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J Ando

Publications and source records attributed to J Ando.

At least 37 records · Page 2Linked to original sources
PubMed2000

P2X(4) receptors mediate ATP-induced calcium influx in human vascular endothelial cells.

ATP induces Ca(2+) influx across the cell membrane and activates release from intracellular Ca(2+) pools in vascular endothelial cells (ECs). Ca(2+) signaling leads to the modification of a variety of EC functions, including the production of vasoactive substances such as nitric oxide and prostacyclin. However, the molecular mechanisms for ATP-induced Ca(2+) influx in ECs have not been thoroughly clarified. Here we demonstrate evidence that a P2X(4) receptor for an ATP-gated cation channel is predominantly expressed in human ECs and is involved in the ATP-induced Ca(2+) influx. Northern blot analysis distinctly showed the expression of P2X(4) mRNA in human ECs cultured from the umbilical vein, aorta, pulmonary artery, and skin microvessels. Competitive PCR revealed that P2X(4) mRNA expression was much higher in ECs than was the expression of other subtypes, including P2X(1), P2X(3), P2X(5), and P2X(7). Treatment of ECs with antisense oligonucleotides designed to target the P2X(4) receptor decreased the P2X(4) mRNA and protein levels to approximately 25% of control levels and markedly prevented the ATP-induced Ca(2+) influx.

Adenosine Triphosphate↗
PubMed2000

Anti-herpes virus activity of Solanum steroidal glycosides.

Since some Solanum-genus plants have traditionally been used for anti-cancer and anti-herpes agents from olden times, we examined anti-herpes simplex virus type 1 (HSV-1) activity of typical steroidal glycosides with the frameworks of spirostane (including nuatigenin glycoside), furostane, solasodane, tomatidane and ergostane (including dimer) obtained from Solanum plants. Among these steroidal glycosides, the spirostanol glycosides were most effective. An inclination was observed for the potency of activity to decrease in the order of spirostane, tomatidane, ergostane, solasodane, nuatigenin type, dimer of ergostane and furostane. It was also suggested that the activity depends on the kind of oligosacchride moiety.

Animals↗
PubMed2000

Genetic structure of the five-factor model of personality in a Japanese twin population.

Dimensional approaches have been used to describe the fundamental dimensions that underlie the entire domain of normal and pathological personality. We tested the five factor model of personality structure in a sample of Japanese twins, to clarify the contributions of genetic and environment. The revised NEO personality inventory (NEO-PI-R) was administered to 251 twin pairs, ranging in age from 15 to 27 years of age. The NEO-PI-R is a 240-item questionnaire which was developed to assess the dimensions of personality. Univariate genetic analysis showed that the AE model in which phenotypic covariances are explained only by additive genetic (A) and nonshared environment (E) is still a plausible model, and that the relative proportion of genetic influence was comparable to that reported by Loehlin (1992). Multivariate genetic analysis of the Japanese data suggested/revealed that the five factors are genetically dependent on each other and one common genetic factor mediates their interdependence. Previous studies have assumed that they are phenotypically independent and robust. Although there are sampling biases in the present study, it is noteworthy that the results for all five factors depicted by the NEO-PI-R were comparable to those reported by Western researchers, and the genetic structure of the five-factor model is complex.

Adolescent↗
PubMed2000

[Randomized comparative study of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) and UFT-tamoxifen regimens as adjuvant chemotherapy after surgery for breast cancer: Tochigi Prefectural Study Group for Post-Breast Cancer Adjuvant Chemotherapy].

This prospective randomized study aimed at establishing the optimal postoperative adjuvant chemotherapy regimen for premenopausal n+ breast cancer patients. The treatments were Regimen A, comprising 6 courses of CMF (cyclophosphamide, 100 mg/body on days 1-14; methotrexate, 40 mg/m2 on days 1 and 8; and 5-fluorouracil, 500 mg/m2 on days 1 and 8), and Regimen B, consisting of UFT (300 mg/day) and tamoxifen (30 mg/day) administered orally each day for 2 years. Telephone registration allocated the patients to the treatment groups by the minimization method in relation to the T category, number of n+ lesions and estrogen receptor status. Forty-five patients were registered, and 44 of them were eligible (22 cases each to Regimen A and Regimen B). The principal background factors showed no biases between the groups. The adverse reaction incidence was significantly higher with Regimen A (90.9% vs 22.7%). The 5-year survival rate was 89.8% with Regimen A and 100% with Regimen B, while the 5-year disease-free rates were 64.5% and 76.3%, showing no statistical significance. Regimen B showed a better QOL rating after 6 months of therapy in relation to nausea-vomiting and hair loss, and after 24 months in relation to appetite, sleep, performance status, happiness, anorexia and hair loss.

