Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.

The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases.     

硝基胍的毒性研究

目的对硝基胍的毒性进行研究,为制订卫生标准提供依据.方法包括急性毒性试验、蓄积毒性试验及亚慢性毒性试验.结果硝基胍大鼠经口LD50为8 066 mg/kg,小鼠经口LD50为10 044 mg/kg,蓄积系数大于5.3.亚慢性毒性试验中,高剂量组雄性大鼠在染毒第3周和第8周,体重有明显的负增长(P＜0.05);高剂量组雄性大鼠睾丸脏器系数明显高于对照组(P＜0.05);红细胞免疫功能测定结果显示,中、高剂量组大鼠红细胞受体花环率分别为10.00±2.37和7.50±2.66,明显低于对照组(P＜0.05,P＜0.01).其余各项指标未见明显改变.结论硝基胍属于微毒级毒物,轻度蓄积,亚慢性毒性试验对动物有一定的影响.     

足叶乙甙与阿糖胞苷联合治疗急性单核细胞白血病疗效初步观察

应用足叶乙甙与阿糖胞苷联合化疗方案治疗13例急性单核细胞白血病取得较好疗效,13例中完全缓解8例（61.5％），部分缓解3例（23.1％），总有效率达84.6％。文中对用药剂量及疗效进行了讨论。     

Importance of Albumin, 25(OH)-Vitamin D and IGFBP-3 as Risk Factors in Elderly Women and Men with Hip Fracture

The relative importance of vitamin D deficiency, secondary hyperparathyroidism, nutritional deficiency and low bone mineral density (BMD) as risk factors for hip fracture is not definitely established. In the framework of a case-control study of risk factors for hip fractured, biochemical markers of bone metabolism and nutrition and femoral BMD data were compared in 136 female and 43 male hip fracture patients, 126 female and 44 male age-matched hospitalized controls, and 47 healthy elderly women (8 men). Patients with hip fracture had lower albumin (−10%9 and 25(OH)-vitamin D (25(OH)D; −19%) compared with hospitalized controls, and lower albumin (−28%) and 25(OH)D levels (−52%) compared with the elderly controls. Serum values of IGFBP-3 were also significantly lower (−33%) in hip fracture patients than in community controls. BMD of femoral neck was lower (p < 0.001) in patients than in hospitalized and community controls. In hip fracture patients, parathyroid hormone (PTH) correlated weakly with BMD (neck: r = −0.19, trochanter: r = −0.17; both p < 0.05). When all women were pooled (n = 233), albumin correlated significantly (age-adjusted) with BMD at all sites (neck: r = 0.27, trochanter: r = 0.25; all p < 0.001). Albumin, but not 25(OH)D, also correlated with skinfold thickness (r = 0.19, p < 0.0025) and with body mass index (BMI) (r = 0.14, p < 0.05). Male patients with hip fracture had lower BMD and albumin (both p < 0.001), 25(OH)D (p = 0.02) and IGFBP-3 levels (p <: 0.005) compared with the controls. When male patients and controls were pooled together, albumin, skinfold thickness and BMI were significantly correlated with each other, but not with BMD. IGFBP-3 was highly correlated with albumin (p < 0.0001), 25(OH)D (p < 0.005) and, less significantly, with PTH (p < 0.05), but not with BMI or skinfold thickness. IGFBP-3 was significantly correlated with BMD at all sites (neck: r = 0.27, p < 0.05); trochanter: r = 0.40, p < 0.0005). In conclusion, low albumin and low BMD were both important risk factors for hip fracture. Low serum albumin was the strongest independent variable correlated with hip fractures. In men, IGFBP-3 was correlated with BMD. The femoral BMD depended only weakly on PTH and 25(OH)D, but was correlated at all sites with albumin, a non-specific parameter of nutrition and general health.     

