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O Ito

Publications and source records attributed to O Ito.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Effect of adenosine on isolated afferent arterioles].

We investigated the direct effect of adenosine on afferent arterioles (Af-Arts) and the receptor subtype that mediates the constrictor or dilator action of adenosine. Af-Arts were isolated from the superficial cortex of rabbit kidney and perfused in vitro. Adenosine added to either the lumen or bath constricted the Af-Arts in a dose-dependent manner. This constriction was blocked by the A1 receptor antagonist, 6-oxo-3-(2-phenylpyrazole(1,5-a)pyridin-3-yl)-1 (6H)-pyridazinebutyric acid (FK838) or 8-cyclopentyl-1, 3-dipropylxanthine(DPCPX). We also examined the effect of adenosine on preconstricted Af-Arts with norepinephrine. Adenosine added to either the lumen or bath further constricted the preconstricted Af-Arts. In the presence of FK838, adenosine added to either the lumen or bath dilated the preconstricted Af-Arts, but in a different dose-dependent manner. Adenosine-induced dilation was inhibited by the A2 receptor antagonist, 3, 7-dimetyl-1-propargylxanthine(DMPX). These data indicate that adenosine constricts Af-Arts via A1 receptors and that adenosine dilates preconstricted Af-Arts via A2 receptors when A1 receptors are blocked.

Adenosine↗
PubMed1999

[Assessing the physiologic significance of intermediate coronary lesions: comparison of coronary flow measurements with exercise electrocardiography].

Angiography may provide limited assessment of intermediate coronary stenoses. Doppler coronary flow reserve has been applied to determine the physiologic significance of such lesions. This study compared coronary flow reserve derived from intracoronary Doppler flow wire with the results of the exercise tolerance test to evaluate the validity of intracoronary flow measurements in the assessment of intermediate stenoses. Sixty eight patients with 91 vessels harboring angiographically mild-to-severe coronary stenoses in the left anterior descending or right coronary artery were studied. All patients had single-vessel disease, and angiography showed the target vessel. Distal coronary flow reserve was measured with the Doppler guide wire during cardiac catheterization. Exercise tolerance tests by bicycle ergometer were performed the day before catheterization. Quantitative coronary angiography showed a mean percentage diameter stenosis of 44 +/- 21%(range 0-90%). Forty seven of 91 vessels combined intermediate lesions(40% to 70%). Percentage diameter stenosis and coronary flow reserve were linearly correlated in both overall and intermediate lesions(r = -0.52 vs -0.42; both p < 0.0001). Percentage diameter stenosis of overall lesions was significantly higher in the positive exercise test group than the negative group(59.8 +/- 17.2% vs 37.7 +/- 18.1%, p < 0.0001), but not significantly different in intermediate lesions(49.1 +/- 7.8% vs 54.7 +/- 6.6%, p = 0.03). The positive exercise test group showed significantly lower coronary flow reserve compared to the negative group in both overall and intermediate lesions(overall: 1.6 +/- 0.5 vs 2.6 +/- 0.9, p < 0.0001; intermediate: 1.6 +/- 0.5 vs 2.5 +/- 0.7, p < 0.0001). Coronary flow reserve < 2.0 and positive exercise test agreed in 38 of 46 intermediate lesions(83%), and percentage diameter stenosis > or = 50% and positive exercise test agreed in 34 of these 46 lesions(74%). Coronary flow reserve, more than percentage diameter stenosis, correlated with the results of the exercise tolerance test, and is considered to be useful to evaluate the functional severity of intermediate stenosis.

Aged↗
PubMed1999

Umbilical reconstruction after repair of omphalocele and gastroschisis.

This article presents our technique of umbilical reconstruction after the repair of omphalocele and gastroschisis. We have treated 8 patients with an average follow-up period of 13 months (range, 6 approximately 24 months). No major complications have occurred; minor complications have included delayed wound healing, decreased umbilical depth, and hematoma. Our procedure is especially useful for patients who have a midline abdominal scar and relatively intact bilateral rectus abdominis muscles. Most of the patients and their parents have been satisfied with the results of umbilical reconstruction.

