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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 145 records · Page 8Linked to original sources

Impaired fibrinolysis early after percutaneous transluminal coronary angioplasty is associated with restenosis.

This study examined the role of fibrinolytic components in the process of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Seventy-two patients with single-vessel disease who underwent successful PTCA were prospectively selected. Tissue plasminogen activator (TPA), free plasminogen activator inhibitor-1 (free PAI-1), TPA/PAI-1 complex, and total PAI-1 antigen levels were measured before, at 1 week after, and at 3 months after PTCA. Six months after PTCA, the study patients were divided into two groups: 41 patients without restenosis and 31 patients with restenosis. There were no significant differences with regard to sex, age, coronary risk factors, or morphologic changes in the target lesions between the two groups. There were no significant differences in plasma TPA, TPA/PAI-1 complex, or total PAI-1 levels at each sampling period, or in the time courses between the two groups, except for total PAI-1 levels at 1 week after PTCA. Although no significant differences in free PAI-1 levels before PTCA were observed, free PAI-1 levels after PTCA in the patients with restenosis were significantly higher than those in the patients without restenosis. In addition, each group had a significant change in the time course of free PAI-1 levels. The results suggest that impaired fibrinolysis early after PTCA might affect the repair process of vascular injury, which leads to restenosis, and also that serial determination of free PAI-1 levels could help predict restenosis.

Angioplasty, Balloon, Coronary↗

Effects of combination therapy with interferon and ofloxacin on chronic type C hepatitis: a pilot study.

Interferon is effective in only a limited number of patients with the 1b type of hepatitis C virus (HCV), indicating that a combination therapy with other antiviral drugs may be essential to obtain better results. In the present pilot study, the effects of a combination therapy with interferon (IFN) and an antibacterial drug, ofloxacin, were analysed. Ten patients with chronic type C hepatitis received the combination therapy (combination group). Six million units of natural IFN-alpha were administered daily for 3 weeks and then three times a week for 21 weeks. The combination therapy was initiated at the beginning of the eighth week of IFN treatment and 600 mg ofloxacin per day was administered for 12 weeks. As a control, changes in HCV-RNA were also analysed in patients who were treated with only IFN for the same period (IFN-alone group). In the combination group, serum transaminase levels and the titres of HCV decreased significantly with ofloxacin administration. Such changes were not observed in the IFN-alone group. The incidence of HCV-negativity at the end of ofloxacin administration of the combination group was significantly higher than in the IFN-alone group. The complete response rate was twice as high in the combination group as in the IFN-alone group. In two patients who did not respond well to the IFN-alone treatment, ofloxacin administration was commenced after the 24th week. Serum transaminase levels were normalized and HCV-RNA became negative in these two patients after the administration of ofloxacin. These results suggest that combination therapy with IFN and ofloxacin may be an effective treatment for chronic type C hepatitis.

Adult↗

Relationship between hepatocellular carcinoma and subtypes of hepatitis C virus: a nationwide analysis.

Although hepatitis C virus (HCV) has now been classified into several subtypes, the clinical significance of HCV subtypes is not well known. Typing of HCV is now routinely performed in Japan. In the present study, HCV subtypes in hepatocellular carcinoma (HCC) patients were analysed from nationwide data collected in Japan using a standard questionnaire. Answers to the questionnaire concerning HCV subtypes in patients with chronic hepatitis (CH), liver cirrhosis (LC) and HCC were obtained from 14 hospitals. The prevalence of the 1b-related subtype, which includes the mixed subtype of 1b and 2a or 2b, in patients with LC and HCC in each hospital was higher than in patients with CH, with few exceptions. However, the differences were not statistically significant because of the small number of patients in each hospital. In summarized data from all 14 hospitals, the 1b-related subtype was found in 1370 of 1922 patients with CH (71.2%). In 356 LC and 426 HCC patients, the prevalence of the 1b-related subtype was 79.8 and 80.5%, respectively. The prevalence of the 1b-related subtype in patients with LC and HCC was significantly higher than in patients with CH. There was no significant difference between the prevalence of the 1b-related subtype in patients with HCC and LC. These results indicate that the oncogenic activity of subtype 1b, although not yet clearly characterized, may be stronger than subtypes 2a and 2b.

