胎盘组织中胰岛素样生长因子 -Ⅰ的定位及定量分析

目的探讨胎盘组织中胰岛素样生长因子Ⅰ（ＩＧＦⅠ）定位，评估ＩＧＦⅠ在胎儿生长发育中的作用。方法用免疫组化法对妊娠胎盘组织中ＩＧＦⅠ细胞进行定位，并采用计算机医学图像分析系统，检测小于胎龄儿（ＳＧＡ）组２２例，适于胎龄儿（ＡＧＡ）组２５例及大于胎龄儿（ＬＧＡ）组２５例的ＩＧＦⅠ，并进行定量分析。用ｔ检验法进行各组间均数检验。结果（１）胎盘ＩＧＦⅠ主要位于绒毛小叶的合体滋养细胞及细胞滋养细胞。此外，也存在于Ｈｏｆｂａｕｅｒ细胞及平滑绒毛层，但染色较以上两种细胞明显减弱，胎膜的羊膜细胞及蜕膜细胞偶尔可见阳性，而绒毛小叶蜕膜细胞则未见阳性着色。（２）与ＡＧＡ组比较，ＳＧＡ组胎盘ＩＧＦⅠ的相对面积及平均吸光度均显著降低（ｔ＝４．６５，Ｐ＜０．００１、ｔ＝２．１５，Ｐ＜０．０５），而ＬＧＡ组胎盘ＩＧＦⅠ的相对面积及平均吸光度均显著升高（ｔ＝８．７２，Ｐ＜０．００１；ｔ＝７．８２，Ｐ＜０．００１）。结论胎盘组织中ＩＧＦⅠ主要定位于胎盘小叶的合体滋养细胞、细胞滋养细胞；胎盘组织合成和分泌ＩＧＦⅠ的多少，与发生ＬＧＡ及ＳＧＡ有关。     

羊水栓塞样血浆对离体肺循环的影响

目的：观察羊水栓塞样血浆（ＡＦＥＰ）与布洛芬血浆对兔离体灌流肺的影响。方法：羊水与血培养后离心制得ＡＦＥＰ，羊水、血和布洛芬一起培养后离心制得布洛芬血浆，在保持呼吸循环功能完整的兔离体肺灌流模型上，分别从肺动脉注入１０ｍｌＡＦＥＰ、布洛芬血浆、原羊水、羊水基液、兔血浆，用计算机系统记录肺动脉压、呼吸压和肺水肿发生情况，并与生理盐水灌流的兔离体肺（对照组）比较。结果：ＡＦＥＰ能导致肺动脉压明显升高（３．５２±０．６４ｋＰａ）（１ｋＰａ＝７．５ｍｍＨｇ）和肺水肿形成，布洛芬（１０ｍｇ／Ｌ）能降低ＡＦＥＰ所致的肺动脉高压（１．８７±０．４３ｋＰａ）和减轻肺水肿，原羊水、羊水基液和兔血浆均不能引起肺动脉压升高和肺水肿形成。结论：羊水进入血液循环可使血细胞释放血管活性物质并引起肺病变，布洛芬能部分缓解ＡＦＥＰＬ对肺的损害。     

胎盘组织中胰岛素样生长因子—I的定位及定量分析

目的 探讨胎盘组织中胰岛素样生长因子－Ｉ（ＩＧＦ－Ｉ）定位,评估ＩＧＦ－Ｉ在胎儿生长发育中的作用。方法 用免疫组化法对对妊娠胎盘组织中ＩＧＦ－Ｉ细胞进行定位,并采用计算机医学图像分析系统,检测小于胎龄儿（ＳＧＡ）组２２例,适于胎龄儿（ＡＧＡ）组２５例及大于胎龄儿（ＬＧＡ）组２５例的ＩＧＦ－１,并进行定量分析,用ｔ检验法进行各组间均数检验。结果 （１）胎盘ＩＧＦ－Ｉ主要位于绒毛小叶的合体滋养细胞滋养     

