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Biomedical subjects

Y Nishio

Publications and source records attributed to Y Nishio.

At least 37 records · Page 2Linked to original sources
PubMed2001

Coordinate upregulation of interleukin-8 and growth-related gene product-alpha is present in the colonic mucosa of inflammatory bowel.

BACKGROUND: Although ãlpha-chemokines, such as interleukin (IL)-8 and epithelial neutrophil-activating peptide 78, are implicated in the pathogenesis of inflammatory bowel disease (IBD), little information is currently available on the expression and cellular source of growth-related gene product-alpha (GROalpha) and its functional relationship to other ãlpha-chemokines in the intestinal mucosa of patients with IBD. METHODS: The contents of IL-8 and GROalpha in organ cultures, the expression of IL-8 and GROalpha mRNA, and the modulatory effects of inflammatory mediators on IL-8 and GROalpha-producing cells were examined using colonic mucosal tissues. In vitro stimulatory effects of IL-8 and GROalpha on neutrophils were investigated in terms of chemotactic migration and superoxide anion generation. RESULTS: The contents of IL-8 and GROalpha in organ cultures were elevated in patients with IBD, especially in those with active ulcerative colitis (UC). Both IL-8 and GROalpha contents increased according to an increase in histological disease activity in patients with UC, but not in those with Crohn disease. In contrast, no significant correlation was found between the contents of these alpha-chemokines and clinical disease activity. In situ hybridization detected increased expression of IL-8 and GROalpha mRNA in macrophages, pericrypt myofibroblasts, and the epithelium of tissue specimens with active lesions of IBD. The secretion of IL-8 and GROalpha from macrophages and myofibroblasts obtained from control patients was upregulated by inflammatory cytokines and bacterial products. The concentrations of recombinant (r)-IL-8, which covered the levels of activity detected in individual organ cultures or cell cultures of fractionated mucosal cells, could induce chemotactic migration and superoxide anion generation in neutrophils in vitro, and r-GROalpha had synergistic effects on r-IL-8-induced neutrophil activation. CONCLUSIONS: A coordinate upregulation of IL-8 and GROalpha may be involved in the tissue injury in patients with IBD through their stimulatory effects on neutrophils.

Adult↗
PubMed2001

Effect of endotoxin on P-glycoprotein-mediated biliary and renal excretion of rhodamine-123 in rats.

The effects of Klebsiella pneumoniae endotoxin on the biliary excretion and renal handling of rhodamine-123 were investigated in rats at different times after intraperitoneal injection (1 mg/kg of body weight). The typical substrates for P glycoprotein, i.e., cyclosporine, colchicine, and erythromycin, inhibited the biliary clearance of rhodamine-123, whereas a substrate for organic cation transporter, cimetidine, did not inhibit clearance, suggesting that rhodamine-123 is transported mainly by P glycoprotein. The biliary, renal, and tubular secretory clearances of rhodamine-123 and the glomerular filtration rate significantly decreased 6 h after injection of endotoxin but returned to control levels by 24 h. These results suggest that endotoxin-induced decreases in P-glycoprotein-mediated biliary excretion and renal handling of rhodamine-123 were probably due to impairment of P-glycoprotein-mediated transport ability. Pretreatment with pentoxifylline (50 mg/kg) significantly inhibited endotoxin-induced increases in tumor necrosis factor alpha (TNF-alpha) levels in plasma, which ameliorated the endotoxin-induced reduction of the biliary excretion of rhodamine-123. It is likely that endotoxin-induced impairment of the transport of rhodamine-123 is caused, in part, by overproduction of TNF-alpha. The effect of endotoxin on the expression of P-glycoprotein mRNA in liver and kidneys of rats was investigated by using a reverse transcriptase PCR. The expression of Mdr1a mRNA in both liver and kidney decreased 6 h after endotoxin injection and returned to control levels after 24 h, whereas the expression of Mdr1b mRNA in liver increased at both times and that in kidney decreased at 24 h. These findings suggest that K. pneumoniae endotoxin dramatically decreases P-glycoprotein-mediated biliary and renal excretion of rhodamine-123 probably by decreasing the expression of Mdr1a, which is likely due to increased plasma TNF-alpha levels.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Clinical features affecting the results of estrogen replacement therapy on bone density in Japanese postmenopausal women.

