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Biomedical subjects

S Yasuda

Publications and source records attributed to S Yasuda.

At least 127 records · Page 7Linked to original sources
PubMed1999

Dietary docosahexaenoic acid enhances ferric nitrilotriacetate-induced oxidative damage in mice but not when additional alpha-tocopherol is supplemented.

Weaning mice were fed a diet supplemented with beef tallow (BT) or BT plus docosahexaenoic acid (DHA) containing 100 mg alpha-tocopherol/kg (alpha-Toc100) or 500 mg alpha-tocopherol/kg (alpha-Toc500) for 4 wk to modify membrane fatty acid unsaturation, and then were administered ferric nitrilotriacetate (Fe-NTA). The mortality caused by Fe-NTA was higher in the group fed the DHA (alpha-Toc100) diet than in the BT diet groups but the DHA (alpha-Toc500) diet suppressed this increase. Serum and kidney alpha-tocopherol contents were slightly influenced by the dietary fatty acids but not significantly. These results indicate that the increased unsaturation of tissue lipids enhances oxidative damage induced by Fe-NTA in mice fed DHA (alpha-Toc100) but not when additional alpha-tocopherol is supplemented. The apparent discrepancy between the observed enhancement by dietary DHA of oxidative damage and the beneficial effects of dietary DHA on the so-called free radical diseases is discussed in terms of strong bolus oxidative stress and moderate chronic oxidative stress.

Animals↗
PubMed1999

A small breast cancer detected by PET.

A small breast cancer was detected by positron emission tomography (PET) in an asymptomatic individual. Physical examination, mammography and magnetic resonance imaging all failed to identify the tumor. Treatment was partial resection of the breast. Based on the resected specimen, the tumor was 6 mm in diameter. Although previous studies have shown PET to be highly sensitive for the detection of primary breast cancer, detectability of tumors smaller than 1 cm is uncertain. Our case suggests the potential utility of PET for the early detection of primary breast cancer.

Breast Neoplasms↗
PubMed1999

Fluorine-18 fluorodeoxyglucose uptake in the retractile testis.

A 51-year-old man with a palpable mass in his right inguinal region had fluorine-18 fluorodeoxyglucose (F-18 FDG) whole-body positron emission tomography (PET) in our cancer screening program. FDG accumulated in the mass, suggesting a metabolically active lesion that was likely malignant. A pelvic MRI and a urologist's palpation revealed that his inguinal mass was a retractile testis. Because a retractile testis is a benign process with no need for interventional therapy, it would be considered a false-positive finding on the cancer screening program using F-18 FDG PET.

False Positive Reactions↗
PubMed1999

Pronounced differences in the dispositon of clomipramine between Japanese and Swedish patients.

The aim of this study was to compare the disposition of the tricyclic antidepressant clomipramine (C) in Japanese and Swedish patients receiving continuous treatment. Therapeutic drug monitoring data for C and the active metabolite N-desmethylclomipramine (DC) in Japanese patients receiving monotherapy (N = 12) and in those receiving C plus benzodiazepines (BZDs) (N = 96) as well as in Swedes receiving C monotherapy (N = 131) and in those receiving C plus BZDs (N = 43) were used. A population kinetic approach with Bayesian feedback was used to estimate the individual clearance values for C. The relationships between kinetic variables and covariates were evaluated by linear multiple regression. The median (25% and 75% quartiles, respectively) oral clearance of C was 12.7 L/hr (11.6, 30.6) in Japanese patients receiving C monotherapy, 18.1 L/hr (5.6, 31.8) in Japanese patients receiving C plus BZDs, 62.7 L/hr (40.0, 90.6) in Swedish patients receiving C monotherapy, and 56.5 L/hr (34.3, 74.1) in Swedish patients receiving C plus BZDs. When combining all populations in a linear multiple regression, clearance was correlated with ethnic group (p < 0.00001) and age (p < 0.0005), but it was uncorrelated with gender, body weight, and administration of BZDs. The C/DC plasma concentration ratios were 1.08 in Japanese patients receiving C monotherapy, 0.90 in Japanese patients receiving C plus BZDs, 0.51 in Swedish patients receiving C monotherapy, and 0.49 in Swedish patients receiving C plus BZDs. Thus, the lower oral clearance of C in Japanese patients compared with that in Swedish patients is not accounted for by the lower body weight in Japanese patients or by concomitant treatment with BZDs and is therefore likely to be a true ethnic difference. The higher C/DC ratio implicates a more pronounced serotonergic than noradrenergic effect in Japanese patients than in Swedish patients.

