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Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 217 records · Page 12Linked to original sources
PubMed1998

All-trans retinoic acid modulates Fas antigen expression and affects cell proliferation and apoptosis in combination with anti-Fas monoclonal antibody in the human myeloma cell line, U266B1.

All-trans retinoic acid (ATRA) is a vitamin A derivative that induces the differentiation of myeloid leukemia cells in vitro and in vivo. Several investigators have recently reported that ATRA downregulates the production of interleukin-6 (IL-6) and the expression of IL-6 receptor (IL-6R) and also inhibits the proliferation of myeloma cells. It has also been reported that myeloma cells express Fas antigen, and in some of these cells apoptosis was induced by treatment with anti-Fas monoclonal antibody (mAb). In the present study, we demonstrated that ATRA increased Fas expression in the human myeloma cell line, U266B1. We observed that both apoptosis induction and growth inhibition were enhanced in cells exposed to a combination of anti-Fas mAb and ATRA compared with cells exposed to either treatment alone. We also examined whether ATRA modulated bcl-2, an anti-apoptosis protein, in U266B1 cells. Flow cytometry analysis revealed that the mean fluorescence intensity of bcl-2 protein was slightly decreased in cells treated with ATRA. These results indicate that in U266B1 cells, combined treatment with anti-Fas mAb and ATRA enhances the induction of apoptosis by modulating the expression of Fas and bcl-2 by ATRA.

Antibodies, Monoclonal↗
PubMed1998

[Recovery from out-of-hospital cardiac arrest after mild hypothermia: report of two cases].

We report two patients with out-of-hospital cardiac arrest who recovered after hypothermia therapy. A 25-year-old man and a 16-year-old boy were transferred to our hospital after cardiopulmonary arrest due to idiopathic ventricular fibrillation and hypertrophic cardiomyopathy, respectively. We carried out hypothermia therapy using cooling blankets, and the patients were maintained at 32-33 degrees C for 96 and 36 h, respectively. After slow rewarming, they regained consciousness and recovered. During hypothermia, hypokalemia and arrhythmia occurred. Their arrest times (no spontaneous circulation and no CPR) were 10 min and 8 min, and CPR times (no spontaneous circulation while CPR was being performed) were 24 min and 20 min, respectively. In cases where the duration of ischemia is prolonged, the prognosis is expected to be poor. Therefore, we believe that hypothermia therapy is beneficial for such patients.

Adolescent↗
PubMed1998

Modifications by superoxide-generating agent, neurotransmitters and neuromodulators of nitroxidergic nerve function in monkey cerebral arteries.

Isolated monkey cerebral arteries denuded of the endothelium responded to transmural electrical stimulation (5 Hz for 40 sec) with relaxations that are mediated by nitric oxide (NO) synthesized from L-arginine. The relaxant response was slightly inhibited by duroquinone, a superoxide anion-generating agent. The agent markedly inhibited the response after treatment with diethylthiocarbamic acid, an inhibitor of copper/zinc superoxide dismutase. The inhibition was partially reversed by superoxide dismutase. The neurogenic relaxation was reduced by acetylcholine acting on prejunctional muscarinic receptors. Neuropeptide Y, morphine, ATP, clonidine and pituitary adenylate cyclase-activating polypeptide did not change the response to nerve stimulation. Sodium nitroprusside in a dose sufficient to produce relaxation attenuated the neurogenic response. It is concluded that the neurotransmitter liberated from vasodilator nerves in monkey cerebral arteries is free NO rather than a stable analog of NO, like S-nitrosocysteine. Substances other than acetylcholine released as neuromodulators do not seem to regulate the NO-mediated nerve function.

Animals↗
PubMed1998

[The relation between platelet aggregation and constitutional and lifestyle variables in two Japanese communities].

