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Hitoo Nakano

Publications and source records attributed to Hitoo Nakano.

72 records · Page 4Linked to original sources

[Can we predict the premature labor in patients with placenta previa?; a retrospective study on maternal symptoms during pregnancy].

OBJECTIVES: This study aimed to predict the gestational weeks by characterizing maternal genital bleeding and uterine contraction during pregnancy in patients with placenta previa. METHODS: Included in this study were 87 patients with placenta previa, diagnosed at the time of delivery at our institution. Genital bleeding and uterine contraction characteristics and clinical data from mothers who delivered at < 37 weeks were compared to that of mothers who delivered at > or = 37 weeks. RESULTS: There were 37 deliveries (42.5%) at < 37 gestational weeks and 50 deliveries (57.4%) at > or = 37 gestational weeks. In 69 of 87 cases (79.3%), genital bleeding was recognized during pregnancy, and in 63 cases (72.4%) genital bleeding was the first symptom to occur during pregnancy. Uterine contraction during pregnancy was recognized in 48 cases (55.2%), including 36 (41.4%) that occurred as the first symptom of pregnancy. Logistic regression analysis revealed that when genital bleeding occurred at < 29 and < 31 weeks, patients were at high risk for delivery at < 34 and < 37 weeks, respectively, and when first uterine contraction occurred at < 29 weeks, they were at high risk for delivery at < 34 weeks. CONCLUSION: In patients with placenta previa, the number of gestational weeks to the occurrence of the first genital bleeding can be used as a predictor of the number of weeks to term.

Adult↗

Genetic polymorphism at the 5' regulatory region of multidrug resistance 1 (MDR1) and its association with interindividual variation of expression level in the colon.

The multidrug resistance 1 (MDR1) is a key molecule in determining not only the resistance of cancer cells to anticancer agents but also the disposition of a variety of drugs in intestinal and other tissues. However, the mechanism underlying interindividual variations in levels of MDR1 activity and expression in various tissues remains unclear. We analyzed the nucleotide sequence polymorphisms in the 5' upstream regulatory region of the gene spanning 4 kb from the transcriptional start site of MDR1 and tried to identify any associations between polymorphisms and MDR1 expression. Within that region, we identified eight single nucleotide polymorphisms (SNPs) in the region in the Japanese population. Of the SNPs identified, -2410T>C, -1910T>C, and 692T>C were in perfect linkage disequilibrium. In normal colorectal mucosa, diplotypes at the region showed more significant association with the expression level of MDR1 mRNA than each SNP did. In an in vitro reporter assay, transcription activity of the minor-type construct carrying haplotypes 2 and 3 was significantly lower than that of the major-type construct carrying haplotype 1. We next identified two DNA binding proteins: one protein bound to the nucleotide sequence carrying -692T but not to that carrying -692C and another bound to the nucleotide sequence carrying -2352G but three times weaker than that carrying -2352A. This suggested the significance of SNP at -692 and -2352 of MDR1 in variable expression in the colon interindividually. This is the first report connecting SNPs and interindividual variety of MDR1 expression rationally.

Alleles↗

TNFalpha-induced apoptosis and integrin switching in human extravillous trophoblast cell line.

Differentiation of extravillous trophoblast cells (EVT) to an invasive phenotype plays an essential role in establishing and maintaining feto-placental organization during human pregnancy. A switch in integrin expression occurs during this differentiation and is accompanied by changes in the extracellular matrix (ECM). Alteration of EVT behavior is also modulated by cytokines. To investigate the molecular interactions involved in the EVT differentiation, we examined the effects of cytokines and ECM on the human EVT cell line, TCL1 cells. We found that tumor necrosis factor alpha (TNFalpha) induced apoptosis in TCL1 cells but not in JEG3 cells derived from choriocarcinoma while the addition of interleukin-1beta, leukemia inhibitory factor, or transforming growth factor had no effect on TCL1 cells. This apoptosis was suppressed when TCL1 cells were seeded on fibronectin (Fn), collagen type I (C1), collagen type IV (C4), or laminin (Ln). Wortmannin, a specific PI3 kinase inhibitor, inhibited this suppression. Spreading assays and adhesion blocking assays indicated that TCL1 cells express integrin-alpha5 and -alpha6 and beta1 and beta4 subunits. Adhesion on Fn is mediated by alpha5beta1, and adhesion on C1, C4, or Ln is mediated by alpha6beta1 integrins. TNFalpha suppressed alpha6 integrin expression and enhanced alpha1 integrin expression in a dose-dependent manner. In addition, aggregation of beta1 subunits on C4 was detected after addition of TNFalpha. Taken together, these results suggest that TNFalpha and ECM, through activation of PI3 kinase mediated by beta1 integrin signaling, might collaboratively regulate differentiation of trophoblast cells through integrin signaling in establishing and maintaining successful pregnancy.

