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101.
Bruce M. Koeppen 《Pflügers Archiv : European journal of physiology》1987,409(1-2):138-141
Intracellular microelectrode techniques were used together with inhibitors of Na+ transport (amiloride) and H+ transport (acetazolamide and SITS1) to identify principal cells and intercalated cells in the outer stripe of the rabbit outer medullary collecting duct. The principal cell (n=9) had a basolateral membrane voltage (V
bl) of –64.7±3.2 mV, a fractional resistance of the apical membrane (fR
a=R
a/R
a+R
bl) of 0.82±0.02, and a K+-selective basolateral membrane. Luminal amiloride hyperpolarizedV
bl by 10.3±2.1 mV and increasedfR
a to near unity (n=7). Bath acetazolamide and SITS were without effect on these parameters. The intercalated cell (n=5) had aV
bl of –25.0±3.2 mV, afR
a of 0.99±0.01, and a Cl–-selective basolateral membrane. Bath acetazolamide or SITS hyperpolarizedV
bl by 26.4±8.2 mV. Luminal amiloride did not alterV
bl of this cell. The differential effects of the inhibitors also indicate that the principal and intercalated cells are probably not directly coupled electrically. 相似文献
102.
L. Stefan Levin Kenneth N. Rosenbaum John M. Brady John P. Dorst 《American journal of medical genetics. Part A》1982,13(4):359-368
Radiologic evaluation of the skeleton and scanning electron microscopic studies of the teeth were performed on an infant boy with a lethal osteogenesis imperfecta (OI) syndrome who died at 10 mo of pneumonia. The skeletal findings included ribs that were focally expanded by fracture calluses, flat vertebral bodies, and wide limb bones. On fractured tooth surfaces, the enamel and dentin were normal as was the dentin calcification front. Although microscopic abnormalities have been noted in teeth from previously reported infants with lethal OI, a few studies also report infants with normal teeth. These differences in dental findings may indicate heterogeneity in OI lethal in infancy. Results of our study indicate that, until the primary biochemical defects in the OI syndromes are elucidated, examination of teeth from other infants with lethal OI and detailed evaluation of other clinical and skeletal features will aid in delineating heterogeneity and variation in expression in lethal OI. 相似文献
103.
C. Robert Cloninger 《American journal of medical genetics. Part A》1994,54(2):83-92
Despite extensive genomic scans, linkage studies of multiplex pedigrees have been unable to produce replicable evidence of genes predisposing to schizophrenia. This indicates that it is unlikely that a single gene accounts for a majority of cases of schizophrenia, even in multiplex pedigrees. It is most likely that schizophrenia is caused by the nonlinear interaction of multiple genetic and environmental factors influencing brain development and function. This conclusion has strong implications for the design of linkage and association studies. Recently designed linkage studies involve several improvements to deal with extensive locus heterogeneity and multiplicative interaction. These improvements include much larger samples of pedigrees, systematic ascertainment and sequential extension rules, and standardized procedures at multiple sites to facilitate collaboration and replication. Future improvements are likely to require advances in the assessment of clinical and neurobiological variability in multiplex pedigrees, more systematic environmental assessment, and advances in analytic methods to deal with multiplicative interaction. Rather than focusing only on schizophrenia as one or more discrete disorders, future linkage efforts should also consider the etiology of individual clinical syndromes or dimensional components of risk that interact to cause the complex pattern of syndromal comorbidity observed within schizophrenics and their families. © 1994 Wiley-Liss, Inc. 相似文献
104.
目的 采用两样本孟德尔随机化研究方法探讨血清生长分化因子15(GDF15)水平与慢性淋巴细胞白血病(CLL)发生之间的关联。方法 基于欧洲人群血清GDF15和CLL的全基因组关联研究公开数据库,筛选与血清GDF15水平相关的遗传变异位点作为工具变量,采用逆方差加权法评估遗传学预测的血清GDF15浓度与CLL发生的关联,采用最大似然比法进行敏感性分析,采用MR-Egger回归探讨工具变量潜在多效性。结果 研究共纳入3个单核苷酸多态位点作为工具变量,逆方差加权法结果显示,血清GDF15水平与CLL发生风险之间存在负相关,GDF15浓度每升高一个标准差(SD),CLL发生风险降低33%(95%置信区间:2%~54%)(P=0.039)。敏感性分析得到了一致的结果。此外,MR-Egger回归未发现存在多效性。结论 本研究结果提示,在欧洲人群中,血清GDF15水平与CLL发生之间可能存在负相关,仍需大样本人群研究及体内外实验进一步阐明GDF15在CLL发生发展中的作用及其潜在生物学机制。 相似文献
105.