Carcinoma, Hepatocellular↗

Distribution of the different subtypes of hepatitis C virus in Japan and the effects of interferon: a nationwide survey.

Interferon (IFN) is now commonly used for the treatment of type C hepatitis; however, its effects differ depending upon the subtype of hepatitis C virus (HCV) being treated. It has been recently confirmed in many studies in Japan that the effectiveness of IFN treatment is poor in patients having type 1b and better in patients having type 2a HCV. However, the effects of IFN treatment on other subtypes of HCV were not clear because of the small number of patients in each hospital. In the present study, the effects of IFN treatment in patients with other HCV subtypes were analysed from nationwide data collected in Japan using a standard questionnaire. From this questionnaire, local differences in the distribution of HCV subtypes in Japan were also analysed. A standard questionnaire, consisting of questions about the number of patients with chronic type C hepatitis with different HCV subtypes and the number of patients showing different responses to IFN treatment, was sent to over 40 study groups in Japan. Answers to the questionnaire concerning HCV subtypes and the effects of IFN treatment were obtained from 26 and 22 hospitals, respectively, throughout Japan. The incidence of HCV type 1b was highest in the Kinki area (south-central Japan). The incidence of type 1b HCV decreased in parallel with distance from this area. The mortality rates of hepatic cancer in different areas were significantly correlated with the incidence of HCV type 1b. The efficacy of IFN treatment was significantly better for both types 2a and 2b HCV than for type 1b HCV; the efficacy of IFN treatment was poor in the mixed type of 1b and 2a and tended to be better in type 1a. The efficacy of IFN treatment for other types of HCV was also better. These results indicate that there are local differences in the distribution of HCV subtypes in Japan and that these differences may be closely associated with the clinical features of HCV-related liver disease. The efficacy of IFN treatment was significantly poorer in patients with the 1b-related type HCV than in patients with other types of HCV.

Carcinoma, Hepatocellular↗

Renal blood flow and serotonin metabolism in tacrolimus treated rats.

BACKGROUND: Serotonin (5-HT) is a potent vasoconstrictor and activator of platelets, endothelial cells and vascular smooth muscle cells. The result of activation by serotonin is platelet aggregation and vasoconstriction. The aim of the present study was to evaluate the role of serotonin metabolism as a mediator of tacrolimus (FK 506) nephrotoxicity. METHODS: The whole blood and plasma levels of serotonin and its major metabolite (5-hydroxyindoleacetic acid: 5-HIAA) as well as renal cortical blood flow were investigated in rats administered FK 506 at doses of 4, 6 or 8 mg/kg b.w. for 14 consecutive days. RESULTS: Renal cortical blood flow declined in a dose-dependent manner in the rats given FK 506, whereas serum creatinine remained unaltered following FK 506 administration. Although there was no significant change in serotonin, the whole blood and plasma 5-HIAA levels increased significantly following FK 506 administration. CONCLUSION: FK 506 may cause acute nephrotoxicity by decreasing renal blood flow and the increase of 5-HIAA suggests some role of serotonin metabolism in the development of FK 506 nephrotoxicity.

Animals↗

Relative risk for the development of hepatocellular carcinoma in alcoholic patients with cirrhosis: a multiple logistic-regression coefficient analysis.

