肝豆状核变性基因连锁图谱的研究

为寻找适于中国人Ｗｉｌｓｏｎ氏病（ＷＤ）基因连锁分析的遗传标记及制定ＷＤ基因所在区域的遗传图谱，我们应用Ｄ１３ｑ１４－２１区域４个ＤＮＡ标记对７５名无亲缘关系个体及９个ＷＤ家系成品进行连锁分析。结果发现４个ＤＮＡ标记中３个标记等位片段与白种人相同而杂合率相异，其中２个ＤＮＡ标记Ｄ１３Ｓ３１，Ｐ１２３Ｍ１．８与ＷＤ基因存在紧密连锁关系。其遗传顺序为：着丝点－Ｒｂ－Ｄ１３Ｓ３１－ＷＮＤ。     

用P^68RS2.0标记多态性对Wilson病的早期诊断及杂合子检测

本研究结合临床铜生化检测结果，应用分子生物学技术对６个Ｗｉｌｓｏｎ＇ｓｄｉｓｅａｓｅ家系进行检测在１３名同胞中共检出２名ＷＤ症状前患者，６名杂合子及１名正常人，另４名无检测意义。     

PCR扩增EBV－DNA酶及NA－1基因片段在鼻咽癌诊断上的应用

对６４例鼻咽部活检组织标本进行ＥＢ病毒（ＥＢＶ）特异性基因片段［ＤＮＡ酶、核抗原－１（ＮＡ－１）］的ＰＣＲ扩增，该结果与血清抗ＥＢＶ－ＤＮＡ酶抗体（ＥＢＶ－ＤＮａｓｅａｎｔｉｂｏｄｙ，ＥＤＡｂ）及初次细胞病理学结果对照，上述３种检测方法检出的阳性质例分别为：ＤＮＡ酶基因４０例（ＮＡ－１基因４１例），ＥＤＡｂ３７例，初次病理３５例，ｘ２检验表明３种检测方法结果相符。对ＤＮＡ酶基因和ＮＡ－１基因扩增阳性而初次病理阴性（诊断为慢性炎症）的８例中的６例（另２例因故未检）进行第２次活检，有５例病理确诊为原位低分化鳞癌。另对４２例头颈部肿大淋巴结的活检组织进行了上述基因片段的扩增，其中病理诊断为转移性低分化鳞癌的１０例中有６例为基因片段扩增阳性，该６例中４例后来在鼻咽部发现原发灶（２例为粘膜下型）。     

肝豆状核变性基因诊断的研究

肝豆状核变性又称Ｗｉｌｓｏｎ氏病（ＷＤ），是一种较常见的以铜代谢障碍为特征常染色体隐性遗传病。其致病基因已定于Ｄ１ ３ｑ １４．２－３。应用两个与ＷＤ基因紧密连锁的侧翼标记对９个ＷＤ家系进行单倍体检测，证实该单倍体可用于该病的症状前诊断和杂合子检出。     

微卫星KG8和CW2的遗传多态性研究

目的：探讨与多囊肾病基因位点１（ＰＫＤ１）连锁的两个微卫星ＫＧ８和ＣＷ２在汉族及壮族人群中的多态性及其等位基因频率是否存在群体差异。方法：用聚合酶链反应（ＰＣＲ）扩增与ＰＫＤ１连锁的两个微卫星，１００ｇ／Ｌ（１０％）非变性聚丙烯酰胺凝胶电泳检测ＰＣＲ产物。结果：ＣＷ２在汉族和壮族人群中均高度多态，而ＫＧ８多态性程度较低；２个ＫＧ８等位基因的频率及４个ＣＷ２等位基因的频率存在群体差异。结论：ＣＷ２可用于汉、壮族人ＰＫＤ１基因诊断。同时，这两个微卫星的等位基因频率分布具有群体差异，在应用它们进行基因诊断和疾病关联性研究时应引起注意。     

