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Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 73 records · Page 4Linked to original sources
PubMed2001

Ginsenoside potentiates NO-mediated neurogenic vasodilatation of monkey cerebral arteries.

The aqueous extract of the Panax ginseng (GE) potentiated the relaxation induced by transmural electrical stimulation or nicotine in monkey cerebral arterial strips denuded of the endothelium and partially contracted with prostaglandin F(2 alpha). The response to electrical stimulation was abolished by tetrodotoxin, whereas that to nicotine was suppressed by hexamethonium. N(G)-nitro-L-arginine abolished both of the neurogenic relaxation. Atropine did not alter the potentiating effect of GE. Relaxations induced by exogenous NO were unaffected by GE. The enhancement by GE, of the neurogenic response, appears to be associated with increment in the synthesis or release of NO from the perivascular nerve. Blockade of muscarinic prejunctional inhibition, superoxide scavenging action and phosphodiesterase inhibition are not involved.

Animals↗
PubMed2001

Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress.

OBJECTIVES: We investigated whether abnormal pteridine metabolism is related to coronary endothelial dysfunction in insulin-resistant subjects. BACKGROUND: Depletion of tetrahydrobiopterin (BH(4)) and elevation of the 7,8-dihydrobiopterin (BH(2)) (activating and inactivating cofactors of nitric oxide synthase [NOS], respectively) contribute to impairment of NO-dependent vasodilation through reduction of NOS activity as well as increased superoxide anion generation in insulin-resistant rats. METHODS: Thirty-six consecutive nondiabetic, normotensive and nonobese subjects with angiographically normal coronary vessels were studied. Traditional coronary risk factors, plasma pteridine levels, activities of erythrocyte dihydropteridine reductase (DHPR), the recycling enzyme that converts BH(2) to BH(4) and lipid peroxide (LPO) levels were measured and coronary endothelial function was assessed with graded infusions of acetylcholine (ACh). RESULTS: When we divided patients into tertiles based on insulin sensitivity, we observed stepwise decreases in the maximal ACh-induced vasodilation and plasma BH(4)/7,8-BH(2) ratio, and increases in coronary LPO production as insulin sensitivity decreased. The ACh-induced vasodilation was positively correlated with insulin sensitivity, BH(4)/7,8-BH(2) ratio and DHPR activity. Furthermore, BH(4)/7,8-BH(2) was inversely correlated with DHPR activity and insulin sensitivity. In multiple stepwise regression analysis, BH(4)/BH(2) was independently related to ACh-induced vasodilation and accounted for 39% of the variance. However, no significant correlation existed between other traditional risk factors and BH(4)/7,8-BH(2). CONCLUSIONS: These results indicate that both abnormal pteridine metabolism and vascular oxidative stress are linked to coronary endothelial dysfunction in the insulin-resistant subjects.

Acetylcholine↗
PubMed2001

Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease.

The plasma levels of a panel of cytokines and cytokine-associated molecules (IL-1alpha, IL-2, IL-4, IL-6, IL-10, IL-12, IL-15, macrophage colony-stimulating factor (M-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), soluble tumor necrosis factor receptor I or II (sTNFRI or II)) were assessed in 56 plasma samples of 13 pediatric patients undergoing hematopoietic stem cell transplantation (HSCT, bone marrow in 12 and cord blood in one) from unrelated donors. Eight patients developed severe (grade III-IV) acute GVHD (aGVHD). The plasma IL-6, IL-10, M-CSF, sTNFRI and II levels were significantly high in the severe aGVHD group compared to the mild aGVHD group (grade 0-II). The plasma IL-15 level increased transiently in the early period following HSCT and remained high in the severe aGVHD group even after 4 weeks following HSCT. Based on analysis of the correlations between the kinetics of the plasma cytokine levels after HSCT and the clinical manifestations of aGVHD, IL-15 and/or M-CSF were involved in the development of aGVHD, following elevation of the plasma IL-10 and sTNFRI or II levels. These kinetics suggest that IL-10 and sTNFRs worked as suppressor cytokines and seemed to suppress clinical manifestations of aGVHD. Furthermore, it seemed that the plasma ratio of IL-10/sTNFRII from 5 to 12 weeks following HSCT was linked to the poor outcome in the patients with severe aGVHD, suggesting that IL-10 plays an important role in protecting hosts from transplantation-related complications, including GVHD.