The hepatitis B virus (HBV) or hepatitis C virus (HVC) markers are frequently positive in alcoholic patients with hepatocellular carcinoma (HCC). However, the role of the relationship between HBV or HCV infection and alcohol drinking in the development of HCC has not been clearly documented. In the present study, the relative risk in 1200 cirrhotic patients with different etiologies who were admitted to five different hospitals in Japan was calculated using the multiple logistic-regression coefficient analysis. In the HCV+ alcohol group, HCC patients tended to be younger, and the odds ratio for the development of HCC was significantly higher compared with the HCV-alone group. Furthermore, the interaction coefficient of alcohol and HCV for the development of HCC was significant statistically. However, the interaction between HBV and alcohol was not significant. Because the proportion of male patients with HCC was significantly higher in the alcohol-alone and HBV-related groups than in the HCV-related group, the multiple logistic-regression analysis was also performed in male patients only. The results were nearly the same as those in male and female patients combined. These results suggest strongly that alcohol and HCV together accelerate the development of HCC. However, a similar relationship was not found between alcohol and HBV.

Adult↗

Serum markers for hepatic fibrosis in alcoholic liver disease: which is the best marker, type III procollagen, type IV collagen, laminin, tissue inhibitor of metalloproteinase, or prolyl hydroxylase?

Although various serum markers for the evaluation of hepatic fibrosis have been introduced, it remains unclear which is the best marker to evaluate the hepatic fibrosis observed in alcoholic liver disease (ALD). In this study, we measured serum concentrations of the immunoreactive beta-subunit of prolyl hydroxylase, procollagen type III peptide, the 7S domain (7S-IV) and triple-helix domain (TH-IV) of type IV collagen, laminin, and tissue inhibitor of metalloproteinase (TIMP) in patients with and without ALD (non-ALD), and controls to evaluate the best serum marker reflecting the characteristic histologic features of ALD. After Azan-Mallory and silver-impregnated reticulin staining, histologic specimens were examined; and the degree of hepatic fibrosis was classified as mild, moderate, or severe. Although serum concentrations of all markers, except for TIMP, in patients with each type and stage of liver disease were higher than cut-off values and these concentrations increases with the progression of liver disease, statistical analyses indicate that serum TH-IV concentration is the best marker to distinguish ALD from non-ALD. A good correlation was also found between the hepatic type IV collagen content and serum TH-IV, but not serum 7S-IV concentration. Moreover, after abstinence from alcohol, serum concentrations of TH-IV decreased more quickly than other serum markers. These results clearly suggest that, compared with other markers, serum concentration of TH-IV may more strongly reflect the histologic features of ALD. However, other serum markers, except for TIMP, may be useful in evaluating the degree of hepatic fibrosis.

Alcohol Drinking↗

An alternative access to a trisaccharide repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 19A.

A chemical synthesis has been achieved for beta-D-ManNAc-(1-->4)-alpha-D-Glc-(1-->3)-L-Rha, a trisaccharide repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 19A, by stepwise link-up of the suitably functionalized, constituent sugar units. A beta-selective glycosylation of trimethylsilylethyl glucoside having free 4-OH with 2-(benzoyloxyimino)-2-deoxyglycosyl bromide, followed by manno-selective hydroboration, N-acetylation, and functionalization of the anomeric center (1-OSE-->1-OH-->1-F), gave a key disaccharide donor, beta-D-ManNAc-(1-->4)-alpha-D-Glc-(1-->F. Ensuing glycosylation of an L-rhamnosyl acceptor with the donor substrate afforded, after deblocking, the target trisaccharide in 6.5% yield over 13 steps from D-glucose.

Carbohydrate Sequence↗

Characteristics of vasospastic angina with exercised-induced ischemia--analysis of parameters of hemostasis and fibrinolysis.

