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Biomedical subjects

Hitoo Nakano

Publications and source records attributed to Hitoo Nakano.

At least 55 records · Page 3Linked to original sources
PubMed2004

Positive effects of conjugated equine estrogen on triglyceride metabolism in oophorectomized women based on a stratification analysis of pretreatment values.

OBJECTIVE: To evaluate the effects of conjugated equine estrogen (CEE) on the triglyceride (TG) metabolism in oophorectomized women based on a stratified analysis. DESIGN: Randomized, clinical study. SETTING: Menopause Clinic of Kyushu University Hospital. PATIENT(S): Three hundred oophorectomized women. INTERVENTION(S): Three hundred oophorectomized women were randomly divided into two groups and treated by the following regimens for a year: group 1 received calcium alone, group 2 received 0.625 mg/day of CEE and calcium. MAIN OUTCOME MEASURE(S): The changes in serum lipid profile were analyzed according to the individual initial levels in each group. Apolipoprotein E was also measured. RESULT(S): A greater reduction in low-density lipoprotein cholesterol (LDL-C) levels was observed in group 2 women with higher initial levels. For high-density lipoprotein cholesterol (HDL-C) a greater increase was observed in group 2 women with lower initial levels. Although TG levels increased as a whole in group 2, a reduction was observed in the high-TG groups. The initial values of apolipoprotein E were higher in the high-TG groups and decreased to greater amounts in group 2 patients. CONCLUSION(S): Administration of CEE induced positive changes in the serum lipid profile according to the individual initial levels, including levels of TG. Therefore, changes in the TG levels shown by the stratification may be related to the apolipoprotein E changes that are observed following CEE replacement.

Apolipoproteins E↗
PubMed2004

Frequent microsatellite instability in synchronous ovarian and endometrial adenocarcinoma and its usefulness for differential diagnosis.

Synchronous tumors of the ovary and endometrium are a well-known phenomenon. There are histological criteria for defining double primary tumors or metastasis from one organ to another, but in some cases a precise diagnosis is difficult. In this study we reviewed 17 cases of synchronous ovarian and endometrial adenocarcinoma by previously reported histological criteria and performed a microsatellite analysis, combined with X-linked clonality analysis. We also analyzed 8 cases of endometrial adenocarcinoma with pelvic lymph node metastasis as a control. Five dinucleotide microsatellite markers were selected, and microsatellite analysis was performed by a high-resolution method using fluorescence-labeled polymerase chain reaction and laser scanning. In synchronous tumors, 11 ovarian carcinomas (65%) and 10 endometrial carcinomas (59%)demonstrated microsatellite instability (MSI). In total, 13 of the 17 patients demonstrated MSI in the ovarian tumor, the endometrial tumor, or both. Four cases of endometrial carcinoma with pelvic lymph nodes metastases displayed MSI, and MSI findings of the endometrial tumor and lymph node metastasis were same in all cases. Based on these findings, we considered that similar MSI findings indicate metastatic tumors. According to the MSI findings, 13 of the 17 patients (76%) had single or double clonal tumors, 11 (67%) with double primary tumors and 2 (13%) with metastatic tumors. Using X-linked clonality analysis, 3 patients were diagnosed with double primary tumors. The molecular diagnosis corresponded with the histological criteria in all but 1 case. In conclusion, using both MSI and X-linked clonality analysis, most patients (82%) could be diagnosed as having single or double clonal tumors. The histological criteria are accurate and useful in most cases; however, in some cases where the relationship between the 2 tumors is difficult to determine, high-resolution MSI analysis may be helpful.

Adenocarcinoma↗
PubMed2004

Endothelium-dependent and independent enhancement of vascular contractility in the ovariectomized rabbit.

