含不同启动子的腺病毒载体介导的人β2肾上腺素能受体基因在心肌细胞的表达

目的：观察不同的启动因子cmv,mlc-2v对腺病毒载体介导的人β2肾上腺素能受体（β2－AR）基因在大鼠心肌细胞中表达,方法：分别构建cmv,mlc-2v启动子并携带人β20－AR基因的重组腺病毒Adcmvβ2AR,Admlc,β2AR,用以感染心肌细胞,并检测心肌细胞对人β2－AR基因的表达及cAMP的含量,结果：经RT－PCR,Western免疫印迹分析证帝感染的心肌细胞均表达人β2－AR,放射性配基检测显示含mlc-2v启动子Admlcβ2AR感染的心肌细胞β2－AR密度低于含cmv启动子的A β2AR感染组（P＜0．01）,经10umol/L异丙肾上腺素作用,感染组的心肌细胞内cAMP含量明显高于对照组,感染组间存在明显差异（P＜0．01）,结论：含不同启动子的腺病毒载休感染心肌细胞后均可表达具有生物活性的人β2－AR,但两者存在差异。     

原发性高血压和动脉硬化性脑梗死及腔隙性脑梗死患者的HLA-DQA1遗传易感性

目的　探讨原发性高血压(EH)、动脉粥样硬化性血栓性脑梗死(ABI)及腔隙性脑梗死(LS)患者HLA-DQA1位点的基因分型及其遗传易感性。方法　采用PCR-SSP方法对EH、ABI及LS共155例患者和正常对照64人进行HLA-DQA1位点的基因分型和遗传易感性分析。结果　EH、ABI及LS组的HLA-DQA1*0301基因频率均明显高于正常对照组,分别为33.6538对17.9688,36.5854对17.9688,33.0645对17.9688（P<0.01）,而HLA-DQA1*0103基因频率却明显低于正常对照组(P<0.05或P<0.01)。结论　HLA-DQA1*0301等位基因可能与EH、ABI及LS的遗传易感性相关,而HLA-DQA1*0103等位基因可能与其保护性相关。     

唐山地区人群肺结核病患者血ABO系统遗传标记

研究依赖于人种属性的肺结核病在不同时期患ＡＢＯ系统的血型。方法 调查唐山市城区肺结核病患的状况,并分析其影响因素。结果 在Ⅲ型结核病患中Ｂ型血患为４０．７８％,在Ⅳ型结核病患３中Ｂ型血患为６０．６０％。结论 肺结核病的类型与ＡＢＯ系统的血型有一定关系。     

A Dutch family with progressive sensorineural hearing impairment linked to the DFNA2 region

We studied a Dutch family with DFNA2-linked progressive sensorineural hearing impairment (SNHI). Recent audiograms were obtained from 18 of the affected persons (age 7–81 years) and were used in a gene-linkage analysis. Linear regression analysis of the audiograms, using binaural mean thresholds, disclosed on average a descending slope of approximately 10 dB/octave at any age and an annual threshold increase at any frequency of about 0.7 dB/year. There may have been substantial congenital impairment at higher frequencies, but longitudinal analysis of hearing impairment in the youngest case, who was followed from age 5 years, suggested that the most significant changes in hearing may have occurred in the first two decades of life. Linkage analysis was carried out with special attention to the DFNA2 region because hearing trends were very similar to families previously linked to DFNA2. Linkage to DFNA2 was established with maximum lod scores of 4.7 and 3.2 for the flanking markers of the DFNA2 region (D1S432;MYCL1). Received: 25 February 1999 / Accepted: 11 June 1999     

多巴胺转运载体基因多态性及帕金森病遗传易感性的关系

目的 探讨多巴胺转运载体（ＤＡＴ）基因３’ＶＮＴＲ多态性与帕金森病（ＰＤ）遗传易感性的关系。方法 选择确诊的ＰＤ患者１７１例和正常人１８０名,利用ＰＣＲ扩散增片段长度多态性（Ａｍｐ－ＦＬＰ）技术检测ＤＡＴ基因３’ＶＮＴＲ多态性,并分析比较ＰＤ组与对照组之间多态性频率的差异。结果 发现ＰＤ组和对照组之间ＤＡＴ基因３’ＶＮＴＲ多态位点基因型分布和等位基因频率差异均有显著意义（Ｐ〈０．０５）。ＤＡＴ基因     

