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T Okamura

Publications and source records attributed to T Okamura.

At least 163 records · Page 9Linked to original sources
PubMed1999

Preoperative clinical radioimmunodetection of pancreatic cancer by 111 In-labeled chimeric monoclonal antibody Nd2.

The present study was carried out with the purpose of evaluating the clinical usefulness of radioimmunodetection (RAID) with 111In-labeled murine/human chimeric monoclonal antibody, Nd2 (c-Nd2) in patients with pancreatic cancer. Nineteen patients suspected to have pancreatic cancer were administered intravenously 74 MBq/2 mg 111In-labeled c-Nd2 in 100 ml of saline containing 2% albumin over 30 min. A scintigram was obtained on the 3rd day after infusion by using single photon emission computed tomography (SPECT) imaging. Of the 14 patients finally diagnosed as having pancreatic cancer on the basis of surgical specimens or progress of disease, specific focal uptake at the site of the tumor was detected in 12 (true positive cases), representing a sensitivity of 85.7% (12/14), and liver metastasis was found in one case with metastasis. Of the 5 patients diagnosed with tumor-forming pancreatitis (TFP), 4 patients demonstrated true negative imaging, but one patient whose tumor demonstrated interesting findings in histology and immunostaining, showed false positive imaging. Of patients investigated for human anti-chimeric antibody (HACA) response, none showed HACA response, and no allergic reaction was seen in any of the patients administered c-Nd2. These results suggest that RAID with 11In-labeled c-Nd2 is useful for differential preoperative diagnosis between invasive pancreatic cancer and TFP.

Aged↗
PubMed1999

Regulatory network of mitomycin C action in human colon cancer cells.

A network composed of activation and inactivation pathways to regulate mitomycin C (MMC) action is suggested to exist in human cancer cells. COLO201 colon cancer cells were stably transfected with human NQO1 cDNA that encodes NAD(P)H:quinone oxidoreductase (DT-diaphorase, DTD), and a clonal cell line with about 57-fold elevated DTD activity was obtained. Northern analysis revealed that expression of the NADPH:cytochrome P450 reductase (P450 reductase) gene was decreased in the transfectant, COLO201/NQO1, associated with the increase of NQO1 expression. Biochemical characterization of the cells showed a significant increase of the glutathione (GSH) content concomitantly with the decrease of the P450 reductase activity. As a result of these coordinated modulations, sensitivity of COLO201/NQO1 to MMC was not increased as compared to the parent cells. Analyses of inhibition by specific inhibitors of DTD, P450 reductase and glutathione S-transferase (GST) in 5 human colon cancer cell lines including the transfectant showed that DTD and P450 reductase play significant roles in MMC activation in cells with sufficiently high DTD activity and with marginal DTD activity, respectively. In contrast, GST appeared to participate in MMC inactivation in cells with a high level of GST activity. These results indicated that DTD, P450 reductase, GSH and GST may act together compensatively or competitively, depending on their levels in cells, to determine the cellular sensitivity to MMC.

Antibiotics, Antineoplastic↗
PubMed1999

Ischemic preconditioning attenuates apoptosis through protein kinase C in rat hearts.

To investigate the role of protein kinase C (PKC) in the mechanism of ischemic preconditioning (IP), infarct size and the incidence of apoptosis caused by ischemia-reperfusion were tested in four groups of Sprague-Dawley rats. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/ml) was administered 5 min before the 30-min coronary occlusion followed by a 6-h reperfusion. Three cycles of 3 min of ischemia followed by 3 min of reperfusion was performed as IP before the 30-min ischemia followed by a 6-h reperfusion with or without calphostin C pretreatment. Infarct size defined by triphenyltetrazolium chloride staining was reduced from 60 +/- 2 to 26 +/- 2% by IP (P < 0.01), but the effect of IP was abolished by calphostin C (51 +/- 3%). Apoptosis defined by in situ terminal deoxynucleotidyl transferase end-labeling (TUNEL) was reduced by IP from 44 +/- 3 to 13 +/- 2% in the subendocardial region (P < 0.01). This effect of IP was abolished by calphostin C (42 +/- 8%). Thus the effect of IP on reducing the infarct size and the incidence of apoptosis are both mediated by PKC in rat hearts.

Animals↗
PubMed1999

Osteopontin expression in prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories. RESULTS: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason's score. CONCLUSIONS: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignancy in prostate cancer.