OBJECTIVE: Estrogen suppresses contractile response and increases vasodilator response, partly by modulating endothelial function. However, the effect of estrogen on the contractility of vascular smooth muscle remains to be elucidated. We investigated the effect of a long-term estrogen deficiency on vascular contractility and the Ca(2+) sensitivity of the contractile apparatus in arterial smooth muscle. METHODS: Female rabbits were divided into the following three groups: control group, an ovariectomized group (OVX), and a group supplemented with 17beta-estradiol after ovariectomy (OVX+E2). Twelve weeks later, the mesenteric artery was isolated, and the vascular contractility was evaluated. RESULTS: In OVX, the contractile responses to phenylephrine and 118 mM potassium were enhanced, and the basal release of nitric oxide decreased in the strips with endothelium compared with either OVX+E2 or control. An enhancement of contraction was also observed in the strips without endothelium. However, the extent of enhancement was smaller than that observed in the presence of endothelium. The simultaneous measurement of calcium ([Ca(2+)](i)) and tension revealed no significant difference in the [Ca(2+)](i) elevations induced by phenylephrine among the three groups. In the alpha-toxin permeabilized strips, the Ca(2+)-tension relationships obtained both with and without phenylephrine and guanosine triphosphate were similar among the three groups. No difference in the myosin expression and the histology of vascular tissue was observed among the three groups. CONCLUSION: Long-term estrogen deficiency increased the vascular tone mainly by enhancing smooth muscle contractility. Endothelial dysfunction is considered to play a minor role in the augmentation of vascular tone.

Animals↗
PubMed2004

Pemirolast potently attenuates paclitaxel hypersensitivity reactions through inhibition of the release of sensory neuropeptides in rats.

The effects of anti-allergic agents on the hypersensitivity reactions to paclitaxel, an anti-cancer agent, were examined in rats. Intravenous injection of paclitaxel (15 mg/kg) caused a marked extravasation of plasma protein in lungs and a transient decrease in arterial partial oxygen pressure (PaO(2)). The paclitaxel-induced protein extravasation was inhibited by low doses (0.1-1 mg/kg) of pemirolast or high doses (30-100 mg/kg) of cromoglycate. However, ketotifen was not effective. The decrease in PaO(2) induced by paclitaxel was also significantly reversed by pemirolast. On the other hand, the paclitaxel-induced plasma extravasation was not attenuated by a histamine H(1) blocker diphenhydramine or an H(2) blocker famotidine, but was significantly reduced by a neurokinin NK(1) antagonist LY303870 (0.5 mg/kg) and an NK(2) antagonist SR48968 (1 mg/kg). The concentrations of proteins and sensory peptides such as substance P, neurokinin A and calcitonin gene-related peptide but not histamine in the rat bronchoalveolar lavage fluid were elevated by paclitaxel injection. Both cromoglycate and pemirolast reduced the paclitaxel-induced rise in proteins and sensory peptides. Therefore, we demonstrated for the first time that sensory nerve peptides are involved in paclitaxel hypersensitivity and that an anti-allergic agent pemirolast attenuates the paclitaxel response by inhibiting the release of sensory nerve peptides.

Animals↗
PubMed2004

Role of substance P in hypersensitivity reactions induced by paclitaxel, an anticancer agent.

The role of substance P in adverse pulmonary reactions induced by an anticancer agent paclitaxel was investigated in rats and humans who undertook post-operative chemotherapy for ovarian cancer. In rats, paclitaxel caused a marked plasma extravasation and edema in lungs with a concomitant decrease in arterial partial oxygen pressure, which were reversed by an NK1 antagonist LY303870. Substance P level in rat plasma and bronchoalveolar lavage fluid increased after paclitaxel injection. In 13 patients, plasma level of substance P but not histamine significantly (P < 0.05) increased during paclitaxel infusion. Therefore, substance P rather than histamine may be involved in paclitaxel hypersensitivity.

Animals↗
PubMed2004

Hormone replacement therapy and breast cancer risk in Kyushu University Hospital: supporting the Women's Health Initiative study.

AIM: The influence of hormone replacement therapy (HRT) on breast cancer has not been clarified in Japan, however the Women's Health Initiative (WHI) trial recently showed breast cancer risk according to use of estrogen plus progestin. We assessed retrospectively the incidence of breast cancer in postmenopausal women who received HRT at our outpatients clinic. METHODS: Among the patients registered at the postmenopausal clinic in Kyushu University Hospital from 1990 to 2003, 917 women who received HRT (estrogen plus progestin, 507 patients; estrogen only, 410 patients) after informed consent were examined by mammography or breast ultrasound tomography. RESULTS: Breast cancer occurred in nine patients: five patients who received estrogen plus progestin and four who received estrogen only. Four of five the patients who used estrogen plus progestin received HRT for more than 5 years. CONCLUSION: Breast cancer risk in patients who used estrogen plus progestin for more than 5 years seemed to be higher than those who used it for less than 5 years. This tendency is similar to the results of the WHI. In addition, breast cancer incidence in patients treated with HRT in our clinic seemed to be higher than the incidence in average Japanese women. Therefore, patients need to be given sufficient information before undergoing HRT.

