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Biomedical subjects

Y Sakata

Publications and source records attributed to Y Sakata.

At least 163 records · Page 9Linked to original sources
PubMed1997

Effect of long-term treatment with complete Freund's adjuvant on KK-Ay mouse, a model of non-insulin-dependent diabetes mellitus.

Nonspecific stimulation with immunoadjuvants significantly improves glucose tolerance in animal models for non-insulin-dependent diabetes mellitus (NIDDM). In this study, we observed the effect of long-term treatment with complete Freund's adjuvant (CFA) on serum factors and histology of various organs in KK-Ay mice with NIDDM. The mice were injected with CFA weekly or every 2 weeks for 12 weeks. Glucose tolerance was significantly improved in the CFA-treated mice throughout the experiment. At the end of the experiment, hypertriglyceridemia was significantly reduced, but serum total protein, glutamic pyruvic transaminase, creatinine, and nonfasting insulin levels were not changed by the treatment. Fatty change of the liver and index of glomerular lesions of the kidney were significantly inhibited in the CFA-treated mice, whereas the pancreatic islet morphology remained unchanged. No toxic effect was observed by the CFA treatment. These results imply that the novel treatment with CFA could control NIDDM and inhibit the development of diabetic glomerular lesions in KK-Ay mice.

Animals↗
PubMed1997

Salutary effect of adjunctive intracoronary nicorandil administration on restoration of myocardial blood flow and functional improvement in patients with acute myocardial infarction.

Salutary effect of nicorandil, a K+ adenosine triphosphate channel opener, on restoration of myocardial blood flow and functional improvement after coronary revascularization was investigated in 20 patients with first anterior acute myocardial infarction. Ten patients received intracoronary administration of nicorandil (2 mg) after coronary revascularization; the other 10 patients received coronary revascularization only and served as control subjects. Myocardial contrast echocardiography and two-dimensional echocardiography were performed to assess microvascular integrity and regional function in the infarcted area. Nicorandil improved peak contrast intensity ratio (p < 0.001), calculated as the ratio of peak contrast intensity in the infarcted and noninfarcted areas, indicating the restoration of myocardial blood flow to the infarcted myocardium. Regional wall motion improved more significantly in 1 month in patients who received nicorandil (p < 0.01). Thus our results suggested the usefulness of intracoronary nicorandil administration after coronary revascularization for restoring blood flow and functional improvement in patients with acute myocardial infarction.

Angioplasty, Balloon, Coronary↗
PubMed1997

Adenovirus-mediated transfer of tissue-type plasminogen activator gene to human endothelial cells.

BACKGROUND: Seeding of vascular grafts with genetically engineered human endothelial cells (hECs) secreting antithrombogenic or fibrinolytic agents has considerable clinical potential. METHODS: An adenoviral vector was used to transfer the human tissue-type plasminogen activator (htPA) gene to hECs, and the ability of the transduced hECs to secrete htPA was examined. Cultured hECs on plates were incubated with various concentrations of recombinant adenoviruses containing the htPA or LacZ gene for various times to determine the optimal transfer conditions. Transduced hECs were seeded onto fibronectin-coated expanded polytetrafluoroethylene grafts (4 mm in diameter), some of which were exposed to pulsatile flow in vitro. RESULTS: Effective transduction of the htPA gene into hECs (htPAhECs) was achieved with viral soup at a multiplicity of infection of 30 after incubation for 1 day, which yielded 4.8 +/- 0.20 x 10(3) ng/10(6) cells/6 hr htPA antigen on plates (n = 3), 2.2 +/- 2.0 x 10(3) ng/10(6) cells/6 hr on grafts (n = 6), and 6.8 +/- 1.7 x 10(2) ng/10(6) cells/6 hr on perfused grafts (n = 6). The retention of htPAhECs by perfused grafts was 84.0% +/- 3.0%, comparable with the noninfected (82.1% +/- 8.0%) and mock-infected (94.2% +/- 0.4%) hEC values. CONCLUSIONS: By adenoviral vector-mediated gene transfer, 10(2-3)-fold enhancement of htPA secretion was demonstrated, which did not affect cell retention by grafts.