Adolescent↗
PubMed1999

Angiotensin II exacerbates lipopolysaccharide-induced contractile depression in rabbit cardiac myocytes.

In sepsis, lipopolysaccharide (LPS) depresses cardiac function by inducing production of nitric oxide (NO) and its second messenger cGMP. LPS also stimulates ANG II production. We hypothesized that ANG II modulates the cardiac response to LPS. Adult rabbit cardiac myocytes incubated with LPS (10 ng/ml) had increased cardiac cGMP after 6 h (but not within 1 h) [527 +/- 43 vs. 316 +/- 27 (SE) fmol/mg protein in controls, n = 16 each group, P < 0.05]. This was associated with depressed cell shortening with no alterations in Ca2+ transients (indo 1 fluorescence), indicating a decreased myofilament responsiveness to Ca2+. ANG II (100 nM) alone had no effect. However, ANG II with LPS produced higher cGMP levels (1,025 +/- 113 fmol/mg protein, n = 16, P < 0.05 vs. LPS alone), more severe contractile depression, impaired Ca2+ handling, and decreased mitochondrial activity (MTS assay). We conclude that ANG II and LPS have synergistic effects on the activation of NO-cGMP pathways to induce dose-dependent impairments in excitation-contraction coupling in cardiac myocytes.

Angiotensin II↗
PubMed1999

Angiotensin-converting enzyme inhibition restores hepatocyte growth factor production in patients with congestive heart failure.

Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectively against endothelial dysfunction. HGF production is downregulated by angiotensin II (Ang II) in vitro. We hypothesized that HGF production is impaired as the result of increased Ang II in patients with congestive heart failure, and that if so, the impaired production should be restored with angiotensin-converting enzyme inhibitors (ACE-I). We studied 16 patients with congestive heart failure caused by previous anterior myocardial infarction in whom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximately 4 weeks after the treatment with ACE-I, blood samples were collected to measure the levels of HGF, Ang II, and brain natriuretic peptide as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was significantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I decreased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response. In conclusion, impaired HGF production was restored after the treatment with ACE-I probably by the mechanism of Ang II suppression. This novel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implication.

Aged↗
PubMed1999

Influence of calcium antagonists on long-term survival of patients treated with coronary angioplasty.

A meta-analysis reported that nifedipine increased mortality dose-dependently in patients with coronary artery disease. However, there have been few studies (specifically in Asians) on the long-term prognosis of patients treated with calcium antagonists after successful coronary angioplasty (PTCA). The subjects consisted of 583 consecutive patients (461 males, aged 59 +/- 10), who underwent successful elective PTCA between 1985 and 1990. First, they were divided into two groups; the calcium antagonist (+) group (n = 560) and the calcium antagonist (-) group (n = 23), and were evaluated in terms of total survival and cardiac events. Second, the calcium antagonist (+) group was further divided into 4 groups according to calcium antagonist type, i.e., short-acting nifedipine group (n = 156), long-acting nifedipine group (n = 203), diltiazem group (n = 184) and the other group (n = 17), and these groups were evaluated in the same way. The primary end-point was set as death from any cause. Secondary end-points were any cardiac events, including non-fatal acute myocardial infarction, coronary artery bypass surgery and repeat PTCA. The mean follow-up period was 4.5 +/- 1.8 years. A multivariate analysis was performed with the Cox proportional-hazard model. The Kaplan-Meier analysis showed that the calcium antagonist (-) group had significantly worse prognoses than the calcium antagonist (+) group (p < 0.05), and that there was no significant difference among the prognoses of the four calcium antagonists groups. The multivariate analysis revealed that the use of a calcium antagonist was one of the independent factors positively contributing to the prognosis. The use of any type of calcium antagonist did not increase mortality in patients who underwent successful elective PTCA, rather, it contributed to a favorable outcome.