Apoptosis↗

Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer.

PURPOSE: Nuclear expression of Y box-binding protein (YB-1), a member of the DNA-binding protein family, was recently reported to have a much higher concentration in cisplatin-resistant cancer cell lines than in their drug-sensitive parental counterparts, suggesting the ability to induce cisplatin resistance. Ovarian cancer has been generally treated with cisplatin-based chemotherapy and often recurs due to acquired cisplatin resistance. The aim of our study is to elucidate the association between nuclear YB-1 and cisplatin resistance in human ovarian cancer using cultured cell lines and surgical specimens. METHODS: Intracellular YB-1 localization was examined by Western blot analysis for both cisplatin sensitive and resistant human ovarian cancer cell lines. Moreover, 35 pairs of surgical specimens derived from primary and matched recurrent ovarian cancers of the same patient were evaluated for their nuclear YB-1 expression by immunohistochemical staining. RESULTS: Western blot analysis for nuclear and cytoplasmic extracts indicated that cisplatin-resistant cells showed much higher nuclear YB-1 expression than sensitive parental cells. Immunohistochemical analysis showed that ten paired cases turned from negative nuclear YB-1 in primary lesions to positive nuclear YB-1 in recurrent lesions, whereas only two paired cases showed a reverse turn from positive to negative. CONCLUSIONS: The expression of YB-1 in the nucleus seems to be associated with acquired cisplatin resistance in ovarian cancers. Nuclear YB-1 might be a useful predictive marker indicating cisplatin sensitivity and/or a target molecule to treat recurring ovarian cancers by cisplatin-based second-line chemotherapy.

Antineoplastic Agents↗

Prognostic significance of microvessel density, vascular cuffing and vascular endothelial growth factor expression in ovarian carcinoma: a special review for clear cell adenocarcinoma.

Our purpose is to demonstrate the relationship between microvessel density (MVD), vascular cuffing (VC), vascular endothelial growth factor (VEGF) expression and clinicopathological parameters in ovarian cancer. Surgical specimens from 105 primary ovarian cancers were examined for vascularization and VEGF expression by immunohistochemical staining. The higher MVD group (MVD> or =70) and the positive VEGF group were associated with better progression-free survival only in early stages. The significant association of the MVD with better progression-free survival was recognized only in the patients with clear cell adenocarcinomas. The complete VC group showed a similar trend as MVD though there was no statistical difference. A multivariate analysis revealed MVD to correlate independently with progression-free survival. In ovarian carcinoma, MVD was found to be an independent prognostic factor. In addition, the higher MVD with clear cell adenocarcinoma had the better prognosis. The clinicopathological role of angiogenesis should be analyzed taking account of histologic type.

Adenocarcinoma, Clear Cell↗

Ovarian endometrioid adenocarcinoma arising from an endometriotic cyst in a postmenopausal woman under tamoxifen therapy for breast cancer: a case report.

BACKGROUND: Ovarian cancer arising from an endometriotic cyst in a postmenopausal woman under tamoxifen therapy is rare. CASE: We herein report the case of a 67-year-old woman with a history of breast cancer, taking tamoxifen citrate 20 mg/day for 4 years, who underwent an operation for left ovarian tumor. The postoperative histological diagnosis was endometrioid adenocarcinoma in an endometriotic cyst with a gradual transition of the degree of cellular atypia noted from typical endometriotic epithelium, to atypical endometriosis, and finally to adenocarcinoma. CONCLUSION: Tamoxifen may cause malignant transformation of endometriosis through atypical endometriosis even in the postmenopausal state. Atypical endometriosis may act as a precancerous lesion in the process of tamoxifen-induced malignant transformation of endometriosis.