人卵巢癌细胞分泌转化生长因子－β对外周血单个核细胞增殖的影响

观察人卵巢癌细胞株ＣＯＣ＿１和ＣＯＣ＿２来源的患者癌性腹水（ＡＳ＿１，ＡＳ＿２）、癌细胞无血清条件培养液（ＳＦＣＭ＿１，ＳＦＣＭ＿２）及荷瘤裸鼠血清（ＮＳ＿１，ＮＳ＿２）对植物血凝素（ＰＩＩＡ）和白细胞介素－２（ＩＬ－２）诱导的外周血单个核细胞（ＰＢＭＣ）增殖的作用，及与转化生长因子－β（ＴＧＦ－β）的关系。结果：ＡＳ＿１和ＡＳ＿２对ＰＢＭＣ增殖有剂量依赖性抑制作用。ＳＦＣＭ和ＮＳ也具有明显抑制ＰＢＭＣ增殖的作用；但在浓度很低时，ＳＦＣＭ＿２对ＰＨＡ诱导，ＳＦＣＭ＿１、ＮＳ＿１和ＮＳ＿２对ＩＬ－２诱导的ＰＢＭＣ增殖，具有一定促进作用。上述作用特点与ＴＧＦ－β作用相似，并可被抗ＴＧＦ－β中和抗体部分阻断。提示：人卵巢癌细胞可通过产生ＴＧＦ－β，抑制宿主免疫。     

环孢菌素A增强顺铂抗癌作用的实验研究

目的：观察环孢菌素Ａ对顺铂抗癌作用的增强效应。方法：采用人卵巢腺癌ＣＯＣ１细胞及其耐药亚株ＣＯＣ１／顺铂（ＤＤＰ）细胞，在裸鼠体内外观察免疫抑制剂环孢菌素Ａ（ＣｓＡ）对ＤＤＰ抗癌作用的增效作用。结果：１～５μｇ／ｍｌ的ＣｓＡ与ＤＤＰ联合应用，可增强对ＣＯＣ１细胞的杀伤作用，表明有协同效应，２ｍｇ／Ｌ的ＣｓＡ可基本克服ＣＯＣ１／ＤＤＰ中等水平的耐药性，其增效作用呈浓度依赖关系。氚－胸腺嘧啶核苷掺入实验表明，ＤＤＰ佐以ＣｓＡ可增强对卵巢癌细胞ＤＮＡ合成的抑制，降低瘤细胞增殖速度。裸鼠体内抑癌实验也证实了体外实验的结果。结论：ＣｓＡ有可能作为ＤＤＰ的增效剂，用于卵巢癌的治疗。     

胎儿幼稚红细胞产前遗传学诊断的研究

目的：探讨利用早期孕妇血中胎儿幼稚红细胞，进行无创伤性胎儿染色体异常产前诊断的可行性。方法：对１３例孕早期（８～１４周）已知孕男性胎儿孕妇外周血中糖蛋白Ａ（ＧＰＡ）表达阳性的细胞，进行荧光激活细胞分离（ＦＡＣＳ）及Ｙ染色体特异的引物介导原位标记（ＰＲＩＮＳ）检测，同时在测定４１例正常孕妇孕早期（８～１４周）血清妊娠相关血浆蛋白Ａ（ＰＡＰＰ┐Ａ）作为正常参考值的基础上，对５例可疑孕Ｄｏｗｎ′ｓ综合征胚胎的高龄孕妇进行ＰＡＰＰ┐Ａ检测、ＧＰＡ阳性细胞的ＦＡＣＳ及２１号染色体ＰＲＩＮＳ检测。结果：１３例孕男性胎儿的孕妇血ＧＰＡ阳性细胞中，胎儿幼稚红细胞的平均含量达到１４．５％；５例高龄孕妇血清ＰＡＰＰ┐Ａ均在正常范围内，ＧＰＡ阳性细胞中胎儿幼稚红细胞的２１号染色体ＰＲＩＮＳ检测未见异常。结论：早期孕妇血中存在胎儿幼稚红细胞，并可利用这些细胞对胎儿染色体非整倍性异常进行产前分子┐细胞遗传学诊断。     