Child↗
PubMed1998

The effect of VIP/PACAP family of peptides on pancreatic blood flow and secretion in conscious dogs.

The effects of PACAP-38, PACAP-27, VIP and secretin on pancreatic blood flow were compared with those of meals in five conscious dogs using an ultrasound transit-time blood flow meter. All peptides (1-100 pmol/kg) induced dose-related increases of pancreatic blood flow, and fluid and bicarbonate secretion. Only PACAPs stimulated protein secretion. Both PACAPs at doses which did not stimulate pancreatic secretion, induced significant pancreatic vasodilatation. VIP was less potent than PACAP-38 and PACAP-27 at lower doses (1-25 pmol/kg), but was similar to PACAPs at higher doses. The maximal effects of PACAPs and VIP were comparable to those observed after meals. Secretin was a significant but weak vasodilator. When pancreatic secretion was maximally stimulated by secretin, a reduction of vascular resistance was 75% of postprandial peak levels. PACAP(6-38), a competitive antagonist of PACAP, inhibited pancreatic vascular responses to PACAPs, but not those to VIP and secretin. Its inhibitory effects on protein response to PACAPs were not significant. Atropine inhibited pancreatic protein but not the vascular effect of PACAP-27. Pancreatic vasodilatation by PACAPs appears to be mediated by both PACAP-specific and VIP/PACAP common receptors in dogs. PACAP, like VIP, is a good candidate for a mediator of atropine-resistant vasodilatation of the pancreas.

Animals↗
PubMed1998

CO binding studies of nitric oxide synthase: effects of the substrate, inhibitors and tetrahydrobiopterin.

The dissociation constant (Kd) for CO from neuronal nitric oxide synthase heme in the absence of the substrate and cofactor was less than 10(-3) microM. In the presence of L-Arg, it dramatically increased up to 1 microM. In the presence of inhibitors such as N(G)-nitro-L-arginine methyl ester and 7-nitroindazole (NI), the Kd value further increased up to more than 100 microM. Addition of the cofactor, 5,6,7,8-tetrahydrobiopterin (H4B), increased the Kd value by 10-fold in the presence of L-Arg, whereas it decreased the value to less than one 250th in the presence of NI. Addition of H4B increased the recombination rate constant (k(on)) for CO by more than two-fold in the presence of L-Arg or N6-(1-iminoethyl)-L-lysine, whereas it decreased the k(on) value by three-fold in the presence of L-thiocitrulline. Thus, the binding fashion of some of inhibitors, such as NI, may be different from that of L-Arg with respect to the H4B effect.

Animals↗
PubMed1998

Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation without causing inhibition of platelet aggregation or altering hemostatic parameters after angioplasty in rat.

An antibody was raised in rabbits against SFFLRNPSEDTFEQF peptide, which is an NH2-terminal peptide of the thrombin-cleaved rat thrombin receptor. In vitro, the antibody inhibited rat smooth muscle cell proliferation but had no effect on rat platelet aggregation or clotting time. These data indicate that the antibody is a specific blocker of the thrombin receptor-signaling pathway in rat smooth muscle cells but does not work as a blocker in rat platelets, suggesting the existence of a second thrombin receptor in the platelets. Using an in vivo balloon catheter-induced injury model in rats, we examined the effect of the anti-rat thrombin receptor IgG on intimal smooth muscle cell accumulation 2 weeks after angioplasty. Analysis of the ratio of intimal to medial cross-sectional areas showed that injection of immune IgG resulted in 43.7% and 53.1% reduction (P<0.01) of neointimal smooth muscle cell accumulation compared with saline and nonimmune IgG treatment, respectively. Moreover, the injection of immune IgG caused a significant decrease of thrombin receptor mRNA expression and also 40.5% and 43.0% decreases (P<0.01) of the proliferating cell nuclear antigen (PCNA) index in the intima compared with the PCNA index after saline and nonimmune IgG treatment, respectively. The suppression of the PCNA index was also observed in the immune IgG-treated group at an early stage after angioplasty. These results suggest that thrombin receptor activation is involved in the proliferation and accumulation of neointimal smooth muscle cells induced by balloon injury.