Acute Disease↗
PubMed2001

KAI1 expression can be a predictor of stage A prostate cancer progression.

The disease progression and rate of cancer death were analyzed in 52 patients with stage A prostate cancer who underwent transurethral resection of the prostate (TURP) or retropubic subcapsular prostatectomy (SCP) between 1987 and 1998. We performed immunohistochemistry on 16 patients to determine the correlation between the expression of the tumor metastasis suppressor gene KAI1 and the subsequent progression of stage A prostate cancer. Nineteen and 33 of the patients had cancer at stage A1 and stage A2, respectively, and their subsequent courses were followed for an average of 53.7 months (24-134 months). Progression to clinical cancer was found in six patients (one with stage A1, and five with stage A2). This progression was evident 40.8 months (5-80 months) after TURP or SCP. Four (66.7%) of the patients died of cancer progression (average 31 months) after prostatectomy. All four patients had stage A2, poorly differentiated adenocarcinoma, and had been followed with administration of diethylstilbestrol diphosphate (DES-P). The disease-free patients (n=10) showed overexpression of KAI1 protein, compared to those with disease progression (n=6). These results indicate that progression arose mainly in the patients with stage A2 cancer, and that poorly differentiated, focal and weak expression of KAI1 protein is highly associated with disease progression. It is suggested that patients in this group should be treated with immediate total androgen blockade, radiation, or radical prostatectomy after diagnosis.Prostate Cancer and Prostatic Diseases (2001) 4, 150-153.

Journal Article↗
PubMed2001

Colour Doppler ultrasonography of a segmental branch of the portal vein is useful for early diagnosis and monitoring of the therapeutic course of veno-occlusive disease after allogenic haematopoietic stem cell transplantation.

We report two cases in which visualization of the segmental branch of the hepatic portal vein with the colour Doppler ultrasonography (US) technique was useful for the early diagnosis of veno-occlusive disease. The change in blood flow in the segmental branch of the portal vein occurred 5 and 6 d before the clinical criteria were fulfilled in the two cases. Reverse flow in the segmental branch began partially in the liver at first, and then spread to the whole liver several days later. All the US findings in both cases disappeared after thrombolytic therapy.

Adult↗
PubMed2001

Surgical strategy for cavernous angioma in hypothalamus.

A very rare case of cavernous angioma in the hypothalamus is presented. The patient was successfully treated by total excision of the haematoma and angioma, and there was no regrowth of the lesion on follow-up MRI. Complete excision of the angioma is the recommended surgical strategy even for patients with deep-seated lesions.

Adult↗
PubMed2001

A nested variant of transitional cell carcinoma of the urinary bladder: a case report.

Nested variants of transitional cell carcinomas (TCC-NVs) are relatively rare neoplasms in the urinary bladder, but at least 25 cases have been described. This disease is characterized by the pathological finding of irregular nests and/or tubules of transitional carcinoma cells infiltrating the lamina propria without involvement of the mucosal layer. In our case, diagnosed by open biopsy, there were scattered tumor cells observed from the muscle layer to the subserosa, with a tendency toward increasing cellular anaplasia with the depth of invasion. Since the prognosis of TCC-NV is generally poor, comprehensive chemotherapy was performed. No changes were observed on computed tomography and the performance status (0) remained the same after 1 year, so the treatment was considered effective. We conclude that open biopsy should be carried out without hesitation when bladder cancer is suspected, even if there are negative findings of repeated urinary cytology examination and/or endoscopic cold cup biopsy. Immunohistochemical analysis may help in the diagnosis of TCC-NVs derived from epithelial cells. Diagnosis and treatment at an early stage should reduce the mortality of patients with TCC-NVs.

Aged↗
PubMed2001

Mechanisms of relaxation induced by angiotensin II in isolated canine and human uterine arteries.