离体异位子宫内膜细胞中单核细胞趋化蛋白-1的测定

目的　探讨异位子宫内膜细胞产生单核细胞趋化蛋白１（ＭＣＰ１）的临床意义。方法　收集１５ 例子宫内膜异位症患者的异位内膜组织进行体外细胞培养,分别加入纯培养液（ 对照组） 、含白细胞介素１β（ＩＬ１β）２ ｎｇ／ｍｌ（ＩＬ１β诱导组）及肿瘤坏死因子α（ＴＮＦα）２０ ｍｇ／ｍｌ（ＴＮＦα诱导组）的培养液培养４ 小时,应用斑点杂交、免疫组织化学及夹心酶联免疫吸附试验检测各组异位细胞中ＭＣＰ１ｍＲＮＡ蛋白的表达水平及其培养上清中ＭＣＰ１ 的含量。结果　与对照组相比,异位内膜细胞经ＩＬ１β及ＴＮＦα作用后表达的ＭＣＰ１ ｍＲＮＡ和蛋白水平显著增加（ Ｐ＜ ０．０１ ,Ｐ＜０．０５）;培养上清中ＭＣＰ１ 的含量也显著增加（Ｐ＜０ ．０１ ,Ｐ＜ ０．０５）。结论　ＩＬ１β及ＴＮＦα可刺激异位内膜细胞中ＭＣＰ１ 的表达显著增加,这可能和子宫内膜异位症的病变发展有关。     

米非司酮及R_（2323）对离体培养人子宫内膜细胞PA与PAI－1生成的影响

孕酮拮抗剂米非司酮（ＲＵ４８６）在离体下对人子宫内膜间质细胞分泌组织型纤溶酶元激活因子（ｔＰＡ）及腺体细胞分泌尿激酶型纤溶酶元激活因子（ｕＰＡ）均有刺激作用，并抑制两种细胞分泌纤溶酶元激活因子的抑制因子（ＰＡＩ－１），其作用与孕酮相反。内美通（Ｒ２３２３）抑制ｔＰＡ和ｕＰＡ而刺激ＰＡＩ－１在二种细胞中的分泌，其作用与孕酮一致。提示ＲＵ４８６催经止孕、Ｒ２３２３抑制异位子宫内膜作用有可能是通过影响两种ＰＡ和ＰＡＩ—１的平衡介导的。     

抗孕激素RU486和ZK98734对双池培养的颗粒细胞和内泡膜细胞分泌功能…

本文观察了ＲＵ４８６和ＺＫ９８７３４对培养在羊膜双池培养系统中的猪卵巢颗粒细胞和内泡膜细胞在甾体激素生成过程中的影响。生长在单膜两侧的颗粒细胞和内泡膜细胞在加入或不加ＦＳＨ、ＬＨ及不同浓度ＲＵ４８６或ＺＫ９８７３４的条件下培养４８ｈ。用ＲＩＡ测定内、外池培养液中的孕酮（Ｐ）和雌二醇（Ｅ２）的浓度并与单独培养的结果相比较，同时亦与大鼠颗粒细胞的结果作比较。结果表明：１．有ＦＳＨ刺激时，两种抗孕激素均     

宫颈阴道分泌物绒毛促性腺激素和甲胎蛋白检测在胎膜 …

目的 探讨宫颈阴道分泌物绒毛膜促激素（ｈＣＧ）和甲胎蛋白（ＡＦＰ）检测，在胎膜早破诊断中的价值。方法 对２０８例胎膜早破发和１２０例正常孕妇的宫颈阴道分泌物进行ｈＣＧ和ＡＦＰ检测。结果 ｈＣＧ诊断胎膜早破的准确率９３．３％，敏感性９４．２％，特异性９１．７％；ＡＦＰ诊断胎膜早破准确率９２．１％，，特异性９１．８％，ＡＦＰ诊断胎膜早破的准确率９２．１％，敏感性８９．４％，特异性９６．７８％。二者差异     

Ovarian Mixed Germ Cell Tumor Composed of Polyembryoma and Immature Teratoma

We report the case of a 41-year-old woman with ovarian mixed germ cell tumor which was composed of polyembryoma and immature teratoma and who had high serum levels of α-fetoprotein (AFP) and human chorionic gonadotropin (hCG). By immunohistochemical methods, AFP was found in yolk sac cells of the embryoid bodies and immature hepatoid tissues, and hCG was found in giant syncytiotrophoblastic cells. She was treated with surgery followed by cisplatin-based combination chemotherapy. She is well, and her serum levels of AFP and hCG have not been elevated for more than 4 years after the treatment.     

