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Biomedical subjects

Norihiro Sugino

Publications and source records attributed to Norihiro Sugino.

At least 19 recordsLinked to original sources

A case of monochorionic twin pregnancy complicated with intrauterine single fetal death with successful treatment of intrauterine blood transfusion in the surviving fetus.

We report a case of monochorionic twin pregnancy complicated with single fetal demise that received successful treatment of intrauterine transfusion for severe anemia of the surviving fetus. A single fetal demise occurred at 20 weeks of gestation and middle cerebral artery peak systolic velocity (MCA-PSV), a marker for fetal anemia, showed marked elevation in the surviving fetus. Fetal blood sampling was immediately done and severe fetal anemia (hemoglobin = 5.5 g/dl, hematocrit = 16.8%) was confirmed, and then intrauterine transfusion was performed. After transfusion, MCA-PSV rapidly decreased to the normal value and remained within normal range until delivery. A healthy 2,640 g male infant was delivered at 35 weeks of gestation without anemic status and no neurological problem was found at 1-year old. The present report supports that intrauterine rescue transfusion is a useful treatment to prevent the adverse outcome of surviving fetus in monochorionic twin pregnancy complicated with single fetal demise, and monitoring of MCA-PSV is also useful to assess anemic status of the surviving fetus.

Adult↗

Changes in vascular leakage and expression of angiopoietins in the corpus luteum during pregnancy in rats.

The present study investigates changes in blood vessel stability and its regulation in the corpus luteum (CL) during pregnancy in the rat. First, blood vessel stability in the CL was evaluated during pregnancy based on vascular leakage, which was quantified by the Evans blue assay. Vascular leakage was highest on day 3, thereafter decreased until day 15 and increased again on day 21. Secondly, to study the regulation of vascular leakage, the expression of angiopoietins was examined in the CL during pregnancy. Angiopoietin-1 (Ang-1) effects maturation and stabilization of newly formed blood vessels, while Ang-2 produces the opposite effect by allowing vascular remodeling. An immunohistochemical study showed both Ang-1 and Ang-2 expression in luteal cells. mRNA and protein levels of Ang-1 were significantly higher on days 12 and 15 than those on days 3 and 21, whereas there was no significant change in Ang-2 expression. Since estradiol contributes to CL development during mid-pregnancy, we finally studied whether estradiol regulates vascular leakage and angiopoietin expression. Rats undergoing hypophysectomy and hysterectomy (hypox-hect) on day 12 were treated with estradiol until day 15. Vascular leakage was increased and Ang-1 expression was decreased by hypox-hect, and these effects were completely reversed by estradiol treatment. In conclusion, blood vessel stability in the CL is likely to be associated with CL development and CL regression, and may be regulated by angiopoietins. Estradiol contributes to blood vessel stabilization in the CL during mid-pregnancy, which is associated with an increase in Ang-1 expression.

Angiopoietins↗

Different expression patterns of intact forms of squamous cell carcinoma antigens between normal and malignant cervical squamous epithelial tissues: nondenaturing polyacrylamide gel electrophoretic analysis.

Squamous cell carcinoma antigen (SCCA), a 45-kDa tumor-associated serpin, mainly consists of two highly homologous molecules, SCCA1 and SCCA2, which possess unique proteinase inhibitory properties. Importantly, our previous study demonstrated that an intact structure of SCCAs, and not a cleaved form yielded by interacting with target proteinase, is essential for their function as a serpin. The aim of this study is therefore, to develop a simple method of analyzing expression patterns of intact forms of SCCAs (functional SCCAs) in cervical squamous epithelial tissues and to investigate whether there are any differences in the expression of intact forms of SCCAs between normal and malignant cervical squamous epithelial tissues. We used nondenaturing polyacrylamide gel electrophoresis (PAGE) with immunoblotting. The newly generated antibody, Pab Y2, recognizes only intact form of SCCAs, while the conventional antibody, Mab 27, reacts with the cleaved form of SCCA1 as well as intact forms of SCCAs. Nondenaturing PAGE using Pab Y2 showed that an intact form of SCCAs in the heat-treated tissue extract at 60 degrees C for 2 h was separated into at least five bands, termed as bands A-E from cathode to anode. By comparison with two-dimensional electrophoresis patterns of SCCAs, it was found that the first three bands, i.e. bands A-C, are derived from the intact form of SCCA1, while the other two bands, i.e. band D and E are from the intact form of SCCA2. Specifically, band E, but not band D, of SCCA2 is apparently increased in squamous cell carcinomas compared with normal squamous epithelium. In conclusion, this novel analytical approach will be useful for investigating the different expression patterns of functional SCCAs between normal and malignant cervical squamous epithelial tissues.

