Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer

Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients. Received: February 6, 1998 / Accepted: July, 3, 1998     

Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis

Pulmonary lymphangioleiomyomatosis (LAM) is a destructive lung disease characterized by a diffuse hamartomatous proliferation of smooth muscle cells (LAM cells) in the lungs. Pulmonary LAM can occur as an isolated form (sporadic LAM) or in association with tuberous sclerosis complex (TSC) (TSC-LAM), a genetic disorder with autosomal dominant inheritance with various expressivity resulting from mutations of either the TSC1 or TSC2 gene. We examined mutations of both TSC genes in 6 Japanese patients with TSC-LAM and 22 patients with sporadic LAM and identified six unique and novel mutations. TSC2 germline mutations were detected in 2 (33.3%) of 6 patients with TSC-LAM and TSC1 germline mutation in 1 (4.5%) of 22 sporadic LAM patients. In accordance with the tumor-suppressor model, loss of heterozygosity (LOH) was detected in LAM cells from 3 of 4 patients with TSC-LAM and from 4 of 8 patients with sporadic LAM. Furthermore, an identical LOH or two identical somatic mutations were demonstrated in LAM cells microdissected from several tissues, suggesting LAM cells can spread from one lesion to another. Our results from Japanese patients with LAM confirmed the current concept of pathogenesis of LAM: TSC-LAM has a germline mutation but sporadic LAM does not; sporadic LAM is a TSC2 disease with two somatic mutations; and a variety of TSC mutations causes LAM. However, our study indicates that a fraction of sporadic LAM can be a TSC1 disease; therefore, both TSC genes should be examined, even for patients with sporadic LAM. Received: August 30, 2001 / Accepted: November 2, 2001     

Effects of 12 weeks of aerobic exercise plus dietary restriction on body composition,resting energy expenditure and aerobic fitness in mildly obese middle-aged women

This study investigated the effects of 12 weeks of aerobic exercise plus voluntary food restriction on the body composition, resting metabolic rate (RMR) and aerobic fitness of mildly obese middle-aged women. The subjects were randomly assigned to exercise/diet (n = 17) or control (n = 15) groups. The exercise/diet group participated in an aerobic training programme, 45–60 min · day ^–1 at 50%–60% of maximal oxygen uptake (VO_2max), 3–4 days · week^–1, and also adopted a self-regulated energy deficit relative to predicted energy requirements (–1.05 MJ · day ^–1 to –1.14 MJ · day ^–1 ). After the regimen had been followed for 12 weeks, the body mass of the subjects had decreased by an average of 4.5 kg, due mainly to fat loss, with little change of fat free mass (m _ff). The absolute RMR did not change, but the experimental group showed significant increases in the RMR per unit of body mass (10%) and the RMR per unit of m _ff (4%). The increase in RMR/m _ff was not correlated with any increase in VO_2max/m _ff. The resting heat production per unit of essential body mass increased by an average of 21%, but the resting heat production rate per unit of fat tissue mass remained unchanged. We concluded that aerobic exercise enhances the effect of moderate dietary restriction by augmenting the metabolic activity of lean tissue.     

