VAMP加逆转剂治疗难治性急性淋巴细胞白血病的体内、外研究

目的：观察VAMP方案加维拉帕米或环孢菌素A逆转治疗难治性ALL的疗效。方法：选择原发和继发耐药的ALL患者13例，采用VAMP方案加维拉帕米或环孢菌素A逆转体内、外研究。结果：13例ALL中7例达CR,3例达PR,3例无效。体外VAMP方案加VRP或CsA可有效逆转耐药。结论：采用VAMP方案加维拉帕米或环孢菌素A逆转治疗难治性ALL,可取得较好的疗效,为争取移植治疗创造了条件。     

Surgical delay in acute admissions on warfarin: are we doing enough?

Warfarin anti-coagulation can cause significant delay in acute surgical admissions. We reviewed fracture neck of femur patients operated over a period of 4 years in our unit. There was an average delay to surgery of 4.36 days in patients on warfarin as against an average delay of 1.78 days in patients not on warfarin (p < 0.001). The review was followed up with a questionnaire-based survey of consultant haematologists, and a general agreement towards a protocol-based use of vitamin K(1) was noted. The reasons for limited use of vitamin K(1) include the lack of studies and guidelines specifically addressing the pre-operative emergency admissions. We highlight a practical problem shared across different specialities and identify the areas for future studies.     

中药多靶点逆转白血病多药耐药机制研究

白血病是血液系统一种常见的恶性肿瘤,是国内十大高发恶性肿瘤之一。白血病的多药耐药是化疗失败的主要原因,化学药逆转剂通常毒副作用大,作用机制单一,制约着其临床应用。而中药有高效、低毒、多靶点的特点,在逆转多药耐药白血病上显示出其独特的优势。通过分析近些年白血病多药耐药的机制,综述中药单体成分、中药复方和单味药白血病多药耐药逆转剂,以探讨中药逆转白血病多药耐药的前景。     

模式翻转视觉诱发电位快速提取的可行性再研究

目的把模式翻转视觉诱发电位快速提取法应用于视神经病变的病人,探讨其临床应用价值。方法应用Galileo视觉诱发电位检测系统对30例正常健康人和17例视神经疾病病人分别进行全视野的PRVEP检测熏每一结果重复检测3次。所得结果应用少次提取法进行处理而得VEP波形。然后将正常对照组3次重复结果两两间分别进行配对t检验,探讨其可重性,并计算出正常值范围,最后参照正常值,分析视神经疾病组的检测结果。结果3次重复结果两两间配对t检验,得P1=0.425>0.05,P2=0.179>0.05,P3=0.110>0.05;参照本研究得出的正常值范围,对病人组的检测结果进行分析,得出这种少次提取法对视神经疾病检测的敏感度90.0%(18/20),特异度92.5%(13/14),准确度91.1%(31/34)。结论用这种少次提取法提取PRVEP,可重性好,稳定可靠。很有临床应用价值。     

Tumour necrosis factor-alpha (TNF-alpha) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions.

Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in reactional nerves then reactional skin. In both reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy reversal reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.     

Stimulus- and response-dependent units from the occipital and temporal lobes of the unanaesthetized monkey performing learnt visual tasks

Summary 43% of units recorded from the foveal prestriate cortex, inferotemporal cortex or amygdala of 15 rhesus monkeys performing visual discrimination or serial reversal tasks were responsive to all or some visual stimuli or other aspects of the task. Six units showed activity during movements required for performance of the task. It was not possible to determine whether unit activity could be related to the learnt association of the visual stimuli with reward.     

Gene dosage imbalances in patients with 46,XY gonadal DSD detected by an in-house-designed synthetic probe set for multiplex ligation-dependent probe amplification analysis

The development of a testis requires the proper spatiotemporal expression of the SRY gene and other genes that act in a dosage-sensitive manner. Mutations in the SRY gene account for only 10–15% of patients with 46,XY gonadal disorder of sex development (DSD). To enable the diagnostics of deletions and duplications of genes known to be involved in different forms of DSD, we developed a synthetic probe set for multiplex ligation-dependent probe amplification (MLPA) analysis. Here, we report the results from the analysis of 22 patients with 46,XY gonadal DSD. The analysis with the DSD probe set has led to the identification of two copy number variations, an 800-kb NR0B1 ( DAX1 ) locus duplication on Xp21 in a patient with isolated partial gonadal dysgenesis and a duplication of the SRD5A2 gene that represents a rare normal variant. The described MLPA kit represents an optimal complement to DNA sequence analysis in patients with DSD, enabling screening for deletions and duplications of several genes simultaneously. Furthermore, the second identification of an NR0B1 locus duplication in a patient with isolated gonadal dysgenesis, without dysmorphic features and/or mental retardation, highlights the importance of evaluating NR0B1 duplication in patients with gonadal dysgenesis.     