Aged↗
PubMed2004

Inhibin-producing ovarian granulosa cell tumor as a cause of secondary amenorrhea: case report and review of the literature.

We report the case of 31-year-old patient with an inhibin B-secreting granulosa cell tumor of the left ovary who presented with secondary amenorrhea. Preoperative serum hormonal levels were as follows: follicle-stimulating hormone (FSH) 0.3 mIU/mL, luteinizing hormone (LH) 9.81 mIU/mL, estradiol 142.0 pg/mL and inhibin B 2429 pg/mL. Gonadotropin-releasing hormone (GnRH) test revealed no FSH response and a normal LH response. After removal of the tumor, the levels of FSH and inhibin B returned to within the normal range, and regular menses resumed 27 days postoperatively. In premenopausal women, secondary amenorrhea may be the initial manifestation of granulosa cell tumor. A low FSH level coupled with normal levels of E2 and LH, the inhibition of the FSH response to GnRH and an elevated inhibin level suggest the presence of an inhibin-secreting ovarian tumor and also rule out the possibility of isolated FSH deficiency.

Adult↗
PubMed2003

In vivo establishment and characterization of a paclitaxel-resistant human ovarian cancer cell line showing enhanced growth properties and drug-resistance only in vivo.

PURPOSE: In order to establish a more faithful model of clinically recurrent ovarian cancer after paclitaxel-based chemotherapy, a paclitaxel-resistant human ovarian cancer cell line was established in vivo, and its biological profiles were compared with the conventional in vitro established drug-resistant cell line. METHODS: An in vivo paclitaxel-resistant subline (OM1/Tvivo) was established from the parental human ovarian cancer cell line (OVMG1) by repeated paclitaxel administration into tumor-bearing mice. As a control, the in vivo drug-sensitive subline (OM1/Cvivo) was made in the same manner, without paclitaxel. An in vitro paclitaxel-resistant subline (OM1/Tvitro) was established by exposure to stepwise increased concentrations of the drug in a cell culture medium. Chromosomal analysis, evaluation of growth, invasiveness and metastasis, in vivo and in vitro drug sensitivity, and a pharmacokinetic study were performed. RESULTS: Both in vivo sublines confirmed their human origin by G-band chromosomal analysis and showed a similar cell growth rate in cell culture. As for in vivo tumor growth, OM1/Tvivo showed enhanced tumor growth property compared with OM1/Cvivo, while OM1/Tvitro lost tumorigenicity. Both OM1/Tvivo and OM1/Cvivo sublines as well as their parental OVMG1 could not form either invasive or metastatic lesions. Compared with the OM1/Cvivo subline, the OM1/Tvivo tumor showed stable drug-resistance and lower drug distribution after paclitaxel administration into mice, whereas cultured OM1/Tvivo cells lost both completely. On the other hand, an unreasonably higher level of drug-resistance and lower drug concentration was detected in vitro only in OM1/Tvitro cells after exposure to the drug in a culture medium. CONCLUSIONS: These results suggest that the in vivo established paclitaxel-resistant cell line, rather than the conventional in vitro established cell line, is a suitable and faithful model for clinically recurrent tumors showing transformed aggressiveness. The in vivo specific drug-resistant mechanism should involve an interaction between the tumor and host stromal tissue rather than only changes in cellular drug sensitivity. The present study is probably the first report of an in vivo established paclitaxel-resistant human ovarian cancer cell line, and the elucidation of such an in vivo drug-resistance mechanism may be clinically important in preventing or overcoming acquired drug-resistant ovarian cancers recurring after paclitaxel-based chemotherapy.

Animals↗
PubMed2003

Role of sensory nerve peptides rather than mast cell histamine in paclitaxel hypersensitivity.