Pei-Sheng Lin 《Statistics in medicine》2022,41(1):146-162
Identifying transmission of hot spots with temporal trends is important for reducing infectious disease propagation. Cluster analysis is a particularly useful tool to explore underlying stochastic processes between observations by grouping items into categories by their similarity. In a study of epidemic propagation, clustering geographic regions that have similar time series could help researchers track diffusion routes from a common source of an infectious disease. In this article, we propose a two-stage scan statistic to classify regions into various geographic clusters by their temporal heterogeneity. The proposed scan statistic is more flexible than traditional methods in that contiguous and nonproximate regions with similar temporal patterns can be identified simultaneously. A simulation study and data analysis for a dengue fever infection are also presented for illustration. 相似文献
106.
Chuyuan Wang Patricia Solís Lily Villa Nayan Khare Elizabeth A. Wentz Aaron Gettel 《Journal of urban health》2021,98(3):344
The objective of the present study was to examine the effects of a confluence of demographic, socioeconomic, housing, and environmental factors that systematically contribute to heat-related morbidity in Maricopa County, Arizona, from theoretical, empirical, and spatial perspectives. The present study utilized ordinary least squares (OLS) regression and multiscale geographically weighted regression (MGWR) to analyze health data, U.S. census data, and remotely sensed data. The results suggested that the MGWR model showed a significant improvement in goodness of fit over the OLS regression model, which implies that spatial heterogeneity is an essential factor that influences the relationship between these factors. Populations of people aged 65+, Hispanic people, disabled people, people who do not own vehicles, and housing occupancy rate have much stronger local effects than other variables. These findings can be used to inform and educate local residents, communities, stakeholders, city managers, and urban planners in their ongoing and extensive efforts to mitigate the negative impacts of extreme heat on human health in Maricopa County. 相似文献
107.
目的探讨ABCB4基因突变合并巨细胞病毒(CMV)感染致婴儿胆汁淤积症(IC)患儿的临床特征、基因检测结果和诊治方案。 方法选择2019年8月3日,于中山大学附属第七医院就诊并确诊为ABCB4基因突变合并CMV感染致IC的1例婴儿(女性,生后9个月)为研究对象。回顾性分析其临床病例资料,包括临床特征、实验室检查结果及基因检测结果。同时,检索国内外数据库中ABCB4基因突变所致IC患儿的相关文献,并进行文献复习。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。 结果本例IC患儿在本院诊治结果如下。①病史采集:系G2P2,足月顺产,外观无异常,否认新生儿黄疸病史,生后2个月龄时出现皮肤及巩膜呈暗绿色,伴反复呕奶,当地医院治疗并诊断为胆汁淤积性肝病、CMV感染和泌尿系统感染,抗病毒治疗2周后好转出院。出院时,其血清总胆汁酸(sTBA)为152.8 μmol/L,CMV-DNA<4×102 copies/mL,口服熊去氧胆酸胶囊10 mg/(kg·d)治疗后,皮肤暗绿色逐渐消退,大、小便正常。出院后定期监测肝功能,sTBA、γ-谷氨酰转肽酶(GGT)仍然较正常值增高。②实验室检查:血清CMV免疫球蛋白(Ig)G抗体呈阳性、CMV IgM抗体呈阴性,CMV-DNA<55×102 copies/mL。基因检测结果:患儿及其父亲均携带ABCB4基因杂合变异。治疗结果:经口服熊去氧胆酸胶囊10 mg/(kg·d)及谷胱甘肽片0.1 g/次× 3次/d治疗后,对患儿定期复查sTBA、GGT。随访到18个月龄时,其各项指标逐渐恢复正常范围。③文献复习结果:共计检索到8篇国内外报道的因ABCB4基因突变引起IC相关文献,纳入14例IC患儿,均被诊断为进行性家族性肝内胆汁淤积3型(PFIC3),伴肝大,sTBA、GGT水平升高等。14例IC患儿中,共检测到ABCB4基因突变位点20个。其中,9例IC患儿接受熊去氧胆酸治疗,7例随访结果显示临床症状及实验室检查指标有所好转。 结论携带ABCB4基因突变,可引起IC。对于sTBA升高、肝酶异常的病因不明确、治疗效果不佳IC患儿,建议完善基因检测进一步排查ABCB4基因突变所致胆汁淤积症。 相似文献
108.