Although estrogen replacement therapy (ERT) has been established as an effective treatment for postmenopausal bone loss, the clinical features which predict the effects of ERT have not been well investigated in Japanese postmenopausal women. We analyzed the role of physical factors influencing the effect of ERT on vertebral bone mineral density (BMD) in 94 Japanese postmenopausal women treated for 2 years or longer. The increase in BMD with ERT is 17.6 +/- 27.6 mg/cm(2)/year (mean +/- SD) during the first 2 years. Rates of BMD change were negatively correlated with the estimated initial BMD, and positively correlated with age and years since menopause, while no correlation was noted with the body mass index by a simple correlation analysis. The relationships between BMD change and estimated initial BMD or age also held in a multiple regression analysis. The estimated initial BMD and age together accounted for 34.4% of the BMD change during ERT. Furthermore, there were very few (2.4%) nonresponders with a negative linear regression slope of BMD in the osteoporosis and osteopenia group, although 32.7% of the normal initial BMD group were nonresponders. These results suggest that the initial BMD and age are potent predictive factors of the ERT effect on BMD change in Japanese postmenopausal women.

Adult↗
PubMed2001

Insulin production in a neuroectodermal tumor that expresses islet factor-1, but not pancreatic-duodenal homeobox 1.

We studied a 60-yr-old female with a brain tumor who showed severe symptoms of hypoglycemia (plasma glucose, 2.2 mmol/L) and hyperinsulinemia (1.28 nmol/L) after radiotherapy. The cystic brain tumor contained proinsulin and insulin at concentrations of 13.6 and 1.22 nmol/L, respectively. Immunohistochemical studies showed the tumor cells were ectodermal in origin but not endodermal, based on three diagnostic features of neuroectodermal tumors 1) pseudorosette formation noted under light microscopy, 2) finding of a small number of dense core neurosecretory granules on electron microscopy, and 3) positive immunostaining for both neuronal specific enolase and protein gene product 9.5. These cells also expressed the transcription factor, neurogenin-3, NeuroD/beta 2, and islet factor I, which are believed to be transcription factors in neuroectoderm as well as in pancreatic islet cells, but not pancreatic-duodenal homeobox 1, Pax4, or Nkx2.2. In addition, they did not express glucagon, somatostatin, or glucagon-like peptide-1. Our results show the presence of proinsulin in an ectoderm cell brain tumor that does not express the homeobox gene, pancreatic-duodenal homeobox 1, but expresses other transcription factors, i.e. neurogenin3, NeuroD/beta 2, and islet factor-1, which are related to insulin gene expression in the brain tumor.

Antigens, Differentiation↗
PubMed2001

Pneumatosis cystoides intestinalis treated with hyperbaric oxygen therapy: usefulness of an endoscopic ultrasonic catheter probe for diagnosis.

A 67-year-old woman was admitted to our hospital with a complaint of abdominal pain. Barium enema examination and colonoscopy showed numerous round polypoid lesions covered with normal mucosa in the area from the ascending colon to the splenic flexure. Endoscopic ultrasound examination with an ultrasonic catheter probe revealed a strong echo with distal acoustic shadowing in the third layer of the diseased colonic wall, which suggested the presence of gas in the submucosa. The gaseous cysts disappeared completely after hyberbaric oxygen therapy at 2 to 3 atmospheres absolute (60 minutes, twice a day) for 30 consecutive days.

Aged↗
PubMed2001

Increased arterial wall stiffness limits flow volume in the lower extremities in type 2 diabetic patients.