Adenoviridae↗
PubMed1997

Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factor-alpha in vitro and in vivo.

It has been reported that angiotensin converting enzyme (ACE) inhibitors have beneficial effects on insulin resistance and congestive heart failure, in which elevations of serum tumor necrosis factor-alpha (TNF-alpha) level have been indicated. Therefore, in this study, we examined effect of ACE inhibitors on TNF-alpha production both in vitro and in vivo by using human blood mononuclear cells and mice, respectively. LPS (20 micrograms/ml)-induced in vitro TNF-alpha production, measured by bioassay and enzyme-linked immunosorbent assay, was significantly inhibited with captopril, delapril and cilazapril in a concentration of 10(-3) mol/l. A single, oral administration of captopril, delapril and cilazapril at more than 10-fold doses of common clinical use in man significantly inhibited LPS (2 mg/kg)-induced serum TNF-alpha activity in Balb/c mice. These results indicate that ACE inhibitors such as captopril, delapril and cilazapril have an inhibitory effect on TNF-alpha production not only in vitro as previously reported, but also in vivo, although relatively high concentrations and large doses were required in this study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Different mechanisms of ischemic adaptation to repeated coronary occlusion in patients with and without recruitable collateral circulation.

OBJECTIVES: The aim of this study was to investigate the interaction between ischemic preconditioning (IP) and collateral recruitment (CR) during ischemic adaptation in patients. BACKGROUND: The mechanism of ischemic adaptation still remains controversial in humans. METHODS: The clinical, electrocardiographic, hemodynamic and echocardiographic responses to three 150-s occlusions of the left anterior descending coronary artery were assessed in relation to CR in 18 patients with effort angina undergoing elective percutaneous transluminal coronary angioplasty. RESULTS: During the first occlusion, recruitable collateral circulation (RCC) to the occluded myocardium was detected by myocardial contrast echocardiography in 6 patients (Group C) and was not seen in 12 (Group N). In Group N, all patients manifested signs of severe ischemia during each inflation. However, their symptoms and ST segment shift significantly decreased from the first to the third occlusions, suggesting the occurrence of IP. The elevation of mean pulmonary artery pressure and deterioration of anterior wall motion were comparable between the first and the third occlusions in Group N. In contrast, myocardial ischemia was significantly less marked during occlusion in Group C than in Group N, and no preconditioning effect was observed. The extent of RCC did not differ between the first and the third occlusions in each group. CONCLUSIONS: Both IP and CR may play independent roles in ischemic adaptation in humans. With RCC, myocardial ischemia was greatly reduced. Without RCC, preconditioning clinically and electrocardiographically lessened myocardial ischemia but failed to preserve left ventricular function.

Angina Pectoris↗
PubMed1997

The RY sequence is necessary but not sufficient for the transcription activation of a winged bean chymotrypsin inhibitor gene in developing seeds.

A winged bean Kunitz-type chymotrypsin inhibitor (WCI) is expressed in seeds and tuberous roots. In seeds, the expression of WCI is restricted to the period between the mid- and late-maturation stage. To understand the mechanisms that regulate the expression of WCI genes, we analyzed the promoter activity of the upstream region of the WCI-3b gene, which encodes a major WCI protein, in transgenic tobacco plants. By using a series of constructs with 5' deletions in the upstream sequences, the region between -882 and -623, relative to the transcription start site, was shown to contain multiple sequences which are responsible for high level expression in mid-maturation stage seeds. However, when this region was fused to the cauliflower mosaic virus 35S core promoter in both orientations, the chimeric promoters showed only a weak transcription activity in transgenic tobacco plants. Further analyses using internal deletion constructs revealed that the region between -882 and -174 is required for the transcription activation. Disruption of the RY sequence at -517, which is conserved in many seed protein genes, resulted in a drastic reduction of the transcription activity in seeds. These results suggest that sequences necessary for high level induction of the WCI-3b gene transcription in developing seeds are dispersed in the region between -882 and -174, and that the RY sequence is one of these sequences.