Aged↗
PubMed1999

[A case of primary Sjögren's syndrome presenting with aseptic meningoencephalitis associated with sarcoidosis].

A 64-year-old Japanese woman with sarcoidosis and primary Sjögren's syndrome was admitted to our hospital in January 1998 for consciousness loss. Physical examination revealed meningeal signs and hyperreflexia in the lower limbs. Laboratory investigations showed hypergammaglobulinemia and high titers of autoantibodies such as RF, ANA, anti SS-A and SS-B antibody. In addition, she had keratoconjunctivitis, and an apple-tree pattern was observed in sialography, but serum ACE was normal. In the cerebrospinal fluid (CSF), the cell count, total protein, and interleukin 6 (IL-6) were increased, but ACE in CSF was normal. We diagnosed the case as primary Sjögren's syndrome presenting with aseptic meningoencephalitis. After treatment with prednisolone, her manifestations and CSF findings including IL-6 resolved. Therefore, the level of IL-6 in CSF may be an indicator for the activity of primary Sjögren's syndrome associated with central nervous manifestations.

Agammaglobulinemia↗
PubMed1999

Antacids have no influence on the pharmacokinetics of rabeprazole, a new proton pump inhibitor, in healthy volunteers.

AIM: This randomized, open-label, crossover study was conducted to evaluate the effect of a single dose of antacid, aluminum and magnesium hydroxide suspension, on pharmacokinetics of rabeprazole in healthy male volunteers. SUBJECTS AND METHODS: Twelve subjects were randomly divided into 6 groups of 2 subjects each, and received 20 mg of rabeprazole either without antacid, concomitantly with antacid, or one hour after administration of antacid in three experimental arms with washout period of one week. The concentrations of rabeprazole in plasma were determined by high performance liquid chromatography. RESULTS: Rabeprazole was well tolerated at the 20 mg dose level when given with or without antacid. The pharmacokinetic parameters, Cmax, t(max), AUC and t1/2, showed no statistically significant differences when rabeprazole was administered alone, concomitantly with antacid or one hour after antacid administration. CONCLUSION: No influence of single dose of antacid on pharmacokinetics of rabeprazole was observed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

[PET evaluation of glucose metabolism in cancer].

Accelerated glycolysis is one of the biochemical characteristics of cancer cells. Based on this fact, positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has been used in the diagnosis of various cancers. After intravenous injection of FDG and PET scans, most cancers are identified by high FDG accumulation. This metabolic tumor imaging method has been used successfully in the differentiation of benign and malignant tumors, in the diagnosis of metastasis or recurrence, in the detection of primary unknown cancers, and in cancer screening. Because the degree of FDG accumulation reflects tumor glucose consumption, quantification of FDG uptake by PET can be used in predicting biological malignancy and in monitoring treatment in both radiation and chemotherapy. The potential utility of Glut-1 and hexokinase, reported to be responsible for increased glucose metabolism, as biological markers of cancers is yet to be determined.

Cancer Care Facilities↗
PubMed1999

Radiotherapy for large hepatocellular carcinoma combined with transcatheter arterial embolization and percutaneous ethanol injection therapy.

This study was performed to determine the effect of radiotherapy (RT) combined with transcatheter arterial embolization (TAE) and percutaneous ethanol injection (PEI) on large HCC. Between 1988 and 1996, 102 patients with unresectable, biopsy proven HCC underwent uniform pretreatment assessment followed by TAE and PEI. Of the 102 patients, 68 (67%) had more than 2 lesions in the liver, and the largest tumor sizes in each patient ranged from 3 to 8 cm in diameter. Immediately after TAE and PEI, external beam RT (36 to 70 Gy) was administered to the largest tumors only in 44 patients. The cause-specific 5-year survival rate for all patients was 39.9%. The 3-year survival rate of the RT group was better than that of the no RT group (81.1% vs. 54.6%). The cumulative local control rates of the largest treated tumors were 53.2% in the RT group and 32.7% in the no RT, respectively (p=0.006). When the survival rate was compared between patients with and without local control in the RT group, that of patients with local control was significantly better than that with local recurrences (p=0.048). No deaths or major treatment related complications occurred. RT combined with TAE and PEI did not clearly show improvement of the survival, however, it effectively controlled large HCC, and demonstrated minimal toxicity. This treatment may represent therapeutic option for some patients with unresectable large HCC.

