Mechanism of Vitamin D Receptor Ligand-Binding Domain Regulation Studied by gREST Simulations.

The vitamin D receptor ligand-binding domain (VDR-LBD) undergoes conformational changes upon ligand binding. In this nuclear receptor family, agonistic or antagonistic activities are controlled by the conformation of the helix (H)12. However, all crystal structures of VDR-LBD reported to date correspond to the active H12 conformation, regardless of agonist/antagonist binding.

Isolation of Jahanene and Jahanane, and Total Synthesis of the Jahanyne Family.

Two new jahanyne analogues, jahanene and jahanane, highly N-methylated lipopeptides, were isolated from a marine cyanobacterium Okeania sp., and their structures were determined by NMR and MS. In addition, we achieved total syntheses of the jahanyne family and assessed their activities.

A-kinase anchoring protein 3 messenger RNA expression in ovarian cancer and its implication on prognosis.

A-kinase anchoring protein 3 (AKAP3) is a sperm protein and its expression appears to be restricted to the testis in normal adult tissues. We investigated AKAP3 mRNA expression in 20 normal ovaries and 54 ovarian cancers of different histological types, grades and stages by reverse transcription-polymerase chain reaction (RT-PCR). The PCR products were analyzed by conventional agarose gel electrophoresis and capillary electrophoresis on a microtip device to determine the expression semiquantitatively.

Expression and potential roles of pregnane X receptor in endometrial cancer.

Estrogen has been shown to contribute greatly to growth and development in endometrial cancer. And recent research has suggested that intratumoral production of estrogen may play important roles in this cancer tissue. On the other hand, pregnane X receptor (PXR), a new member of nuclear receptors, has been shown to mediate the genomic effects of steroid hormones, including estrogen and xenobiotics.

Increased plasma adrenomedullin in women with recurrent pregnancy loss.

Objective: To evaluate vascular changes and uterine perfusion in women with recurrent pregnancy loss.

Methods: We measured plasma levels of adrenomedullin of 100 pregnant women in the midluteal phase of a nonpregnant cycle (control group: n = 62; recurrent pregnancy loss group: n = 38). We measured the pulsatility index (PI) in the uterine arteries by transvaginal pulsed Doppler ultrasonography at the same time.

Nafamostat mesilate suppresses NF-kappaB activation and NO overproduction in LPS-treated macrophages.

Nafamostat mesilate (NM), a clinically used serine protease inhibitor, suppressed the overproduction of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in RAW264.7 murine macrophages treated with lipopolysaccharide (LPS, 100 ng/ml); however, it had little effect on endothelial NOS (eNOS) in human umbilical vein endothelial cells (HUVEC). Electrophoretic mobility shift assay (EMSA) revealed that LPS activated nuclear factor-kappaB (NF-kappaB) in RAW264.

The relationship between Doppler indices from inferior vena cava and hepatic veins in normal human fetuses.

This study was conducted to determine the gestational age-related reference range of the preload index [peak velocity during atrial contraction (A)/peak velocity during ventricular systole (S)] for the inferior vena cava (IVC), the right hepatic vein, the middle hepatic vein and the left hepatic vein. The slope and the intercept of the regression line for each preload index were compared among the 4 veins using analysis of covariance. Doppler measurements were obtained for the 4 veins of 316 normal fetuses at 22-40 weeks of gestation.

Changes in the aortic and pulmonary diameters in a fetus with hypoplastic left heart syndrome.

We diagnosed hypoplastic left heart syndrome in a 26-week-old fetus using fetal echocardiography. Color Doppler ultrasonography was helpful for evaluating the structural abnormalities. The diameters of the aorta and the pulmonary artery were measured periodically from 26 to 38 weeks of gestation.

Prediction markers for respiratory distress syndrome: evaluation of the stable microbubble test, surfactant protein-A and hepatocyte growth factor levels in amniotic fluid.

Surfactant treatment in infants with respiratory distress syndrome (RDS) has decreased neonatal mortality. With the advent of this therapy, it has become important to predict accurately the fetal lung maturity of a fetus before delivery. We evaluated the stable microbubble test (SMT), surfactant protein-A (SP-A) and hepatocyte growth factor (HGF) in amniotic fluid as predicting markers for RDS.