To investigate the contribution of the platelet aggregation in the development of cardiovascular diseases, we examined the relation of constitutional and lifestyle variables with platelet aggregation for a total of 306 males aged 50 to 70 in Ikawa town, Akita prefecture (n = 163) and Noichi town, Kochi prefecture (n = 143). The examination of platelet aggregation was completed within 3 hours of obtaining blood samples. We used ADP (Adenosine 5'-diphosphate) as an agonist and obtained PATI (the platelet aggregatory threshold index) by nephelometry. Platelet count, mean platelet volume, white blood cell count, serum fatty acid compositions were also examined and dietary intake of fish, seafood and soy bean foods were inquired using one-week dietary records. PATI indicated a logarithmic normal distribution in both Ikawa and Noichi. The mean of logarithmic transformed PATI (log PATI) was higher in Ikawa than in Noichi. Thus platelet aggregation was lower in Ikawa than in Noichi. According to multiple regression analysis, age, platelet count in platelet rich plasma, mean platelet volume in platelet rich plasma, and white blood cell count were inversely associated with log PATI. Serum arachidonic acid composition tended to be inversely related with log PATI. Serum n3-polyunsaturated fatty acid composition was positively related with log PATI, and log gamma-GTP tended to be positively associated with log PATI. Soy protein intake and cigarette smoking showed no consistent associations with log PATI. This cross-sectional study suggests that serum n3-polyunsaturated fatty acid, and gamma-GTP, as an index of alcohol intake, reduce platelet aggregation while age, white blood cell count, platelet count, mean platelet volume, and serum arachidonic acid raise platelet aggregation.

Age Factors↗
PubMed1998

[Survival and disability in stroke by stroke subtype based on computed tomographic findings in three rural Japanese communities].

PURPOSE: We conducted an epidemiological study of survival and disability in stroke in three Japanese communities to seek community strategies for improvement in survival and disability. METHODS: A total of 297 first-ever strokes were identified between 1988 and 1992 in three rural communities (total population = 47,000) located in Akita and Ibaraki. We analyzed survival rates and activity of daily living by sex, age-group and stroke subtypes. Successful review of computed tomography (CT) for 84 percent of the strokes (249 out of 297) was possible and the data were used for subtype analyses. RESULTS: For all strokes (n = 297) survival rates were 85% for 30 day, 70% for one year, 62% for three year. The rates tended to be lower in women than in men. The rates were lowest in ages less than 60 at thirty day, and in ages 80 and older at the end of the first and third year. Intracerebral hemorrhage with ventricular rupture, subarachnoid hemorrhage and cortical cerebral infarction had lower survival rates than intracerebral hemorrhage without ventricular rupture and lacunar infarction. Based on Cox's proportional hazard model, risk ratio for death was 2.07 in ages 70-79, and 3.80 in ages 80 and older compared with ages 60-69. The risk ratio was 3.46 for intracerebral hemorrhage with ventricular rupture, 3.38 for subarachnoid hemorrhage and 2.46 for cortical cerebral infarction compared with lacunar infarction. The proportion of stroke survivors who need assistance from others in the first and third years tended to be higher in women than in men. The proportion was higher in older patients than in the younger, and higher for intracerebral hemorrhage with ventricular rupture and cortical cerebral infarction than in other subtypes of stroke. From logistic regression analysis, the odds ratio for disability in the first year was 6.55 for ages 80 and older compared with ages 60-69. The odds ratio was 5.61 for intracerebral hemorrhage with ventricular rupture, 4.53 for cortical cerebral infarction compared with lacunar infarction. In the third year the odds ratio was significant for ages 70-79, and decreased for intracerebral hemorrhage with ventricular rupture (odds ratio = 2.98), and increased for cortical cerebral infarction (odds ratio = 6.06). CONCLUSIONS: Survival and disability in stroke depended on age and stroke subtypes. Even after age adjustment, stroke subtypes with large cerebral involvement had worse prognosis than stroke subtypes. Community-based hypertension control programs are important to prevent any subtypes of stroke. Stroke subtypes as well as age should be taken into account to develop effective care and medical treatments for strokes.

Activities of Daily Living↗
PubMed1998

[CABG after patch angioplasty of the left main coronary: artery report of a case].

A 57-year-old man was admitted to our hospital because of restenosis of the left main coronary trunk (LMT) after patch angioplasty for the LMT lesion. PTCA was repeated four times during three years after patch angioplasty, but recent coronary angiogram still demonstrated 75% restenosis of the LMT lesion. Double-CABG was performed to LAD and LCX using the left internal thoracic artery and saphenous vein graft. Postoperative coronary angiogram revealed an excellent result. A careful consideration must be given to the indication of the patch angioplasty of the LMT lesion.