OBJECTIVE: To document an association between arterial wall stiffness and reduced flow volume in the lower-extremity arteries of diabetic patients. RESEARCH DESIGN AND METHODS: We recruited 60 consecutive type 2 diabetic patients who had no history or symptoms of peripheral arterial disease (PAD) in the lower extremities and normal ankle/brachial systolic blood pressure index at the time of the study (non-PAD group) and 20 age-matched nondiabetic subjects (control group). We used an automatic device to measure pulse wave velocity (PWV) in the lower extremities as an index of arterial wall stiffness. At the popliteal artery, we evaluated flow volume and the resistive index as an index of arterial resistance to blood flow using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. RESULTS: Consistent with previous reports, we confirmed that the non-PAD group had an abnormally higher PWV compared with that of the control group (P < 0.001). To further demonstrate decreased flow volume and abnormal flow pattern at the popliteal artery in patients with a higher degree of arterial wall stiffness, we assigned the 60 non-PAD patients to tertiles based on their levels of PWV. In the highest group, magnetic resonance angiograms of the calf and foot arteries showed decreased intravascular signal intensity, indicating the decreased arterial inflow in those arteries. The highest group was also characterized by the lowest late diastolic and total flow volumes as well as the highest resistive index among the groups. From stepwise multiple regression analysis, PWV and autonomic function were identified as independent determinants for late diastolic flow volume (r(2) = 0.300; P < 0.001). CONCLUSIONS: Arterial wall stiffness was associated with reduced arterial flow volume in the lower extremities of diabetic patients.

Aged↗
PubMed2001

[A case of human chorionic gonadotropin-producing bladder cancer].

An 86-year-old man consulted our hospital complaining of gross hematuria. Cystoscopy revealed a nodular broad-based cancer at the dome of the bladder. The patient was initially treated by transurethral resection of bladder tumor. Since histological examination showed grade 3 transitional cell carcinoma containing giant cells that were positive for beta-human chorionic gonadotropin (beta-HCG), we made a diagnosis of beta-HCG-producing bladder cancer. Because of his advanced age and poor general condition, the patient underwent partial cystectomy alone without adjuvant chemotherapy. One month later, a chest X-ray film revealed multiple lung metastases, and he developed paraplegia of the lower extremities suggesting spinal metastases. One month later, he was brought to our hospital with cardiopulmonary arrest. This is, to our best knowledge, the 22nd case report of beta-HCG-producing bladder cancer in Japan.

Aged↗
PubMed2001

[A case of craniopharyngioma with chemical meningitis as an initial symptom].

We reported a rare case of craniopharyngioma with chemical meningitis due to spontaneous rupture of the tumor. A 50-year-old woman was admitted with high fever, headache, and nausea. On physical examination, she had nuchal rigidity. The examination of her cerebral spinal fluid(CSF) revealed pleocytosis(mononuclear cell dominant), low value of glucose level and high content of protein. The feature of her CSF findings suggested tuberculosis or fungal meningitis, but bacteriologic culture of the CSF was negative. The CT scan showed an isodensity mass in the suprasellar region and a spotty calcification in the third ventricle. The MRI with gadolinium enhancement suggested that the tumor must be craniopharyngioma and that meningitis was a type of chemical meningitis due to spontaneous rupture of craniopharyngioma. The corticosteroid therapy was rather effective to the symptoms of fever and headache. Then the operation was performed by neurosurgeons, and the diagnosis of craniopharyngioma was pathologically confirmed. Spontaneous rupture of craniopharyngioma rarely occurred and was followed by chemical meningitis. This case was an extremely rare condition that presented with chemical meningitis as an initial symptom.

Craniopharyngioma↗
PubMed2001

[Molecular mechanisms of endothelial dysfunction in diabetes mellitus].

Diabetes is a strong risk factor for vascular diseases. Recent studies have shown that disruption of endothelial cell function results in vascular injury. One of causes underlying the endothelial dysfunction in diabetics is hyperglycemia. Many epidemiological studies demonstrated that hyperglycemia increased the incidence of macrovascular diseases. In contrast to the microvascular complications in diabetes, however, the macrovascular complication often develops even in patients with good glycemic control, suggesting that some factors other than hyperglycemia may contribute to it. Insulin resistance is one of possible candidates for that. In fact, it is shown that insulin resistance is an independent risk factor for atherosclerosis. In this article, we reviewed recent hypothesis explaining how hyperglycemia or insulin resistant state caused endothelial dysfunction.

