The Liposome as a Model Membrane in Correlations of Partitioning with α-Adrenoceptor Agonist Activities

The apparent partition coefficients of a group of imidazoline -adrenoceptor agonists in liposome/buffer systems (K_m) and in the n-octanol/buffer system (P) have been compared in quantitative structure–activity relationships (QSAR) employing biological activities and receptor binding affinities. A parabolic relationship between log K _m and log P was found, and log K _m was greater than log P for all liposome compositions. In liposomes, log K _m decreased in the order, negatively charged > neutral > positively charged. Overall, hyper- and hypotensive activities of these drugs correlated better with log K _m than with log P; however, poor correlations were obtained between partition coefficients and in vitro binding affinities. Linear correlations of log K _m with hypotensive activities were obtained with negatively charged liposomes, whereas correlations with hypertensive activities were obtained using positively charged liposomes. Multiple regressions of biological activities with binding affinities showed positive correlations with hypotensive but not hypertensive activities with or without the inclusion of log K _m or log P. Thus, the liposome represents a more selective model membrane system than a bulk oil phase for predicting the biological activities of imidazoline -adrenoceptor agonists.     

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.     

“Nowadays it isn't easy to advise the young”: Grandmothers and granddaughters among Abaluyia of Kenya

Among Abaluyia of Kenya relative age (seniority) structures relationships hierarchically among co-wives, siblings and females of different generations. Ambiguous equality and affectionate informality in grandmother-granddaughter relationships mute the hierarchical implications of their different age and generation statuses. This facilitates grandmothers' educational roles although, as grandmothers say, Nowadays it isn't easy to advise the young. Increased physical, cognitive and experiential distances between these generations resulted from radical changes in the female lifecourse associated with modernization and delocalization. Nevertheless, reciprocal exchanges continue. Granddaughters are also intermediaries in exchanges between older women and their adult daughters. Some grandmothers are denied the companionship and assistance of granddaughters caught in the middle of mother-in-law/daughter-in-law conflicts. Many grandmothers assume parental responsibilities as they deal with the modern problem of daughters' premarital pregnancies. All in all, these intergenerational relationships reveal both cultural persistence and the effects of social change, and continue to have instrumental and expressive value for both grandmothers and granddaughters.