Angioplasty, Balloon, Coronary↗
PubMed1998

[Characteristics and outcome of stroke patients discharged from hospitals in an urban area of Japan].

The purpose of this study was to obtain the overall characteristics and outcome in stroke patients in an urban area of Japan, in order to develop some strategies for a community-based care system for improvement of the prognosis and activities of daily life in stroke patients. The present study, based on 4 hospitals in Yao city in Osaka, showed results as follows: 1) The number of stroke patients discharged from 4 hospitals during a recent one year period was 377 (216 men and 161 women). 2) The proportion of patients who died was 27%. Of the living patients, the proportions of patients who had motor paralysis or speech disturbance at discharge were 54% and 27%, respectively. 3) The proportion of patients who were to return to their home was 77% for all living patients. The proportion of patients who were not able to walk by themselves, or needed assistance in at least one of the activities of daily life was 31% and 28%, respectively, for all living patients who were to return to their home. This study showed that stroke registry from major hospitals in an urban area is useful for obtaining the overall characteristics of stroke patients in the area and promote community-wide programs in the prevention and home care of stroke.

Activities of Daily Living↗
PubMed1998

Positron emission tomographic imaging of pleomorphic adenoma in the parotid gland.

We studied the possible correlation between 2-18F-2-deoxy-D-glucose (FDG) uptake and histopathological findings in mass lesions of the parotid gland. Thirteen pleomorphic adenomas of the parotid gland were evaluated by computed tomography (CT), magnetic resonance imaging (MRI), Gallium scintigraphy, Technetium scintigraphy and FDG-positron emission tomography (PET). Standardized uptake values (SUV) and time-activity curves (TAC) were determined for all mass lesions. Pleomorphic adenomas were histologically classified into the following three types: epithelial, intermediate and mesenchymal, based on their dominant histological components. The numbers of epithelial, intermediate, and mesenchymal types were 5, 2, and 6, respectively. The levels of SUVs were 4.02 +/- 1.91 (range: 1.97-7.07) in the epithelial type, 5.05 +/- 1.12 (range: 4.26-5.58) in the intermediate type and 3.98 +/- 7.74 (range: 1.98-7.74) in the mesenchymal type, respectively. The accumulation of FDG did not differ significantly among the three types. Since the accumulation of FDG was significantly correlated with the tumor size, FDG-PET could reflect tumor growth ability more apparently than the other nuclear or imaging modalities.

Adenoma, Pleomorphic↗
PubMed1998

Monitoring of response to radiotherapy with fluorine-18 deoxyglucose PET of head and neck squamous cell carcinomas.

We examined the usefulness of positron emission tomography (PET) using fluorine-18 deoxyglucose (FDG) in determining the therapeutic effects of irradiation and chemotherapy on head and neck malignant tumors. Twenty-two patients with head and neck lesions who underwent histological examinations were studied. Squamous cell carcinoma was histologically diagnosed in all cases. Sixteen of them underwent radiotherapy with approximately 40 Gy in combination with carboplatin therapy. The remaining 6 patients underwent radiotherapy alone. After these treatments, 11 underwent surgery. For PET study, each patient was injected with intravenous FDG 185-370 MBq. We evaluated the degree of FDG accumulation using scanned images taken 40-55 min after the injection. We measured the standardized uptake value (SUV), a semiquantative evaluation, ROI activity divided by the dosage per weight of each patient. FDG-PET, CT and MRI were performed twice for each patient, before and after treatment. FDG uptake, but not the tumor size in CT or MRI, was significantly reduced in each patient after the treatment. Therefore, our findings have clearly demonstrated that FDG-PET provides for more valuable therapeutic outcomes than conventional imaging such as CT and MRI. FDG-PET should thus provide a new dimension in the management of head and neck malignant tumors.

Carcinoma, Squamous Cell↗
PubMed1997

Effect of Ca2+/calmodulin-dependent protein kinase II inhibitors on the neurogenic cerebroarterial relaxation.