Animals↗
PubMed2000

Inhibition of BAD phosphorylation either at serine 112 via extracellular signal-regulated protein kinase cascade or at serine 136 via Akt cascade sensitizes human ovarian cancer cells to cisplatin.

We studied the roles of the phosphatidylinositol 3-kinase (PI-3K)-protein kinase B/Akt-BAD cascade in both cisplatin-resistant Caov-3 and -sensitive A2780 human ovarian cancer cell lines. Treatment of both Caov-3 and A2780 cells with cisplatin but not with the trans-diaminodichloroplatinum (transplatin) isomer stimulated the activation of Akt, and the PI-3K inhibitor wortmannin blocked the cisplatin-induced activation of Akt. Treatment of both Caov-3 and A2780 cells with cisplatin but not with the trans-diaminodichloroplatinum isomer also stimulated the phosphorylation of BAD at both the Ser-112 and Ser-136 sites. Whereas the phosphorylation of BAD at Ser-136 was blocked by treatment with wortmannin, its phosphorylation at Ser-112 was blocked by a MAP/ERK kinase inhibitor, PD98059. Exogenous expression of a dominant-negative Akt in both Caov-3 and A2780 cells decreased the cell viability after treatment with cisplatin. In contrast, no sensitization to cisplatin was observed in cells expressing wild-type Akt. We further examined the role of BAD in the viability after cisplatin treatment using BAD mutants. Exogenous expression of each of the singly substituted BADS112A or BADS136A in both Caov-3 and A2780 cells decreased the viability after treatment with cisplatin to a degree intermediate between that caused by exogenous expression of wild-type BAD and doubly substituted BAD2SA. Cisplatin did not stimulate the phosphorylation of BAD Ser-136, but did stimulate the phosphorylation of BAD Ser-112 in cells expressing a dominant-negative Akt, suggesting that BAD Ser-136 but not Ser-112 was phosphorylated by Akt. Our findings suggest that cisplatin-induced DNA damage causes the phosphorylation of both BAD Ser-112 via an extracellular signal-regulated protein kinase (ERK) cascade and BAD Ser-136 via a PI-3K-protein kinase B/Akt cascade and that inhibition of either of these cascades sensitizes ovarian cancer cells to cisplatin.

Adenocarcinoma, Papillary↗
PubMed2000

Estrogen induces the Akt-dependent activation of endothelial nitric-oxide synthase in vascular endothelial cells.

Although estrogen is known to activate endothelial nitric oxide synthase (eNOS) in the vascular endothelium, the molecular mechanism responsible for this effect remains to be elucidated. In studies of both human umbilical vein endothelial cells (HUVECs) and simian virus 40-transformed rat lung vascular endothelial cells (TRLECs), 17beta-estradiol (E2), but not 17alpha-E2, caused acute activation of eNOS that was unaffected by actinomycin D and was specifically blocked by the pure estrogen receptor antagonist ICI-182,780. Treatment of both TRLECs and HUVECs with 17beta-E2 stimulated the activation of Akt, and the PI3K inhibitor wortmannin blocked the 17beta-E2-induced activation of Akt. 17beta-E2-induced Akt activation was also inhibited by ICI-182,780, but not by actinomycin D. Either treatment with wortmannin or exogenous expression of a dominant negative Akt in TRLECs decreased the 17beta-E2-induced eNOS activation. Moreover, 17beta-E2-induced Akt activation actually enhances the phosphorylation of eNOS. 17beta-E2-induced Akt activation was dependent on both extracellular and intracellular Ca(2+). We further examined the 17beta-E2-induced Akt activity in Chinese hamster ovary (CHO) cells transiently transfected with cDNAs for estrogen receptor alpha (ERalpha) or estrogen receptor beta (ERbeta). 17beta-E2 stimulated the activation of Akt in CHO cells expressing ERalpha but not in CHO cells expressing ERbeta. Our findings suggest that 17beta-E2 induced eNOS activation through an Akt-dependent mechanism, which is mediated by ERalpha via a nongenomic mechanism.

Animals↗
PubMed2000

Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats.