多巴胺D_2受体基因多态性与精神分裂症的关系

目的：探讨多巴胺Ｄ＿２受体基因多态与精神分裂症的关系。方法：运用人为介入内切酶位点的ＰＣＲ技术，对１０５名精神分裂症患者及１０８名对照成员进行多巴胺Ｄ＿２受体（ＤＲＤ２）基因第３ｌｌ密码子Ｓｅｒ３１１→Ｃｙｓ３ｌｌ错义突变检测。结果：Ｓｅｒ３ｌｌ／Ｃｙｓ３ｌｌ基因型在患病组和对照组中出现比例经统计学检验无显著差异，Ｓｅｒ３１１／Ｃｙｓ３１１占低发病年龄组和有家族史组的比例略高于对照组。结论：ＤＲＤ２基因结构多态性可能与精神分裂症某些亚型相关。     

肝肿瘤的MRI诊断

本文对２０８例常见肝肿瘤（肝癌１００例，血管瘤６２例，肝囊肿４６例）的磁共振（ＭＲＩ）表现进行病变形态学和信号强度分析。Ｔ１Ｗ图象上，３种肿瘤多为偏低信号强度；Ｔ２Ｗ图象上表现为中高信号强度影。利用多回波序列扫描，观察到ＴＥ＝２０～４０ｍｓ时，肝囊肿的信号强度低于肝癌和肝血管瘤：ＴＥ＝８０ｍｓ以上时，肝癌的信号强度明显低于其它２种病变。Ｇｄ－ＤＴＰＡ增强后，各自也有不同的强化形式，为肝脏肿瘤提供了又一有效的影像方法。本研究认为常规扫描自旋回波Ｔ１Ｗ和含有２个回波的Ｔ２Ｗ序列基本上可满足肝脏病变的诊断要求。建议Ｔ２Ｗ的２个回波时间ＴＥ为３０ｍｓ，１２０ｍｓ。如常规扫描上述序列仍不能确定诊断，可作多回波序列、Ｔ２Ｗ脂肪压抑或Ｔ１增强等进一步检查。     

肝豆状核变性基因12号外显子突变特征的研究

目的 研究中国人肝豆状核变性（ＷＤ）基因１２号外显子的突变特征,为建立直接基因诊断的方法提供理论依据。方法 应用聚合酶链反应－单链构象多态（ＰＣＲ－ＳＳＣＰ）技术,对４４例无亲缘关系的确诊患者和６０名正常对照组进行ＷＤ基因第１２号外显子的突变检测,并用ＤＮＡ测序证实其突变性质和位置。结果 ８例患者在１２号外显子检测到２种错义突变,占１８％（８／４４）,其中６例为Ｔｈｒ９３５Ｍｅｔ突变,２例为Ｇｌｙ     

中国人细胞色素P450_2D_6基因第1号和第9号外显子多态性

利用聚合酶链反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）技术对８３名正常中国人ＣＹＰ２Ｄ６基因的第１号和第９号外显子的多态性做了分析。结果发现，在ＣＹＰ２Ｄ６基因的第１８８位点Ｃ→Ｔ的频率为０．５９，第４２６８位点Ｇ→Ｃ的频率为０．６６，而且Ｔ１８８／Ｔ１８８纯合子及Ｃ４２６８／Ｃ４２６８纯合子的比率分别为０．３８和０．３４。与国外报道比较，发现中国人ＣＹＰ２Ｄ６基因的这２个位点的多态性分布规律与西方人有明显的不同。这可能有助于解释中国人在药物代谢及某些疾病（如帕金森病等）的易感性方面与西方人的差异。     

SHR和WKY大鼠主动脉hsp 70 mRNA水平的比较研究

本工作应用热激蛋白７０ＫＤ核酸分子杂交方法，检测了：（１）自发性高血压主动脉和离体培养的主动脉平滑肌细胞受热激后ｈｓｐ ７０ｍＲＮＡ水平的变化；（２）不同细胞培养时间的ＳＨＲ、ＷＫＹ主动脉ｈｓｐ ７０ｍＲＮＡ水平。结果提示ＳＨＲ主动脉ｈｓｐ ｍＲＮＡ水平增加，ＳＨＲ细胞培养受热激后２ｈ，ｈｓｐ ７０ｍＲＮＡ水平明显高于ＷＫＹ鼠者，６周较３个月的ＳＨＲ细胞ｈｓｐ ７０ｍＲＮＡ水平高；６个月的ＳＨＲ细     

HLA ANTIGEN DISTRIBUTION AND HAPLOTYPE SEGREGATION IN CHINESE PATIENTS WITH PSORIASIS

Tissue typing was performed on lymphocytes of 74 unrelated patients and 12 families with multiple affected siblings. HLA-B13, Aw19, B17 (Bw57), Cwl, DRl were found increased. The analysis of haplotype showed that one or two haplotype sharing among affected siblings occurred more frequently than expected (p<0.0001). The result of lods score for 4 families was l.940. These findings suggest that there may be at least one disease gene linked with MHC involved in this disease.     