In canine cerebral artery strips contracted with prostaglandin F2alpha, transmural electrical stimulation (5 Hz for 40 s) produced a relaxation which was abolished by tetrodotoxin. The neurogenic response was inhibited moderately by [S]-5-isoquinolinesulfonic acid,4-[2-[(5-isoquinolinyl-sulfonyl)methylamino]-3-oxo-(4-phenyl-1-piperazinyl)-propyl] phenyl ester (KN62), an inhibitor of Ca2+ /calmodulin-dependent protein kinase II, which however did not alter or only slightly reduced the relaxant response to electrical nerve stimulation in canine coronary arterial strips that is mediated via beta-adrenoceptors stimulated by norepinephrine. Nicotine-induced relaxation, mediated by nitric oxide (NO) derived from perivascular nerves, was also attenuated by KN62, whereas the response to exogenous NO was unaffected. The nicotine-induced increase in the cyclic GMP content in cerebral arteries was depressed by KN62. The neurogenic relaxation was not influenced by phorbol 12-myristate 13-acetate, an activator of protein kinase C. 8-Bromo-cyclic GMP and 8-bromo-cyclic AMP did not significantly alter the response to nerve stimulation. It is concluded that the phosphorylation pathway involving Ca2+/calmodulin-dependent protein kinase II, but not other protein kinases so far tested, appears to be involved in the function of vasodilator nerves innervating the cerebral artery.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Molecular targeting of mitomycin C chemotherapy.

In 10 human cancer cell lines, the activity of mitomycin C (MMC) was found to be determined by an interplay between activation by DT-diaphorase (DTD) and inactivation by glutathione S-transferase (GST). NADPH/cytochrome P-450 reductase was not responsible for MMC activation and expression of MDRI (Mr 170,000 P-glycoprotein), and MRP (multidrug resistance-associated protein) genes did not relate to MMC resistance. Gene expression analysis for NQO1 (DTD gene) and GSTpi predicted which enzyme activity predominated in a cell line, except K562 and K562/DOX. For tumors with DTD activity only, MMC given by itself was most active. In cell lines in which DTD action was predominant, tumor selectivity was achieved by enhancing DTD-mediated activation with m-iodobenzylguanidine and hyperglycemia, which reduced the intra-tumoral pH. KW2149, a novel MMC analogue activated by glutathione, was most active against tumors in which GSTpi predominated. These various enzyme-specific effects could be observed even in cell lines derived from tumors with multidrug resistance. Such MMC treatment based on cell enzymology may enhance significantly MMC efficacy, helping to overcome multidrug resistance.

Animals↗
PubMed1997

Biotechnological potential of P450 monooxygenases high-level production of bovine cytochrome P450c17 monooxygenase during medium cell density culture of a recombinant yeast, Saccharomyces cerevisiae GRF 18 (YEp-Toku1).

Bovine cytochrome P450c17 monooxygenase was produced in a 30-L fermenter by Saccharomyces cerevisiae GRF18 (YEp-Toku1), harboring the GAL10 promoter, and using conditions of medium cell density culture. Upon addition of D-galactose as an inducer and FeCl3 as a cofactor, cells began to produce the P450 hemoprotein. The yield of this enzyme reached a maximum after 31 h but its formation continued for more than 60 h after induction. The amount of P450c17 produced was 4.7-fold as compared to shake flask experiments.

Cell Count↗
PubMed1997

Flunarizine, an anti-migraine agent, impairs nitroxidergic nerve function in cerebral arteries.

Flunarizine is an anti-migraine agent that blocks the Ca2+ entry across cell membrane. In order to obtain a clue of mechanisms underlying the migraine headache, modifications by flunarizine of the response to nitric oxide (NO), a cerebral vasodilator and algogenic agent, derived from perivascular nerves were evaluated. Relaxations due to nerve stimulation by electrical pulses (5 Hz) and nicotine (10(-4) M) in canine cerebral arterial strips were attenuated by treatment with flunarizine dose-dependently, whereas the responses to exogenous NO (10(-7)-10(-6) M) and nitroprusside (10(-8)-10(-6) M) were unaffected. The inhibition by the Ca2+ entry blocker of the response to electrical nerve stimulation and nicotine was obtained in a concentration (10(-6) M) that did not significantly relax the arterial strips. NO derived from perivascular nerve may be one of the factors involved in the genesis of migraine attack, which is expected to be relieved by a reduction of neural NO synthase activity associated with a decreased Ca2+ influx by flunarizine during nerve activation.

