上海地区汉人瘦素受体基因G1n223Arg变异的研究

目的探讨瘦素受体基因Gln223Arg变异与肥胖的关系。方法359例无亲缘关系的上海地区汉人及66例白种人运用PCR-RFLP方法（MspI限制性内切酶）检测瘦素受体基因Gin223Arg变异的基因型。结果中国人中GG、GA及AA基因型频率分别为0.789,0.200及0.011;G及A等位基因频率分别为0.889及0.111,与本研究组中白种人的基因型及等位基因频率分布有显著差异（P=2.98×10-16,3.46×10-18）。在中国人正常体重组与超重组间该基因变异的基因型及等位基因频率分布无显著差异（P=0.369,0.344）。结论瘦素受体基因Gln223Arg变异,在中国人肥胖的发病中可能无重要作用。     

黄韧带骨化的病理组织学研究

目的 :探讨黄韧带骨化的病理变化特点和发生机理。方法 :利用组织病理学和组织化学方法对比研究正常黄韧带和 5例病变黄韧带的病理形态学特点、胶原纤维、网状纤维、弹力纤维以及粘液物质的改变。结果 :根据大体形态特点可将黄韧带骨化分为结节型 (增生性 )骨化、周围型骨化和弥漫型骨化 3种类型。组织学上可见病变早期出现胶原纤维肿胀、融合 ,进一步发生软骨化生 ,最终出现钙化和骨化。在肿胀融合的胶原纤维和软骨化生处可见阿新蓝 (pH 2 5 )阳性的粘液性物质。结论 :黄韧带骨化的大体类型代表着同一病变发展的不同阶段 ;韧带的退行性改变是黄韧带骨化的基本原因 ;胶原纤维的肿胀融合及其粘液样变性是黄韧带骨化的起始病变。     

P53与ras癌基因产物对直肠癌的诊断价值

目的提高直肠癌术前活检的诊断率。方法5年来手术治疗的168例直肠癌病人中,有20例（11．9％）第一次手术前活检不能明确诊断。对其中17例患者的活检组织石蜡标本（实验组）和10例正常肠粘膜活检标本（对照组）进行常规病理、P53与ras癌基因产物检测。结果实验组中P53与ras基因表达阳性率分别为71％与47％,阳性率均高于常规病理,有显著性差异。17例标本中,11例为不典型增生,5例仅有慢性炎症。不典型增生的P53与ras基因表达分别为11例和7例,而慢性炎症则全部为阴性。二者之间,两种基因表达阳性率均有显著差异。实验结果还显示P53与ras基因表达有较好的一致性。对照组的10例正常肠粘膜的活检标本P53与ras基因检测结果均阴性,与实验组比较,P53阳性率有显著差异。结论P53与ras基因表达检测,可以作为常规病理的补充,提高直肠良恶性病变的鉴别力。     

胺碘酮抑制缺血浦肯野纤维起搏离子流

目的观察正常及模拟“缺血”时胺碘酮对绵羊心室浦肯野纤维起搏离子流（Ｉｆ）的影响。方法双微电极电压钳制术,使膜电位过度极化以激活Ｉｆ。结果胺碘酮１×１０－５ｍｏｌ／Ｌ在正常台氏液中显著降低浦肯野纤维Ｉｆ幅值;模拟“缺血”也使Ｉｆ幅值降低,在此基础上,胺碘酮使Ｉｆ幅值进一步减小,加剧了“缺血”对Ｉｆ离子流的抑制作用。结论提示胺碘酮能抑制心肌缺血时心室正常自律性活动。     

阳离子脂质体介导细胞因子基因对小鼠肝癌抑制的作用

目的观察阳离子脂质体介导细胞因子ＴＮＦ－ａ及ＩＬ－２基因对小鼠肝癌的抑制作用。方法构建含细胞因子ＴＮＦ－ａ及ＩＬ－２的质粒载体,用阳离子脂质体ＬｉｐｏｆeｃｔＡＭＩＮＥ或ＤＯＳＰＥＲ介导的含细胞因子ＴＮＦ－ａ及ＩＬ－２的质粒ＤＮＡ分别体外转染小鼠肝癌细胞株ＭＭ４５Ｔ．Ｌｉ,并在荷瘤小鼠体内分别直接注射上述阳离子脂质体－ＤＮＡ复合物,观察瘤体大小及小鼠生存期。结果两种阳离子脂质体介导的细胞因子转染后都具有生物学活性,转染效率为１０％左右,瘤内注射后均能延长荷瘤小鼠的生存期。ＤＯＳＰＥＲ介导细胞因子的治疗效果较佳。结论ＬｉｐｏｆｅｃｔＡＭＩＮＥ或ＤＯＳＰＥＲ介导细胞因子ＴＮＦ－ａ及ＩＬ－２基因均具有抑制小鼠肝癌生长、延长荷瘤小鼠生存期的作用,ＤＯＳＰＥＲ的效果较好。     

Maternal plasma phospholipid polyunsaturated fatty acids in pregnancy with and without gestational diabetes mellitus: relations with maternal factors.