DETECTION OF ARYLSULFATASE A IN LEUKOCYTES AND URINES OF LATE INFANTILE METACHROMATIC LEUKODYSTROPHY REPORT OF 3 CASES

Two male siblings and one female from two unrelated families were affected by late infantile metachromatic leukodystrophy (MLD) with similar clinical manifestations. Ary:sulfatase A (ASA) activi- ties in dialyzed urines and in leukocytes were deter mined. Urinary ASA activities of patients at a pH opti- mum of 5.0 were below the lower limit of the nor mals, but increased when assays were carried out at pH 5.6, while it fell in normals or non-MLD pa tients with a rise in pH. Leukocyte ASA activities in a proband were also below the lower limit of normal controls. Urinary ASA activities of 3 0f 4 parents were normal. Leukocyte ASA activities in all of the parents were intermediate between those of the pro bands and those of normal controls. Urinary ASA determination might be used as a screening test for MLD patients but not reliable for heterozygote detection. The confirmation of the diagnosis should rely upon leukocyte or fibroblastic ASA determination.     

血红蛋白水平影响食管癌放疗疗效的前瞻性研究

目的：探讨促红细胞生成素干预对食管癌放疗疗效的影响情况。方法：2000年7月至2001年02月，S4例经病理证实的中晚期食管癌接受放射治疗的病例。治疗前血红蛋白浓度均小于100g／1．随机分成两组。一组为对照组。一组为治疗组。两组均采用6MV或者18MVX射线放射治疗，食管癌原发灶剂量60∽68Gy，区域淋巴结剂量50∽60Gy。对照组放疗过程中予以支持治疗。而干预组除支持治疗外。每周注射促红细胞生成索．3000IU／次，2／周。同时口服铁剂。放射治疗前、后均测定血红蛋白量。两组病例合并行影响生存时间因素的COX回归分析；对比两组局部控制率和生存率的差别。结果：病变大小、血红蛋白水平为生存时间的影响因素；干预组的局部控制时间与生存时间优于对照组。结论：促红索的使用有益于食管癌放疗患者血红蛋白水平的提升，从而改善其局部控制率和生存率。升高可使食管癌的局部控制率及远期生存率提高。     

NOR(核仁组织区)活性和Ag-AA代谢补偿的研究

本文对一例额外小染色体(两臂末端,存在随体区)携带者及其同胞兄妹的中期染色体进行了银染核仁组织区(Ag-NOR)和银染近端着丝粒染色体联合(Ag-AA)分析。结果表明:(1)额外小染色体(E.S.C)携带者的Ag-AA与同胞(无E.S.C)间无显著性差异(P>0.25);(2)E.S.C携带者的Ag-NOR阳性率显著高于其同胞兄妹(P<0.025);(3)若不计数ESC的Ag-NOR阳性率或仅计数其任何一端,则与同胞间无显著性差异(P>0.25;P>0.5)。     

氯沙坦治疗老年性高血压病的临床研究

目的 观察氯沙坦对老年高血压患者的临床疗效和安全性。方法４０例老年高血压患者口服氯坦５０ｍｇ或与双氢克尿塞２５ｍｇ联合应用,疗程为６周。结果 降压总有效率为８２．５％,服药６后,平均收缩压（ＳＢＰ）及舒张压（ＤＢＰ）分别下降１９．１ｍｍＨｇ及１１．３ｍｍＨｇ。２４ｈ动态血压监测显示氯沙能有效降低２４ｈ血压及昼夜血压均值,白昼与夜间降压幅度大致相等且不影响血压昼夜节律。治疗前后的２４ｈ心率也无显著变     

GENETIC STUDY OF 1055 CASES WITH CLEFTLIPS AND CLEFT-PALATES

All of 1055 cleft-lip and/or cleft-palate cases with their 1055 families were investigated. As the results." the incidence of siblings of propositi is 2.2% (39/1791). The incidences of the first, second and third degree relatives were 1.53% (60/3927), 0.22% (25/11359), 0.30% (31/10296) respectively. In 17 cases, either of propositi's parents had cleft, the incidence of cleft among propositi's siblings was 9.52% (2/21). In 34 cases, the incidence of rest propositi's siblings beyond those whose one sib had cleft or more is 5% (4/80), whereas both their parents were normal. Based on above, all incidences of different order relatives were higher than population ones. Furthermore, it is demonstrable that the closer the consanguinity is, the higher the incidence is, and if there was cleft in one family, the incidence increased obviously among his siblings or children, revealing apparent family tendency. In this group, the heritability is 46.80%.     