Aged↗
PubMed1999

[Anesthetic management of a patient with postthymectomy myasthenia gravis].

A 56-year-old male who had received total thymectomy for treatment of myasthenia gravis was scheduled for sigmoidectomy under general anesthesia. Since his symptoms had become worse after the thymectomy along with increased anti-acetylcholine receptor antibody titer, preoperatively we could not estimate his sensitivity to non-depolarizing muscle relaxants. We initially tried tracheal intubation without using a non-depolarizing muscle relaxant immediately after intravenous injection of propofol 2 mg.kg-1 and fentanyl 4 micrograms.kg-1. Since the intubation was unsuccessful, however, vecuronium 0.01 mg.kg-1 was repeatedly administered until TOF ratio reached 0%. Successful intubation was performed with 3.5 mg of vecuronium. We conclude that the initial trial of tracheal intubation should be performed without a non-depolarizing muscle relaxant in patients with myasthenia gravis whose symptoms have become worse after thymectomy. If first attempt is unsuccessful, the tracheal intubation should be performed with a smaller dose of vecuronium using an electrical nerve stimulator.

Anesthesia, Epidural↗
PubMed1999

[Lidocaine metabolism associated with epidural anesthesia in patients for hepatic surgery].

We measured plasma concentrations of lidocaine and its principal metabolite, monoethylglycinexylidide (MEGX) associated with thoracic epidural anesthesia using continuous infusion of lidocaine in 10 patients for hepatectomy and other 10 patients for elective abdominal surgery as a control. Plasma concentrations of lidocaine and MEGX were analysed by fluorescence polarization immunoassay and high performance liquid chromatography, respectively. Plasma lidocaine concentration increased gradually, and peaked to 5.1 +/- 2.3 micrograms.ml-1 (mean +/- SD) at the end of surgery in the hepatectomy group, but not in the control group. No significant differences were observed in plasma MEGX concentration between these two groups. Our findings suggest that MEGX formation by the hepatic cytochrome P-450 system might be impaired associated with hepatic surgery. Hypoperfusion of the liver induced by surgical manipulation may have contributed to this impaired metabolism.

Aged↗
PubMed1998

Nonpeptide angiotensin II receptor antagonist recognizes inter-species differences in angiotensin AT1 receptors.

Oral administration of the angiotensin AT1 receptor antagonist 3-methyl-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl ]methoxy] pyridine (ME3221) inhibited the pressor response to angiotensin II at doses of 0.3-1.0 mg/kg in rats. A higher dose of ME3221 (3-10 mg/kg) was required to obtain the same inhibitory potency in dogs. The antagonistic potency of ME3221 for angiotensin II-induced contraction in the rabbit aorta (pA2 = 8.82) was about five times higher than that in the canine aorta (pA2 = 8.18). The inhibition constant of ME3221 for displacing [125I]angiotensin II binding to membrane fractions from the rabbit aorta (Ki = 3.84 nM) and rat liver (Ki = 2.55 nM) was significantly lower than that for the canine aorta (Ki = 84.5 nM), canine liver (Ki = 122 nM) and bovine adrenal cortex (Ki = 21.5 nM). In contrast, [Sar1, Ala8]angiotensin II had a similar inhibition constant (Ki = 0.85-4.67 nM) in the species investigated. Treatment with 5 mM dithiothreitol significantly (P < 0.01) reduced the angiotensin II-induced contractile response to 1.2% in the rabbit aorta, but it did not significantly reduce the response in the canine aorta (83.2%). Dithiothreitol reduced [125I]angiotensin II binding to membrane fractions from the rabbit aorta and the rat liver but partially inhibited binding in preparations that had a low affinity for ME3221. These data indicate a species difference in the angiotensin AT1 receptor: the canine and bovine angiotensin AT1 receptor has a relatively low affinity for ME3221 and is slightly resistant to dithiothreitol. The species difference in the angiotensin AT1 receptor reflects the in vivo efficacy of ME3221 in rats and dogs.