Antigens, Neoplasm↗

Suppression of SCC antigen promotes cancer cell invasion and migration through the decrease in E-cadherin expression.

Squamous cell carcinoma antigen (SCCA) is a useful tumor marker for diagnosis and management of squamous cell carcinoma. Recent studies have shown that SCCA can influence the behavior of cancer cells. It is well known that cell-cell adhesion is an important factor for the progression of cancer. The present study, therefore, was undertaken to investigate the effect of SCCA2 on the cell adhesion related molecule, E-cadherin, and cancer cell behavior. For this purpose, antisense SCCA2 cDNA was transfected into human uterine cancer cell lines, SKG IIIa and SiHa, which express SCCA2. Suppression of SCCA2 expression by antisense SCCA2 cDNA transfection decreased E-cadherin expression and promoted cell migration and invasion as well as the blockage of E-cadherin function by anti-E-cadherin antibody administration. In conclusion, SCCA2 regulates cell migration and invasion via E-cadherin expression, suggesting that SCCA2 may be involved in cancer behavior such as invasion or metastasis.

Antigens, Neoplasm↗

Angiogenesis in the human corpus luteum: changes in expression of angiopoietins in the corpus luteum throughout the menstrual cycle and in early pregnancy.

CONTEXT: Blood vessel stabilization is regulated by angiopoietins and important for angiogenesis in the corpus luteum. OBJECTIVE: To study angiogenesis and blood vessel stabilization in the human corpus luteum, changes in expression of angiopoietin (Ang)-1, Ang-2, and their specific receptor, Tie-2, together with the number of blood vessels and pericytes were examined in the corpus luteum throughout the menstrual cycle and in early pregnancy. DESIGN: The number of blood vessels and pericytes was determined by immunohistochemistry for CD34 and alpha-smooth muscle actin, respectively. Ang and Tie-2 expression were examined by immunohistochemistry or RT-PCR. RESULTS: The number of blood vessels increased during the early luteal phase, whereas the number of pericytes was small in the early luteal phase and increased in the midluteal phase, suggesting that angiogenesis is undergoing during the early luteal phase and blood vessels are stabilized in the midluteal phase. Blood vessels and pericytes decreased in number during the late luteal phase. The increased number of both blood vessels and pericytes seen in the corpus luteum of early pregnancy suggests that angiogenesis is undergoing accompanied by blood vessel stabilization. Ang-2 expression with low Ang-1 expression was found during the early luteal phase. Thereafter, increasing Ang-1 expression during the midluteal phase, declining Ang-1 expression with continued Ang-2 expression during the late luteal phase, and relatively high Ang-1 expression in early pregnancy were observed. CONCLUSIONS: The change in Ang expression is closely associated with angiogenesis, blood vessel stabilization, and blood vessel regression during the divergent phases of luteal formation, luteal regression, and luteal rescue by pregnancy.

Actins↗

Promoter analyses of SCC antigen genes.

SCC antigen (SCCA) has been used as a tumor marker for squamous cell carcinoma. Analyses of the SCCA1 and SCCA2 genes, which are almost identical, and their promoters have been reported. Recently it was found that both SCCAs were stimulated by interleukin (IL)-4 and IL-13. Here we analyzed the promoter activity of both SCCAs in the 5'-flanking region, exon 1, and intron 1 to evaluate a putative STAT6 binding site. The addition of intron 1 to the luciferase assay constructs including the 5'-flanking region significantly augmented the promoter activity of both SCCA1 and SCCA2. Furthermore, deletion analyses of intron 1 revealed that a 50-bp fragment of intron 1 that includes putative STAT6 binding site was responsible for the increased promoter activity. Although the sequences of SCCA1 and SCCA2 are very similar in the 5'-flanking region, the analysis of the -337 single nucleotide polymorphism of SCCA2 indicated that this polymorphism may underlie the difference in promoter activity between SCCA1 and SCCA2.

Amino Acid Sequence↗

Gastric emptying cycles in the human fetus.