Adult↗
PubMed2000

[Shear stress].

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Animals↗
PubMed1999

Salmon gonadotropin IIbeta subunit promoter contains multiple DNA elements responsible for stimulation by gonadotropin-releasing hormone through protein kinase C-dependent and -independent pathways.

Gonadotropin-releasing hormone (GnRH) stimulates gonadotropin (GTH) production by activating GTH subunit gene transcription. In salmonid fish, the expression of the beta subunit gene of GTH II (sGTH IIbeta) is stimulated by GnRH at the final stages of reproduction. DNA elements required for the GnRH stimulation were examined by analyzing sGTH IIbeta promoter activity by transfection studies in a gonadotrope-derived cell line, alphaT3-1. A GnRH analog (GnRHa) specifically stimulated the sGTH IIbeta promoter (3358 bp) expression 3.6-fold, while phorbol myristate acid (PMA) stimulated it 6.2-9-fold. Analysis of a series of 5'-deletion mutants has revealed that a proximal region (-258 to -199) was important in GnRHa stimulation through protein kinase C (PKC)-independent signal transduction pathways, because an internal deletion mutant (delta(246 - 217)/3358) showed a significant decrease in the level of GnRHa stimulation, but showed no change in stimulation by PMA. A large upstream region (-3358 to -1260) showed an enhancing activity of the GnRHa stimulation, and a far upstream 530 bp segment in this region (-3358 to -2829) may be responsible for this activity. The present results suggest that sGTH IIbeta gene may be controlled by GnRH through multiple DNA elements including those responsive to PKC-dependent and -independent signal transduction pathways.

Animals↗
PubMed1999

Significance of Steroid Sulfatase Expression in Human Breast Cancer.

The sulfatase pathway has been thought to be a primary means of local production of estrone in human breast cancer tissue. We measured steroid sulfatase (STS) mRNA levels in 97 breast cancers and evaluated its association with disease-free survival. High levels of STS mRNA proved to be a significant predictor of reduced relapse-free survival, both as a continuous variable (log STS mRNA; P = 0.028) and as a dichotomous variable with an optimized cutoff point (P=0.002). In multivariate analysis a high level of STS mRNA was an independent factor for predicting relapse-free survival. These results suggest a putative role of STS in breast cancer growth and metastasis, and administration of sulfatase inhibitors to breast cancer patients with high levels of STS mRNA might be an additional treatment option.

Journal Article↗
PubMed1999

Hepatotoxicity and consequently increased cell proliferation are associated with flumequine hepatocarcinogenesis in mice.

It has been reported that flumequine (FLU) induces hepatic tumors in mice when given orally for 18 months. We investigated possible underlying mechanisms using a two-stage mouse hepatocarcinogenesis model. After initiation with a single intraperitoneal injection of 100 mg/kg body weight diethylnitrosamine (DEN) or saline, male CD-1 mice were given 4000 ppm FLU in the diet or 500 ppm phenobarbital (PB) in drinking water for 9, 19, 24 or 30 weeks. Toxicity, evidenced by centrilobular swollen and polar hepatocytes with fatty droplets, infiltration of inflammatory cells and increased numbers of mitosis in hepatocytes, was apparent in the livers of mice treated with FLU at all time points, but its severity declined towards the termination. FLU did not induce cytochrome P-450 enzymes such as 1A1, 2B1 and 3A2 as assessed immunohistochemically, while positive expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was increased in hepatocytes of both DEN + FLU and FLU groups compared with the relevant controls. In animals given PB, eosinophilic swelling of hepatocytes was prominent, and the hepatocytes showed strongly positive reactions for CYP 1A1 and 3A2. Altered cell foci were induced in the livers of FLU-treated animals both with and without DEN initiation, especially the former, and their development paralleled the degree of hepatic toxicity. These results suggest that FLU hepatocarcinogenicity in mice is dependent on hepatotoxic damage and consequently increased cell proliferation. Oxidative damage to DNA may also be a crucial factor.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Transplacental administration of diethylstilbestrol (DES) causes lesions in female reproductive organs of Donryu rats, including endometrial neoplasia.