The present study aimed to determine the action of angiotensin II and to pharmacologically analyze mechanisms of their action in isolated uterine arteries. Canine and human uterine artery strips were suspended in Ringer-Locke solutions for isometric tension recording. Canine and human uterine arteries responded to angiotensin II with transient contraction followed by relaxation, which were abolished by losartan, an AT1 receptor subtype antagonist. Cyclooxygenase inhibitors augmented the contraction and abolished the relaxation. The relaxation was also abolished or suppressed by tranylcypromine, a prostaglandin I2 synthesis inhibitor. The relaxant response of dog uterine arteries to angiotensin II was partially suppressed by endothelium denudation but was not influenced by nitric oxide synthase inhibitor. Conversely, the response of human uterine arteries to the peptide was unaffected by endothelium denudation. The antagonists used and endothelium denudation did not inhibit the relaxation caused by a prostaglandin I2 analogue. It appears that the angiotensin II-induced relaxation is mediated by vasodilator prostaglandins, possibly prostaglandin I2, released from both endothelium and subendothelial tissues in dog uterine arteries. In human uterine arteries, the vasodilator prostaglandin is released from subendothelial tissues due to AT1 receptor stimulation by the peptide.

Adult↗
PubMed2001

Intravesical combined chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin is not indicated for superficial bladder cancer.

PURPOSE: The short-term effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) administered repeatedly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 24 patients aged a median of 70 years between March 1996 and February 1999, and were compared with those of BCG monotherapy in 50 patients from March 1990 to February 1999. PATIENTS AND METHODS: The patients underwent intravesical instillation of the Tokyo strain BCG with or without epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1-2 weeks after TUR, epirubicin (40 mg) and BCG (80 mg) were istilled into the bladder by turns once a week for 12 weeks. For the group receiving only BCG, 80-mg instillations were done with the same schedule. Thereafter, the patients were followed by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. RESULTS AND CONCLUSIONS: At 2 years after treatment, the simple recurrence rate was 26.1% (6/23) in patients with chemoimmunotherapy and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of symptoms of severe bladder irritation due to the instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was finally found to be inferior in comparison with BCG monotherapy for the prophylaxis of recurrence of superficial bladder cancer.

Adjuvants, Immunologic↗
PubMed2001

Granzyme-B-containing lymphocyte involvement in epidermal injury in graft-versus-host disease.

BACKGROUND: Skin lesions from graft-versus-host disease (GVHD) show histological features of epidermal cell death with lymphocyte infiltration. Perforin and granzyme B are involved in the process of apoptosis induced by cytotoxic T lymphocytes (CTL). OBJECTIVE: To elucidate the role of CTL in the mechanism of epidermal injury in GVHD. METHODS: We studied immunohistochemical staining for granzyme B and perforin in the skin lesions of 8 patients who developed GVHD after bone marrow transplantation. RESULTS: Granzyme-B-positive lymphocytes were CD8 positive and were observed in the epidermis of 3 out of 6 specimens in acute GVHD, and of 5 specimens of chronic GVHD except for 1 sclerotic type in which it was negative. Perforin-positive lymphocytes were observed in the epidermis of the specimens from 1 acute and 1 chronic GVHD. CONCLUSIONS: Granzyme B derived from CTL may be involved in the mechanisms of epidermal injury in GVHD.

Acute Disease↗
PubMed2001

Effects of in vivo gene transfer of fibroblast growth factor-2 on cardiac function and collateral vessel formation in the microembolized rabbit heart.

The effects of gene transfer of the secreted form of fibroblast growth factor-2 (FGF-2) were tested using an adenovirus vector in the microembolized rabbit heart. Japanese white rabbits underwent an intracoronary injection of 25-microm microspheres followed by recombinant adenovirus vectors encoding a secreted form of FGF-2 (FGF group), LacZ (LacZ group), or saline (saline group). Left ventricular (LV) systolic function was serially assessed by echocardiography. Vascular density was measured at 14 days with Azan and CD31 staining. The development of collateral vessels was assessed by measuring myocardial blood flow before and after the occlusion of the left anterior descending coronary artery. Percent fractional shortening (%FS) decreased after the microembolization, and improved gradually for 14 days in the FGF group only (41+/-1% (FGF) vs 32+/-1% (LacZ), 31+/-1% (saline), p<0.01). The vascular density and myocardial collateral blood flow were significantly higher in the FGF group in comparison with other groups. Transcoronary arterial gene transfer of the secreted form of FGF-2 was beneficial for the recovery of LV systolic function and development of collateral vessels in the microembolized rabbit heart.

Animals↗
PubMed2001

Effects of calcium antagonists on the nitrergic nerve function in canine corpus cavernosum.