BACKGROUND: The fatty acids arachidonic acid (AA; 20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) are essential for fetal growth and development, but their metabolism may be altered in insulin resistance. OBJECTIVES: The objectives were to determine maternal plasma phospholipid polyunsaturated fatty acid concentrations in pregnant women receiving dietary therapy for gestational diabetes mellitus (GDM) and to identify maternal factors associated with plasma phospholipid AA and DHA concentrations in the third trimester. DESIGN: Fasting plasma phospholipid fatty acids were determined in women with GDM (n = 15) receiving dietary therapy only and in healthy, pregnant women without GDM (control group, n = 15) at 27-30, 33-35, and 36-39 wk gestation. RESULTS: Maternal plasma phospholipid (as % by wt of total fatty acids and mg/L) linoleic acid (18:2n-6), AA, and 22:5n-6 concentrations did not differ significantly between women with GDM and control subjects. The other n-6 long-chain polyunsaturated fatty acids (% by wt) were lower in GDM subjects than in control subjects. Plasma phospholipid (expressed as % by wt and mg/L) linolenic acid (18:3n-3) and summed precursors of DHA were lower and DHA (% by wt and mg/L), adjusted for dietary DHA intake, was 13% higher in GDM subjects than in control subjects. Maternal blood hemoglobin A1C was inversely related to plasma phospholipid AA (% by wt) (r = -0.56, P = 0.03) in control subjects and positively associated with plasma phospholipid AA (% by wt) in women with GDM (r = 0.76, P = 0.001). Pregravid body mass index was negatively associated with plasma phospholipid DHA (% by wt) in control subjects (r = -0.55, P = 0.04) and in women with GDM with a body mass index (in kg/m2) <30 (r = -0.76, P = 0.007). CONCLUSIONS: This is the first report documenting alterations in maternal plasma phospholipid PUFAs in pregnant women receiving dietary therapy for GDM. In pregnant woman, both with and without GDM, maternal glycemic control and pregravid BMI appear to be significant predictors of plasma phospholipid AA and DHA, respectively, during the third trimester. Additionally, dietary DHA significantly affects phospholipid DHA concentrations.     

Fish consumption and mortality from all causes, ischemic heart disease, and stroke: an ecological study.

BACKGROUND: The present study examined the relation between fish consumption and mortality from all causes, ischemic heart disease, and stroke. METHODS: The fish consumption data in 1961-1963, 1979-1981, and 1989-1991 and mortality data, age-standardized to 45-74 years, mean of the latest available 3 years, mostly around 1992-1993, in 36 countries, were obtained from the Food and Agriculture Organization and the World Health Organization, respectively. RESULTS: There exists an inverse univariate correlation between log fish consumption in 1961-1963, 1979-1981, and 1989-1991 and log all-cause (P < 0.01 to < 0.001) and ischemic heart disease (P < 0.05 to < 0.01) mortality in both sexes. An inverse univariate correlation between log fish consumption and log stroke mortality was found only for the period 1961-1963 in both sexes (P < 0.05). Log fish consumption was independently, significantly, and inversely associated with log all-cause (all P < 0.001), ischemic heart disease (P < 0.01 to < 0.001), and stroke (P < 0.05 to < 0.001) mortality in all three time periods in both sexes, after adjusting for confounding factors. These associations remained significant even after exclusion of Iceland and Japan, countries with the highest amount of fish consumption and the lowest all-cause mortality rate. CONCLUSIONS: Fish consumption is associated with a reduced risk from all-cause, ischemic heart disease, and stroke mortality at the population level.     