The effects of transplacental administration of diethylstilbestrol (DES) on female reproductive organs were investigated using Donryu rats. The animals were given subcutaneous injections of DES dissolved in olive oil at doses of 0.01 or 0.1 mg/kg on days 17 and 19 of gestation. In female offspring, clinical signs, body weights and estrous cycles were continuously assessed until all survivors were killed at month 18. A low mean litter size and shortening of period of pregnancy were recognized in the 0.1 mg/kg group. Disorder and/or suspension of the estrous cycle (so called persistent estrus) also appeared very early in the 0.1 mg/kg group. Macroscopically, the incidences of hypoplasia of the oviduct, cystic dilatation of the uterus and small size of the uterine cervix were higher in the 0.1 mg/kg group than those in the control group. Histologically, in the ovary, the incidence and degree of atrophy were increased in both 0.01 and 0.1 mg/kg groups. In the uterus, total incidences of endometrial hyperplasias were about the same in all groups. However, endometrial adenocarcinomas were dose-dependently increased in the treated groups, the incidence in the 0.1 mg/kg group being significant, compared to that in the control. In the vagina, mucification was more prominent in the treated animals, especially at the higher dose, but no tumors were observed. The present results indicate that prenatal exposure to DES can produce uterine adenocarcinomas in rats, as reported earlier for mice, although its carcinogenic activity is not so strong. Increase of endometrial adenocarcinoma incidence might depend on hormonal imbalance resulting from the ovarian atrophy due to transplacental treatment of DES.

Adenocarcinoma↗
PubMed1999

Steroid sulfatase expression is an independent predictor of recurrence in human breast cancer.

Steroid sulfatase (STS) hydrolyzes several sulfated steroids such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate. In the present study, we have measured STS mRNA levels in 97 breast cancers by reverse transcription-PCR using a fluorescent primer in the presence of an internal standard RNA and evaluated its association with disease-free and overall survival. The median value was 728.0 amol/ng RNA (range, 0-11,778 amol/ng RNA). Levels were significantly higher in tumors demonstrating lymph node metastasis than in those without nodal involvement (P = 0.033) and in patients who experienced a recurrence during the follow-up period (mean, 40.8 months; median, 39 months) compared with those with no evidence of further disease (mean, 49.2 months; median, 48 months; P = 0.029). No significant associations were found between STS mRNA expression and age, menopausal status, tumor size, histological grade, estrogen receptor status, or postoperative adjuvant therapy. High levels of STS mRNA proved to be a significant predictor of reduced relapse-free survival as a continuous variable (log STS mRNA; P = 0.028). As a dichotomous variable with an optimized cutoff point of 1,240 amol/ng RNA, expression was also associated with a significantly shorter relapse-free survival rate (P = 0.002), but no significant correlation was found between the STS mRNA level and overall survival. Expression was found to be an independent factor for predicting relapse-free survival on multivariate analysis. The results thus support a putative role of STS in breast cancer growth and metastasis.

Adult↗
PubMed1999

Expression of salmon corticotropin-releasing hormone precursor gene in the preoptic nucleus in stressed rainbow trout.

The behavior of genes encoding the corticotropin-releasing hormone (CRH) precursor in response to stress has not been extensively studied in teleosts. To clarify this problem, CRH cDNAs were isolated from a hypothalamic cDNA library of sockeye salmon, Oncorhynchus nerka, by screening with PCR products amplified from the hypothalamic mRNA with primers deduced from the sequence of the sucker CRH precursor. Two types of PCR products with a high degree of sequence homology were identified (CRH-I and CRH-II). A cDNA encompassing the entire coding sequence of the salmon CRH-I precursor was isolated. The salmon CRH-I cDNA encodes a 167-amino-acid precursor, which consists of a signal sequence, a cryptic peptide, and the carboxyl terminal 41-amino-acid sequence of CRH. The deduced amino acid sequence of salmon CRH peptide exhibits 66 to 80% homology with mammalian, Xenopus, and sucker CRHs, whereas it shows about 50% homology with sucker, carp, or sole urotensin I, a CRH-related neuropeptide in teleost fish. In situ hybridization histochemistry demonstrated CRH mRNA-positive perikarya in the preoptic nucleus in rainbow trout, Oncorhynchus mykiss, when the fish were stressed by confinement. Adjacent sections hybridized with probes for salmon vasotocin (VT) precursor showed many VT mRNA-positive neurons also in the preoptic nucleus, suggesting a colocalization of CRH and VT mRNAs in the same magnocellular neurons in the rainbow trout brain. The present results suggest that CRH may have important roles in the control of stress responses in salmonid fish.