No evidence for an altered mRNA expression or protein level of haematopoietic cell phosphatase in CD34+ bone marrow progenitor cells or mature peripheral blood cells in polycythaemia vera

Abstract: Polycythaemia vera (PV) is a myeloproliferative disorder characterized by haematopoietic progenitor cells being hypersensitive to cytokines such as erythropoietin, interleukin-3, stem cell factor and insulin-like growth factor 1, which results in an increased production of mature blood cells. The pathogenetic cellular mechanism(s) behind this hypersensitivity to cytokines is unknown, but the number of cytokine receptors and the interaction between ligand and receptor are normal in PV. Interest has therefore focused on post-receptor mechanism(s). Haematopoietic cell phosphatase (HCP) is an intracellular tyrosine phosphatase that has been demonstrated to regulate proliferative signals negatively induced by the cytokines mentioned above. Moreover, motheaten mice that genetically lack HCP have an increased amount of erythroid progenitors that are hypersensitive to Epo, and patients with familial polycythaemia have been shown to exhibit a mutation of the Epo receptor gene that includes the docking site for HCP. We therefore studied mRNA expression of HCP in pure populations of CD34⁺ cells, granulocytes, platelets and lymphocytes from patients with PV, chronic myeloid leukaemia (CML) or essential thrombocythemia (ET), as well as healthy controls. Using a polymerase chain reaction analysis employing specific primers for HCP, we failed to detect any abnormalities of HCP expression in PV in any of the cell populations that were examined. Moreover, HCP mRNA expression was similar in ET and CML compared to controls. Finally, Western blot analysis revealed a normal HCP protein content in PV granulocytes and platelets. We therefore conclude that neither an impaired expression of the HCP gene nor a defect in HCP protein synthesis is present in PV, and does not seem to play a role in the aetiology of this disorder.     

白血病患者血清铜、锌的变化

本文报道57例白血病血清铜,锌含量的测定结果。白血病治疗前血清铜升高,铜/锌值增大;治疗后,病情缓解者下降,未缓解者则更高。血清锌在治疗前后无何差异。急性淋巴细胞性白血病骨髓中白血病细胞百分数与血清铜浓度呈正相关。检测血清铜,锌对白血病疗效的预测及判断预后有一定意义。     

肝癌患者用生物免疫制剂后单核细胞及枯否细胞体外抗人肝癌细胞效应

15例肝癌患者施行外科治疗,12例兼用卡介苗、混合菌苗及干扰素,3例不用免疫治疗为对照。分离患者血单核细胞(MC)与淋巴细胞(LC)及肝枯否细胞(KC),以人肝癌细胞株为靶细胞(TC)。结果:①首次用免疫制剂7d后,MC对TC抑增殖作用及杀伤作用明显高于用药前,3次用药后MC抑TC效应提高至84％,对照组的仍为45％;②首次用药后7d,KC对TC的抑增殖率和杀伤率分别较对照组高0.5倍和1倍;③用免疫制剂后,血T细胞总数及Th数持续升高,T_s则显著下降。研究表明三联免疫制剂可有效地增强患者抗肝癌细胞的免疫功能。     

A simple method for screening assessment of acute toxicity of chemicals

We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD₅₀ values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD₅₀ values reported in the literature. Our toxicological data also showed that LD₅₀ values were about 2–2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD₅₀ of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD₅₀ values of chemicals and for screening for necessity for classical full LD₅₀ test using many animals.This work was supported by a grant from Ministry of Health and Welfare in Japan (No. 467 and 511)     

Inhibition of rat heart allograft rejection by a PUVA treatment of the graft recipient

Treatment of rat heart grafts with PUVA, the combination of the photosensitizer 8-methoxypsoralen and longwave ultraviolet light, leads to a prolonged transplant survival in allogeneic recipients. A PUVA treatment of the recipient rats, performed for 7 consecutive days after transplantation, prolonged graft survival even more effectively. This may be due to the systemic immunomodulatory effects of PUVA in the recipient. One of the mediators is urocanic acid, which is transformed by ultraviolet light in the skin from its trans- to the cis-isomer, which, in turn, acts as a mediator on the immune system. An injection of cisurocanic acid into graft recipients for 7 consecutive days after transplantation resulted in prolonged graft survival; in 40% of the rats, permanent graft acceptance was observed. The significance of these results for clinical organ transplantation is discussed.     

P53基因突变、人乳头瘤病毒16，18型感染与肺鳞癌发病的关系

应用单链构象多态性分析多聚酶链反应ＥＢ染色法（ＰＣＲ－ＳＳＣＰ－ＥＢ）对４０例肺癌组织标本的Ｐ５３基因序列５～８外显子突变进行分析，同时应用ＰＣＲ方法检测上述标本及１８例肺良性疾病组织标本中ＨＰＶ１６、１８型ＤＮＡ相关序列，旨在分析二者在肺鳞癌发病中的作用及相互关系，并就肺鳞癌与Ｐ５３基因结构和功能异常的关系进行初步探讨。