Aged↗

Aortic pulse waveforms for evaluating cardiac performance in the human fetus.

Pulse waveforms of the fetal descending aorta were obtained using an echo-tracking system to clarify the gestational age-related changes and the usefulness for detecting cardiac dysfunction. Peak systolic (PSD) and end diastolic diameter (EDD), pulse amplitude (Amp) and Amp:EDD ratio, calculated from the pulse waveforms, were adopted for analysis. In 196 normal fetuses after 20 weeks, the PSD, EDD and Amp increased, and Amp:EDD ratio decreased linearly with advancing gestation. The 19 fetuses with suspected cardiac dysfunction were divided into healthy and altered cardiac function subgroups, according to the values of fractional shortening and preload index. Of these, 7 fetuses with cardiac dysfunction had significantly higher incidence of low Amp (p < 0.01) and Amp:EDD ratio (p < 0.001) than remaining 12 fetuses with normal cardiac function. The pulse waveform analysis in the fetal descending aorta proved useful for detecting fetal cardiac dysfunction in utero.

Aorta, Thoracic↗

Proton gradient-dependent transport of valproic acid in human placental brush-border membrane vesicles.

PURPOSE: To investigate the transport mechanism of valproic acid across the human placenta, we used human placental brush-border membrane vesicles and compared them with that of lactic acid. METHODS: Transport of [3H]valproic acid and [14C]lactic acid was measured by using human placental brush-border membrane vesicles. RESULTS: The uptakes of [3H]valproic acid and [14C]lactic acid into brush-border membrane vesicles were greatly stimulated at acidic extravesicular pH. The uptakes of [3H]valproic acid and [14C]lactic acid were inhibited by various fatty acids, p-chloromercuribenzene sulfonate, alpha-cyano-4-hydroxycinnamate, and FCCP. A kinetic analysis showed that it was saturable, with Michaelis constants (Kt) of 1.04 +/- 0.41 mM and 1.71 +/- 0.33 mM for [3H]valproic acid and [14C]lactic acid, respectively. Furthermore, lactic acid competitively inhibited [3H]valproic acid uptake and vice versa. CONCLUSION: These results suggest that the transport of valproic acid across the microvillous membrane of human placenta is mediated by a proton-linked transport system that also transports lactic acid. However, some inhibitors differentially inhibited the uptakes of [3H]valproic acid and [14C]lactic acid, suggesting that other transport systems may also contribute to the elevated fetal blood concentration of valproic acid in gravida.

Adult↗

Spontaneous rupture of the renal pelvis during pregnancy: a case report and review of the literature.

We report a case with spontaneous rupture of the renal pelvis during pregnancy. A 34-year-old Japanese woman was referred at 20 weeks' gestation because of sudden severe right flank pain. She had severe colic pain radiating to the right lower abdomen with percussion tenderness at the right costovertebral angle and was initially suspected to have renal/ureteral calculi. Ultrasonography and intravenous pyelography showed urine extravasating from the renal pelvis, indicating rupture of the right renal pelvis. Immediately following the insertion of a double-J indwelling catheter, her symptoms and perirenal extravasation ceased. She had no further urological problems during pregnancy and a male infant was delivered at 41 weeks' gestation. Cases with spontaneous rupture of the renal pelvis in pregnancy are reviewed.

Adult↗

H(+)-linked transport of salicylic acid, an NSAID, in the human trophoblast cell line BeWo.

