-inflicted, life events and increased alcohol use was observed and interpreted as probably a two-way influence.     

Molecular characterization of human factor XSan Antonio

Enzymatic amplification technique was used to isolate all eight exons and sequences around the splice junctions, putative promoter, and polyadenylation sites of human factor X DNA from a patient with factor X deficiency. Two genetic changes in factor X have been observed in this patient. The patient is most likely a compound heterozygote since there is only 14% activity associated with factor X. A point mutation that resulted in the substitution of cysteine (TGC) for arginine (CGC) at amino acid 366 was found in exon VIII of one allele of the factor X gene. This mutation, which occurs in the catalytic domain, can affect the formation of a disulfide bridge and thus could result in a reduction in factor X activity. Sequencing all the regions revealed a second mutation: a deletion of one nucleotide (TCCT to TCT) in exon VII that would cause a frame shift at amino acid 272 followed by termination. We have also shown that the point mutation in exon VIII creates an ApaL1 restriction site and destroys the HinP1 site. Enzymatic DNA amplification followed by restriction digestion provides a quick, reliable, and sensitive method for carrier detection and antenatal diagnosis in affected kindreds. This is the first characterization of factor X deficiency at the molecular level. We propose to name this mutation Factor XSan Antonio.     

髓核内注射预TGF-β1防软骨终板退行性变的实验研究

目的 探讨髓核内注射转化生长因子-β1(transforming growth factor-β1,TGF-β1)对预防椎间失稳后软骨终板退行性变的作用.方法 选用6月龄日本大耳白兔36只,随机分为对照组和预防组,每组18只.所有实验动物均制作为腰5-6、腰6-7椎间失稳模型.对照组不予任何处理.预防组在完成椎间失稳手术后立即于同一切口通过侧后方入路显露腰5~6、腰6-7椎间盘,并行髓核内注射TGF-β1.于术后3、6个月各取8只进行HE染色及Mankin评分.结果 术后3、6个月预防组较对照组软骨终板退行性变明显减缓(P＜0.05,P＜0.01).结论 髓核内注射TGF-β1对椎间失稳后软骨终板退行性变具有明显的预防作用.     

髓核内注射预TGF-β1防软骨终板退行性变的实验研究

目的 探讨髓核内注射转化生长因子-β1(transforming growth factor-β1,TGF-β1)对预防椎间失稳后软骨终板退行性变的作用.方法 选用6月龄日本大耳白兔36只,随机分为对照组和预防组,每组18只.所有实验动物均制作为腰5-6、腰6-7椎间失稳模型.对照组不予任何处理.预防组在完成椎间失稳手...     

新疆疏附县2005-2012年炭疽流行病学分析

目的 分析疏附县炭疽流行病学特征,为制订炭疽防控策略提供依据和参考.方法 对疏附县2005-2012年网络报告的炭疽发病资料进行描述性流行病学分析.结果 2005-2012年疏附县共报告炭疽137例,占同期全国病例总数的5.09％,年平均发病率为5.34/10万.病例全部为皮肤型炭疽,多为散发;夏秋两季高发,7月为高峰月份;男女性别比为1.36∶1,男性发病率高于女性.超过54％的病例为20岁以下儿童和青年,10-14岁高发.病例职业多为农牧民和学生,民族以维吾尔族为主（99.27％）.结论 疏附县炭疽发病率极高且呈低龄化特点,应采取针对性措施进一步加强其预防控制.