Biomedical subjects

Hitoo Nakano

Publications and source records attributed to Hitoo Nakano.

At least 37 records · Page 2Linked to original sources

PubMed2005

Tumor necrosis factor and vascular endothelial growth factor induce endothelial integrin repertories, regulating endovascular differentiation and apoptosis in a human extravillous trophoblast cell line.

Angiogenesis is crucial in human development. Extravillous trophoblast (EVT) cells mimic endothelial cells in angiogenesis during endovascular differentiation, inducing a remodeling of spiral arteries that increases blood flow toward the intravillous space. We have previously shown that tumor necrosis factor (TNF) alpha regulates expression of ITGA6 and ITGA1, which are involved in cell survival, in the human EVT cell line TCL1. To further investigate endovascular differentiation, we examined the effects of vascular endothelial growth factor (VEGF), TNF, and extracellular matrix (ECM) on TCL1 cells. Seeded on Matrigel, TCL1 cells show tube-like formation that specifically recalls morphological changes in endothelial cells. Anti-ITGAV/ITGB3 antibodies significantly reduced the size of the capillary network (P < 0.05) on Matrigel and also suppressed TNF-induced apoptosis (P < 0.05) in TCL1 cells. VEGF induced expression of ITGAV/ITGB3 subunits and protein aggregation, as in the case of TNF, which in turn, induces synthesis of VEGF in TCL1 cells. Soluble FLT1 suppressed these activities in TCL1 cells, indicating that signals involving VEGF axis are essential for endovascular differentiation. These results suggest that TNF, VEGF, and ECM collaboratively regulate EVT behavior, including cell survival and endovascular differentiation, through integrin signaling during establishment and maintenance of successful human pregnancies.

Apoptosis↗

PubMed2005

Diffusion-weighted echo-planar MR imaging and ADC mapping in the differential diagnosis of ovarian cystic masses: usefulness of detecting keratinoid substances in mature cystic teratomas.

PURPOSE: To elucidate whether apparent diffusion coefficient (ADC) values calculated from echo-planar diffusion-weighted MR imaging (EPDWI) are useful in the differential diagnosis of ovarian cystic masses. MATERIALS AND METHODS: EPDWI was performed in 131 patients with ovarian cystic masses (54 mature cystic teratomas, 35 endometrial cysts, four other benign cysts, 14 benign neoplasms, and 24 malignant neoplasms). The areas of the highest signal intensity on EPDWI (b = 1000 seconds/mm(2)) and the lowest ADC values within the cystic component were evaluated. RESULTS: On qualitative and quantitative analyses, mature cystic teratomas tended to show higher signal intensity and had areas of lower ADC values than endometrial cysts and other benign and malignant neoplasms (P < .005). In vitro scanning of the cystic contents of mature cystic teratomas confirmed that high signal on DWI or low ADC value was attributable to the keratinoid substance within the tumors. The difference in ADC between malignant and benign lesions were significant when mature cystic teratomas and endometrial cysts were included, but was not significant when they were excluded. CONCLUSION: The ADC value may add useful information to the differential diagnosis of ovarian cystic masses in limited populations, such as those with mature cystic teratomas with a small amount of fat.

Adult↗

PubMed2005

Noninvasive measurement of isovolumetric contraction time during hypoxemia and acidemia: Fetal lamb validation as an index of cardiac contractility.

OBJECTIVES: The objectives of this study are firstly to clarify how the Doppler isovolumetric contraction time (ICT) is influenced by arterial oxygen pressure (PaO2) or pH, and secondly to confirm the relationship between the Doppler ICT and myocardial contractility during hypoxemia and/or acidemia in the fetal lamb. MATERIAL AND METHODS: In 12 pregnant ewes, fetal hypoxemia and acidemia were induced by giving ewes a variable mixture of gases for 120 min. The chronological change of fetal PaO2, pH, Doppler ICT and maximum first derivative of the left ventricular pressure waveform (Max dp/dt) was recorded every 30 min. RESULTS: Doppler ICT and PaO2 had no significant regression. On the other hand, Doppler ICT and pH demonstrated a significant negative regression. Moreover, one critical given pH point was indicated with statistical significance at 7.20 and the prolongation of the Doppler ICT was found more markedly in the range below the pH of 7.20 compared with the range above 7.20. A significant negative linear regression was found between the Doppler ICT and the Max dp/dt. CONCLUSION: The measurement of Doppler ICT enables us to predict severe acidosis and a decrease of myocardial contractility in the fetus.

