4G/5G variant of plasminogen activator inhibitor-1 gene and severe pregnancy-induced hypertension: subgroup analyses of variants of angiotensinogen and endothelial nitric oxide synthase.

Background: Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3).

Specific ultrasound findings associated with fetal chromosome abnormalities.

Cytogenetic amniocentesis (CA) has been performed as a reliable prenatal diagnostic method for decades. The aims of the present study were to reveal the frequency of fetal chromosome abnormalities according to medical indications of CA, and to assess the risks of specific abnormal ultrasound findings. Data on chromosome karyotypes of fetuses from 5043 Japanese mothers were collected.

Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan.

Objective: To investigate whether somatic mutations in cell cycle checkpoint genes, TP53 and p21, are involved in the development of ovarian cancer with or without BRCA1 germline mutation.

Methods: We analyzed somatic genetic alterations of TP53 and p21 in 46 ovarian cancer patients with BRCA1 germline mutations and 93 sporadic patients, using direct sequencing for the entire coding sequences in TP53 and p21.

Results: TP53 somatic mutations were detected in 25 of the 46 BRCA1 cases and 40 of the 93 sporadic cases (54.

Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and preeclampsia in Japanese patients.

To clarify whether the homozygous deletion (DD) genotype of angiotensin-converting enzyme gene ( ACE) is a genetic risk factor for preeclampsia in Japanese women, we performed ACE genotyping in patients with preeclampsia and healthy pregnant women, and analyzed the relationship between preeclampsia and ACE genotype, taking into account some well-known contributing factors for preeclampsia, such as primiparity, positive family history of hypertension, prepregnancy body mass index < 24, and heterozygosity and homozygosity of T235 (MT+TT) genotypes of the angiotensinogen ( AGT) gene. Among all of the subjects, the frequency of the DD genotype was not different between patients with preeclampsia and controls (16% and 12%, respectively). Regarding primiparity, prepregnancy body mass index < 24, and MT+TT genotypes of AGT, no significant differences in the frequency of the DD genotype of ACE were found between patients with preeclampsia and controls, although in a subgroup positive for family history of hypertension, the frequency of the DD genotype tended to be higher in patients with preeclampsia (25%) than in controls (8%; p = 0.

The egogram is a potent, independent risk factor for hypertension in pregnancy.

To assess the association between the egogram and hypertension in pregnancy (HP), a case-control study was carried out. Seventy-one HP cases, primiparous aged 20 to 34 years, and 109 controls, were enrolled among pregnant women who visited our hospitals for obstetrical care. Data from a self-administered questionnaire containing a Self Grow-Up Egogram (SGE) were subjected to univariate and multivariate analyses with prepregnancy body mass index (BMI) and angiotensinogen (AGT) genotype.

MTHFR C677T Polymorphism and factor V Leiden mutation are not associated with recurrent spontaneous abortion of unexplained etiology in Japanese women.

To determine whether the C677T polymorphism of the methylenetetrahydrofolate reductase ( MTHFR) gene and the Leiden mutation of coagulation factor V (FV) are associated with recurrent spontaneous abortion (RSA) of unexplained etiology in Japanese participants, the genotypes of the two polymorphisms were determined and compared between cases of unexplained RSA and normal pregnant controls. Eighty-three Japanese participants, consisting of 45 women with explained RSA and 38 women with unexplained RSA, and 174 controls were recruited in the study. The frequencies of the T677 allele/TT genotype were not significantly different among women with explained RSA (35.

GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients.

Androgens have an anti-proliferative effect on endometrial cells. Human androgen receptor (AR) gene contains two polymorphic short tandem repeats of GGC and CAG, and a single-nucleotide polymorphism on exon 1 that is recognized by the restriction enzyme, StuI. Prior studies have shown that the lengths of the CAG repeat are inversely and linearly related to AR activity and associated with endometrial cancer.

Human papilloma virus type 16 infection and the early onset of cervical cancer.

Human papilloma viruses (HPV), particularly type 16, have been associated with cervical cancer. It has been noted that the average onset of cervical cancer is occurring in younger women coupled with a higher prevalence of cervical HPV infection. However, the correlation between HPV 16 infection and the early onset of cervical cancer is still unclear.

Distribution of a single nucleotide polymorphism on codon 211 of the androgen receptor gene and its correlation with human renal cell cancer in Japanese patients.