Adenocarcinoma↗
PubMed1999

Plasma level of homocysteine is correlated to extracranial carotid-artery atherosclerosis in non-hypertensive Japanese.

BACKGROUND: Results of some epidemiologic studies in Western countries have clarified that hyperhomocysteinemia is a plausible risk factor for atherosclerotic vascular disease, but its role in Japanese communities is not known. DESIGN: A community-based cross-sectional design. METHODS: We performed a cross-sectional study of 474 elderly men aged 60-74 years in two Japanese rural communities (Noichi in southwestern Japan and Ikawa in northeastern Japan). We examined the association between plasma concentrations of homocysteine and the maximum intima-media thickness (assessed by ultrasonography). RESULTS: The prevalence of thickening was 10.7% for the lowest tertile of homocysteine level and 21.1% for the highest tertile. For the subjects without hypertension, the odds ratio for having carotid intima-media thickening was 5.8; it was significantly higher for the highest tertile of homocysteine level than it was for the lowest after adjusting for age, hypercholesterolemia, hypoalphalipoproteinemia, diabetes, and smoking by using a multiple logistic regression model. However, its correlation was not evident for those with hypertension. CONCLUSIONS: High levels of plasma homocysteine are correlated to extracranial carotid artery atherosclerosis in elderly men without hypertension in Japanese rural communities.

Aged↗
PubMed1999

An increase in histone acetylation and IL-2 antagonizing the immunoinhibitory effect are necessary for augmentation by butyrate of in vitro anti-TNP antibody production.

We investigated the role of histone acetylation in the promotion of antigen-specific antibody production in murine B cells induced by sodium butyrate (NaBu) plus interleukin 2 (IL-2). NaBu dose dependently increased the acetylation levels of histone H4 at concentrations which effectively enhanced anti-trinitrophenyl (TNP) antibody production in the presence of IL-2. Among other short-chain fatty acids and NaBu analogs, propionate, valerate and vinylacetate were effective in the presence of IL-2 in increasing both antibody production and the histone H4 acetylation level, but acetate, alpha-, beta- and gamma-hydroxybutyrates and alpha-, beta- and gamma-aminobutyrates were not effective, even in the presence of IL-2. The effect of the specific histone deacetylase inhibitor trichostatin A (TSA), which enhances anti-TNP antibody production without IL-2, was markedly inhibited by adding NaBu simultaneously. However, the effect of TSA was neither inhibited nor potentiated by NaBu in the presence of IL-2. Splenic B cells treated with NaBu, TSA and both together in the presence or absence of IL-2 showed almost the same increased acetylation level of histone H4. These results suggest that the NaBu-induced enhancement of anti-TNP antibody production in the presence of IL-2 is mediated through a moderate increase in the level of histone acetylation and that NaBu has both stimulating and inhibiting activities for anti-TNP antibody production, the latter of which is overcome by IL-2.

Acetylation↗
PubMed1999

Abnormal coronary flow profiles at rest and during rapid atrial pacing in patients with hypertrophic cardiomyopathy.

To examine the mechanism of myocardial ischemia in hypertrophic cardiomyopathy (HCM), coronary flow velocity was measured in the left anterior descending coronary artery (LAD) using a Doppler guide wire in 11 patients with HCM and in 8 normal controls. The average peak velocity (APV), percent increase of APV (%APV), and APV during systole (Vs) and diastole (Vd) were calculated at rest and during rapid atrial pacing. The APV in HCM reached a peak value at a heart rate of 90 beats/min, while in the controls the APV increased continuously until the heart rate reached 130 beats/min [%APV (130 beats/min); 103+/-30% in HCM vs 139+/-23% in controls, p<0.04]. During rapid atrial pacing, Vs in the controls increased, whereas Vs in HCM decreased further. During high-rate pacing, Vd in HCM reached a peak value at a heart rate of 90 beats/min, whereas in the controls, Vd increased continuously until the heart rate reached 130 beats/min. The acceleration rate of early diastolic flow was significantly lower in HCM than in the controls (1.85+/-0.66 vs 3.18+/-1.62 m/s2, p<0.03). This abnormal response might be due to an increase in the reverse systolic flow and a decrease in the diastolic flow, probably caused by a slow acceleration of early diastolic flow velocity in the LAD.

Adult↗
PubMed1999

[Cohort study on risk factors for subarachnoid hemorrhage among Japanese men and women].