Chymotrypsin↗
PubMed1997

A battery of monoclonal antibodies that induce unique conformations to evolve cryptic but constitutive functions of plasminogen.

Two groups of anti-plasminogen monoclonal antibodies, whose epitope was either in the kringle 1 + 2 + 3 domain (F3P2, F11P5, F11P6, and F12P18) or the kringle 5 domain (F1P6 and F12P16), were isolated and their effects on the conformation of plasminogen were explored. All antibodies except F1P6 had 3- to 10-fold higher affinity toward Lys-plasminogen than Glu-plasminogen. F1P6 exhibited a comparable affinity to Glu- and Lys-plasminogen. Among these, only F11P5 binding was inhibited by epsilon-amino-nu-caproic acid (EACA) in a concentration-dependent manner, with half maximal inhibition at 3 mM. From a competition assay, we concluded that the epitopes of F11P5, F11P6, and F12P18 should be very close, and located at or near the low affinity lysine binding site on the kringle 2 + 3. These three antibodies dramatically enhanced the binding of Glu-plasminogen to the other antibodies, except to F1P6. Interestingly, F3P2, whose non-overlapping epitope was in the kringle 2 + 3 domain, also augmented the binding of Glu-plasminogen to the other antibodies. In contrast, we did not observe enhanced binding of Lys-plasminogen to one antibody in the presence of the other antibodies, and the binding of Glu-plasminogen to these antibodies did not increase in the presence of 10 mM EACA. In the presence of these antibodies, including F1P6, Glu-plasminogen bound more efficiently to immobilized degraded fibrin, with a binding profile similar to Lys-plasminogen. All antibodies except F1P6 enhanced the conversion rate of plasminogen to plasmin remarkably. Taken together, we propose that these two groups of monoclonal antibodies can dissociate the intramolecular interactions of Glu-plasminogen and induce the conformational transition of Glu-plasminogen to Lys-plasminogen. In addition, the kringle 2 + 3 and kringle 5 structures of Glu-plasminogen liganded with EACA are distinct from the Lys-plasminogen structure.

Animals↗
PubMed1997

Disappearance of the 'no-reflow' phenomenon after adjunctive intracoronary administration of nicorandil in a patient with acute myocardial infarction.

Adjunctive intracoronary administration of nicorandil, an ATP-sensitive potassium channel opener, after successful coronary revascularization was performed in a 54-year-old patient with acute myocardial infarction. The 'no-reflow' phenomenon disappeared after nicorandil administration and significant functional recovery of the infarcted myocardium was achieved. This suggests that nicorandil could eliminate the 'no-reflow' phenomenon after successful coronary revascularization.

Coronary Circulation↗
PubMed1997

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Adult↗
PubMed1997

The effect of YNK-01 (an oral prodrug of cytarabine) on hepatocellular carcinoma.

Thirty-two patients with hepatocellular carcinoma (HCC) were treated with YNK-01, a prodrug of cytarabine for oral administration. A dose of 200 mg/d of YNK-01 was administered to 17 cases and 300 mg/d to 15 cases. One course was 2 weeks in duration, and this was repeated every 4 weeks for as long as the patients were able to tolerate it. There were five partial responses (15%) and 13 patients with no change (41%). A higher partial response rate was observed in the 300 mg/d group (27%) compared with the 200 mg/d group (6%). The average durations of partial response and no change were approximately 4 and 3 months, respectively. The main side effects of YNK-01 were anemia, leukopenia, thrombocytopenia, and symptoms of the alimentary tract (nausea, anorexia, diarrhea, etc). These results suggest that YNK-01 is a potentially useful oral agent for chemotherapy of hepatocellular carcinoma.

Administration, Oral↗
PubMed1997

The effect of central angiotensin II receptor blockade on interleukin-1beta- and prostaglandin E-induced fevers in rats: possible involvement of brain angiotensin II receptor in fever induction.