We have reported that a deficiency of tetrahydrobiopterin (BH(4)), an active cofactor of endothelial NO synthase (eNOS), contributes to the endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O(2)(-)) generation in the insulin-resistant state. To further confirm this hypothesis, we investigated the effects of dietary treatment with BH(4) on endothelium-dependent arterial relaxation and vascular oxidative stress in the aortas of insulin-resistant rats. Oral supplementation of BH(4) (10 mg. kg(-1). d(-1)) for 8 weeks significantly increased the BH(4) content in cardiovascular tissues of rats fed high levels of fructose (fructose-fed rats). Impairment of endothelium-dependent arterial relaxation in the aortic strips of the fructose-fed rats was reversed with BH(4) treatment. The BH(4) treatment was associated with a 2-fold increase in eNOS activity as well as a 70% reduction in endothelial O(2)(-) production compared with those in fructose-fed rats. The BH(4) treatment also partially improved the insulin sensitivity and blood pressure, as well as the serum triglyceride concentration, in the fructose-fed rats. Moreover, BH(4) treatment of the fructose-fed rats markedly reduced the lipid peroxide content of both aortic and cardiac tissues and inhibited the activation of 2 redox-sensitive transcription factors, nuclear factor-kappaB and activating protein-1, which were increased in fructose-fed rats. The BH(4) treatment of control rats did not have any significant effects on these parameters. These results indicate that BH(4) augmentation is essential for the restoration of eNOS function and the reduction of vascular oxidative stress in insulin-resistant rats.

Administration, Oral↗
PubMed2000

The Rayleigh Color Matches in Idiopathic Macular Holes Treated by Vitrectomy.

Purpose: The Rayleigh color matches were measured to investigate the optical density in the cone photopigment of the central retina in patients with macular holes that had closed after vitrectomy.Methods: The Rayleigh equation was measured with the IF-2 anomaloscope in 7 patients with macular holes in one eye, that had closed after vitrectomy and gained an improvement in visual acuity of 0.5 or better. Reductions in the pigment optical density of cone photoreceptors of the opposite eyes were estimated with Rayleigh equations obtained in this experiment.Result: The Rayleigh equations of the affected eyes were shifted toward protanomalous setting compared with that of the opposite eyes. The optical densities of cone photoreceptors of the affected eyes were lower than those in the opposite eyes, even in patients with visual acuity of 1.0 or better.Conclusion: These findings suggest that the recovery of the visual acuity may precede that of the optical density in cone photopigment of central retina. The Rayleigh equation is more sensitive than visual acuity for evaluating visual function after vitrectomy for macular holes.

Journal Article↗
PubMed2000

Evidence that 3'-phosphorylated polyphosphoinositides are generated at the nuclear surface: use of immunostaining technique with monoclonal antibodies specific for PI 3,4-P(2).

Phosphatidylinositol (PI) 3,4-P(2) is a phosphoinositide that has been shown to be important for signal transduction in growth factor stimulation. We have produced monoclonal antibodies specific for PI 3,4-P(2), which were able to detect PI 3,4-P(2) generated in 293T cells treated with H(2)O(2), or in MKN45/BD110 cells expressing activated PI 3-kinase in immunostaining. Prolonged treatment with 0.05% Tween 20 resulted in detection of staining not only at the plasma membrane, but also at the nuclear surface, indicating that 3'-phosphorylated phosphoinositides can be generated and function in the nucleus.

Animals↗
PubMed2000

Evaluation of endothelial free radical release by vascular tension responses in insulin-resistant rat aorta.

Mechanical responses to superoxide anion scavengers and nitric oxide (NO) synthase inhibitors in aortic endothelial cells were compared in normal chow-fed rats and those made insulin-resistant by feeding of fructose. Cu(2+), Zn(2+)-superoxide dismutase-induced vascular relaxation and superoxide production, measured by the lucigenin-enhanced chemiluminescence method, were greater in aortas from fructose-fed rats than in those from normal chow-fed rats. N(G)-nitro-L-arginine-induced contractions due to suppression of NO synthase activity were smaller in aortas from fructose-fed rats. Vascular mechanical responses may reflect the generation of superoxide and NO by the endothelium. Thus, isometric tension studies may be a useful tool for evaluating the production of these radicals in blood vessels.

Animals↗