Angiotensin Receptor Antagonists↗
PubMed1998

Fas/FasL interaction is not involved in apoptosis of activated CD4+ T cells upon HIV-1 infection in vitro.

In HIV-1-infected individuals, Fas expression and Fas/FasL-mediated apoptosis of mature T cells are known to increase compared with those in normal individuals. To elucidate a relation between acute HIV-1 infection and the regulation of Fas/FasL system upon T-cell activation, resting CD4+ T cells were acutely infected or uninfected with HIV-1 and subsequently activated by phorbol myristate acetate and ionomycin (PMA/IM). Four days after infection, when HIV-1 env gp120 is expressed in more than one half of activated T cells, Fas/FasL expression was analyzed by flow cytometry, and apoptosis-inducing activity of these activated primary CD4+ T cells on Fas+ Jurkat cells was examined. The level of Fas or FasL expression was not altered during acute HIV-1 infection. The enhanced apoptosis-inducing activity upon HIV-1 infection was observed in some individuals, but its activity was not Fas/FasL-mediated. These results indicate that HIV-1 infection is not necessarily associated with either upregulation of Fas/FasL expression or Fas/FasL-mediated apoptosis.

Antibodies, Monoclonal↗
PubMed1998

NMDA receptors in the inferior colliculus are critically involved in audiogenic seizures in the adult rats with neonatal hypothyroidism.

The effects of N-methyl-d-aspartate (NMDA) and non-NMDA receptor antagonists were compared on audiogenic seizures in the rats neonatally exposed to propylthiouracil (PTU). The rats treated with 0.02% PTU through mother's milk during days 0-19 after delivery showed a high incidence of audiogenic seizures consisting of running fit (RF) followed by generalized tonic-clonic seizure (GTCS) after matured. The systemic administration with MK-801, a NMDA receptor antagonist dose-dependently inhibited both RF and GTCS. NBQX (6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione), a non-NMDA receptor antagonist, when systemically administered, failed to block audiogenic seizures. Audiogenic seizures caused a marked induction of c-fos messenger RNA (mRNA) in septal nucleus, bed nucleus of stria terminalis, amygdaloid nuclei, peripeduncular nucleus, and inferior colliculus, which was almost completely blocked by the pretreatment with MK-801. Bilateral microinjection of MK-801 into the inferior colliculus showed a tendency for inhibiting GTCS, but not RF, whereas CPP (3-(R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid), a competitive NMDA receptor antagonist produced a significant inhibition against both RF and GTCS. These NMDA receptor antagonists administered into cisterna ambience, the floor of which is composed of inferior colliculus and neighboring structures, have shown potent blocking effects on both RF and GTCS. The present results suggest that NMDA receptors in the inferior colliculus, presumably in the subnucleus of external cortex may play the critical role in the initiation of audiogenic seizures in PTU-treated rats.

Acoustic Stimulation↗
PubMed1998

Four cases of Warthin's tumor of the parotid gland detected with FDG PET.

In the cancer screening with FDG PET for 1,872 medical health club members, high FDG accumulation in the parotid gland was found in four males (age, 57-70 years). Warthin's tumor was confirmed by surgical pathology. The exact mechanism of high FDG accumulation in Warthin's tumor is not yet known. This tumor may be found incidentally during FDG PET studies. When high FDG accumulation is found in the parotid gland, integrated consideration of the results of the physical examination, medical history and 99mTc-pertechnetate scintigraphy makes it possible to differentiate Warthin's tumor from other lesions.

Adenolymphoma↗