Acidosis↗

PubMed2005

Invasive potency related to RCAS1 expression in uterine cervical cancer.

OBJECTIVES: RCAS1 expression is significantly associated with clinical prognosis in various human cancers, which suggests that RCAS1 may be involved in acquisition of malignant phenotypes. To investigate the relationship between RCAS1 and one such characteristic, tumor invasiveness, we examined RCAS1 expression in cervical neoplasms ranging from the precancerous state to invasive cancer. METHODS: RCAS1 expression was studied retrospectively via immunohistochemical methods. Samples consisted of biopsy tissue from 90 patients with intraepithelial neoplasia and resected tumor tissue from 154 patients with invasive cancer. Statistical analysis was done to correlate RCAS1 expression and clinicopathologic variables in patients with a depth of cancer cell invasion into stromal tissue of >5 mm. RESULTS: RCAS1 expression was detected in patients with intraepithelial cancer and invasive cancer but not in patients with dysplasia. The occurrence and degree of RCAS1 expression increased with the depth of invasion. In patients with invasive cancer, RCAS1 overexpression was significantly correlated with invasion of the lymph-vascular space, lymph node metastasis in two or more sites, and tumor volume; RCAS1 expression was not associated with histologic subtype. Overall survival rates for patients with RCAS1 overexpression were significantly shorter than those for patients without RCAS1 overexpression. In connective tissue surrounding tumor cells, the number of cells expressing vimentin significantly decreased in relation to RCAS1 expression level. Moreover, significant associations between expression levels of RCAS1 and those of MMP-1 and laminin-5 were found. CONCLUSION: RCAS1 may contribute to acquisition of malignant uterine cervical phenotypic characteristics including invasion, metastasis, and tumor growth via connective tissue remodeling.

Adult↗

PubMed2005

Enhancement of trypsin-induced contraction by in vivo treatment with 17beta-estradiol and progesterone in rat myometrium.

We have previously reported that the contractile response to thrombin and trypsin was enhanced in the pregnant rat myometrium. We herein determined whether or not sex hormones contribute to this enhancement and the expression of protease-activated receptors (PARs). The nonpregnant rats received daily injections of either 17beta-estradiol or progesterone, and then the contractile response of the myometrium was examined ex vivo. Treatment with either 17beta-estradiol or progesterone had almost no significant enhancing effect on the high K(+)- or oxytocin-induced contraction. On the other hand, both 17beta-estradiol and progesterone dose-dependently enhanced the contractile response to trypsin. A maximal enhancement was obtained at 25 and 40 mg kg weight(-1) day(-1) for 17beta-estradiol and progesterone, respectively. The extent of the enhancement of the trypsin-induced contraction seen in the sex hormone-treated rats in the present study was comparable to that reported in the pregnant rats. However, the contractile response to thrombin and PAR1/PAR2-AP, SFLLRNP was not enhanced either by progesterone or 17beta-estradiol. PAR2-AP and PAR4-AP failed to induce contraction under any conditions. PAR1 mRNA was scarcely detected in the control myometrium by an RT-PCR analysis, while it slightly increased only in the progesterone-treated rats. Neither PAR2 nor PAR4 mRNA was detected. We thus conclude that the responsiveness to trypsin, but not thrombin, is controlled by sex hormones. A novel type of receptor, other than PAR1, PAR2 or PAR4, is suggested to mediate the trypsin-induced contraction as in the case of the pregnant rat myometrium.

Animals↗

PubMed2005

Postpartum retroperitoneal fasciitis: a case report and review of literature.