Angioplasty↗
PubMed1998

Early-appearing tumor-infiltrating natural killer cells play an important role in the nitric oxide production of tumor-associated macrophages through their interferon production.

Both natural killer (NK) cells and macrophages are thought to be the main effectors responsible for early antitumor defense. In this study, we investigated the role of tumor-infiltrating NK cells in initiating nitric oxide (NO) production by tumor-associated macrophages (TAM). The in vivo depletion of NK cells prior to the i.p. inoculation of melanoma cells resulted in a significant decrease in the NO production of the TAM prepared from the peritoneal exudate cells (PEC). Such prior NK cell depletion also decreased the ability of TAM to show any antitumor activity in vitro. The addition of NG-monomethyl-L-arginine (Me-L-Arg) to the culture partially inhibited the ability of TAM to suppress the proliferation of melanoma cells and also decreased their cytolytic activity against melanoma cells. These results suggest that the TAM exhibited both cytostatic and cytolytic activities through their NO production. In an in vivo assay, the administration of Me-L-Arg permitted the more rapid growth of i.p. inoculated melanoma cells compared with the control. On the other hand, the decreased NO production of TAM, resulting from the prior NK cell depletion, was restored by the i.p. administration of interferon gamma (IFN gamma). In addition, the in vivo administration of anti-IFN gamma mAb into mice inoculated i.p. with melanoma cells also significantly decreased the NO production of TAM in peritoneal exudate cells. Furthermore, the tumor-infiltrating NK cells produced a considerable level of IFN gamma. Overall, these results indicate that early-appearing tumor-infiltrating NK cells play an important role in the NO production of TAM through their IFN gamma production.

Animals↗
PubMed1998

Vaccination with activated B cells pulsed with tumor-lysates can induce tumor-specific CD4+ T cells in vivo.

Activated B cells, pulsed with tumor-lysates, were examined for their potential to induce tumor-specific CD4+ T cells in vivo, MH2 cells, which are CD4+ T cells and can also recognize purified protein derivative from mycobacterium tuberculosis (PPD), showed a proliferative response in the presence of both syngeneic activated B cells and PPD in a major histocompatibility complex class II-restricted manner. For B cells to function as efficient antigen presenting cells, they need to be activated. Both irradiation and several inhibitors for antigen-processing were observed to block the antigen-presenting ability of activated B cells. Based in these findings, the possibility of anti-tumor vaccination with activated B cells was thus investigated. The spleen cells from mice, which were immunized with activated B cells pulsed with B16 melanoma-lysates, produced a higher level of interferon (IFN)-gamma than those from mice, which were immunized with either non-pulsed activated B cells or the tumor-lysates alone, after in vitro restimulation. This IFN-gamma production was also dependent on the CD4+ T cells. Moreover, the splenic CD4+ T cells in such mice were suggested to increase their ability to generate B16 melanoma-specific cytotoxic T lymphocytes after in vitro restimulation. Even more importantly, immunization with B16 melanoma lysate-pulsed activated B cells elicited a protective immunity against B16 melanoma at rechallenge. Collectively, these results indicate that an anti-tumor effect could be induced by immunization with activated B cells, pulsed with the tumor-lysates, by eliciting tumor-specific IFN-gamma producing CD4+ T cells in vivo.

Animals↗
PubMed1998

Localization of cytochrome P-450 4A isoforms along the rat nephron.