Effects of calcium antagonists on nitrergic nerve function were examined in the isolated canine corpus cavernosum. In the cavernous strips precontracted with phenylephrine, transmural electrical stimulation elicited frequency-dependent (2 - 5 Hz) relaxations that were abolished by N(G)-nitro-L-arginine (10(-5) M), a nitric oxide (NO) synthase inhibitor; 1H[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10(-6) M), a soluble guanylate cyclase inhibitor; and tetrodotoxin (3 x 10(-7) M). The relaxations were not affected by treatment with nifedipine or nicardipine (10(-8) - 10(-6) M), L-type specific calcium channel inhibitors, but were significantly inhibited by amlodipine or cilnidipine, inhibitors of L- plus N-type calcium channels, in a concentration-related manner (10(-7) - 10(-6) M). All of the inhibitors used did not affect the relaxations induced by exogenous NO (acidifed NaNO2). These findings suggest that N-type, but not L-type, calcium channels are responsible for increasing cytosolic free calcium, a prerequisite for the synthesis of NO, in the nitrergic dilator nerves innervating the corpus cavernosum.

Amlodipine↗
PubMed2001

Characteristics of wine produced by mushroom fermentation.

Saccharomyces cerevisiae is the main microorganism used in wine brewing, because this microbe has potent ability to produce alcohol dehydrogenase. We have recently discovered that some genera of mushroom produced alcohol dehydrogenase, and made wine by using a mushroom in place of S. cerevisiae. The highest alcohol concentration in this wine was achieved with Pleurotus ostreatus (2.6 M, 12.2%). In the case of Agaricus blazei, the same alcohol concentration (1.7 M, 8%) was produced under both aerobic and anaerobic conditions. This wine produced by A. blazei contained about 0.68% beta-D-glucan, which is known to have a preventive effects against cancer. The wine made by using Flammulina velutipes showed thrombosis-preventing activity, giving a prolonged thrombin clotting time 2.2-fold that of the control. Thus, the wine made by using mushroom seems to be a functional food which can be expected to have preventive effects against cancer and thrombosis.

Agaricales↗
PubMed2001

Hypothermia on NO-mediated neurogenic relaxation and on hypoxic inhibition in the response of canine cerebral arteries.

Cerebral arteries are innervated by nitric oxide (NO)-mediated vasodilator nerves, and hypoxia has been shown to attenuate neurogenic vasorelaxation. The present study examines the effects of hypothermia on neurogenic vasorelaxation and on the hypoxia-induced inhibition of the neurogenic vasorelaxation response. In isolated canine cerebral arteries, relaxant responses to transmural electrical stimulation (5 Hz for 40 s), mediated via NO synthesized from L-arginine, were not influenced by lowering the bathing media temperature from 37 degrees C to 30 degrees C but were attenuated at 25 degrees C. On the other hand, relaxations caused by nicotine and exogenous NO were not significantly attenuated but were prolonged by cooling to 25 degrees C. The responses associated with nerve stimulation by electrical pulses or nicotine were depressed by hypoxia (from about 500 mmHg of partial O2 pressure to about 45 mmHg) under normothermia. However, hypothermia at 25 degrees C prevented the inhibition by hypoxia of the neurogenic relaxation. It is concluded that the hypothermia-induced inhibition in the response to electrical nerve stimulation is not associated with a decreased synthesis and release of NO in vasodilator nerves nor with a reduced ability of smooth muscle to relax in response to NO. Interference with the propagation of action potentials might be involved in the inhibition via a fall of temperature. The fact that the hypoxia-induced impairment of vasodilator nerve function was prevented by cooling may partially explain the efficacy of hypothermia in protecting against ischemic neuronal injury in the brain.

Animals↗
PubMed2001

Evaluation of ionic pollutants of acid fog and rain using a factor analysis and back trajectories.

Fog and rain water samples were collected at the same time in the Akita Hachimantai mountain range in northern Japan from June to September in 1998 and 1999. The various ion concentrations in these samples were analyzed, and the fog droplet sizes were measured for each fog event. As the fog droplet size increased, the ion concentration decreased. The slope of log-log plots of the concentration versus the droplet size differed with the kind of ion. In order to characterize the air pollutant, moreover, these data were quantitatively analyzed by an oblique rotational factor analysis. We found that three factors were extracted as the air pollutant source: (NH4)2SO4, acids (HNO3 + H2SO4) and sea-salt. Combining the factor analysis with the 72 h back-trajectory at 850 hPa level, we found that the contribution of each factor varied with the transport pattern of air masses.

Acid Rain↗