The capacity for differentiation and production of human chorionic gonadotropin and alpha-fetoprotein in human embryonal carcinoma cell lines

The capacity for differentiation of five human embryonal carcinoma (EC) cell lines was studied by examination of the morphology of xenograft tumors in nude mice. In addition to morphology, differentiation into extraembyronic elements was studied by examining the evidence of human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) production. The EC cell lines can be divided into two groups: pluripotent (NEC 14 and Tera 2) and nullipotent (NEC 8, NEC 15, and ITO-II) cell lines. In nude mice, the pluripotent NEC 14 and Tera 2 cells produced EC mixed with various somatic elements such as glandular, neuronal, and cartilaginous tissue. However, typical extraembryonic elements, such as choriocarcinoma and yolk sac elements, were not usually observed. Production of hCG and/or AFP was identified in the tumors by both radioimmunoassay and the immunoperoxidase reaction. These results indicate that some human EC cell lines retain the capacity for differentiation into somatic and extraembryonic elements and that hCG and/or AFP appears to be produced by transitional types of cells that still retain the morphology of EC cells.     

Linkage of human chorionic gonadotrophin and placental lactogen biosynthesis to trophoblast differentiation and tumorigenesis

Normal trophoblast of the human placenta elaborates at least two major protein hormones, chorionic gonadotrophin (hCG) and placental lactogen (hPL). Molar and choriocarcinoma tissues characteristically synthesize large amounts of hCG and hPL. To examine the role of trophoblast differentiation in the expression of the hCG and hPL genes, we studied the cytological distribution of their mRNAs in tissue sections of human hydatidiform mole and choriocarcinoma by in situ hybridization. Histologically, these tissues are in different stages of cellular differentiation. In normal placenta, hCG alpha/beta mRNA can be localized to some cytotrophoblasts and primarily to the syncytium, whereas hPL mRNA appears only in the syncytial layer. In hydatidiform mole, which still retains placental villous morphology, the hPL gene and hCG alpha and beta genes are expressed but are poorly localized because of the admixture of cyto- and syncytiotrophoblasts. By contrast, choriocarcinoma, which is devoid of placental villous pattern but in which the cyto- and syncytiotrophoblast-like components are distinguishable, expresses hCG alpha and beta in the syncytial-like areas but little, if any, hPL. These results suggest that a certain level of trophoblast differentiation, such as villous formation, is associated with hPL expression, while the hCG alpha gene and the hCG beta gene can be expressed in more disorganized tissues which contain cytotrophoblastic elements.     

Detection of maternal serum hCG glycoform variants in the second trimester of pregnancies affected by Down syndrome using a lectin immunoassay

AIM: To assess whether glycoform variants of human chorionic gonadotrophin (hCG) are present in altered concentrations in the maternal serum in pregnancies affected by Down syndrome. METHODS: In a series of 50 cases of pregnancies complicated by Down syndrome and 278 unaffected pregnancies, we have examined maternal serum levels of hCG glycoforms (GlyhCG) in samples collected in the second trimester (14 to 21 weeks) using a sialic acid binding lectin immunoassay. We have compared these levels with those of other second trimester serum markers (Free beta-hCG, alpha fetaprotein (AFP) and Total hCG) and modelled detection rates and false positive rates of various biochemical markers in conjunction with maternal age using a maternal age standardized population. RESULTS: Maternal serum GlyhCG in cases of Down syndrome was significantly elevated (Median MoM 1.81) with 15 of 50 (30%) cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (Median MoM 2.16) with 18 of 50 (36%) cases above the 95th centile. AFP levels were reduced (Median MoM 0.75) with 9 of 50 (18%) cases below the 5th centile. Total hCG levels whilst elevated (Median MoM 1.88) had only 15 of 50 (30%) cases above the 95th centile. Maternal serum GlyhCG levels showed significant correlation with total hCG and free beta-hCG (r = 0.6880 and 0.6922) in the Down group but not with AFP (r = 0.1237). When GlyhCG was combined together with AFP and maternal age, at a 5% false positive rate, the modelled detection rate was 53%, some 13% lower than when free beta-hCG was used and some 7% lower than when total hCG was used. CONCLUSION: Maternal serum GlyhCG, as measured by the sialic acid-binding lectin immunoassay is unlikely to be of additional value when screening for Down syndrome in the second trimester.     