PURPOSE: To examine the risk factors for subarachnoid hemorrhage, for few prospective data have been available on risk factors of subarachnoid hemorrhage among Japanese. METHODS: A 9.4-year cohort study was conducted on 12,372 men and women, aged 40-69 years, free of history of stroke in six communities in Japan. RESULTS: During the follow-up, seventy-one incidents of subarachnoid hemorrhage occurred. After adjusting for age, serum total cholesterol, body mass index, history of diabetes mellitus, blood pressure category and drinking category, current smokers had a significantly increased risk of subarachnoid hemorrhage compared with 'never-smokers': multivariate relative risk (RR) [95% confidence interval (95% CI)] = 3.1(1.4-6.9) for women, 1.5(0.4-5.3) for men and 2.7(1.3-5.5)for men and women. Hypertensives had a significantly increased risk of subarachnoid hemorrhage compared with normotensives: multivariate RR(95% CI) = 3.1(1.6-6.0) for women, 4.3(1.5-12.0) for men and 3.4(2.0-5.9) for men and women. For men, heavy drinkers (> = 69 g per day ethanol), had a significantly increased risk of subarachnoid hemorrhage compared with 'never-drinkers': multivariate RR(95% CI) = 4.3(1.1-16.8). For women, the relationship between heavy drinking and risk was not examined due to the small number of heavy drinkers (n = 13). Multivariate RR(95% CI) for men who smoked currently and drank heavily compared with men who did not smoke currently nor drink heavily was 6.0(1.8-20.1). Multivariate RR(95% CI) for hypertensive men who drank heavily compared with normotensive or borderline hypertensive men who did not drink heavily was 13.0(3.9-43.9). Multivariate RR(95% CI) for hypertensive men and women who smoked currently compared with normotensive or borderline hypertensive men and women who did not smoke currently was 6.1(1.3-28.7) for men and 6.3(1.4-28.0) for women. Furthermore, the combination of smoking, hypertension and heavy drinking raised the risk of subarachnoid hemorrhage substantially: multivariate RR(95% CI) = 17.5(3.4-90.2). CONCLUSION: Smoking and hypertension appeared to increase the risk of subarachnoid hemorrhage. For men, although the association of smoking with the risk of subarachnoid hemorrhage was weak compared with women, the combination of smoking, hypertension and heavy drinking increased the risk substantially. For women, smoking appeared to be an independent risk of subarachnoid hemorrhage, and the combination of smoking and hypertension increased the risk in additive fashion.

Adult↗
PubMed1999

Abnormal biopterin metabolism is a major cause of impaired endothelium-dependent relaxation through nitric oxide/O2- imbalance in insulin-resistant rat aorta.

To investigate underlying mechanisms responsible for the impaired nitric oxide (NO)-dependent vascular relaxation in the insulin-resistant state, we examined production of both NO and superoxide anion radical (O2-) and those modulating factors in aortas obtained from normal (CTR), insulin-treated (INS), or high fructose-fed (FR) rats. FR rats showed insulin resistance with endogenous hyperinsulinemia, whereas INS rats showed normal insulin sensitivity. Only FR aortic strips with endothelium elicited impaired relaxation in response to either acetylcholine or calcium ionophore A23187. Endothelial NO synthase (eNOS) activity and its mRNA levels were increased only in vessels from INS rats (P < 0.001), whereas eNOS activity in FR rats was decreased by 58% (P < 0.05) when compared with CTR rats. NO production from aortic strips stimulated with A23187 was significantly lower in FR than CTR rats. In contrast, A23187-stimulated O2- production was higher (P < 0.01) in FR than CTR rats. These differences were abolished when aortic strips were preincubated in the media including (6R)-5,6,7,8-tetrahydrobiopterin (BH4), an active cofactor for eNOS. Furthermore, as compared with CTR rats, aortic BH4 contents in FR rats were decreased (P < 0.001), whereas the levels of 7,8-dihydrobiopterin, the oxidized form of BH4, were increased, with opposite results in INS rats. These results indicate that insulin resistance rather than hyperinsulinemia itself may be a pathogenic factor for decreased vascular relaxation through impaired eNOS activity and increased oxidative breakdown of NO due to enhanced formation of O2- (NO/O2- imbalance), which are caused by relative deficiency of BH4 in vascular endothelial cells.

Acetylcholine↗
PubMed1999

Neurogenic vasodilatation of canine isolated small labial arteries.