SRY-negative 46,XX male with normal genitals, complete masculinization and infertility

XX maleness is a rare syndrome with a frequency of 1 in 20,000-25,000 males. XX males exist in different clinical categories with ambiguous genitalia or partially to fully mature male genitalia, in combination with complete or incomplete masculinization. In this study, we report a case of SRY-negative XX male with complete masculinization but infertility. The patient had fully mature male genitalia with descended but small testes and no signs of undervirilization. PCR analysis for SRY, ZFY, Amelogenin, AZFa, AZFb, AZFc genes, a pair of primers from heterochromatic region and six Y-STRs showed the absence of any Y-chromosome-derived material. Absence of SRY gene was confirmed by three independent PCRs for each of two sets of primers covering an increasing length of the gene. Sequence analysis of the coding regions of SOX9 and DAX1 genes did not reveal any mutation. Real-time PCR assay revealed normal copy number for SOX9 gene. Microsatellite analysis showed no evidence of 17q (SOX9 gene) or 22q duplication. Genotyping with X-STRs ruled out the possibility of any deletion on X chromosome. Development of the male phenotype in the absence of SRY probably resulted from the loss of function mutation in some unknown sex-determining gene, which normally inhibits the male pathway, or from a gain of function mutation in a gene downstream to SRY in male pathway.     

Embryonic testicular regression sequence: A part of the clinical spectrum of 46, XY gonadal dysgenesis

With the identification of the cystic fibrosis (CF) gene and its major mutations in 1989, there has been considerable debate among health professionals as to whether population-based carrier testing should be instituted. This paper presents the results of a survey to determine the attitudes of physicians and genetics professionals towards CF carrier testing. Factors associated with differences in attitudes also were examined. A questionnaire was mailed to primary care physicians and psychiatrists in 10 states who graduated from medical school between 1950 and 1985. For comparison, medical geneticists and genetic counselors in the same states also received the questionnaire. A total of 1,140 primary care physicians and psychiatrists (64.8%) and 280 medical geneticists and genetic counselors (79.1%) responded. Although 92% of respondents believed that a couple should be tested after asking about a test that detected 80% of carriers, only 43.9% of respondents believed such a test should be offered routinely. Those specialists most likely to have been involved in genetic services were most opposed to routine screening. The most important reason reported for opposition to routine screening was the consequences of an 80% detection rate. When presented with a hypothetical “error-free” test, 75.9% of respondents favored routine testing. Our findings suggest that there was little support for routinely offering the CF carrier test available at the time of this study among the physicians and professionals most involved in the provision of genetic services. © 1994 Wiley-Liss, Inc.     

桑抹茶对THP-1源性泡沫细胞脂质沉积的作用研究

目的 明确桑抹茶对THP-1泡沫细胞脂质沉积的改善作用。方法 实验分为正常对照组：佛波酯诱导的THP-1源性巨噬细胞,模型对照组：佛波酯+Ox-LDL诱导的THP-1源性泡沫细胞,药物干预组：THP-1源性泡沫细胞+不同浓度（10、20、40、80、160、320、640 μg/ml）桑抹茶提取物,同时设RPMI 1640培养基为空白对照。MTT法检测各组细胞活力;油红O染色观察细胞内脂质沉积;荧光显微镜观察THP-1巨噬细胞内吞Dil-Ox-LDL情况;Western blotting检测各组细胞介导细胞内胆固醇流出蛋白ABCA1及PPARγ蛋白表达水平。结果 桑抹茶提取物能浓度依赖地抑制THP-1源性泡沫细胞对Ox-LDL的摄取,减少THP-1泡沫细胞内脂质沉积;与对照组比较,模型组泡沫细胞内脂质水平显著升高[(0.974±0.033)比(0.794±0.030),P<0.01],ABCA1蛋白表达量增加[(0.702±0.005)比(0.575±0.014),P<0.01],PPARγ表达量降低[(0.099±0.004)比(0.875±0.019),P<0.01]。与模型组比较,93、186、372 μg/mL桑抹茶提取物能显著降低泡沫细胞内脂质水平[(0.876±0.032)、(0.835±0.019)、(0.815±0.028)比(0.974±0.033),P<0.01],增加PPARγ蛋白表达量[(0.270±0.006)、(0.328±0.014)、(0.706±0.020)比(0.099±0.004),P<0.01],93、372 μg/mL桑抹茶能提高ABCA1蛋白表达量[(0.823±0.041)、(1.411±0.048)比(0.702±0.005),P<0.01]。结论 桑抹茶可能通过减少Ox-LDL摄取,促进细胞内胆固醇流出,减少细胞内脂质沉积。