Effects of air pollution on respiratory health of adults in three Chinese cities

The authors examined potential associations between air-pollution exposures and respiratory symptoms and illnesses of 4,108 adults who resided in 4 districts of 3 large, distinct Chinese cities. Data on respiratory health outcomes and relevant risk factors for parents and children were obtained via standardized questionnaires in the winter of 1988. (The effects in children were described previously.) The yearly averages of ambient levels of total suspended particles in the 4 districts for the years 1985-1988 differed greatly. The authors constructed logistic-regression models to assess the respiratory health parameters of parents of the children. The results revealed significant and strong effects, by district, on prevalence rates of cough, phlegm, persistent cough and phlegm, and wheeze for both the mothers and the fathers. In addition, the odds ratios increased as ambient total suspended particle concentration increased across the 3 urban districts. Other local within-city risk factors, however, may have confounded the total suspended particles-effects association, especially for asthma prevalence. Findings for adults were similar to those found for their children. A strong adverse effect of active tobacco smoking on the fathers' respiratory health was observed. The children appeared to be more strongly affected by passive smoking exposure received in their homes than their mothers.     

Size effect in resin/glass composite flexure strengths

The objective of this study was to test the hypothesis that composite restorative materials possess an elastic-brittle nature and therefore will exhibit a size effect for flexure strength data. The experimental material consisted of 20 wt% 60:40 BISGMA:TEGDMA, 10 wt% colloidal silica, and 70 wt% Sr glass and was cured by light irradiation. Two sizes of flexure specimens were fabricated: 3.2x1.6x35 mm, and 6.25x3.1x35 mm. Half of the specimens made were soaked to equilibrium weight gain in 50:50 ethanol:water. The fracture strengths were measured in four-point bending tests. The beams under load were modelled by the finite element package ABAQUS. A statistical fracture mechanics methodology embodied in a public domain computer program called CARES/LIFE, developed by NASA, utilized the ABAQUS input and the fracture strengths of the smaller specimens to predict the fracture strengths of the larger specimens. In making the computation it used an approach that combines a Weibull distribution of flaw size with Batdorf's fracture mechanical model for failure at a material flaw. Both the soaked and unsoaked specimens exhibited Weibull behaviour, with shape parameters ranging from 4.04 to 8.15. Soaking had a clearly detrimental effect on the strengths of specimens of both sizes, and produced a comparable percentage reduction in the estimated scale parameter of the fracture strength distribution. Both the soaked and unsoaked specimens also exhibited a clear and comparable size effect, i.e. the larger specimens had a fracture strength that was lower than that of the smaller specimens by roughly the same percentage. Moreover, the magnitude of the size effect was well predicted by the CARES/LIFE methodology for both the soaked and the dry specimens. The elastic-brittle character of both soaked and unsoaked composite specimens was validated by load-deflection data, the magnitude of the Weibull shape parameters of the observed fracture strength data (<10), and the observed effect of specimen size. The accuracy of CARES/LIFE in predicting the magnitude of the observed size effect in beams of two different sizes strongly suggests that CARES/LIFE will be useful for computation of failure probabilities for clinically relevant structures.     

A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma

In hepatocellular carcinoma (HCC), autoantibodies to intracellular antigens are detected in 30-40% of patients. Patients with chronic hepatitis or liver cirrhosis develop HCC, and when this occurs, some patients exhibit autoantibodies of new specificities. It has been suggested that these novel autoantibody responses may be immune system reactions to proteins involved in transformation-associated cellular events. One HCC serum shown to contain antibodies to unidentified cellular antigens was used to immunoscreen a cDNA expression library, and a full length cDNA clone was isolated with an open reading frame encoding 556 amino acids with a predicted molecular mass of 62 kD. The 62-kD protein contained two types of RNA-binding motifs, the consensus sequence RNA-binding domain (CS-RBD) and four hnRNP K homology (KH) domains. This protein, provisionally called p62, has close identity (66-70%) to three other proteins at the amino acid sequence level, and all four proteins may belong to a family having CS-RBD in the NH2-terminal region and four KH domains in the mid-to-COOH- terminal region. The homologous proteins are: KH domain-containing protein overexpressed in cancer (Koc); zipcode binding protein, a protein which binds to a conserved nucleotide element in chicken beta-actin mRNA (ZBP1); and a protein which binds to a promoter cis element in Xenopus laevis TFIIIA gene (B3). p62 protein is cytoplasmic in location, and autoantibodies were found in 21% of a cohort of HCC patients. Patients with chronic hepatitis and liver cirrhosis, conditions which are frequent precursors to HCC, were negative for these autoantibodies, suggesting that the immune response might be related to cellular events leading to transformation. However, the possible involvement of p62 autoantigen as a factor in the transformation process remains to be elucidated.