We investigated the transport of salicylic acid and L-lactic acid across the placenta using the human trophoblast cell line BeWo. We performed uptake experiments and measured the change in intracellular pH (pH(i)). The uptakes of [(14)C]salicylic acid and L-[(14)C]lactic acid were temperature- and extracellular pH-dependent and saturable at higher concentrations. Both uptakes were also reduced by FCCP, nigericin, and NaN(3). Various nonsteroidal anti-inflammatory drugs (NSAIDs) strongly inhibited the uptake of L-[(14)C]lactic acid. Salicylic acid and ibuprofen noncompetitively inhibited the uptake of L-[(14)C]lactic acid. alpha-Cyano-4-hydroxycinnamate (CHC), a monocarboxylate transporter inhibitor, suppressed the uptake of L-[(14)C]lactic acid but not that of [(14)C]salicylic acid. CHC also suppressed the decrease of pH(i) induced by L-lactic acid but had little effect on that induced by salicylic acid or diclofenac. These results suggest that NSAIDs are potent inhibitors of lactate transporters, although they are transported mainly by a transport system distinct from that for L-lactic acid.

Acids↗

Characteristics of L-lactic acid transport in basal membrane vesicles of human placental syncytiotrophoblast.

The characteristics of L-lactic acid transport across the trophoblast basal membrane were investigated and compared with those across the brush-border membrane by using membrane vesicles isolated from human placenta. The uptake of L-[(14)C]lactic acid into basal membrane vesicles was Na(+) independent, and an uphill transport was observed in the presence of a pH gradient ([H(+)](out) > [H(+)](in)). L-[(14)C]lactic acid uptake exhibited saturation kinetics with a K(m) value of 5.89 +/- 0.68 mM in the presence of a pH gradient. p-Chloromercuribenzenesulfonate and alpha-cyano-4-hydroxycinnamate inhibited the initial uptake, whereas phloretin or 4,4'-diisothiocyanostilbene-2,2'-disulfonate did not. Mono- and dicarboxylic acids suppressed the initial uptake. In conclusion, L-lactic acid transport in the basal membrane is H(+) dependent and Na(+) independent, as is also the case for the brush-border membrane transport, and its characteristics resemble those of monocarboxylic acid transporters. However, there were several differences in the effects of inhibitors between basal and brush-border membrane vesicles, suggesting that the transporter(s) involved in L-lactic acid transport in the basal membrane of placental trophoblast may differ from those in the brush-border membrane.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

IGF-related proteins at birth in a case of antenatally diagnosed Silver-Russell syndrome.

We report here a case with severe intrauterine growth restriction from the first trimester and clinical features of Silver-Russell syndrome including microcephaly, low-set ear, atrial septum defect, ventricular septum defect, diaphragmatic relaxation, and rocker bottom feet. Silver-Russell syndrome is thought to result from deletion of the distal long arm of chromosome 15 on which the IGF-I receptor (IGF-IR) gene is located. We measured both the maternal and cord blood levels of GH, IGF-I, and IGF-binding protein and performed an immunohistochemical study of IGF-IR in the placenta to investigate whether these IGF-related proteins were affected in this patient. The hormonal level of these proteins did not significantly differ from normal neonates, and immunohistochemical analysis suggested IGF-IR protein levels in the placenta were comparable to normal term neonates. These results support the hypothesis that growth insufficiency could occur in patients with monosomy of the distal long arm of chromosome 15 and suggest a critical threshold for IGF-related fetal growth in early pregnancy.

Abnormalities, Multiple↗

ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma.

PURPOSE: The purpose of this study is to attempt to characterize patients with unfavorable clinical outcome by the relative mRNA levels of ABC transporter expression in their tumor samples and to examine whether relative mRNA levels of each of the ABC transporters can be a useful predictor of progression-free survival in advanced ovarian carcinoma. EXPERIMENTAL DESIGN: We examined tumor samples taken from 30 patients with primary serous papillary adenocarcinoma of the ovary for the expression of MDR1 and MRP1, MRP2, and MRP3 mRNA by using real-time reverse transcription-PCR, and we evaluated its correlation with clinical outcome. All 30 patients were divided into three groups according to clinical outcome after debulking surgery and platinum-based chemotherapy: 8 patients were classified into the unfavorable group; 11 were classified into the favorable group; and 11 were classified into intermediate group. RESULTS: The relative mRNA levels of MRP1 and MRP3 were significantly different among the three groups, and the mRNA levels of MRP1 and MRP3 in the unfavorable group were significantly higher than those in the favorable group by multiple comparison. The relative mRNA levels of MRP1 expression were significantly correlated with those of MRP3 expression. In the 30 patients with serous papillary adenocarcinoma, univariate and multivariate analysis demonstrated that the high relative mRNA levels of MRP1 expression were significantly correlated with a short period of progression-free survival. CONCLUSIONS: In patients with advanced ovarian serous papillary adenocarcinoma, these results suggest that patients with an unfavorable clinical outcome are characterized by increased levels of coordinated MRP1 and MRP3 mRNA expression in their tumor samples. Furthermore, a higher level of MRP1 mRNA expression can be a candidate for a useful predictor of a shorter period of progression-free survival.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Fetal monitoring].