Involvement of peroxynitrite in LPS-induced apoptosis of trophoblasts.

Objective: To examine whether or not peroxynitrite was involved in trophoblastic apoptosis induced by a bacterial endotoxin, lipopolysaccharide (LPS).

Methods: Levels of nitrite/nitrate, stable metabolites of nitric oxide (NO), in culture medium of trophoblasts, were determined using Griess reagents. Trophoblastic apoptosis was identified morphologically and confirmed using in situ nick end labeling technique.

[Paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy in elderly patients].

To evaluate the validity of administration of paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy in elderly patients with gynecologic cancer, we explored the efficacy and safety of these regimens. From October 1, 1998 to September 30, 2001, we administered paclitaxel and carboplatin with or without THP-ADR pursuant to the chart we prepared originally as first line chemotherapy in patients with gynecologic cancer. Eleven elderly patients (age > 70 years) and 62 younger patients (age < 70 years) were entered into the present study.

Impaired uterine arterial blood flow in pregnant women with recurrent pregnancy loss.

Objective: This study was undertaken to evaluate uterine perfusion, which regulates uterine receptivity, in women with recurrent pregnancy loss.

Methods: We evaluated the blood flow resistance in the uterine arteries of 104 pregnant women at 4 to 5 weeks' gestation by transvaginal pulsed Doppler ultrasonography (control group, n = 52; and recurrent pregnancy loss group, n = 52). Blood tests for antinuclear and antiphospholipid antibodies were also performed.

Cervical carcinoma with full-thickness stromal invasion: efficacy of dynamic MR imaging in the assessment of parametrial involvement.

The purpose of this study was to investigate the efficacy of dynamic MR imaging in the assessment of parametrial involvement by cervical carcinoma with full-thickness stromal invasion on thin-section oblique axial T2-weighted images. Dynamic MR images of 24 patients with cervical carcinoma with full-thickness stromal invasion on thin-section oblique axial T2-weighted images were evaluated with pathologic correlation. Dynamic MR imaging was performed using a turboFLASH, 3D-FISP, or 2D-FLASH technique.

Differential blood flow in uterine, ophthalmic, and brachial arteries of preeclamptic women.

Objective: To develop a method that employs noninvasive, pulsed Doppler ultrasonography combined with measurement of flow-mediated vasodilation to evaluate characteristic endothelial dysfunction in various degrees of preeclampsia.

Methods: Uterine, ophthalmic, and brachial arterial blood flow of 99 pregnant women (control group [n = 32], non-preeclamptic intrauterine growth restriction group (n = 15), mild preeclampsia group [n = 25], and severe preeclampsia group [n = 27]) were evaluated by pulsed Doppler ultrasound or flow-mediated vasodilation.

Results: Uterine, orbital, and brachial circulation were altered in preeclampsia, whereas no significant differences were observed between the non-preeclamptic intrauterine growth restriction and control groups.

Bisphenol A stimulates NO synthesis through a non-genomic estrogen receptor-mediated mechanism in mouse endothelial cells.

Biological actions of bisphenol A (BPA), an environmental chemical, have not been fully elucidated. We studied effect of BPA on nitric oxide (NO) synthesis in the murine endothelial cell line, MSS31. BPA (1-100 microM) increased nitrite/nitrate, a stable metabolites of NO, levels in culture medium of MSS31.

A long-term transdermal nitric oxide donor improves uteroplacental circulation in women with preeclampsia.

Objective: To determine the effects of long-term transdermal administration (range, 4-30 days; mean +/- SD, 11.1+/-7.2 days) of isosorbide dinitrate, a nitric oxide donor, in preeclamptic women.

The biological effects of antiadhesion agents on activated RAW264.7 macrophages.