The human androgen receptor (AR) gene contains a single nucleotide polymorphism (SNP) on codon 211 and two polymorphic short tandem repeats of CAG and GGC in the N-terminal domain that may influence transcription efficiency of AR gene. We previously reported that the lengths of the CAG and GGC repeats are inversely and linearly related to AR activity and associated with several cancers. However, little is known about this SNP on codon 211 of the AR gene in human renal cell cancer.

Prenatal trisomy 21 screening using the Lens culinaris agglutinin-reactive alpha-fetoprotein ratio.

For the purpose of improving the clinical efficacy of alpha-fetoprotein (AFP)-L3% in prenatal screening for trisomy 21, we calculated the multiple of the median (MoM) of AFP-L3% (L3 MoM) and the ratio of L3 MoM to AFP MoM (L3 MoM/AFP MoM) in maternal serum. Maternal serum samples from 1822 women (maternal age 37.3 +/- 3.

A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene.

Hypertension in pregnancy (HP) is a multifactorial disease manifested due to a complex combination of environmental factors and several predisposing genes including factors in the renin angiotensin system. The aim of this study was to assess the association between the A1166C variant of the angiotensin II type 1 receptor (AT1) gene and severe HP. We carried out association studies and multivariate analyses including other candidate causal factors of HP such as the M235T variant of the angiotensinogen (AGT) gene, prepregnancy body mass index (BMI), and family history of hypertension in Japanese subjects.

Polymorphisms of the CYP1B1 gene as risk factors for human renal cell cancer.

Purpose: CYP1B1 activates various environmental carcinogens in human tissues, including renal tissues. We hypothesize that certain polymorphisms of the CYP1B1 gene are risk factors for renal cell cancer. The rationale for this hypothesis is that chemical procarcinogenic compounds require metabolic activation by oxidative enzymes such as CYP1B1 to be transformed into potentially carcinogenic forms.

The potential function of steroid sulphatase activity in steroid production and steroidogenic acute regulatory protein expression.

The first step in the biosynthesis of steroid hormones is conversion of cholesterol into pregnenolone. StAR (steroidogenic acute regulatory) protein plays a crucial role in the intra-mitochondrial movement of cholesterol. STS (steroid sulphatase), which is present ubiquitously in mammalian tissues, including the placenta, adrenal gland, testis and ovary, desulphates a number of 3beta-hydroxysteroid sulphates, including cholesterol sulphate.

Association between a variant of the glutathione S-transferase P1 gene (GSTP1) and hypertension in pregnancy in Japanese: interaction with parity, age, and genetic factors.

Hypertension in pregnancy (HP), including preeclampsia (PE), is known to be a multifactorial disease. Recently, an Ile105Val variant of the glutathione S-transferase P1 gene ( GSTP1) was shown to be associated with PE in The Netherlands. We therefore performed an association study of the Ile105Val variant comparing 131 patients with HP and 327 normal pregnant controls in Japan.

The polyglycine and polyglutamine repeats in the androgen receptor gene in Japanese and Caucasian populations.

Human androgen receptor (AR) gene contains two polymorphic trinucleotide repeats of CAG and GGC, which code for polyglutamine and polyglycine tracts in the N-terminal domain in which the receptor activity resides. Longer repeats induce decrease of transactivation function in the AR receptor, weaken an anti-proliferative effect on various steroid-related tissues, and may promote the carcinogenesis of these cancers, such as breast, endometrial, and ovarian cancers. However, the incidences of these steroid-related cancers are remarkably lower in Japanese than in Caucasians.

Cytogenetic analysis of uterine leiomyoma: the size, histopathology and GnRHa-response in relation to chromosome karyotype.

Objective: The aim of this study was to elucidate the clinical characteristics of uterine leiomyomas having abnormal chromosome karyotype.

Study Design: A total of 394 myomas were obtained from 213 patients for cytogenetic analysis. The size (number of nodules=144), histopathology (n=302), and gonadotropin-releasing hormone analogue (GnRHa)-response (n=58) were investigated in relation to chromosome karyotype in myomas.

Steroidogenic acute regulatory protein-binding protein cloned by a yeast two-hybrid system.

