异常黑胆质成熟剂中各单味药对HL-60细胞增殖的抑制作用

异常黑胆质成熟剂是维吾尔医复方制剂,由甘草、红枣、破布木、牛舌草、铁线蕨、地锦草、小茴香、薰衣草、蜜蜂花和刺糖10味药组成,用于治疗由异常黑胆质所导致的肿瘤、糖尿病和心血管疾病等。研究了异常黑胆质成熟剂中各单味药(除刺糖外)对HL-60细胞增殖的抑制作用。HL-60细胞暴露于各单味药两种不同提取物(二氯甲烷和甲醇),于37℃、CO2体积分数为5%的恒温孵箱中培养后24、48、72h,用台盼蓝染色法检测细胞存活率。结果表明,各单味药的二氯甲烷提取物除小茴香外均显著降低HL-60癌细胞的存活率(P<0.05)。在甲醇提取物中,只有甘草和地锦草两味药的甲醇提取物可显著降低HL-60癌细胞的存活率(P<0.05)。与各单味药甲醇提取物相比,其二氯甲烷提取物均显著降低HL-60癌细胞的存活率(P<0.05)。结果显示,破布木、地锦草、铁线蕨、甘草、红枣、薰衣草、牛舌草和蜜蜂花8味药的二氯甲烷提取物和甘草、地锦草两味药的甲醇提取物均能抑制HL-60癌细胞的体外增殖。各单味药二氯甲烷提取物对HL-60细胞增殖的抑制作用均明显强于其相应的甲醇提取物。     

MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis

The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1-associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR = 5.0, 95% CI = 3.5-7.1; P = 4 x 10(-23), n = 852). This association extended to hypertensive ESKD (OR = 2.2, 95% CI = 1.5-3.4; n = 433), but not type 2 diabetic ESKD (n = 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.     

Superspreading and the effect of individual variation on disease emergence

Population-level analyses often use average quantities to describe heterogeneous systems, particularly when variation does not arise from identifiable groups. A prominent example, central to our current understanding of epidemic spread, is the basic reproductive number, R(0), which is defined as the mean number of infections caused by an infected individual in a susceptible population. Population estimates of R(0) can obscure considerable individual variation in infectiousness, as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous 'superspreading events' in which certain individuals infected unusually large numbers of secondary cases. For diseases transmitted by non-sexual direct contacts, such as SARS or smallpox, individual variation is difficult to measure empirically, and thus its importance for outbreak dynamics has been unclear. Here we present an integrated theoretical and statistical analysis of the influence of individual variation in infectiousness on disease emergence. Using contact tracing data from eight directly transmitted diseases, we show that the distribution of individual infectiousness around R(0) is often highly skewed. Model predictions accounting for this variation differ sharply from average-based approaches, with disease extinction more likely and outbreaks rarer but more explosive. Using these models, we explore implications for outbreak control, showing that individual-specific control measures outperform population-wide measures. Moreover, the dramatic improvements achieved through targeted control policies emphasize the need to identify predictive correlates of higher infectiousness. Our findings indicate that superspreading is a normal feature of disease spread, and to frame ongoing discussion we propose a rigorous definition for superspreading events and a method to predict their frequency.     

Lectin-induced lymphocyte stimulation in pigs — a kinetic study of NORs

Summary Early reactions of rRNA-cistrons in lectin-stimulated PBL cultures of domestic pigs are shown. Interphases showing 3 or more clusters of stained areas were attributed mainly to cells after first division. Clear differences are shown between PHA-and ConA-induced NOR-expression patterns compared to the patterns in PW-stimulated cultures.We thank Dr W. Gratze for valuable techniqual assistance, Dr M. Kundi from the Institute of Environmental Health of the University of Vienna for the statistical treatment of our data and the Ludwig Boltzmann Society for financial support.     

Drosophila small cytoplasmic 19S ribonucleoprotein is homologous to the rat multicatalytic proteinase

All eukaryotic cells so far analysed contain 19S particles which share a cylinder-like shape and are composed of a set of proteins of relative molecular mass ranging typically from 19,000 to 36,000 (refs 1-10). Proposed functions have included synthetase activity, transfer RNA processing or messenger RNA repression, but their biological importance remains obscure. A multicatalytic proteinase (MCP) of similar size and shape has been isolated from mammalian tissues. The apparent similarities of these high molecular weight complexes suggest a biochemical and functional homology between the small cytoplasmic 19S particle from Drosophila melanogaster (19S-scRNP) (ref. 7) and rat MCP (ref. 14). By means of electron microscopy, immunological techniques, RNA identification and proteinase activity assays, we were able to show that the two structurally similar complexes are immunologically related ribonucleoproteins (RNPs) with similar proteolytic activity.     

The TSH receptor and its role in thyroid disease

The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiology and disease. TSH, acting through the TSH receptor, is the major stimulator of thyroid cell growth, differentiation and function. In Graves' disease, the TSH receptor is the target of stimulating antibodies that cause hyperthyroidism. Although still a topic of debate, the TSH receptor has been implicated in the pathogenesis of the endocrine ophthalmopathy associated with Graves' disease. Blocking antibodies against the TSH receptor are involved in the development of hypothyroidism in a subset of patients with autoimmune hypothyroidism. Transplacental passage of stimulating or blocking TSH receptor antibodies from a mother with autoimmune thyroid disease may result in transient hyper- or hypothyroidism in early infancy. During pregnancy, the placental hormone human choriogonadotropin (hCG) can cause gestational hyperthyroidism through cross-reaction with the TSH receptor. Gestational hyperthyroidism may also be involved in the pathogenesis of hyperemesis gravidarum. Trophoblast tumors secreting hCG are a rare cause of hyperthyroidism. Somatic activating mutations of the TSH receptor have been identified as a molecular cause of toxic adenomas, whereas activating mutations in the germline give rise to nonautoimmune familial hyperthyroidism or sporadic congenital hyperthyroidism. These gain-of-function mutations are dominant, and one mutated allele is sufficient to result in disease. Inactivating germline mutations of both TSH receptor alleles lead to variable degrees of resistance to TSH, encompassing a spectrum ranging from euthyroid hyperthyrotropinemia to overt hypothyroidism with thyroid hypoplasia. Received 31 January 2001; received after revision 3 April 2001; accepted 3 April 2001     

Genetic control and evolution of sexually dimorphic characters in Drosophila

Sexually dimorphic abdominal pigmentation and segment morphology evolved recently in the melanogaster species group of the fruitfly Drosophila. Here we show that these traits are controlled by the bric à brac [corrected] (bab) gene, which integrates regulatory inputs from the homeotic and sex-determination pathways. bab expression is modulated segment- and sex-specifically in sexually dimorphic species, but is uniform in sexually monomorphic species. We suggest that bab has an ancestral homeotic function, and that regulatory changes at the bab locus played a key role in the evolution of sexual dimorphism. Pigmentation patterns specified by bab affect mating preferences, suggesting that sexual selection has contributed to the evolution of bab regulation.