To characterize the vasospastic angina patients with exercise-induced ischemia, we measured hemostasis (platelet factor 4; PF4, fibrinopeptide A; FPA) and fibrinolytic parameters (tissue plasminogen activator antigen; t-PA, free plasminogen activator inhibitor-1 antigen; free PAI-1) in 15 normal subjects and 33 vasospastic angina patients without significant coronary artery stenosis (less than 50% stenosis). All of the vasospastic angina patients began to feel chest pain within 3 months before diagnostic coronary angiography. Blood samples were obtained from all of the study patients at 8:30-9:30 am before exercise 201Tl emission computed tomography. Vasospastic angina patients were divided into 2 groups; 15 patients with exercise-induced ischemia (group 1) and 18 patients without exercise-induced ischemia (group 2). On coronary angiography, the severity of coronary artery stenosis at the site of spasm in group 1 (34 +/- 5%) was greater than that in group 2 (18 +/- 3%). Plasma FPA and PF 4 levels in group 1 were also significantly higher than those in normal subjects and group 2. Plasma t-PA and free PAI-1 levels in group 1 were significantly higher than those in normal subjects and group 2. Plasma levels of free PAI-1 group 2 were also significantly higher than those in normal subjects. The present study demonstrated that all of the patients with vasospastic angina had impaired fibrinolysis, and these patients with exercise-induced ischemia showed enhanced platelet activation, an enhanced coagulation system, and advanced atherosclerotic lesions. These results suggest that vasospastic angina with exercise-induced ischemia puts patients at increased risk for thrombus formation.

Adult↗

Angiotensin-II-induced hypertension chemotherapy: evaluation of hepatic blood flow with oxygen-15 PET.

We quantitatively measured blood flow in liver parenchyma and hepatic tumors in two patients using 15O-carbon dioxide (steady state) and 15O-water (dynamic) PET imaging. Images were acquired before and during administration of angiotensin-II to achieve a hypertensive state. Blood flow in the hepatocellular carcinoma was greater than that of the parenchyma. Blood flow in the colon metastasis was similar to that in the parenchyma and lower in the center than in the periphery. During a hypertensive state induced by angiotensin II, blood flow in both the primary and secondary liver tumors did not change, while blood flow in the liver parenchyma decreased. As a result, there was a relative increase in tumor blood flow during the hypertensive state on PET images. Furthermore, blood flow to the spleen decreased to 55% of baseline during the hypertensive state. These findings suggest that hypertensive cancer chemotherapy may protect normal tissue. Furthermore, PET imaging may be able to predict the efficacy of hypertensive cancer chemotherapy in the patients with liver tumors.

Angiotensin II↗

Influence of MCI-9042, a novel 5-HT2 receptor blocker on blood vessels of the rat.

We demonstrated that MCI-9042 potently inhibited the vasoconstrictory effects of serotonin in the isolated perfused hindlegs of the rat. Concentrations of MCI-9042 in the range of 0.01-1 mumol/l caused a dose-dependent inhibition of the vasoconstrictory effect of serotonin (1-30 micrograms/0.1 ml). The maximal inhibitory effect of MCI-9042 was about 97% (1 mumol/l). MCI-9042 caused a concentration-dependent shift to the right of concentration-response curve to serotonin in the rat tail artery. The present data demonstrate MCI-9042 as a potent 5-HT2 receptor antagonist.

Animals↗

Effect of DV-7028, a novel serotonin 5-HT2 receptor antagonist on the cardiovascular system in rats.

The response of the cardiovascular system to DV-7028 demonstrated the complex action of this substance. In anaesthetized rats DV-7028 decreased the blood pressure and heart rate. These effects did not occur in pithed rats. The hypotensive action and bradycardia was partially reduced in vagotomized animals. DV-7028 potently inhibited the vasoconstrictory effects of serotonin in isolated perfused hindlegs of rat and caused a concentration-dependent shift to the right of response curve to serotonin in the rat tail artery. The present data demonstrate that DV-7028 is a potent 5-HT2 receptor antagonist. Besides its peripheral action, DV-7028 exerts central effects which cause hypotension and bradycardia.

Animals↗

Changes in blood and plasma serotonergic measurements in rats--effect of nicotine and/or exposure to different stresses.