The expression of P-450 4A isoforms responsible for the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) was examined using the reverse transcription and polymerase chain reaction in various nephron segments and preglomerular arterioles microdissected from the kidneys of Sprague-Dawley rats. Expression of cytochrome P-450 4A1, 4A2, 4A3, and 4A8 mRNA could be detected in RNA extracted from the whole kidney. The expression of P-450 4A1, 4A3, and 4A8 mRNA was similar in the kidney of male and female rats, whereas the expression of 4A2 mRNA was fourfold greater in the kidney of male vs. female rats. At the single-nephron level, P-450 4A1 mRNA could not be detected in either preglomerular arterioles or any nephron segments. P-450 4A2 mRNA was readily detected in preglomerular arterioles, glomeruli, proximal convoluted tubule (PCT), proximal straight tubule (PST), medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD). P-450 4A3 mRNA was also detected in every nephron segment, but the expression of this isoform was barely detectable in preglomerular arterioles. The expression of P-450 4A8 mRNA was detected in the glomerulus, PCT, PST, CTAL, and CCD. It was not detectable in preglomerular arterioles, MTAL, OMCD, or IMCD. Immunoblot analysis using a P-450 4A antibody exhibited a strong signal for P-450 4A protein in the proximal tubule. Smaller signals were also observed in glomerulus, MTAL, and preglomerular arterioles, but no signal could be detected in the IMCD. A similar pattern of P-450 4A protein expression was seen in kidney sections immunostained with this antibody. These results indicate that the expression of P-450 4A isoforms in the kidney of rats is sex dependent and that different P-450 4A isoforms are expressed throughout various nephron segments and the renal vasculature of rats.

Animals↗
PubMed1998

Role of inducible nitric oxide synthase and cyclooxygenase-2 in endotoxin-induced cerebral hyperemia.

BACKGROUND AND PURPOSE: Bacterial lipopolysaccharide (LPS), an endotoxin, has been reported to induce the expression of inducible isoforms of both nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in various cell types. LPS is also known to dilate systemic vasculature, including cerebral vessels. This study aimed to determine to what extent LPS induces iNOS and COX-2 expression in the brain and whether NO and/or cyclooxygenase metabolites derived from iNOS and/or COX-2 contribute to the LPS-induced cerebral hyperemia. METHODS: Regional cerebral blood flow (rCBF) was measured by laser-Doppler flowmetry in halothane-anesthetized, artificially ventilated rats for 4 hours after intracerebroventricular administration of LPS. RESULTS: LPS at doses of 0.01 mg/kg to 1 mg/kg caused dose-dependent, progressive increases in rCBF at 1 to 4 hours after administration. The increase in rCBF was attenuated by systemic administration of the selective iNOS inhibitor aminoguanidine (100 mg/kg IP) or the selective COX-2 inhibitor NS-398 (5 mg/kg IP), and it was abolished by preventing induction of these isoforms with dexamethasone (4 mg/kg IP). LPS significantly increased iNOS and COX-2 mRNA, iNOS protein, and iNOS and cyclooxygenase enzyme activity. The increases in iNOS and cyclooxygenase enzyme activity were eliminated by aminoguanidine and NS-398, respectively. Dexamethasone also prevented the increase in iNOS and cyclooxygenase activity. CONCLUSIONS: These results indicate that induction of iNOS and COX-2 expression and the increased production of NO and vasodilator prostanoids in the brain contribute to the elevation in CBF after intracerebroventricular administration of LPS.

Animals↗
PubMed1998

Islet cell tumor in von Hippel-Lindau disease.

We describe a 42-year-old man with von Hippel-Lindau disease and islet cell tumor of the pancreas. He had retinal and cerebellar hemangioblastomas. His sister had pheochromocytoma. A pancreatic tumor was detected by ultrasonography at his periodical medical checkup. Contrast enhanced computed tomography and abdominal angiography revealed a hypervascular tumor in the pancreatic head. Histological examination of the resected tumor revealed characteristics of islet cell tumor of the pancreas, which was positive for chromogranin-A, S-100 protein, and pancreatic polypeptide, but was negative for insulin, gastrin, glucagon, somatostatin, vasoactive intestinal peptide, serotonin, and adrenocorticotropic hormone.

Adenoma, Islet Cell↗
PubMed1997

Priming effect of N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine in human neutrophils and tyrosyl phosphorylation of 45 kDa protein.