We present a case of a postpartum female with iliopsoas fasciitis in the puerperium. Two days after a spontaneous vaginal delivery at 38 weeks without any complications, the patient complained of pain in the left thigh and hip, associated with a temperature of 38 degrees C. Consequently, she could not walk 4 days after delivery and her body temperature had increased to 39 degrees C. Extreme left flank pain and tenderness in the left pelvic wall were prominent, whereas the tenderness in the pelvis was moderate. Magnetic resonance imaging led us to diagnose iliopsoas fasciitis. This was complicated by sepsis but improved after a protracted antibiotic treatment without any surgical intervention. A literature review revealed that serious complications, including sepsis or permanent functional disturbance, could arise although retroperitoneal fasciitis and/or abscesses are very rare after vaginal delivery. Iliopsoas fasciitis could be considered when patients complain of extreme pain in the pelvic wall, sacroiliac joint region, or thigh-symptoms that are uncommon in uncomplicated endometritis.

Adult↗

PubMed2005

Differential diagnosis between complete and partial mole by TSSC3 antibody completely correlates to DNA diagnosis.

Complete hydatidiform moles (CHMs) are a type of androgenetic fertilization without an ovum. Cases of CHM exhibit a generalized swelling of the villi and are known to be highly associated with persistent disease or carcinoma. In contrast, partial hydatidiform moles (PHMs) also show characteristic hydropic changes among the villi, but the incidence of secondary disease is relatively low. Because PHMs are fertilized by one ovum and two sperm and CHMs are fertilized by one or two sperm alone, we considered whether or not maternally imprinted genes might be useful for achieving a differential diagnosis. The validity of the imprinted genes in CHMs was assessed by implementation of a microarray technique. Among the genes examined, TSSC3, SLC22A1L, KCNQ1, and Decorin were shown to be down-regulated, and TSSC3 was the most markedly suppressed of these genes. In this study, 20 cases of CHM, the diagnosis of which was confirmed by DNA polymorphism, were investigated. In all of these cases, the expression of TSSC3 was completely absent, as determined by Western blot analysis. Conversely, 12 cases of PHM, also diagnosed by DNA polymorphism, were examined here; in all of these 12 cases, TSSC3 was found to be expressed normally. Immunohistochemical (IHC) analysis also produced the same results. The complete silencing of TSSC3 in cases of CHM will provide a novel, convenient strategy for the diagnosis of molar lesions in the placenta.

Antibodies↗

PubMed2005

Expression of RCAS1 in female genital organs.

Receptor-binding antigen expressed on a human uterine adenocarcinoma cell line, SiSo (RCAS1), has been reported to be a prognostic factor of various malignant tumors, and it has also been proven to induce apoptosis of lymphoid cells. However, its normal distribution and function have not yet been elucidated. The purpose of this study was to disclose the distribution of RCAS1 expression in normal female genital organs. Immunohistochemical staining using anti-RCAS1 and anti-MIB-1 antibodies was performed on 123 surgical specimens of a histologically normal uterus, ovary, or fallopian tube from 66 patients, and the apoptotic index was determined. In uterine cervical glands, the expression of RCAS1 was seen in 93% of the cases, and it was mainly localized in the superficial cervical glands. Near the areas of squamous metaplasia, RCAS1 was strongly expressed in all samples. In the uterine cervical squamous epithelium, RCAS1 was seen in 84% of cases. In the uterine corpus, RCAS1 was seen in 87% of all cases, and it was mainly expressed in the endometrial glands of basalis layer. There was significant positive correlation between age and RCAS1 expression, but no significant difference was found regarding the endometrial status and RCAS1 expression in endometrium. No significant correlation was found between RCAS1 expression and MIB-1 index/apoptotic index. RCAS1 may affect these metaplastic processes and tumor progression.

Adult↗

PubMed2005

Short-term combinational therapy of low-dose estrogen with selective serotonin re-uptake inhibitor (fluvoxamine) for oophorectomized women with hot flashes and depressive tendencies.