We investigated the role of the brain angiotensin II (Ang II) receptor subtypes AT1 and AT2 in the development of fever induced in freely moving rats by administration of interleukin-1beta (IL-1beta) or prostaglandin E2 (PGE2). Intraperitoneal (i.p.) injection of IL-1beta (2 microg/kg) induced a marked fever of rapid onset. Intracerebroventricular (i.c.v.) administration, immediately before IL-1beta injection, of a selective AT2 receptor antagonist, CGP42112A (5 or 20 microg), reduced the fever in a dose-related manner. Rats given an i.c.v. injection of PGE2 (200 ng) developed a monophasic fever response that was attenuated by i.c.v. treatment with CGP42112A (10 or 20 microg) in a dose-related manner. The IL-1beta (2 microg/kg i.p.)- and PGE2 (200 ng i.c.v.)-induced fevers were unchanged by the selective AT1 receptor antagonist losartan (60 microg i.c.v.). Treatment with exogenous Ang II (100 ng i.c.v.), which itself had no effect on resting body temperature, resulted in an enhancement of the PGE2 (50 ng i.c.v.)-induced fever. The administration of CGP42112A (2 and 5 microg) into the rostral hypothalamus (preoptic/anterior hypothalamic region) reduced fevers induced by IL-1beta (2 microg/kg i.p.) or intrahypothalamic (i.h.) PGE2 (100 ng). Moreover, i.h. injection of Ang II (25 ng) augmented the PGE2 (25 ng i.h.)-induced fever. Finally, the i.h. administration, 15 min before i.h. PGE2 (100 ng), of the angiotensin-converting enzyme (ACE) inhibitor lisinopril (5 and 10 microg) attenuated the PGE2-induced fever. These results suggest that brain AT2 receptors contribute to the induction of such febrile responses in rats.

Angiotensin II↗
PubMed1997

[Pharmacokinetic and clinical evaluation of cefozopran in premature and newborn patients].

Cefozopran (SCE-2787, CZOP), which is already on the market with a variety of approved indications in infectious diseases for adult patients, was administered to premature and newborn patients to evaluate the pharmacokinetics and the clinical efficacy. 1. Pharmacokinetics CZOP was intravenously administered at doses of 10.0 mg/kg, 21.4 mg/kg and 40.0 mg/kg to premature and newborn patients, and the blood concentrations and urinary excretion rate were examined. The blood CZOP concentrations were 31.7 and 65.5 micrograms/ml at 30 minutes after administration of 10.0 mg/kg and 40.0 mg/kg, respectively. The elimination half life was 1.78 hours and 2.31 hours, and the urinary recovery was 110.7% and 53.7% within 6 hours after administration, respectively. In the patient given 21.4 mg/kg, the blood CZOP concentration was 36.4 mg/kg at 1 an hour after administration and the elimination half life was 3.97 hours. The urinary recovery was 29.6% within 5 hours after administration. 2. Clinical results The clinical efficacy was evaluated in 19 patients and judged "good" or better in 13 of them with the efficacy rate or 68.4%. The bacteriological response was evaluated in 10 patients from whom Gram-positive cocci of S. aureus (6 strains), S. pneumoniae (1 strain) and E. faecalis (1 strain) and Gram-negative bacilli of H. influenzae (2 strains) and E. coli (2 strains) were isolated as possible causative organisms. With exception of 1 strain each of S aureus and H influenzae, which were not tested after the treatment with CZOP, all of these strains were found to be eradicated. 3. Adverse drug reactions (ADRs) of signs and symptoms and abnormal alterations of laboratory test values. Safety evaluation was made in 24 patients. ADRs of signs and symptoms were recognized in none of them. As abnormal alterations of laboratory test values, increased eosinophils in 3 patients, elevated GOT in one and elevated GPT in one were recognized. These results indicate that CZOP is a drug useful for treatment of infections in premature and newborn patients.

Bacterial Infections↗
PubMed1997

[Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics].

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.

Adolescent↗