Steroidogenic acute regulatory (StAR) protein plays a key role in the transport of cholesterol from the outer mitochondrial membrane to the inner membrane. A StAR mutant protein lacking the first 62 amino acids (N-62 StAR protein) has been reported to be as effective as wild-type StAR protein. In the present study, we examined the mechanism by which StAR protein stimulates steroidogenesis.

Live birth rate varies with gestational history and etiology in women experiencing recurrent spontaneous abortion.

Objectives: The aims of this study were to assess pregnancy outcome in relation to etiologic factors of recurrent spontaneous abortion (RSA).

Study Design: The pregnancies from consecutive 216 RSA women were assessed for live birth rates (LBR) according to etiology. The LBR in 110 pregnancies from RSA women with unexplained etiology was investigated according to various therapies.

Hypermethylation can selectively silence multiple promoters of steroid receptors in cancers.

Multiple promoters and differential splicing of 5' upstream exons are often found in various nuclear receptor genes including steroid receptors. Three promoters control the expression of human estrogen receptor alpha (ERalpha) isoforms: ERalpha-A, ERalpha-B, and ERalpha-C, and two promoters control the expression of human progesterone receptor (PR) isoforms: PR-A and PR-B. The expression levels of these isoforms differ with respect to each other in certain target tissues.

CYP1B1 gene in endometrial cancer.

Metabolic activation of estradiol has been shown to be a key factor in endometrial carcinogenesis. 4-hydroxy estrogens (CYP1B1 metabolites) received particular attention because of their causative role in malignant transformation of various organs including endometrium. CYP1B1 displays the highest level of expression in endometrium.

Estrogen receptor alpha polymorphisms and renal cell carcinoma--a possible risk.

Renal cell carcinoma is the most common form of kidney cancer. However, the genetic basis of renal cancer is not fully understood. Estrogens and their receptors (ERs) have been shown to play a role in various cancers and it is speculated that they can also affect the human kidney.

Combined use of magnetic resonance imaging, CA 125 assay, histologic type, and histologic grade in the prediction of lymph node metastasis in endometrial carcinoma.

Objective: The aim of this study was to predict retroperitoneal lymph node metastasis during the preoperative examination of patients with endometrial carcinoma and to determine whether lymphadenectomy must be performed.

Study Design: This study was carried out on 214 patients with endometrial carcinoma. Preoperative evaluators were volume index, depth of myometrial invasion (as assessed by magnetic resonance imaging), serum CA 125 level, histologic type, and histologic grade.

Cytoreductive surgery combined with organ resection for advanced ovarian carcinoma.

Background: The survival effects of combined organ resection in cytoreductive surgery for advanced ovarian carcinoma with regard to the site and the number of organs involved have not yet been clarified.

Methods: Data obtained from 143 patients with stage III/IV ovarian carcinoma were used for analysis. Combined organ resection (COR) was employed in 21 patients in whom optimal cytoreduction (defined as a residuum View Article and Find Full Text PDF

Lipopolysaccharide induces interleukin-8 production by human cervical smooth muscle cells.

Objective: We examined the effect of lipopolysaccharide (LPS), a component of the outer wall of gram-negative bacteria, on expression of the neutrophil chemoattractant interleukin-8 (IL-8) and the effects of IL-8 treatment on release of matrix metabolizing enzymes in human cervical smooth muscle cells (CSMCs).

Methods: Human CSMCs were exposed to Escherichia coli LPS, and the expression of IL-8 mRNA was analyzed by Northern blotting. The IL-8 promoter activity was examined by dual luciferase assay, and the IL-8 concentration was assessed by enzyme-linked immunosorbent assay.

Increased levels of interleukin-6 in cervical secretions and assessment of the uterine cervix by transvaginal ultrasonography predict preterm premature rupture of the membranes.

Objective: The objective of this study was to investigate the predictive factors of premature rupture of the membranes (preterm PROM).

Methods: The study was undertaken with cervical secretions collected from 72 consenting singleton pregnant women between 20 and 33 weeks of gestation. The levels of interleukin (IL) 1alpha, IL-1beta, IL-6, IL-8, matrix metalloproteinase (MMP) 1, MMP-2, MMP-9, tissue inhibitors of matrix metalloproteinase (TIMP) 1, TIMP-2, granulocyte elastase, and fetal fibronectin in cervical diluted specimens were measured by immunoassay, and the uterine cervix was assessed by transvaginal ultrasonography.