Mechanisms underlying vasodilatation to nerve stimulation by electrical pulses and nicotine were analyzed in isolated canine small labial arteries. Transmural electrical stimulation (5 and 20 Hz) produced a contraction followed by a relaxation in labial arterial strips denuded of the endothelium, partially contracted with prostaglandin F2alpha. The contraction was abolished by prazosin or combined treatment with alpha, beta-methylene ATP. In the treated strips, neurogenic relaxation was abolished by NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, and restored by L-arginine. The D-enantiomers were without effect. Nicotine (10(-4) M) also relaxed the arteries, in which the contractile response was abolished by prazosin and alpha, beta-methylene ATP. The relaxant response was attenuated but not abolished by L-NA; the inhibition was reversed by L-arginine. The remaining relaxation by nicotine was abolished by calcitonin gene-related peptide (CGRP)-[8 to 37], a CGRP1 receptor antagonist. Relaxations elicited by a lower concentration of nicotine (2 x 10(-5) M) sufficient to produce similar magnitudes of response to those induced by 5-Hz electrical nerve stimulation were also inhibited partially by L-NA. Histochemical study with the NADPH-diaphorase method demonstrated positively stained nerve fibers and bundles in the arterial wall, suggesting the presence of neuronal NO synthase. It is concluded that the relaxation induced by electrical nerve stimulation of small labial arteries is mediated exclusively by NO synthesized from L-arginine in nerve terminals, whereas nicotine in the concentrations used evokes relaxations by a mediation of nerve-derived NO and also CGRP, possibly from sensory nerves. The reason why nicotine but not electrical pulses stimulates sensory nerves and elicits vasorelaxation remains unsolved.

Animals↗
PubMed1999

Neurogenic vasoconstriction as affected by cholinergic and nitroxidergic nerves in dog ciliary and ophthalmic arteries.

PURPOSE: To determine the involvement of noradrenergic and other vasoconstrictor nerves in the contraction of ocular arteries and the modification by cholinergic and nitroxidergic nerves of vasoconstrictor nerve function. METHODS: Changes in isometric tension were recorded in helical strips of the canine posterior ciliary and external ophthalmic arteries denuded of the endothelium, which were stimulated by transmurally applied electrical pulses (5 Hz). Vasoconstrictor mediators were analyzed by pharmacological antagonists, such as prazosin, alpha,beta-methylene ATP, a P2alpha-purinoceptor antagonist, and BIBP3226, a neuropeptide Y receptor antagonist. RESULTS: Transmural electrical stimulation produced contractions that were potentiated by N(G)-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The contraction was partially inhibited by prazosin and abolished by combined treatment with alpha,beta-methylene ATP but was not influenced by BIBP3226. Stimulation-induced contraction was attenuated by physostigmine and potentiated by atropine. Contractions induced by exogenous ATP were reversed to relaxations by alpha,beta-methylene ATP. In the strips treated with L-NA, prazosin, and alpha,beta-methylene ATP, the addition of L-arginine elicited relaxations by nerve stimulation. The ATP-induced relaxation was attenuated by aminophylline, whereas neurogenic relaxation was unaffected. CONCLUSIONS: Ciliary and ophthalmic arterial contractions by nerve stimulation are mediated by norepinephrine and ATP, which stimulate alpha1-adrenoceptor and P2X purinoceptor, respectively. ATP from the nerve is unlikely involved in vasodilatation. Acetylcholine derived from the nerve impairs the neurogenic contraction, possibly by interfering with the release of vasoconstrictor transmitters, and neurogenic NO also inhibits the contraction postjunctionally by physiological antagonism.

Acetylcholine↗
PubMed1999

[Diagnosis and treatment of nontraumatic dissecting aneurysm in the middle cerebral artery].