Paclitaxel is one of the most extensively used anticancer agents, however, its use is often limited by severe hypersensitivity reactions, including respiratory distress, bronchospasm, and hypotension, which can occur despite premedication with dexamethasone and histamine H1 and H2 antagonists. The present study was designed to determine the mechanisms of paclitaxel hypersensitivity. In rats, paclitaxel (15 mg/kg, intravenously) caused a marked increase in pulmonary vascular permeability and edema. PaO2 decreased, whereas PaCO2 increased, transiently after paclitaxel injection. The paclitaxel-induced pulmonary vascular hyperpermeability was blocked by dexamethasone but not by histamine H1 or H2 antagonists. Paclitaxel increased the vascular permeability in lungs of mast cell-deficient rats Ws/Ws(-/-) to almost the similar extent as that elicited in wild-type rats. On the other hand, the paclitaxel-induced pulmonary vascular hyperpermeability was reversed by sensory denervation with capsaicin or pretreatment with LY303870 and SR48968, NK1 and NK2 antagonists, respectively. Consistent with these findings, a marked elevation of sensory neuropeptides such as substance P, neurokinin A, and calcitonin gene-related peptide was observed in rat bronchoalveolar lavage fluid after paclitaxel injection. These findings suggest that sensory nerves rather than mast cells are implicated in the etiology of paclitaxel hypersensitivity.

Analysis of Variance↗
PubMed2003

Predicting the effects of estrogen replacement therapy on lumbar bone mineral density in oophorectomized women: analysis of a 10-year longitudinal study.

The purpose of this study was to investigate whether it is possible to predict the long-term effects of estrogen replacement therapy (ERT) on lumbar bone mineral density (BMD) of oophorectomized women based on changes in BMD. In this study, we retrospectively investigated the changes in lumbar BMD of 70 oophorectomized women under ERT for more than 10 years, and examined whether it was possible in the early stage of ERT to predict the amount of lumbar BMD based on various parameters. Seventy oophorectomized Japanese women (56.8+/-3.9 years old) treated with conjugated equine estrogen (oral) at a dosage of 0.625 mg/day for 10 years were enrolled. Lumbar (L2-L4) BMD was measured annually by dual-energy X-ray absorptiometry (DXA; CV<1.0%). The correlation between changes in BMD after 10 years on ERT (DeltaBMD10) and several clinical factors was examined using a stepwise multiple regression model. The change in BMD after 1 year on ERT (%DeltaBMD1) was the only independent factor that correlated with changes in BMD after 10 years on ERT; the coefficient of correlation was R(2)=0.557 ( R=0.750, P<0.001). Based on the %DeltaBMD1, the 70 women were divided into two groups: women with a positive change in the 1st year (%DeltaBMD1 >or=0%) in group A ( n=40) and those with a negative value in the first year ( %DeltaBMD1<0%) in group B ( n=30). We investigated the sensitivity and specificity in the coincidence of %DeltaBMD1 changes in BMD after 10 years on ERT. The %DeltaBMD1 coincided with changes in BMD after 10 years on ERT; the sensitivity was 92.5% and specificity was 70.0%. In conclusion, changes in lumbar BMD on ERT can be predicted from the changes in lumbar BMD at the end of the 1st year.

Bone Density↗
PubMed2003

Expression of angiogenesis factors in monolayer culture, multicellular spheroid and in vivo transplanted tumor by human ovarian cancer cell lines.

We examined the expression of four angiogenesis factors (vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), platelet-derived endothelial cell growth factor (PD-ECGF) and basic fibroblast growth factor (bFGF)) in five human ovarian cancer cell lines by Northern blot analysis and immunohistochemical staining. The cancer cells were grown as a subconfluent monolayer culture, a multicellular aggregate (spheroid) in a three-dimensional culture, and a nude mouse-transplanted subcutaneous tumor in order to simulate the cellular conditions of ovarian cancers in peritonitis carcinomatosa, i.e. floating single tumor cells, multicellular aggregates and peritoneally implanted tumors. In each cell line, the expression of VEGF was detected in a monolayer culture and obviously enhanced in a three-dimensional culture. IL-8 was expressed in two of five cultured cell lines, but neither PD-ECGF nor bFGF was detected. Each cell line-derived transplanted tumor expressed immunohistochemical products of the four angiogenesis factors examined. These observations were confirmed by surgical specimens and suggested that ovarian cancer cells expressed different kinds and/or doses of angiogenesis factors depending on the form of the changed tumor cells during peritoneal implant formation.