OBJECTIVE: Fetal swallowing contributes greatly to amniotic fluid homeostasis and fetal somatic development. Despite the absorption and recirculation of significant volumes of amniotic fluid, little is known about the rates of fetal gastric emptying or gastrointestinal absorption. We sought to determine the patterns of human fetal gastric emptying cycles across gestation. STUDY DESIGN: The gastric emptying cycle of 80 normal human fetuses at 12 to 39 weeks of gestation was studied. Real-time ultrasound examination of the fetal stomach (defined as the largest gastric area inclusive of the pylorus) was recorded continuously for a minimum of 1 hour (60-112 minutes). Images were replayed with measurements of gastric size every minute. The gastric area ratio was defined as the ratio of the fetal gastric area divided by the area of the fetal abdominal transverse section. The changes in gastric area ratio of all subjects were analyzed with the discrete Fourier transform method. The calculable maximum cycle was 60 or 112 minutes, and the minimum cycle was 2 minutes. The highest and second highest peaks of all power spectrum were recorded, and each cycle was converted from frequency of each peak. RESULTS: The gastric emptying cycles of the highest peak before 24 weeks of gestation were scattered between 30 and 100 minutes with low power. At 32 to 35 weeks of gestation, cycles were focused at approximately 40 minutes with increased power. At term, the cycles increased to >80 minutes. The gastric emptying cycles of the second highest peak were constant at 20 minutes, with stronger power after 24 weeks of gestation. CONCLUSION: Fetal gastric emptying cycles normalize during the early third trimester. The near-term evidence of delayed emptying may contribute to newborn infant feeding satiation.

Adult↗

Ultrasonographic findings of facial dysmorphism in Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome has characteristic craniofacial dysmorphism with severe fetal growth restriction. We present a case that revealed facial dysmorphism characteristic of Wolf-Hirschhorn syndrome with two- and three-dimensional ultrasonography. The facial dysmorphic features in the present case were dolichocephaly; high forehead; large rectangular nose continuing to the eyebrows; hypertelorism; short philtrum; carp-shaped mouth; microretrognathia; and large, simply modeled, low-set ears. Chromosome analysis of amniotic fluid cells was 46,XX,del(4)(p15.2), confirming the ultrasonographic result. Examination with two- and three-dimensional ultrasonography is useful to observe the face of fetuses with severe intrauterine growth restriction to diagnose multiple congenital anomaly syndromes.

Abnormalities, Multiple↗

Ontogeny of gastric emptying patterns in the human fetus.

OBJECTIVE: Fetal swallowing and gastric emptying contribute importantly to amniotic fluid (AF) homeostasis and fetal gastrointestinal development. We speculated that fetal gastric emptying must be functional early in gestation to prevent rapid increases in AF. We sought to determine the human fetal ontogenic pattern of gastric emptying. STUDY DESIGN: Gastric emptying of eighty normal fetuses at 12-39 weeks was studied. Real-time ultrasound of the fetal stomach was continuously recorded for 1 hour. The gastric area ratio (GAR) was defined as the gastric area divided by the abdominal transverse area. The delta GAR was defined as the change between the maximum and the minimum gastric area ratiox100 (expressed as percent). A change of the fetal gastric area more than the 10th percentile of the delta GAR at 36-39 weeks was used to define gastric emptying. RESULTS: The 10th, 50th and 90th percentile of delta GAR at 36-39 weeks' was 5.2, 6.5 and 8.7%, respectively. Fetal gastric emptying was detected as early as 12 5/7 weeks of gestation. The proportion of fetuses demonstrating gastric emptying (>10th percentile delta GAR) increased with gestational age: 4/33 (12.1%) 12-23 weeks, 3/9 (33.3%) at 24-27 weeks, 8/11 (72.7%) at 28-31 weeks, 12/14 (85.7%) at 32-35 weeks, and 11/13 (84.6%) at 36-39 weeks. CONCLUSIONS: Fetal gastric emptying occurs by the beginning of the second trimester, contributing to AF regulation. The increased frequency of gastric emptying in late gestation is likely secondary to increased swallowing, altered fetal behavioral state or endogenous production of gastrointestinal motility factors.

Cross-Sectional Studies↗

Prenatal diagnosis and management for a large fetal cardiac tumor complicated with hydrops fetalis.

Fetal cardiac tumor is a rare disease, and its prognosis varies in relation to the complications such as arrhythmia and out-flow obstruction. Hydrops fetalis is one of severe complications that result in an unfavorable outcome. A case is presented herein of a large fetal cardiac tumor diagnosed at 28 weeks gestation. At 30 weeks gestation, the fetus complicated with hydrops fetalis because of impaired cardiac function. Increased peak systolic velocity in the ascending aorta and marked reversed flow in the ductus venosus were observed. Oral digoxin therapy was administered to the mother as a cardiotonic agent and the hydropic condition was immediately diminished. After normal delivery, the cardiac tumor gradually decreased in size and the infant developed normally, but required an antiarrhythmic drug. The case indicates that the in utero digoxin therapy could be a choice for hydrops fetalis caused by cardiac tumor.

Adult↗

Tumor-associated serpin, squamous cell carcinoma antigen stimulates matrix metalloproteinase-9 production in cervical squamous cell carcinoma cell lines.