Human peripheral blood polymorphonuclear leukocytes were preincubated with N-acetylcystathionine and N-acetyl-S-(3-oxo-3-carboxy-n-propyl)cysteine (NAc-OCPC) found in the urine of a patient with cystathioninuria. NAc-OCPC significantly enhanced the N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation, whereas N-acetylcystathionine did not enhance the superoxide generation. When the cells were incubated with NAc-OCPC, the tyrosyl phosphorylation of 45 kDa protein of the cell was markedly increased with time. The phosphorylation process was dependent on the concentration of NAc-OCPC. Both the superoxide generation and the tyrosyl phosphorylation of 45 kDa protein increased by NAc-OCPC were inhibited by genistein and herbimycin A, the inhibitors of protein tyrosine kinase, but were rather enhanced by staurosporine, an inhibitor of protein kinase C.

Amino Acids↗
PubMed1997

Local injection of OK432 can augment the TH1-type T-cell response in tumor-draining lymph node cells and increase their immunotherapeutical potential.

The effect of local injections with streptococcal preparation OK432 on the therapeutical potential of tumor-draining lymph node (LN) cells was investigated in mice. Peritumoral injections with OK432 on days 2, 4, 6, 8 and 10 showed no effect on the in vivo growth of s.c. inoculated B16F10 melanoma. The B16F10-draining OK432-treated LN cells, however, showed a high level of anti-B16F10 cytolytic activity after an in vitro culture first with both anti-CD3 monoclonal antibody (MAb) and activated B cell blasts, and subsequently with interleukin (IL)-2 without in vitro restimulation. Such in vitro expanded LN cells showed a remarkable antitumor effect against pulmonary metastasis of B16F10 melanoma, even without the concurrent administration of IL-2. In addition, the therapeutical protocol was also found to be moderately effective against poorly immunogenic MCA fibrosarcoma, and the in vivo antitumor effect was specific to the tumor from which the LNs were harvested. Interestingly, 2 kinds of comparative analyses of the cytokines revealed that the B16F10-bearing state induced the draining LN cells to develop a Th2-type response. However, the OK432 treatment was able to effectively augment their Th1-type response. Collectively, our results suggest that peritumoral injections with OK432 significantly increased the therapeutical potential of the tumor-draining LN cells by augmenting their Th1-type response.

Animals↗
PubMed1997

Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice.

We investigated both the effect and the mechanism of oral (p.o.) administration of PSK, a protein-bound polysaccharide derived from Basidiomycetes, on the anti-tumor T-cell response in gut-associated lymphoid tissue (GALT). The p.o. administration of PSK significantly suppressed the growth of colon 26 carcinoma (C-26) inoculated into the subserosal space of the cecum (i.c.), and augmented the tumor-neutralizing activity of the draining mesenteric lymph node (LN) cells. PSK treatment also significantly decreased the levels of immunosuppressive factors such as plasma transforming growth factor (TGF)-beta in the i.c. C-26-inoculated mice. We also evaluated the improving effect of PSK on the anti-tumor T-cell response in GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The PSK treatment promoted the rejection of i.c.-inoculated B7/P815 and restored the CD4+ T-cell-dependent proliferative response of the draining mesenteric LN cells against in vitro restimulation. Furthermore, the treatment also decreased the TGF-beta production but increased the IFN-gamma production of these cells. The p.o. administration of PSK, however, showed no effect in the CD8+ T-cell-dependent cytolytic activity of the draining mesenteric LN cells after in vitro restimulation. Overall, these results indicate that the p.o. administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in GALT, mainly through a suppression of TGF-beta production and a restoration of IFN-gamma production.

Administration, Oral↗
PubMed1997

Effect of a prostaglandin I2 analogue, beraprost sodium, on burn-induced gastric mucosal injury in rats.