AIM: To examine whether low-dose and short-term estrogen-replacement therapy (ERT) plus selective serotonin re-uptake inhibitor (SSRI) treatment is effective or not in the treatment of climacteric disorders, hot flashes and depressive symptoms, in oophorectomized women. METHOD: Forty-two oophorectomized women with hot flashes and depressive symptoms were assigned randomly to two groups. We examined the efficacy rates of climacteric disorders, particularly hot flashes and depressive symptoms in 21 women on low-dose ERT (conjugated equine estrogens [CEE] 0.3125 mg/day) and 21 women on low-dose ERT (CEE 0.3125 mg/day) plus SSRI (fluvoxamine 50 mg/day) treated for 8 weeks. We used questionnaires to evaluate the efficacy for depression, namely the Self-rating Depression Scale (SDS) and the Self-rating Questionnaire for Depression (SRQ-D), and for anxiety with the State-Trait Anxiety Inventory (STAI). In the statistical analysis, in the mixed-effect model, for the score against time and adjusted with age, treatment and treatment as the fixed effects. RESULTS: The average scores on the SDS in both groups were decreased by the treatment (P < 0.001). But the efficacy of the ERT + SSRI group in the time x treatment SDS and SRQ-D scores was significantly higher compared with those of ERT (P = 0.0025, 0.0162) and there was a significant difference in the decrease in the frequency of hot flashes by 8 weeks between the two groups (P = 0.036). CONCLUSIONS: A combination of low-dose and short-term ERT + SSRI is more effective than low-dose estrogen alone in relieving the depressive symptoms and hot flashes of oophorectomized women.

Adult↗

PubMed2005

Regional difference of endothelium-dependent contractility in human umbilical artery.

To investigate whether vascular reactivity of the umbilical artery influences differences in Doppler waveform depending on the sampling site along the cord, we studied a regional difference of endothelium-dependent vascular contractility in human umbilical artery using mechanical responses to the quick stretch of vascular smooth muscle strips. The umbilical artery resistance index (RI) values for the fetal end were significantly higher than those for the placental end. In endothelium-intact strips, stretch-induced contraction of the umbilical artery appears to decrease from the fetal to the placental end of the umbilical artery. No significant differences were noted between strips from the two locations when endothelial cells were rubbed, indicating that this regional difference is related to endothelial cell function. Indo-methacin decreased the stretch-induced contraction of endothelium-intact strips, but tetrodotoxin did not affect this association, suggesting that arachidonic acid metabolism via the cyclooxygenase pathway contributes to modulation of human umbilical artery responsiveness to stretch. These findings suggest that the difference in Doppler waveform of the umbilical artery depending on the sampling site is related to differences in vascular resistance that result from endothelium-related function.

Biomechanical Phenomena↗

PubMed2005

Relationship between eye movement period and micturition in newborn infants differs from that of human fetuses at term.

AIM: To investigate the relationship between the onset of eye movement periods and micturition in human fetuses and in neonates with the intention of clarifying the transition in relationship during the perinatal period. METHODS: Data were acquired during 1-4 days and/or 1 month (29-33 days) from 6 normal neonates born at term. Eye movements, crying, and eye open periods were observed with a video recorder until micturition occurred. In 29 term fetuses, the time lag between the onset of an eye movement period and micturition was measured by real-time ultrasound instruments. RESULTS: The time lag between the onset of an eye movement period and micturition in neonates (2 minutes; range, 0-57 minutes) was significantly (P=0.027) different from the time lag for fetuses (14 minutes; range, 2-32 minutes) and the frequency of micturition occurring within 8 minutes (33) was significantly lower (P=0.017) than that seen for term fetuses (72%). CONCLUSION: The relationship between the onset of an eye movement period and micturition is different in term human fetuses and neonates of less than 1 month of age. This suggests that the neuronal relationship among brain centers for micturition, rapid-eye-movement sleep, and awakening is dramatically altered perinatally.

Arousal↗

PubMed2004

Akt plays a central role in the anti-apoptotic effect of estrogen in endothelial cells.

Estrogen has been reported to inhibit apoptosis in vascular endothelial cells. However, its precise mechanism still remains to be elucidated. Here we determined the role of Akt in the anti-apoptotic effect of estrogen. 17Beta-estradiol prevented the apoptosis induced by TNF-alpha in bovine aortic endothelial cells, as evaluated by double staining with fluorescein isothiocyanate-conjugated annexin V and propidium iodide. Introducing a dominant negative mutant of Akt by using a cell-penetrating peptide of Tat protein inhibited the anti-apoptotic effect of estrogen in a concentration-dependent manner, and resulted in the complete inhibition of the anti-apoptotic effect of 17beta-estradiol at 1nM and higher concentrations. The dominant negative mutant without the cell-penetrating peptide and Tat peptide-conjugated protein A had no effect. The intracellular protein transduction was confirmed by immunoblot analysis. Our observations thus provide first direct evidence that Akt plays a central role in the anti-apoptotic effect of estrogen in vascular endothelial cells.