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Central Nervous System↗

[Bone metabolism in hypo-estrogenic young women].

Hypo-estrogenic state induces the increased bone turnover finally into osteoporosis. Most typical case of hypo-estrogenic bone metabolism is that of postmenopausal women. We pay attention to other bone metabolism in hypo-estrogenic state women; (1) Amenorrhea patients in young women; (2) Oophorectomized young women; (3) Patients on GnRH analogue therapy. These patients should be evaluated their bone metabolism carefully. It is also important to prevent their bone loss with hormone replacement therapy.

English Abstract↗

Effects of antibiotic treatment on the concentrations of interleukin-6 and interleukin-8 in cervicovaginal fluid.

OBJECTIVE: We investigated to see the effect of antibiotics on interleukin (IL)-6 and IL-8 in cervicovaginal fluid in patients with premature rupture of the membranes. STUDY DESIGN: Cervicovaginal fluid was sampled on admission and before delivery for measurement of IL-6 and IL-8 from 31 patients with less than 35 weeks of gestation. Concentrations of IL-6 and IL-8 were measured by ELISA. RESULTS: The concentrations of IL-6 in cervicovaginal fluid in patients who were delivered because of clinical chorioamnionitis with antibiotics (n = 6) were significantly higher than in patients who were delivered because of active labor with (n = 14, p = 0.0133) and without antibiotics (n = 11, p = 0.0067). A significant change in the concentrations of IL-6 and IL-8 in cervicovaginal fluid was not observed in patients with and without antibiotics who were delivered because of active labor. CONCLUSIONS: The concentrations of IL-6 and IL-8 in cervicovaginal fluid might be influenced by the presence of clinical chorioamnionitis, but not by antibiotic administration.

Anti-Bacterial Agents↗

Antenatal sonographic detection of vesicoureteral reflux. A case report.

We report a case with vesicoureteral reflux (VUR), diagnosed antenatally. A 31-year-old Japanese woman was referred at 37 weeks' gestation because of the fetus having unilateral renal pelvis dilatation. The real-time ultrasound revealed a right renal pyelectasia with periodic changes in size over intervals lasting several minutes. The simultaneous examinations of both anteroposterior dimension of the renal pelvis and the ellipse size of urine-filled bladder area demonstrated that they varied in size in a reciprocal fashion, leading us to diagnose the fetus as having VUR. Postnatally, bilateral VUR was confirmed by the voiding cystogram. This case has typical ultrasonographic findings of fetal VUR, in which both the renal pelvis and urinary bladder dimensions change periodically in a reciprocal manner with each other, when the reflux really occurred.

Adult↗

Intermittent 'double bubble' sign in a case of congenital pyloric atresia.

We report a case of congenital pyloric atresia in which two cystic masses in the fetal upper abdomen and polyhydramnios were observed from 24 weeks' gestation to term. The two cystic masses were thought to indicate the 'double bubble' sign in utero, leading to a misdiagnosis of congenital duodenal obstruction. At 33 weeks' gestation, continuous ultrasound observation of the two cystic masses was made for 60 min. During the periods when gastric peristalsis was absent, the 'double bubble' sign was observed. However, during the periods when gastric peristalsis was present, the 'double bubble' sign disappeared. In retrospect, both cystic masses were stomach and the 'double bubble' sign disappeared with peristalsis of the antrum. In order to differentiate from congenital duodenal obstruction, whole stomach configuration should be delineated by continuous observation covering periods when gastric peristalsis is active as well as quiet.

Adult↗