The objective of this study is to determine the biological effects of various antiadhesion agents on macrophages, which play an essential role in wound healing and adhesion. To determine these effects, RAW264.7 macrophages were activated with lipopolysaccharide in the presence of antiadhesion agents: oxidized regenerated cellulose (oxyC), sodium hyaluronate (HA), dexamethasone (Dex), or chondroitin sulfate (CS).

[The effect of L-Glutamine and Shakuyaku-Kanzo-to for paclitaxel-induced myalgia/arthralgia].

Myalgia/arthralgia is a crucial side effect of paclitaxel, and may become the major dose-limiting side effect. However, this is a situation where there is little effective preventive treatment. L-Glutamine was reported as a neuroprotective agent for vincristine-induced neurotoxicity.

Inhibition of placental ornithine decarboxylase by DL-alpha-difluoro-methyl ornithine causes fetal growth restriction in rat.

The roles of polyamines in intrauterine growth restriction (IUGR) is studied. The DL-alpha-difluoromethyl ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC) which is a rate limiting enzyme of polyamine synthesis was administrated to pregnant rats so that we obtained rat fetuses with IUGR. The changes of maternal nutrition, damage of the placenta, and the direct effect of DFMO on the fetus were examined in this IUGR model.

Effect of a nitric oxide donor on the ophthalmic artery flow velocity waveform in preeclamptic women.

Objective: To evaluate the effects of an antihypertensive agent on the orbital circulation of preeclamptic women.

Methods: We studied the ophthalmic arteries of 10 healthy pregnant women and 10 women with severe preeclampsia by pulsed Doppler ultrasonography and evaluated the effect of transdermal isosorbide dinitrate, a nitric oxide donor, on preeclamptic women.

Results: The average pulsatility index and resistive index were significantly lower, whereas the average end-diastolic velocity, time-averaged mean peak velocity, and peak ratio, which quantifies characteristic changes in the ophthalmic artery flow velocity waveform, were higher in preeclamptic women.

Rapid and sensitive detection of physical status of human papillomavirus type 16 DNA by quantitative real-time PCR.

A rapid quantitative real-time PCR method was employed to quantify the copy number of E2 and E6 genes for analysis of the physical status of human papillomavirus type 16 (HPV-16) DNA. Significant differences with respect to both copy numbers were found when more than 40% of HPV-16 DNA was integrated with disruption of the E2 gene in an experimental model. The physical status of HPV-16 DNA in 50 clinical samples was exclusively episomal in 21 cases (42%), concomitant in 14 cases (28%), and integrated in 15 cases (30%).

Neoadjuvant treatment with docetaxel and the effects of irradiation for human ovarian adenocarcinoma and cervical squamous cell carcinoma in vitro.

The in vitro radiosensitizing effects of docetaxel have been reported, but the DNA damage caused by the irradiation after docetaxel exposure has not been investigated. In this study, the authors attempted to evaluate the radiosensitizing effects in terms of cell survival and DNA single-strand breaks in a human ovarian adenocarcinoma cell line (known as line BG-1) and a human cervical squamous cell carcinoma cell line (known as line SiHa). The cell lines were exposed to various concentrations of docetaxel (from 2.

Optimal surgery and diagnostic approach of stage IA2 squamous cell carcinoma of the cervix.

Background: Most patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2 squamous cell carcinoma of the cervix, opt for radical surgery at present.

Objective: To review surgical and diagnostic approaches in such patients.

Study Design: Our patient population consisted of 394 patients with a diagnosis of stage I squamous cell cervical carcinoma (with depth of stromal invasion 10mm or less) according to the 1995 FIGO definition.

Cervical carcinoma with full-thickness stromal invasion: relationship between tumor size on T2-weighted images and parametrial involvement.

Purpose: The purpose of this work was to investigate the relationship between tumor size on T2-weighted images and parametrial involvement by cervical carcinoma with full-thickness stromal invasion and to evaluate whether the size of the tumor on T2-weighted images is a useful index of parametrial involvement.

Method: T2-weighted images of 33 patients with cervical carcinoma showed full-thickness stromal invasion. Three-dimensional diameters (transverse, anteroposterior, and craniocaudal) of the primary tumor were measured on T2-weighted images.