REPEATED RECURRENCE OF OSTEOSARCOMA TREATED BY RESECTIONS AND CHEMOTHERAPY

This paper presents 5 patients with repeated recurrence of osteoeareoma (RROS). The primary focus of 3 patients were in the distal portion of femur, and 2 patients were in the proximal portion of tibia. Three patients, whose chest X ray film were negative, were treated by amputation and chemotherapy. Two patients had isolated metastatic focus 1.5cm in diameter in lung, were treated by amputation after 1 week of chemotherapy and then treated by lobectomy after 2 weeks of chemotherapy. After operation, the chemotherapy was carried out for 3 courses of treatment. The roentgenogram of chest and affected limb were taken once every two months. There were metastatic focuses found in the lung of 1 patient and in the distal portion of femur of 2 patients. One patient was operated on for 4 times. Up to now, 3 patients havebeen living for 5 years and 2 patients for 6 years after operation.     

急性白血病血清白细胞介素6和肿瘤坏死因子的检测

采用敏感的白细胞介素６（ＩＬ６）依赖细胞株ＫＤ８３增殖实验检测６０例急性白血病（ＡＬ）患者血清ＩＬ６活性，同时用ＥＬＩＳＡ法测定相应患者血清肿瘤坏死因子（ＴＮＦ）水平，发现ＡＬ患者血清ＩＬ６和ＴＮＦ水平明显高于正常对照（Ｐ＜０．０１），并与白血病的分型有关。动态观察４６例ＡＬ患者，发现疗效不同ＩＬ６和ＴＮＦ的水平及变化情况也不同。本研究提示，ＩＬ６和ＴＮＦ可能参与了ＡＬ的发病过程，测定ＡＬ患者血清ＩＬ６和ＴＮＦ水平可能对病情监测和疗效判断有一定的参考价值。     

Isolated congenital heart defects in first degree relatives of 185 affected children. Prospective study in Mexico City.

Parents (n = 355) and siblings (n = 313) of 185 index cases (IC) with congenital heart disease (CHD) were cardiologically evaluated. In the consecutive sample (2 years) Mendelian and chromosome syndromes were excluded. Four patients and nine siblings had CHD. The frequency of affection in siblings was 2.6% (8 in 313 siblings). All affected relatives are under medical care at the Centro Médico Nacional Siglo XXI, IMSS. In 10 of the 12 affected relatives found, the type of CHD was discordant from that of the IC. Discordance was found also in 9 of 36 IC with two or more CHD. An interpretation is given: if the mutated gene(s) has its effect in early embryological stages, affected relatives may have any type of CHD, but if the alteration occurs later, concordance is expected to be found. This model contributes also in explaining the remarkable genetic heterogeneity that exists in CHD.     

舌鳞癌DNA倍体性和S期细胞比率与其预后关系

对７２例舌鳞癌根治术后病者作随访复查和用流式细胞仪对其石蜡包埋标本作ＤＮＡ含量测量。结果５年生存率为５６．９％，５年内死亡者和５年存活者异倍体率分别为６４．５％和４１．５％（Ｐ＞０．０５），而高Ｓ期细胞比率（ＳＰＦ）分别为９０．３％和４１．５％（Ｐ＜０．０１）。有颈淋巴转移者五年生存率（２８．６％）低于无颈淋巴转移者（６８．６％）（Ｐ＜０．０５）。两者异倍体率和高ＳＰＦ分别有显著差异和非常显著差异。高ＳＰＦ在临床期之间、Ｃ１和Ｇ２之间均有明显差异。提示ＤＮＡ倍体性与舌鳞癌５年生存率无关，而高ＳＰＦ则有密切关系。认为ＳＰＦ作为估测舌鳞癌的预后有较高的价值。