Angiogenesis Inducing Agents↗
PubMed2003

Expression of lysophosphatidic acid receptors and vascular endothelial growth factor mediating lysophosphatidic acid in the development of human ovarian cancer.

Lysophosphatidic acid (LPA) receptors including LPA(1), LPA(2), and LPA(3) mediate lysophosphatidic acid signals. We analyzed the expression of LPA receptors, vascular endothelial growth factor (VEGF), and interleukin-8 in 97 patients from normal ovary to ovarian cancer, using reverse transcription polymerase chain reaction. LPA(2), LPA(3), and VEGF expression ratios significantly increased in cancer, compared to those in non-cancerous state (P<0.05). A significant correlation in the expression ratios between LPA(2) or LPA(3) and VEGF was found (gamma=0.617, P<0.0001; gamma=0.431, P<0.001) in patients with cancer. These results suggested that LPA(2) and LPA(3) may be involved in VEGF expression mediated by LPA signals in human ovarian oncogenesis.

Endothelial Growth Factors↗
PubMed2003

Spatial and temporal expression of folate-binding protein 1 (Fbp1) is closely associated with anterior neural tube closure in mice.

Periconceptional folate supplementation is widely believed to have significant preventive effects on the production of neural tube defects. Folate-binding protein 1 (FBP1) is one of the membrane proteins that mediate cellular uptake of folate. Although recent studies suggest that Fbp1 is essential for neural tube closure, the pattern of Fbp1 expression in embryonic tissues has not been examined in detail. To elucidate how Fbp1 contributes to neural tube closure, we examined the spatial and temporal expression patterns of Fbp1 in the developing neural folds and tube of mouse embryos by in situ hybridization. Fbp1 showed a distinct expression pattern in the neural folds, which preceded initiation of neural tube closure at the cervical region and the prosencephalic/mesencephalic boundary. Fbp1 expression was mainly localized to the most dorsal regions of the neural folds where fusion was to occur. With proceeding of neural fold fusion, Fbp1 expression extended to the adjacent unfused neural folds. In the rhombencephalon, robust expression of Fbp1 was observed in rhombomere2 (r2) and r6, suggesting its roles in development of neural crest cells. Fbp1 also showed intense expression in the yolk sac, indicating that FBP1 may mediate transferring maternal folate to embryos during neurulation. These findings indicate close association between Fbp1 and anterior neural tube closure.

Animals↗
PubMed2003

Histological classification of ovarian cancer.

The histology of ovarian tumors exhibits a wide variety of histological features. The histological classification of ovarian tumors by the World Health Organization (WHO) is based on histogenetic principles, and this classification categorizes ovarian tumors with regard to their derivation from coelomic surface epithelial cells, germ cells, and mesenchyme (the stroma and the sex cord). Epithelial ovarian tumors, which are the majority of malignant ovarian tumors, are further grouped into histological types as follows: serous, mucinous, endometrioid, clear cell, transitional cell tumors (Brenner tumors), carcinosarcoma, mixed epithelial tumor, undifferentiated carcinoma, and others. Clear cell and endometrioid carcinomas are highly associated with endometriosis. In stage distribution, serous carcinoma is found predominantly is stage III or IV. In contrast, clear cell and endometrioid carcinomas tend to remain confined to the ovary. Clear cell and endometrioid carcinomas may be unique histological types compared with serous carcinomas with respect to stage distribution and association with endometriosis.

Adenocarcinoma, Clear Cell↗
PubMed2003

Kinetic analysis of P-glycoprotein-mediated transport by using normal human placental brush-border membrane vesicles.