术前颈椎过伸功能与颈椎后路单开门椎管扩大成形术后前凸角度丢失的关系

目的 探讨术前颈椎过伸功能与颈椎后路单开门椎管扩大成形术后前凸角度丢失的关系。方法 回顾性分析首都医科大学大兴教学医院骨科2017年1月-2018年12月58例行颈椎后路单开门椎管扩大成形术患者临床资料,其中男45例、女13例,年龄49~85岁(平均64.8岁)。术前测量患者中立侧位X线片上的T₁倾斜角、矢状面垂直轴(SVA),以及中立侧位、过伸位X线片的C₂~C₇ Cobb角。随访12~24个月,术后再次测量中立侧位X线片上的C₂~C₇ Cobb角。术前颈椎过伸功能测量值为术前过伸位X线片C₂~C₇ Cobb角度减去术前中立侧位X线片C₂~C₇ Cobb角。前凸角度丢失量为术前中立侧位片C₂~C₇ Cobb角减去末次随访时中立侧位片C₂~C₇ Cobb角。依据58例患者术前颈椎过伸功能均值(8.7°)分为两组,≥8.7°为A组,＜8.7°为 B 组。比较两组患者术前及术后影像及临床资料,同时对58例患者的影像学资料与临床资料进行相关性分析。结果 A组25例患者年龄54~83岁,B组33例患者年龄49~85岁,两组患者术前年龄、性别、疾病种类差异均无统计学意义(P值均>0.05)。术前A组颈椎过伸功能(14.09°±4.75°)大于B组(4.62°±2.54°),A组T₁倾斜角(17.00°±3.40°)小于B组(29.68°±6.34°),颈椎前凸角度丢失[1.10(-0.85,4.00)]小于B组[8.60 (7.70,12.40)],差异均有统计学意义(P值均＜0.01)。颈椎过伸功能与前凸角度丢失之间呈负相关(r=-0.965, P＜0.01),T₁倾斜角与前凸角度丢失之间呈正相关(r=0.954, P＜0.01),颈椎过伸功能与T₁倾斜角呈负相关(r=-0.900, P＜0.01);SVA与T₁倾斜角、颈椎过伸功能、术后前凸角度丢失均无相关性(r=-0.065、0.216、-0.202, P＞0.05)。术后JOA评分改善率与过伸角度变化、SVA及T₁倾斜角均无相关性(r=0.201、-0.034、-0.213, P值均＞0.05)。A组术后JOA改善率为69%±23%,B 组术后JOA改善率为62%±23%,两组差异无统计学意义(t=1.147, P＞0.05)。术后Odom's分级评价A组优良率为88.0%(22/25),B组优良率为63.6%(21/33),差异有统计学意义(χ² =4.403, P<0.05)。结论 对于后路单开门椎管扩大成形术患者,颈椎过伸功能与前凸角度丢失存在相关性,术前过伸功能越低,术后越易发生前凸角度丢失,可作为术前预判术后颈椎曲度变化的参数之一。     

错配修复蛋白表达缺失在子宫内膜癌中的临床病理意义

目的:探究错配修复(MMR)蛋白表达缺失在子宫内膜癌(EC)中的临床病理意义。方法:选取惠州市第一人民医院2019年3月至2022年12月收集的EC患者术后石蜡包埋子宫内膜组织标本50例,采用免疫组织化学检测法检测MMR蛋白表达,包含MLH1、MSH2、MSH6及PMS2,观察MMR蛋白表达缺失率,对不同年龄及EC病理特征的MMR蛋白表达缺失情况进行比较。结果:(1)50例EC患者MMR蛋白表达缺失发生率为36.00%。MMR蛋白MLH1、MSH2、PMS2、MSH6表达缺失率分别为22.00%、6.00%、30.00%、6.00%,其中单项缺失4例(8.00%),两项表达缺失14例(18.00%)。(2)≤50岁EC患者MMR蛋白缺失表达率(56.00%)高于> 50岁EC患者(16.00%),差异具有统计学意义(P <0.05)。(3)不同细胞分化程度、肌层浸润程度及淋巴结转移情况患者MMR蛋白表达缺失情况比较,差异均无统计学意义(P> 0.05)。结论:MMR蛋白在EC中表达缺失率较高,以PMS2表达缺失为主,且MMR蛋白表达缺失率在≤50岁EC患者中更高,故需...     