Effects of two kinds of stress on plasma and whole blood serotonergic measurements were studied in nicotine administered rats. Plasma tryptophan levels increased after footshock stress. Stress given to nicotine administered rats resulted in decrease in plasma tryptophan levels. Although there was no change in 5-HT levels in whole blood, footshock increased plasma levels of 5-HT, and restraint stress decreased its levels. Plasma and whole blood 5-HIAA levels increased in rats given stress and nicotine. 5-HIAA/5-HT ratio (the turnover rate of 5-HT) in plasma and blood increased only in rats given stress and nicotine. These results indicate that nicotine administration may decrease stress induced increase in plasma 5-HT levels by increasing its degradation.

Analysis of Variance↗

Daily variation of serum lipids in relation to the circadian rhythm of platelet aggregation in healthy male persons.

The circadian rhythm of platelet aggregation was compared with that of serum lipids in seven healthy male persons. Daily variations of remnant lipoprotein-cholesterol and of remnant lipoprotein-triglycerides were related to those of arachidonic acid-, ADP (adenosine diphosphate)-, and collagen-induced aggregation in platelet-rich plasma and to ADP-induced aggregation in whole blood, respectively. Statistical analyses indicate that the time course of remnant-cholesterol was correlated to that of ADP-induced aggregation in platelet-rich plasma and the time courses of blood cholesterol and triglyceride were correlated to arachidonic acid- and serotonin-induced platelet aggregation in platelet-rich plasma, respectively. In whole blood, the time course of remnant lipoprotein-triglyceride was correlated only to ADP-induced platelet aggregation. In contrast, the daily variation of HDL (high density lipoprotein)-cholesterol did not influence either that of platelet aggregation in platelet-rich plasma or that in whole blood. Our findings are of clinical interest regarding the development of atherosclerosis and thrombotic events in persons with an elevated level of serum lipids.

Adolescent↗

The cleavage and inactivation of plasminogen activator inhibitor type 1 by neutrophil elastase: the evaluation of its physiologic relevance in fibrinolysis.

The effect of the proteolytic cleavage of plasminogen activator inhibitor type 1 (PAI-1) by human neutrophil elastase (HNE) on fibrinolysis was investigated. HNE cleaved active PAI-1 and produced low molecular weight forms of inactive PAI-1, as previously reported. Latent PAI-1 was resistant to HNE treatment. Vitronectin (VN) partially protected the cleavage. NH2-terminal sequence analysis indicated that the cleavage site was Val355-Ser356 (P4-P3). The effects of PAI-1 cleavage by HNE on clot lysis was studied in a purified system. Clot lysis time without PAI-1 was 20.0 +/- 5.0 minutes and was prolonged to 86.7 +/- 2.9 minutes by 68 nmol/L of PAI-1. It was shortened when HNE (from 0.6 nmol/L to 80 nmol/L) was added and returned to the value obtained without PAI-1 by 80 nmol/L of HNE (20.0 +/- 5.8 minutes). However, in the absence of PAI-1, elastase did not enhance clot lysis at all. Euglobulin clot lysis time was also shortened after HNE treatment. The cleavage and inactivation of PAI-1 by HNE was shown to be a novel pathway to enhance fibrinolysis.

Amino Acid Sequence↗

Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum.

The free radical scavenging and antihepatotoxic activity from Ganoderma lucidum, Ganoderma formosanum and Ganoderma neo-japonicum were studied. Treatment with the water extract of Ganoderma lucidum, Ganoderma formosanum and Ganoderma neo-japonicum caused a marked decrease in the CCl4-induced toxicity in rat liver, made evident by their effect on the levels of glutamic oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) in the serum. The scavenging potency of the water extracts of the crude drugs was evaluated in terms of their ability to reduce the peaks of spin adducts using electron spin resonance (ESR) spin-trapping techniques. The results indicated that Ganoderma formosanum showed the greatest antihepatotoxic activity and the greatest free radical scavenging activity.

Alanine Transaminase↗