Access to clinically indicated genetic tests for pediatric patients with Medicaid: Evidence from outpatient genetics clinics in Texas

PurposeLittle is known about how Medicaid coverage policies affect access to genetic tests for pediatric patients. Building upon and extending a previous analysis of prior authorization requests (PARs), we describe expected coverage of genetic tests submitted to Texas Medicaid and the PAR and diagnostic outcomes of those tests.MethodsWe retrospectively reviewed genetic tests ordered at 3 pediatric outpatient genetics clinics in Texas. We compared Current Procedural Terminology (CPT) codes with the Texas Medicaid fee-for-service schedule (FFSS) to determine whether tests were expected to be covered by Medicaid. We assessed completion and diagnostic yield of commonly ordered tests.ResultsAmong the 3388 total tests submitted to Texas Medicaid, 68.9% (n = 2336) used at least 1 CPT code that was not on the FFSS and 80.7% (n = 2735) received a favorable PAR outcome. Of the tests with a CPT code not on the FFSS, 60.0% (n = 1400) received a favorable PAR outcome and were completed and 20.5% (n = 287) were diagnostic. The diagnostic yield of all tests with a favorable PAR outcome that were completed was 18.7% (n = 380/2029).ConclusionMost PARs submitted to Texas Medicaid used a CPT code for which reimbursement from Texas Medicaid was not guaranteed. The frequency with which clinically indicated genetic tests were not listed on the Texas Medicaid FFSS suggests misalignment between genetic testing needs and coverage policies. Our findings can inform updates to Medicaid policies to reduce coverage uncertainty and expand access to genetic tests with high diagnostic utility.     

2型糖尿病核心家系的遗传易感性研究

通过对２型糖尿病（ＮＩＤＤＭ）核心家系的分析,探讨了遗传因素在核心家系成员中所起作用的程度。结果表明：病例核心家系一级亲属ＮＩＤＤＭ 的发病率非常显著的高于对照组,χ２ ＝ １７．０,Ｐ＜ ０．００１,相对危险度（ＲＲ）为３．３０,９５％ 可信区间为１．８０～６．０５。不论父母、同胞和子女,均以病例亲属的发病率显著高于对照;病例组各亲属中,不论男女和年龄,标准化发病率比（ＳＩＲ）均明显高于对照人群的１００,经统计学Ｚ检验有极显著意义;病例核心家系的ＲＲ、归因危险度（ＡＲ）％ 也明显较高,进一步说明血缘关系与ＮＩＤＤＭ 之间有较强的联系。     

重组人神经营养因子-4/5蛋白抗三氧化二砷神经毒作用

目的初步观察重组人神经营养因子-4／5（hNT－4／5）蛋白对三氧化二砷毒性的抑制作用。方法利用hNT－4／5蛋白具有抗神经毒性的特点,采用本实验室克隆表达及部分纯化的具有天然hNT－4／5蛋白生物学活性的重组hNT-4／5蛋白,以不同水平的重组hNT4／5蛋白（0－100μl）与不同浓度的As2O3（0－160μmol／L）同时加入各组鸡胚前脑神经细胞和PC12细胞培养液中共同孵育24－48小时,观察其对染毒鸡胚前脑神经细胞存活和PC12细胞突起生长的影响作用。结果在鸡胚前脑神经细胞和PC12细胞中与As2O3共同培养48小时后,对照组与实验组的细胞存活率差异有显著性,而且细胞存活率和突起数目随hNT－4／5浓度增高而提高和增加。结论初步观察到重组hNT4／5蛋白具有抑制As2O3的毒性作用,为从基因工程途径寻找抗环境毒物因子提供了依据。     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.