上海市居民期望寿命与健康期望寿命的差异分析

目的 分析不同年龄、性别的上海市居民期望寿命和健康期望寿命的差异。方法 分析比较上海市和全球长寿国家/地区期望寿命的变化趋势;利用全球疾病负担研究建立的疾病和健康结局的失能权重,应用Sullivan法测算上海市居民健康期望寿命,并分析不同年龄、性别人群的健康寿命损失。结果 近40年,上海市期望寿命增长了10.86岁,2016年上海市居民期望寿命为83.18岁,其中男性80.83岁,女性85.61岁。健康期望寿命为69.46岁,其中男性为68.68岁,女性为70.23岁;与期望寿命的差距分别为13.72、12.15和15.38岁;分别占期望寿命的16.49%、15.02%和17.97%。与期望寿命相同,各年龄组女性的健康期望寿命均高于男性,平均差距为1.76岁,两者差距在20~24岁组最小为1.36岁,70~74岁组最大为2.24岁。健康期望寿命损失率随着年龄的上升而上升,<65岁女性高于男性,≥65岁则相反。结论 上海市期望寿命已达世界领先水平,但健康寿命损失较大,需要在降低死亡率的基础上进一步提高寿命质量,尤其是女性和≥65岁男性是重点关注人群。     

胃癌7号染色体长臂的杂合性缺失分析

目的:检测胃癌患者7号染色体长臂微卫星位点的杂合性缺失(loss of heterozygosity,LOH),以初步确定7号染色体长臂上与胃癌相关基因连锁最密切的微卫星多态位点及LOH的临床意义.方法:在70例原发性胃癌中应用多重PCR技术扩增覆盖整个7号染色体长臂的9个微卫星位点(平均遗传距离为10cm),聚丙烯酰胺凝胶电泳分离PCR产物,用GeneScan、Genotyper软件进行分析.结果:9个微卫星位点的LOH均可发生于原发性胃癌,总的LOH频率为34.3%(24/70),其中D7S486和D7S798位点的LOH频率较高,分别为24.0%(12/50)和19.2%(5/26);总的LOH频率随临床分期而显著增高(P=0.046),D7S486位点的LOH频率在淋巴结转移者显著高于无淋巴结转移者(P=0.015).结论:在7号染色体长臂D7S486和D7S798位点附近,可能存在与胃癌发展相关的抑癌基因.     

宫颈癌患者基因组遗传不稳定性分析

目的 研究中国宫颈癌高发区宫颈癌患者基因组遗传不稳定性改变，为寻找宫颈癌相关内源因子提供依据。方法 从GenBank中选取8对微卫星DNA引物，采用PCR-变性PAGE-银染方法检测50例宫颈癌(来自高发区)活检组织及其对照(同病例血液)样品的杂合性丢失(LOH)和微卫星不稳定(MI)。结果 LOH总检出率为66％(33／50)，其中，D18S474(染色体18q21)LOH达40．5％；染色体3p21．2—3p21．3中微卫星位点D3S1478，LOH达31．7％；并且在原位癌与浸润癌中，LOH分布也有一定差异。MI在宫颈癌患者基因组中仅存在少数微卫星位点，总的发生率较低，为8％(4／50)。结论 除高危型人乳头瘤病毒(HPVhr)感染外，细胞内源基因的改变在宫颈癌发生发展过程中也起着重要作用。高频LOH位点18q21 D18S474、3p21．2-3p21．3 D3S1478可能存在潜在的宫颈癌抑癌基因。     

LOSS OF HETEROZYGOSITY AT 17p13 IN GASTRIC CANCER AND COLORECTAL CANCER

Bothgastriccancerandcolorectalcancerarecommonhumantumors.Althoughlittleisknownregardingthemolecularpathogenesisoftheneonlasms,itisnowgenerallyacceptedthattheactivationofoncogenesandinactivationoftumorsuppressorgenesmightbecriticalforthetumorcarcinogenesisandprogression.Inthepresentstudy,weemployedtheSouthernhybridizationbyprobesphP53BandPYNZ22,whichwereobtainedfromtheAmericanTypeCultureCollection,todetectthelossofheteroZygosity(LOH)at17pl3ingastriccancerandcolorectalcancer.Wefurtheranaly…