Stress ulcers still have a high mortality in critically burned patients and the pathophysiology remains relatively unknown. Impaired gastric mucosal perfusion is one of the factors contributing to gastric mucosal ulceration. Burn injury causes thrombosis and vascular occlusion by increasing the blood viscosity, resulting in decreased organ perfusion. Reduced blood flow is one of the most important factors in gastric mucosal ulceration. Beraprost sodium is a chemically stable prostaglandin I2 (PGI2) analogue with antiplatelet, vasodilator and cytoprotective actions. In the present study, we examined the effects of a PGI2 analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan) on burn-induced gastric mucosal changes in rats. Twenty male Sprague-Dawley rats weighing an average of 400 g were burned with hot water (90 degree C) and then divided into two groups of 10 animals. One group received 0.015 mg of beraprost sodium intraperitoneally immediately after burn injury, while the control group received the same volume of saline. Gastric mucosal blood flow was measured with a laser Doppler flowmeter and the area of mucosal necrosis was also determined macroscopically and histologically. Gastric mucosal damage was significantly reduced in the beraprost sodium-treated rats and gastric mucosal blood flow was significantly improved (p < 0.05). These findings demonstrate that PGI2 plays a very important role in the pathophysiology of burn-induced Curling's ulcer and that beraprost sodium can improve gastric mucosal blood flow and reduce mucosal damage.

Animals↗
PubMed1997

Reduction of burn-induced gastric mucosal injury by an endothelin receptor antagonist in rats.

Burn-induced stress ulcers may be a major complication in critically burned patients. The pathophysiology of gastric mucosal ulceration is relatively unknown, however reduced gastric mucosal blood flow is one contributing factor. Endothelin (ET) is a well known vasoconstrictor peptide produced by vascular endothelial cells. Endothelin has been reported to have a fundamental role in the regulation of the systemic circulation. The plasma ET level is increased by burn injury, which also causes thrombosis and vessel occlusion. Endothelin has potent ulcerogenic and vasoconstrictor actions in the stomach where it induces gastric mucosal damage and increases gastric vascular tone. In the present study, we examined the effects of a new non-selective ET receptor antagonist, TAK-044, on burn-induced gastric mucosal injury in rats. Twenty male Sprague-Dawley rats weighting an average of 400 g were burned with hot water (90 degrees C) and then divided into two equal groups. The treatment group received 1 mg/kg of TAK-044 via the dorsal vein of the penis immediately after burn trauma, while the control group received the same volume of saline. Gastric mucosal blood flow was measured with a laser Doppler flowmeter and the area of mucosal necrosis was also determined macroscopically and histologically. Inhibition of ET activity by TAK-044 after burn injury significantly improved microvascular perfusion in the gastric mucosa and prevented the progression of mucosal damage in the stomach (P < 0.05). The present study supports the role of ET in burn-induced gastric ulceration (Curling's ulcer).

Animals↗
PubMed1997

Tyrosine kinase, phosphatidylinositol 3-kinase, and protein kinase C regulate insulin-stimulated NaCl absorption in the thick ascending limb.

We have previously shown a direct stimulatory effect of insulin on NaCl absorption in the medullary thick ascending limb of Henle's loop (mTAL). To further investigate the signal transduction involved, we determined whether tyrosine kinase, phosphatidylinositol 3-kinase (PI3-kinase), and/or protein kinase C (PKC) regulate insulin-stimulated NaCl absorption in the mTAL by in vitro microperfusion methods. In control experiments, insulin increased transepithelial voltage (V(te)) and net lumen-to-bath Cl- flux (J(Cl)). Genistein and methyl 2,5-dihydroxycinnamate, two specific tyrosine kinase inhibitors, abolished the effects of insulin. Wortmannin, a specific PI3-kinase inhibitor, inhibited the action of insulin. The effects of insulin also were inhibited by staurosporin and calphostin C, which are dissimilar inhibitors of PKC. These results indicate that insulin stimulates NaCl absorption in the mTAL through tyrosine kinase, PI3-kinase, and PKC-mediated mechanisms. Moreover, because we have reported previously that insulin causes no detectable change in cytosolic free Ca2+ in the mTAL cells, the present results also suggest that insulin-induced PKC activation is not related to inositol 1,4,5-triphosphate (IP3) production.

Absorption↗