Animals↗

PubMed2004

Fetal habituation correlates with functional brain development.

In this study, we divided 26 fetuses at 32-37 weeks of gestation into three groups using combined criteria of gestational age and behavioral indicators. We investigated fetal habituation to vibroacoustic stimulation (VAS). Fetuses showed habituation from at least 32 weeks of gestation. Furthermore, fetuses less developed from behavioral standpoint took significantly more trials to achieve habituation than developed fetuses even in the same gestational age. Taken together with these data, it was proved that there was a relationship between aspects of behavioral development and habituation.

Acoustic Stimulation↗

PubMed2004

Similarity and difference in the acute lung injury induced by a radiographic contrast medium and an anticancer agent paclitaxel in rats.

Paclitaxel is one of the most frequently used anticancer agents but its use is sometimes limited because of the incidence of severe hypersensitivity reactions. The clinical symptoms of the reactions, including dyspnea and pulmonary edema, are similar to those induced by iodinated contrast medium during radiographic examination. Therefore, the premedication for the prophylaxis of hypersensitivity reactions to paclitaxel is carried out in accordance with that for radiographic contrast medium. In the present study, we compared the effects of paclitaxel and an iodinated radiocontrast medium ioxaglate on vascular permeability and pulmonary function in rats. Both paclitaxel (15 mg/kg) and ioxaglate (4 g iodine/kg) caused perivascular edema, plasma extravasation and decrease in arterial PaO2. Dexamethasone inhibited plasma extravasation induced by the two compounds. In contrast, histamine H1 and H2 antagonists attenuated the effects of ioxaglate without inhibiting those of paclitaxel. On the other hand, a neurokinin NK1 antagonist (LY303870: 0.5 mg/kg) significantly inhibited the pulmonary responses induced by paclitaxel but not by ioxaglate. Therefore, it is suggested that paclitaxel and ioxaglate cause similar acute lung injury but the mechanisms are different between the two compounds, in which histamine and substance P are involved in the pulmonary dysfunction induced by ioxaglate and paclitaxel, respectively. These findings also raise a possibility that more effective premedication is required for the prophylaxis of paclitaxel hypersensitivity.

Animals↗

PubMed2004

Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy.

Ovarian cancer is the most frequent cause of cancer death among all gynecologic cancers. We demonstrate here that lysophosphatidic acid (LPA)-induced ectodomain shedding of heparin-binding EGF-like growth factor (HB-EGF) is a critical to tumor formation in ovarian cancer. We found that among the epidermal growth factor receptor (EGFR) family of growth factors, HB-EGF gene expression in cancerous tissues and HB-EGF protein levels in patients' ascites fluid were significantly elevated. The human ovarian cancer cell lines SKOV3 and RMG-1 form tumors in nude mice. Tumor formation of these cells was enhanced by exogenous expression of pro-HB-EGF and completely blocked by pro-HB-EGF gene RNA interference or by CRM197, a specific HB-EGF inhibitor. Transfection with mutant forms of HB-EGF indicated that the release of soluble HB-EGF is essential for tumor formation. LPA, which is constitutively produced by ovarian cancer cells, induced HB-EGF ectodomain shedding in SKOV3 and RMG-1 cells, resulting in the transactivation of EGFR and the downstream kinase extracellular signal-regulated kinase/mitogen-activated protein kinase. LPA-induced transactivation was abrogated by HB-EGF gene RNA interference or by CRM197. Introduction of lipid phosphate phosphohydrolase, which hydrolyzes LPA, decreased the constitutive shedding of HB-EGF, EGFR transactivation, and the tumorigenic potential of SKOV3 and RMG-1 cells. These results indicate that HB-EGF is the primary member of the EGFR family of growth factors expressed in ovarian cancer and that LPA-induced ectodomain shedding of this growth factor is a critical step in tumor formation, making HB-EGF a novel therapeutic target for ovarian cancer.

Animals↗

PubMed2004

Prenatal diagnosis of slow-rate ventricular tachycardia using fetal electrocardiography.