Squamous cell carcinoma antigen (SCCA) is clinically used as a tumor marker for patients with squamous cell carcinoma of various organs. SCCA1 and its highly homologous molecule, SCCA2, belong to the serine proteinase inhibitors (serpins) family, suggesting that these proteins may be involved in the malignant behavior of squamous cell carcinoma cells. The aim of this study is to functionally characterize these tumor-associated serpins regarding the potential to influence the production of matrix metalloproteinases (MMPs), which play a key role in tumor cell invasion and metastasis. Cervical squamous cell carcinoma cell lines, CaSki cells and SKG-IIIa cells were incubated with SCCA1 or SCCA2 and MMP production was analyzed by gelatin zymography. Both SCCA1 and SCCA2 significantly increased production of proMMP-9, but not proMMP-2. These stimulatory effects were still observed when cells were treated with SCCA mutants lacking the proteinase inhibitory activity of serpins. Furthermore, treatments with various forms of SCCAs, which are generated by interacting with their target proteinases, diminished the stimulatory effect of SCCAs, implying the importance of the conformational structure of SCCAs in the stimulatory effects of SCCAs on proMMP-9 production. In addition, in vitro invasion assay showed that SCCA1 and SCCA2 significantly promoted the activity of cell invasion. It is concluded that SCCAs can alter the invasive phenotype of cervical squamous cell carcinoma cells, probably by stimulating proMMP-9 production, and that intact conformational structure of SCCAs, but not proteinase inhibitory activity of serpins, is required for its stimulatory activity on proMMP-9 production.

Antigens, Neoplasm↗

Withdrawal of ovarian steroids stimulates prostaglandin F2alpha production through nuclear factor-kappaB activation via oxygen radicals in human endometrial stromal cells: potential relevance to menstruation.

The present study was undertaken to investigate whether withdrawal of estrogen and progesterone (EP-withdrawal) stimulates prostaglandin F2alpha (PGF2alpha) production through oxygen radical (ROS)-induced NF-kappaB activation in human endometrial stromal cells (ESC). To study the EP-withdrawal, ESC that had been treated with estradiol (E, 10(-8) M) and medroxyprogesterone acetate (MPA, 10(-6) M) for 12 days were then incubated with or without E+MPA for a further 11 days. PGF2alpha concentrations in the medium and cyclooxygenase-2 (COX-2) mRNA levels were significantly increased after EP-withdrawal, while they were unchanged by the continuous treatment with E+MPA. When ESC were incubated with N-acetyl-L-cysteine (Nac, 50 mM), an antioxidant, during EP-withdrawal, Nac blocked the increases in PGF2alpha production and COX-2 mRNA expression caused by EP-withdrawal. Next, we examined whether ROS generated in response to EP-withdrawal acted through NF-kappaB activation. Electrophoretic mobility shift assay revealed that EP-withdrawal caused marked increases in NF-kappaB DNA binding activity, which was completely suppressed by Nac. Furthermore, when ESC were incubated with MG132 (3 microM), which inhibits NF-kappaB activation, during EP-withdrawal, MG132 blocked the increases in PGF2alpha production and COX-2 mRNA expression caused by EP-withdrawal. In conclusion, EP-withdrawal stimulates COX-2 expression and PGF2alpha production through ROS-induced NF-kappaB activation, suggesting a possible mechanism for menstruation.

Acetylcysteine↗

Regulation of squamous cell carcinoma antigen production by E-cadherin mediated cell-cell adhesion in squamous cell carcinoma cell line.

Squamous cell carcinoma antigen (SCCA) is a useful tumor marker for diagnosis and management of squamous cell carcinoma. It is well known that cell-cell adhesion is important for progression of cancer. However, it is not clarified whether cell-cell adhesion affects SCCA production in squamous cell carcinoma. The present study was, therefore, undertaken to investigate whether E-cadherin-mediated cell-cell adhesion affects SCCA production in squamous cell carcinoma of the uterine cervix. SKG-IIIa cells or CaSki cells, cervical squamous cell carcinoma cell lines, were treated with anti-E-cadherin antibodies (1 microg/ml) up to 72 h. The cells were dissociated, and SCCA content in the cytosol and SCCA mRNA levels were significantly decreased compared to the control group treated with mouse IgG. Secondly, the signaling pathway for SCCA production mediated by E-cadherin was examined. Phosphatidylinositol (PI) 3-kinase is a well-known mediator of E-cadherin-mediated biological events. The treatment with a PI 3-kinase inhibitor suppressed SCCA production in SKG-IIIa cells. It is concluded that E-cadherin mediated cell-cell adhesion maintains SCCA production through PI 3-kinase in squamous cell carcinoma.

Antibodies, Neoplasm↗