Screening for triploidy by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation

In 25 cases of triploidy at 10-14 weeks of gestation, compared with 947 controls, the median multiple of the median (MoM) fetal nuchal translucency (NT) thickness was significantly increased (1.89 MoM), and maternal serum total and free beta-human chorionic gonadotrophin (hCG) were increased (3.13 MoM and 4.59 MoM respectively), alpha fetoprotein (AFP) was increased (2.14 MoM), and pregnancy associated plasma protein A (PAPP-A) was decreased (0.12 MoM). There are two types of triploidy. In type I, where the additional chromosome set is of paternal origin, the placenta is partially molar and the fetus is relatively well-grown. Type II, where the extra chromosome set is of maternal origin, is characterized by a small normal looking placenta and severe asymmetrical fetal growth restriction. In type I triploidy there was increased fetal NT (2.76 MoM), maternal serum total hCG (4.91 MoM), free beta-hCG (8.04 MoM), and AFP (3.22 MoM), and mildly decreased PAPP-A (0.75 MoM). In type II triploidy fetal NT was not increased (0.88 MoM), and there was a decrease in maternal serum total hCG (0.16 MoM), free beta-hCG (0.18 MoM), PAPP-A (0.06 MoM) and AFP (0.77 MoM). We conclude that a large proportion of triploidy cases of both phenotypes could be identified in the first trimester using NT, maternal serum free beta-hCG and PAPP-A with a combination of trisomy 21 risk and an atypicality approach.     

Alteration in age-specific risks for chromosomal trisomy by maternal serum alpha-fetoprotein and human chorionic gonadotropin screening.

Maternal serum screening for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) increases the detection rate of Down's syndrome (DS) pregnancies. To estimate the risk of a DS pregnancy for a particular woman, Wald et al. combine a trivariate function of AFP, hCG, and unconjugated oestriol with age-specific risk. Calculation of independent likelihood ratios (LRs) for AFP and hCG has allowed us to examine the predictive value of each test alone and the combination. AFP and hCG were measured in stored serum samples from 672 normal, 8 trisomy 21 (DS), 9 trisomy 18, and 2 trisomy 13 pregnancies. AFP and hCG multiples of the median (MOM) were calculated for each sample. The LRs for AFP MOM and hCG MOM were calculated and combined with age-specific risk. Of eight DS pregnancies, six had increased risk based on age and AFP. Addition of hCG detected two additional DS pregnancies. Of nine trisomy 18 pregnancies, four (44 per cent) had hCG MOM under 0.25. Three out of nine would have been classified as high risk by AFP, but none by combined AFP and hCG. Amniocentesis would have been recommended in 74 per cent of aneuploid pregnancies if both age and serum screening were used. Abandonment of amniocentesis based on age alone would have excluded two abnormal pregnancies from detection. Screening programmes should note that combined risk figures are specific for DS and do not include other trisomies. Detection of other trisomies requires inclusion of low hCG level as a discriminator and continuation of age-based testing.     