OBJECTIVES: We report a case in which fetal ventricular tachycardia (VT) could be diagnosed, in utero, using a transabdominal fetal electrocardiogram (fECG) with motion-mode (M-mode) echocardiography. METHODS: The fetus was referred at 32 weeks' gestation due to tricuspid atresia. The fetal cardiotocogram demonstrated paroxysmal tachycardia with a ventricular rate of 155 to 160 bpm within the confines of normal sinus rhythm. RESULTS: M-mode echocardiography showed atrioventricular dissociation with a rather slow ventricular rate. To identify the level of the ectopic focus for tachyarrhythmias, we attempted to detect the electrical signals of the fetal heart and succeeded in recording the fECG. Morphological assessment of the fECG allowed for the extraction of both the normal QRS complex and apparently dissimilar ectopic QRS beat, which has a different polarity despite a relatively similar width. CONCLUSION: Consequently, the case proved to have VT at a slow rate, probably originating from the focus near the atrioventricular junction inside the ventricle.

Adult↗

PubMed2004

Postoperative adjuvant chemotherapy with cisplatin, cyclophosphamide, and anthracycline (doxorubicin, epirubicin, pirarubicin) for endometrial cancer.

BACKGROUND: Doxorubicin and cisplatin are the most commonly used chemotherapeutic agents in the treatment of endometrial cancer, but their clinical efficacy is still controversial. The aim of this study was to retrospectively assess the efficacy and toxicity of combination chemotherapy using cisplatin, cyclophosphamide, and anthracy-clines in patients with stage III/IV adenocarcinoma of the endometrium. METHODS: Forty patients with advanced endometrial cancer received postoperative adjuvant combination chemotherapy, using cisplatin (50 or 70 mg/m2), cyclophosphamide (500 mg/m2), and one of three anthracyclines (10 patients with doxorubicin [50 mg/m2], 18 with epirubicin [50 mg/m2], and 12 with pirarubicin [40 mg/m2]), from 1987 to 1999. All patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with pelvic lymph node dissection in 36 patients and paraaortic lymph node biopsy in 38 patients. Patients were considered eligible if they had adnexal metastasis, paraaortic lymph node metastasis, positive peritoneal cytology, or distant metastasis. The patients were divided into two groups: patients with no measurable lesion (group 1; n = 27), and those with residual measurable lesion (group 2; n = 13) after surgery. The response rate and progression-free survival rate were evaluated in group 2. RESULTS: In group 1, 7 patients (26%) had recurrence, and all of them died of the disease. No patients in stage IIIa (n = 10), however, had recurrence. In group 2, 6 of the 13 (46%) showed response to chemotherapy (complete response [CR], 31%; partial response [PR], 15%). Toxicity was moderate: 10 patients had grade 4 neutropenia; and dose reductions were mandated in 12 patients. CONCLUSION: In group 1, the survival of patients receiving chemotherapy was considered favorable, but patients with recurrent lesions had poor prognosis. On the other hand, in group 2, the efficacy of the chemotherapy was almost equal to that reported in the literature; however, this regimen did not contribute to an improvement in the survival rate. In conclusion, a new effective regimen of postoperative adjuvant therapy is highly desirable in patients with measurable residual lesions.

Adenocarcinoma↗

PubMed2004

Does maternal blood cortisol entrain fetal diurnal rhythm?

AIMS: To evaluate whether maternal blood cortisol acts as an entrainer of the fetus, we compared diurnal variations in the fetal heart rate (FHR) of two cases with Cushing's syndrome, under condition of glucocorticoid replacement therapy after adrenalectomy. SUBJECTS: The Maternal cortisol concentration in Case 1 showed bimodal change, at 31 and 38 weeks' gestation, while the concentration in Case 2 was found to have an abnormally high level with no diurnal variation at 30 weeks and a monomodal pattern at 34 weeks. RESULTS: The FHR patterns in both cases demonstrated similar developmental change: a remarkable diurnal rhythm comparable to control cases was observed at 34-38 weeks. Analysis of spectral 1/f characteristics revealed, however, that Case 1 exhibited a pattern equivalent to control cases, whereas in Case 2, FHR values did not display overt diurnal variation. CONCLUSIONS: The diurnal rhythm of FHR develops irrespective of daily variation in maternal cortisol concentration.

Adult↗