Two cases of nontraumatic dissecting aneurysm of the middle cerebral artery (MCA) are reported. A 59-year-old woman presented with subarachnoid hemorrhage, mainly in the right sylvian fissure. On admission, the right carotid angiogram revealed a dissecting aneurysm with a double lumen extending from segment M1 to M2 of the right MCA, and an unruptured saccular aneurysm in the right internal carotid artery. Emergency surgery revealed a discolored protrusion of the arterial wall in the right MCA, which was thought to be the cause of her subarachnoid hemorrhage. The protrusion of the arterial wall was clipped and coated with Bemsheet soaked in Biobond. However, disturbance of consciousness persisted and she died of paralytic ileus two months after the operation. The other patient was a hypertensive 33-year-old woman with right hemiparesis and motor dysphasia. CT scans obtained on the day of admission showed no abnormalities. She was treated conservatively with clinical improvement, but CT scans obtained 3 days after the ictus revealed an infarction deep in the left frontal lobe. A left carotid angiogram was made 4 days after ictus and demonstrated severe stenosis of the proximal segment of the left MCA with poor filling of its superior trunk. Despite improvement of her hemiparesis, CT scans obtained 3 weeks after the ictus showed hemorrhagic infarction in the left frontal lobe. Repeat left carotid angiogram revealed a double lumen in the C1 and M1 portions with improvement of the previous severe stenosis of the M1. The 23 reported cases of DA in the MCA with our cases are reviewed and their neuroradiological and clinical features are discussed.

Adult↗
PubMed1999

Intraspinal extradural cysts communicating with adjacent herniated disks: imaging characteristics and possible pathogenesis.

We report two cases of intraspinal extradural cysts communicating with an adjacent herniated disk that we term "disk cysts." These cysts were well defined and homogeneous, and were present in the ventrolateral extradural space adjacent to a lumbar herniated disk. They had rim enhancement on contrast-enhanced MR images, and communication with a herniated disk was revealed by diskography.

Adult↗
PubMed1999

[Factors relate to participation in medical checkups in a rural community an analysis including social network scores].

Since 1969, community-based stroke prevention programs have been conducted in N town, Kochi prefecture. To clarify factors related to participation in medical checkups including social networks, a cross-sectional questionnaire survey was performed on 6,704 residents aged 40 and over in N town in 1996. 1. Location of the workplace, types of medical insurance and interest in health were significantly associated with participation in medical checkups. 2. Participation in medical examinations provided at the workplace was significantly, inversely related with participation rates in community checkups in the group aged 40 to 59 years. 3. Low independence level in daily activities was inversely associated with participation rates for medical checkups in groups aged 60 years and older. 4. Visiting medical facilities was inversely associated with the participation rate for medical checkups in female groups. 5. The group with the highest social networks score (5 points) had the highest participation rate for medical checkups. After adjusting for other participation related factors, social networks scores had a significantly positive association with the participation rate for medical checkups provided by the Health Services for the Elderly Act.

Adult↗
PubMed1999

[Malignant lymphoma with c-myc gene rearrangement in a patient receiving long-term treatment for multiple myeloma].

We encountered a 65-year-old woman with diffuse large B-cell lymphoma showing t(8;14)(q24;q32) and c-myc gene rearrangement that developed following 12 years of melphalan-based chemotherapy for multiple myeloma. Short-term remission was obtained by CHOP chemotherapy. However, shortly thereafter the patient died of an aggressive progression of lymphoma. It was suspected that the lymphoma was a secondary malignancy related to the treatment with cytotoxic agents and radiation for prolonged multiple myeloma. The chromosomal abnormality t(8;14)(q24;q32) is rare in secondary malignancies. Overexpression of c-myc by gene rearrangement may be associated with clinical courses manifested by the rapid progression of lymphoma.

Aged↗
PubMed1998

Promotion of antigen-specific antibody production in murine B cells by a moderate increase in histone acetylation.

By employing the specific histone deacetylase inhibitor trichostatin A (TSA), we investigated whether histone acetylation modulates the production of antigen-specific antibodies in murine splenocytes in vitro. TSA caused a marked increase in both anti-sheep red blood cell (SRBC) and anti-trinitrophenyl (TNP) plaque-forming cell (PFC) responses in splenocytes at much lower concentrations than sodium butyrate. It also dose dependently augmented the production of anti-trinitrophenyl antibodies in splenic B cells with a concomitant, moderate increase in the level of histone H4 acetylation. Its optimal concentration for promoting the production of these antibodies was 10 nM. However, to gain such an effect on antibody production, TSA had to be added to cells before Day 2 in culture. Trichostatin C, an analog of TSA and a less potent inducer of Friend leukemia cell differentiation, also increased both the anti-trinitrophenyl PFC response and histone H4 acetylation in B cells, but at higher concentrations than TSA. TSA did not stimulate the production of lipopolysaccharide-induced polyclonal immunoglobulin M in B cells. These results suggest that a moderate increase in histone acetylation may play a significant role in promoting antigen-specific antibody production in B cells.

Acetylation↗