Amniotic fluid human chorionic gonadotrophin and alpha-fetoprotein levels in pregnancies conceived after assisted reproduction

OBJECTIVES: To study the alteration in the second-trimester maternal serum levels of human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) in pregnancies conceived after assisted reproduction. METHODS: We compared the amniotic fluid hCG and AFP concentrations of 45 pregnancies with fresh embryo transfer and 25 pregnancies with frozen-thawed embryo transfer with 269 spontaneous pregnancies. Wilcoxon rank-sum test was used for analysis. RESULTS: The median amniotic fluid hCG MoM in pregnancies conceived after frozen-thawed embryo transfer was significantly increased to 1.41 compared to 1.00 (p = 0.01) in naturally occurring pregnancies and 0.96 (p = 0.049) in pregnancies after fresh embryo transfer. Further analysis showed that this was only observed in frozen embryos fertilized by conventional insemination with MoM of 1.59. The AFP MoMs were similar among the groups. CONCLUSIONS: The observed raised amniotic fluid hCG level in IVF-FET pregnancies may reflect the elevated maternal serum level in these pregnancies. Further studies should be directed towards exploring the underlying pathophysiology.     

First trimester maternal serum AFP and total hCG in aneuploidies other than trisomy 21

Total human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) were measured in maternal serum at 10-14 weeks of gestation from 53 pregnancies affected by trisomy 18, 42 cases with trisomy 13, 46 with Turner's syndrome and 13 with other sex aneuploides. The only significant association was the finding of reduced levels of total hCG in cases of trisomy 18 and 13. The association of increased levels of AFP in cases of trisomy 18 with ventral wall defects and the slight increase in AFP in cases of sex chromosomal anomalies other than Turner's syndrome was found. AFP and total hCG are not likely to replace the markers free beta-hCG and PAPP-A in first trimester screening for chromosomal anomalies.     

Risk of fetal Down's syndrome based on maternal age and varying combinations of maternal serum markers

Serum samples from 320 women with chromosomally normal fetuses and from 50 women with fetuses affected by Down's syndrome were assayed retrospectively for human chorionic gonadotropin (hCG), pregnancy-specific β ₁ glycoprotein (SP1), alpha fetoprotein (AFP), and unconjugated estriol (uE3) between 14 and 21 weeks of gestation. Nonparametric discriminant analysis was applied to calculate Down syndrome risks on the basis of various combinations of serum parameters. At a risk threshold that falsely identifies 5% of controls as being affected, 46 to 48% of Down syndrome pregnancies were detected by combinations of hCG/AFP, hCG/AFP/uE3, and hCG/AFP/uE3/SP1 respectively. HCG, AFP, and uE3 were assayed in 652 serum samples from women who underwent amniocentesis because of maternal age (≥35 years in this prospective study). 49% of women with euploid fetal karyotype, 8 of 10 pregnancies with Down's syndrome, and 3 pregnancies with sex chromosomal anomalies were identified as being at an increased risk (>1:380). Received: 30 June 1993 / Accepted: 26 January 1994     

Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities

The alpha subunit of human chorionic gonadotropin (alpha-hCG), human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) were measured in the serum of 25 women with chromosomally abnormal fetuses between 18 and 25 weeks of gestation and in 74 normal pregnancies. AFP levels less than 0.5 multiples of the median (MoM) or greater than 2.5 MoM were observed in 24 per cent of the abnormal pregnancies and in 6.76 per cent of the normal pregnancies. A low concentration of hCG (less than 0.25 MoM) was observed in 8 per cent of abnormals and in 2.7 per cent of normals while an elevated concentration of hCG (greater than 2.5 MoM) was observed in 56 per cent of abnormals and in 1.35 per cent of normals. Elevated hCG-alpha (greater than 2.5 MoM) was observed in 28 per cent of abnormals and in none of the normals. Determination of elevated levels of hCG-alpha or hCG resulted in detection of 68 per cent of pregnancies with chromosomally abnormal fetuses with a false positive rate of 1.35 per cent. Determination of both elevated and depressed gonadotropin levels resulted in detection of 76 per cent of abnormal pregnancies with a false positive rate of 4.05 per cent. Measurement of hCG and hCG-alpha in maternal serum samples can be used as a screening procedure for detecting pregnancies at risk for fetal chromosome abnormalities.