目的:为了解广西壮族人群D1S80位点群体遗传资料,方法,使用扩增片段长度多态性(Amp-Flp)和PCR结合聚丙烯酰胺凝电脉及银染技术,对300名文本地区壮族无关个体D1S80位点多态性分析,结果,观察到23个等位基因,74个基因型,杂合度,非交排除率,个体识别力及多态信息含量分别为0.824,0.763,0.968,0.875,其基因频率分布符合Hardy-weinberg定律,对5个家系相关个体分析符合孟德尔定律,结认,该方法具有快速,简便,特异性强,灵敏度高特点。 相似文献
109.
目的 :探讨胰高血糖素受体 (GCG R)基因外显子 2Gly40Ser突变是否与中国人迟发型非胰岛素依赖型糖尿病 (non -insulin -dependentdiabetesmillitus,NIDDM)相关。方法 :选择湖南地区汉族人NIDDM患者 82例及正常对照136例 ,应用聚合酶链反应———限制性片段长度多态分析方法 ,检测Gly40Ser突变。结果 :受检者均不存在Gly40Ser的错义突变。结论 :该突变不是引起中国人NIDDM的重要遗传因素。文献报道白种人GCG R基因Cly40Ser与NIDDM相关 ,本研究提示此种相关有种族差异性 相似文献
110.
Daniel J. Schaid Shannon K. McDonnell Liesel M. FitzGerald Lissa DeRycke Zachary Fogarty Graham G. Giles Robert J. MacInnis Melissa C. Southey Tu Nguyen-Dumont Geraldine Cancel-Tassin Oliver Cussenot Alice S. Whittemore Weiva Sieh Nilah Monnier Ioannidis Chih-Lin Hsieh Janet L. Stanford Johanna Schleutker Cheryl D. Cropp Stephen N. Thibodeau 《European urology》2021,79(3):353-361
BackgroundFamily history of prostate cancer (PCa) is a well-known risk factor, and both common and rare genetic variants are associated with the disease.ObjectiveTo detect new genetic variants associated with PCa, capitalizing on the role of family history and more aggressive PCa.Design, setting, and participantsA two-stage design was used. In stage one, whole-exome sequencing was used to identify potential risk alleles among affected men with a strong family history of disease or with more aggressive disease (491 cases and 429 controls). Aggressive disease was based on a sum of scores for Gleason score, node status, metastasis, tumor stage, prostate-specific antigen at diagnosis, systemic recurrence, and time to PCa death. Genes identified in stage one were screened in stage two using a custom-capture design in an independent set of 2917 cases and 1899 controls.Outcome measurements and statistical analysisFrequencies of genetic variants (singly or jointly in a gene) were compared between cases and controls.Results and limitationsEleven genes previously reported to be associated with PCa were detected (ATM, BRCA2, HOXB13, FAM111A, EMSY, HNF1B, KLK3, MSMB, PCAT1, PRSS3, and TERT), as well as an additional 10 novel genes (PABPC1, QK1, FAM114A1, MUC6, MYCBP2, RAPGEF4, RNASEH2B, ULK4, XPO7, and THAP3). Of these 10 novel genes, all but PABPC1 and ULK4 were primarily associated with the risk of aggressive PCa.ConclusionsOur approach demonstrates the advantage of gene sequencing in the search for genetic variants associated with PCa and the benefits of sampling patients with a strong family history of disease or an aggressive form of disease.Patient summaryMultiple genes are associated with prostate cancer (PCa) among men with a strong family history of this disease or among men with an aggressive form of PCa. 相似文献