Animals↗
PubMed1997

Analysis of the vasodilator nerve function by nicotine in isolated dog skin artery.

Mechanisms underlying the relaxation induced by nicotine were analyzed in cutaneous arterial strips isolated from dogs and with the endothelium removed. In the strips treated with prazosin and precontracted with prostaglandin F2 alpha, nicotine produced relaxations which were not influenced by atropine but abolished by hexamethonium. Relaxations induced by nicotine were partially inhibited by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor; the remaining relaxations were abolished by desensitization to calcitonin gene-related peptide (CGRP) or treatment with CGRP-(8-37), a CGRP receptor antagonist, or with capsaicin. Desensitization to vasoactive intestinal polypeptide (VIP) or a VIP receptor antagonist did not influence the nicotine-induced relaxation. In the strips densensitized to CGRP, the nicotine-induced relaxation was abolished by L-NA; the inhibitory effect was reversed by L-arginine. Perivascular nerves containing NADPH diaphorase and CGRP immunoreactivity were histochemically identified in the cutaneous artery. CGRP immunoreactivity was abolished by treatment with capsaicin. It is concluded that nicotine produces relaxation in dog cutaneous arterial strips, possibly mediated by NO and CGRP liberated from vasodilator nerves.

Animals↗
PubMed1997

18F-fluorodeoxyglucose positron emission tomography and the prognosis of patients with pancreatic adenocarcinoma.

BACKGROUND: Fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) can be used to measure the glycolytic activity of tumor cells. Though the prognosis of patients with pancreatic adenocarcinoma is usually poor, a subset of patients with good prognoses may be discovered by determining the degree of FDG integration into tumors. METHODS: Fourteen patients with histologically proven pancreatic adenocarcinoma underwent 18F-FDG PET. The standardized uptake value (SUV) of 18F-FDG was calculated, and the patients were divided into high (> or = 3.0) and low (< 3.0) SUV groups. RESULTS: The two groups were not significantly different in terms of age, tumor location and size, staging, and treatment. However, analysis by the Kaplan-Meier method revealed that the groups had different prognoses (log rank test, P < 0.05). The mean survival of patients with high SUV was 5 months, whereas that of patients with low SUV was 14 months. There were not strong correlations between the SUVs and tumor size (0.56), serum carbohydrate antigen 19-9 (0.39), or carcinoembryonic antigen (0.52). CONCLUSIONS: SUV calculated with 18F-FDG can be utilized as a prognostic factor for patients with pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Inhibition of nitroxidergic nerve function by neurogenic acetylcholine in monkey cerebral arteries.

1. Modification by endogenous or exogenous acetylcholine and vasoactive intestinal polypeptide (VIP) of vasodilatation mediated by nitric oxide (NO) released from nitroxidergic nerves was studied in isolated monkey cerebral arteries. In arterial strips denuded of endothelium, transmural electrical stimulation (2-20 Hz) produced relaxations that were abolished by tetrodotoxin. 2. The relaxation response was attenuated by acetylcholine, and the attenuation was reversed by atropine. Attenuation was also observed with AF-DX 116, an antagonist of the muscarinic acetylcholine receptor subtype, M2. NO-induced relaxation was not affected by acetylcholine. Neurogenic relaxation was also inhibited by physostigmine and potentiated by atropine. 3. VIP in concentrations that elicited slight relaxation did not alter the response to nerve stimulation. In the strips showing tachyphylaxis to VIP, the neurogenic response was not inhibited. 4. Histochemical studies of whole-mount preparations revealed nerve fibres with NO synthase and VIP immunoreactivity, and also acetylcholinesterase, suggesting the presence of perivascular nitroxidergic, VIPergic and cholinergic innervation. 5. It is concluded that the actions of nitroxidergic nerve fibres on the monkey cerebral artery are inhibited by nerve-released acetylcholine acting on prejunctional muscarinic receptors, possibly of the M2 subtype. Despite the presence of VIP immunoreactive nerve fibres and the ability of exogenous VIP to relax the artery, there is no evidence supporting either a prejunctional modulation of nitroxidergic nerve function by VIP or a role for VIP as a vasodilatory neurotransmitter.

Acetylcholine↗