Amino Acid Sequence↗
PubMed1999

The effect of flow on the neutrophil-mediated Ca2+ responses in human vascular endothelial cells stimulated by endotoxin.

Leukocyte-vascular endothelial cell (EC) interactions which promote inflammatory and immune reactions involve bidirectional signaling between two cell types. We investigated the effects of flow on neutrophil-mediated changes in endothelial intracellular Ca2+ levels ([Ca2+]i). Cultured human umbilical vein ECs stimulated by endotoxin were labeled with Fura-2 and exposed to fluid flow with neutrophils. The individual changes in [Ca2+]i were monitored. The application of flow with neutrophils to stimulated ECs led to an increase in [Ca2+]i although either flow without neutrophils or neutrophils without flow rarely induced a rise in [Ca2+]i. Furthermore, flow application with neutrophils to unstimulated ECs also rarely promoted a rise in [Ca2+]i. These findings suggest that the flow might thus induce or enhance the inflammatory process by the induction of Ca2+ signaling in endotoxin-stimulated endothelium facing neutrophils in the blood flow.

Calcium↗
PubMed1999

Schedule-dependent interactions between vinorelbine and paclitaxel in human carcinoma cell lines in vitro.

Vinorelbine and paclitaxel are new anticancer agents that bind to distinct sites on tubulin and affect microtubules in opposite ways. Clinical studies of combinations of these agents have been in progress against breast cancer and some solid tumors. To clarify the optimal schedule for this combination, we studied the schedule-dependent cytotoxic effects of vinorelbine and paclitaxel against the human lung carcinoma cell line A549, the breast carcinoma cell line MCF7, the ovarian carcinoma cell line PA1, and the colon carcinoma cell line WiDr in vitro. Tumor cells were incubated with vinorelbine and paclitaxel simultaneously for both 24 h and 5 days. Cells were also incubated with vinorelbine for 24 h, followed by a 24-h exposure to paclitaxel and vice versa. Cell growth inhibition after 5 days was determined by MTT assay. The effects of drug combinations at the concentration producing 80% cell growth inhibition (IC80) were analyzed by the isobologram method (Steel and Peckham). The simultaneous exposures to vinorelbine and paclitaxel for both 24 h and 5 days produced additive effects for all four cell lines. The sequential exposure to vinorelbine followed by paclitaxel produced additive effects for the PA1 and WiDr cells, additive and antagonistic effects for the A549 cells, and antagonistic effects for the MCF7 cells. The sequential exposure to paclitaxel followed by vinorelbine produced additive effects for the A549, and PA1 cells, additive and antagonistic effects for the MCF7 cells, and antagonistic effects for the WiDr cells. Our findings suggest that the simultaneous rather than the sequential administration of vinorelbine and paclitaxel may be the optimal schedule for this combination of these two agents. Applications of this schedule dependency may be beneficial for the treatment of breast cancer and other solid tumors.

Antineoplastic Agents, Phytogenic↗
PubMed1999

A phase I/II study of continuous intra-arterial chemotherapy using an implantable reservoir for the treatment of liver metastases from breast cancer: a Japan Clinical Oncology Group (JCOG) study 9113. JCOG Breast Cancer Study Group.

BACKGROUND: Liver metastasis from breast cancer has a poor prognosis. While there are some reports of good response rates of hepatic metastasis from breast cancer by hepatic intra-arterial infusion chemotherapy, no phase I study including pharmacokinetic analysis has been reported. We performed a phase I/II study of intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find the maximum tolerated dose and response rate in patients with advanced or recurrent breast cancer. METHODS: A hepatic arterial catheter with an access port was inserted into the proper hepatic artery. Patients received 30 mg/m2 adriamycin on days 1 and 8 and 100 mg/m2 5-fluorouracil at level 1, 200 mg/m2 at level 2,300 mg/m2 at level 3 and 400 mg/m2 at level 4 continuously from day 1 through day 14 every 28 days. At least two cycles were required before evaluation. Twenty-eight patients were entered into this study and 26 patients were evaluable. Seventeen patients had hepatic metastasis only, although nine patients had additional metastasis to other sites. RESULTS: Dose-limiting toxicity of thrombocytopenia and neurotoxicity occurred at level 4. Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in three (12%) and anemia in two (8%) patients. There were 11 catheter-related complications which were not dose dependent. Seven out of 13 evaluable patients (54%) responded at level 3. The median duration of response was 5.8 months (range, 1-23+) and median survival was 25.3 months (range, 6.2-54.7+). CONCLUSION: Hepatic arterial infusion therapy appears to be safe and effective but catheter-related complications must be overcome before starting a phase III trial.