PURPOSE: P-Glycoprotein (Pgp) plays an important role in drug disposition and excretion in various tissues such as the brain, intestine, and kidney. Moreover, we have demonstrated that Pgp is expressed on the brush-border membranes of trophoblast cells in the placenta and restricts drug transfer from the maternal circulation to the fetus. However, the transport kinetics of physiologically expressed Pgp has scarcely been investigated. METHODS: In this study, we assessed the functional kinetics of transport mediated by Pgp that is physiologically expressed in normal tissue by using human placental brush-border membrane vesicles (BBMVs). Digoxin and vinblastine were used as typical substrates of Pgp. RESULTS: The uptakes of [3H]digoxin and [3H]vinblastine into BBMVs were significantly increased in the presence of an ATP-regenerating system. The ATP-dependent uptakes of [3H]digoxin and [3H]vinblastine into BBMVs exhibited saturable kinetics. The Michaelis constants (Kt values) were 2.65 +/- 1.80 microM and 21.9 +/- 3.37 microM, respectively. In the presence of a Pgp inhibitor such as verapamil, cyclosporine A, or progesterone, the ATP-dependent uptakes of [3H]digoxin and [3H]vinblastine into BBMVs were significantly reduced. Anti-Pgp monoclonal antibody C219 completely inhibited the uptake of [3H]digoxin. CONCLUSIONS: The transport kinetics of [3H]digoxin and [3H]vinblastine by physiologically expressed Pgp were successfully evaluated by using BBMVs prepared from normal human placenta. The present method enabled us to evaluate the function of physiologically expressed Pgp and is superior to the use of cultured transfectants in terms of the yield of vesicles. The present method may also be applicable to investigating the influence of various factors such as the genotype of the MDR1 gene or various pathophysiologic states of neonates on the function of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

The efficacy of autologous cord-blood transfusions in neonatal surgical patients.

PURPOSE: Allogenic blood transfusions have a risk of infection owing to unknown organisms, graft-versus-host reaction, and immunosupression; however, the use of autologous blood has been reported to be safe. Cord blood has been reported to be useful as a source of stem cell transplantation for the treatment of leukemia and genetic disease. Furthermore, autologous cord-blood transfusions (ACBT) have been reported to be effective for the treatment of anemia in premature infants. The authors examined the efficacy of ACBT in neonatal surgical patients. METHODS: Autologous cord-blood was stored from 12 infants at delivery, including 2 transvaginal and 10 cesarean section deliveries, from 1998 to 2001. All infants had surgically correctable malformations diagnosed antenatally. The mean gestational age was 37.2 +/- 1.6 weeks, and the birth weight was 2,597 +/- 1.6 g. The results of the blood count, serum electrolyte, and liver function tests of the patients who underwent ACBT only (group 1, n = 7) were compared with those of the 7 neonates who underwent an allogenic transfusion during the same period (group 2, n = 7). RESULTS: The mean volume of the stored blood was 64 +/- 35.6 g (range, 20 to 100). Eleven of the 12 patients underwent transfusions. Ten of 11 patients received autologous cord blood. A mean of 44.1 +/- 37.3 g of cord blood was used. Three of 10 cases also required an allotransfusion because of ECMO circuit preparation and a shortage of the stored blood. One patient underwent allotransfusion only. As a result, 7 of 11 babies (64%) who required transfusion were able to avoid an allotransfusion. The blood potassium levels were lower in group 1 than in group 2. No significant complications were recognized clinically. CONCLUSIONS: ACBT is considered beneficial because it enables neonatal surgical patients to avoid allotransfusions. Therefore, autologous cord-blood storage should be considered in the patients antenatally diagnosed to have surgical malformations. However, the storage volume varies for each case. Improved techniques to obtain an adequate amount of blood also should be developed.

Blood Loss, Surgical↗
PubMed2003

A case of pregnancy complicated by the development of a tubo-ovarian abscess following in vitro fertilization and embryo transfer.

Tubo-ovarian abscess is an uncommon complication in pregnant women. In this report, we present a patient who developed a tubo-ovarian abscess during pregnancy following in vitro fertilization and embryo transfer (IVF-ET). Despite treatment with intravenous antibiotics she delivered at 22 weeks of gestation. After delivery, she underwent a left salpingo-oophorectomy. Review of the literature revealed only 26 reported cases of tubo-ovarian or pelvic abscess during pregnancy. Pelvic inflammatory disease, previous laparotomy, and structural genital anomalies are known risk factors for pelvic abscess during pregnancy. Pelvic abscess resulting as a complication of vaginal oocyte retrieval has been reported. Therefore, although enabling women with organic pelvic disease such as endometriosis and hydrosalpinx to achieve pregnancy, assisted reproductive techniques may potentially result in pelvic infection during pregnancy. This case suggests that a preconception evaluation and treatment for such conditions should be considered for women undergoing treatment for infertility.

Abscess↗