Adolescent↗
PubMed1998

Inhibitory effects of uterine endometrial carcinogenesis in Donryu rats by tamoxifen.

The effects of tamoxifen (TAM) on uterine carcinogenesis were investigated in female Donryu rats. The effects were initiated by a single intrauterine treatment with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at a dose of 20 mg/kg body weight via the vagina at 10 weeks of age. TAM tubes (cholesterol tubes containing 50% TAM) were implanted into the backs of the rats for 13 months (full TAM group) or for the second-half of this period (half TAM group). In the control group treated with ENNG alone, various proliferative lesions were induced in the uterine endometrium and the incidence of endometrial adenocarcinomas was about 30%. In contrast, the uteri in both TAM-treated groups showed severe atrophy and the incidences of uterine proliferative lesions were limited to a few endometrial hyperplasias in the half TAM group. Most of the vaginas in both TAM-treated groups showed mucification, while cornification was common in the vaginal epithelium of controls. The ovaries demonstrated similar atrophy with cystic follicles and no corpora lutea in all groups. Other estrogen responsive endocrine organs, such as the pituitaries and adrenals, were small in the TAM-treated groups. Serum estrogen levels in the TAM-treated groups were lower than in the control group but progesterone levels did not differ. These results indicated that TAM acts as an anti-estrogen on the adult rat uterus, inhibiting the development of endometrial adenocarcinomas initiated by ENNG.

Adrenal Glands↗
PubMed1998

Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene.

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a recently identified receptor for oxidized low-density lipoprotein, one of the major atherogenic substances. Although LOX-1 was reported to be expressed abundantly in endothelial cells, including atheromatous lesions, the regulation of LOX-1 gene has not yet been clarified. In the present study, we isolated the rat LOX-1 gene and investigated the regulation of gene expression. The rat LOX-1 gene was encoded by a single copy gene spanning over 19 kilobases and consisted of eight exons. Exon boundaries correlated well with the functional domain boundaries of the receptor protein. The promoter region contained putative TATA and CAAT boxes and multiple cis-elements such as NF-kappaB, AP-1 and AP-2 sites, and a shear stress response element. Northern blot analysis revealed that LOX-1 gene expression was up-regulated 9-fold by shear stress, 21-fold by lipopolysaccharide, and 4-fold by tumor necrosis factor-alpha, in cultured vascular endothelial cells. LOX-1 was also expressed in macrophages but not in vascular smooth muscle cells. These data provide important information for elucidating the molecular mechanisms of LOX-1 gene regulation and suggest a role for LOX-1 in the pathophysiology of atherosclerotic cardiovascular disease.

Animals↗
PubMed1998

Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells.

Fluid shear stress has been shown to modulate various endothelial functions, including gene expression. In this study, we examined the effect of fluid shear stress on the expression of lectin-like oxidized LDL receptor-1 (LOX-1), a novel receptor for atherogenic oxidized LDL in cultured bovine aortic endothelial cells (BAECs). Exposure of BAECs to the physiological range of shear stress (1 to 15 dyne/cm2) upregulated LOX-1 protein and mRNA in a time-dependent fashion. LOX-1 mRNA levels peaked at 4 hours, and LOX-1 protein levels peaked at 8 hours. Inhibition of de novo RNA synthesis by actinomycin D totally abolished shear stress-induced LOX-1 mRNA expression. Furthermore, nuclear runoff assay showed that shear stress directly stimulates transcription of the LOX-1 gene. Chelation of intracellular Ca2+ with quin 2-AM completely reduced shear stress-induced LOX-1 mRNA expression; furthermore, the treatment of BAECs with ionomycin upregulated LOX-1 mRNA levels in a dose-dependent manner. Taken together, physiological levels of fluid shear stress can regulate LOX-1 expression by a mechanism dependent on intracellular Ca2+ mobilization. Inducible expression of LOX-1 by fluid mechanics may play a role in localized expression of LOX-1 and atherosclerotic lesion formation in vivo.

Animals↗