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Biomedical subjects

S Yoshitake

Publications and source records attributed to S Yoshitake.

At least 19 recordsLinked to original sources

Activation of 5-HT(1A) autoreceptors enhances the inhibitory effect of galanin on hippocampal 5-HT release in vivo.

The microdialysis technique was used to examine interactions between 5-HT(1A) and galanin receptors in the dorsal raphe nucleus (DRN), by measuring the extracellular levels of 5-HT in the ventral hippocampus of awake rats. The rats were pretreated with the 5-HT(1A) receptor agonist (R,S)-8-OH-DPAT (0.3 mg/kg, s.c.) or saline. 8-OH-DPAT caused a time-dependent reduction of basal 5-HT levels down to 43-48% at 40 min while at 140 min, the hippocampal 5-HT had returned to control values. At that time point, the rats received a second injection of 8-OH-DPAT or galanin (0.15, 0.5 and 1.5 nmol/0.5 microl) infused into the lateral ventricle. The second injection of 8-OH-DPAT caused a significantly smaller reduction of hippocampal 5-HT levels. In contrast, galanin at all three doses in the 8-OH-DPAT-pretreated groups, was significantly more potent in reducing 5-HT levels (maximal reduction to 74%, 52% and 49%, respectively) than it was in saline-pretreated rats (maximal reduction to 96%, 85% and 69%, respectively). The inhibitory effect of galanin (1.5 nmol) on extracellular 5-HT levels in the rat hippocampus was significantly attenuated by co-administration of the 5-HT(1A) receptor antagonists WAY-100635 (0.3 and 0.6 mg/kg s.c.) and, to a lesser extent, with pindolol (20 mg/kg s.c.). These data provide direct in vivo evidence of agonistic 5-HT(1A)-galanin receptor interaction at the presynaptic level. Furthermore, the findings indicate that a down-regulation of the somato-dendritic 5-HT(1A) autoreceptors, following their stimulation with 8-OH-DPAT and possibly also indirectly with 5-HT reuptake inhibitors, may be compensated by a subsequent 'sensitization' of the inhibitory galanin receptors in the DRN. Thus, the enhanced galanin receptor-mediated inhibition of 5-HT neurotransmission may contribute to the pathophysiology of depression or to the reduced and delayed efficacy of antidepressant therapies.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Analgesic effects of flecainide on postherpetic neuralgia.

Sodium channel blockers have been reported to be effective in relieving neuropathic pain. However, although intravenous lidocaine has proved to be effective, in some patients oral mexiletine fails to produce adequate pain relief. In this study, we investigated the analgesic effect of flecainide, a long-lasting antitachyarrhythmic drug, on postherpetic neuralgia. Twenty patients with postherpetic neuralgia received an intravenous infusion of flecainide and 15 (75%) of those who achieved pain relief subsequently received oral flecainide. The patients were assessed using a 100 mm visual analog scale 1 month after treatment. Significant improvement compared with the pretreatment reading was found. This study suggests that the action of flecainide in blocking the sodium channel is potent and long-lasting and that, like the intravenous formulation, the oral formulation has a stable analgesic effect on postherpetic neuralgia.

Aged↗

Transient EDTA-dependent pseudothrombocytopenia in a patient with sepsis.

Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is the phenomenon of a spurious low platelet count due to antiplatelet antibodies that cause platelet clumping in blood anticoagulated with EDTA. We describe a case of EDTA-PTCP that appeared transiently with the development of sepsis. A 50-year-old man underwent Bentall's aortic root replacement for acute aortic dissection with aortic insufficiency. Postoperatively the patient suffered paralytic ileus followed by methicillin-resistant Staphylococcus aureus enteritis and septicemia with endotoxemia. EDTA-PTCP appeared with the development of sepsis, and disappeared with its resolution. To avoid incorrect diagnoses and inappropriate treatment, EDTA-PTCP should always be considered as a possible cause of reported low platelet counts, even in patients with sepsis.

Aortic Dissection↗

Unwashed shed blood infusion causes deterioration in right ventricular function after coronary artery surgery.

We investigated right ventricular function after infusion of unwashed shed blood collected from mediastinal and chest tube drainage. Changes in thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and prostacyclin respectively, were also investigated. The amount of infused shed blood was 484 +/- 76 ml (mean +/- SD). Right ventricular ejection fraction decreased rapidly after the infusion and did not return to its original level until 120 minutes later (P < 0.05). Mean pulmonary artery pressure rose after infusion of the shed blood (P < 0.05). The TXB2 level in the unwashed shed blood was about 20,000 times higher than the preoperative plasma level. The plasma TXB2 level at 30 minutes after the infusion was significantly elevated (P < 0.05), and at 120 minutes it had returned to the original level. Unwashed shed blood may contain vasoactive substances that induce the release of TXA2 and increase right ventricular afterload.

6-Ketoprostaglandin F1 alpha↗

[Hemodynamic effects of propofol as an anesthesia induction agent in hyperthyroidism patients on chronic beta-blocker].

This study was designed to investigate the effect of propofol on the heart rate and blood pressure in the patients on chronic beta-blocker. Seventy two hyperthyroidism patients scheduled for subtotal thyroidectomy were enrolled. Thirty six patients who were on chronic beta-blocker received either propofol (group beta-P) or thiamylal (group beta-T) as an anesthesia induction agent. In control groups, patients who were not on beta-blocker also received either propofol (group C-P) or thiamylal (group C-T). Anesthesia was maintained with nitrous oxide in oxygen and sevoflurane. Heart rate and systolic blood pressures were monitored and recorded before and during anesthesia. Heart rate decreased significantly in group beta-P compared to three other groups through this study. Significant decreases in systolic blood pressure were observed in the groups beta-P and beta-T compared to group C-P. These results suggest that careful attention should be paid to the patients on chronic beta-blocker when propofol was selected as an anesthesia induction agent.

Adrenergic beta-Antagonists↗

[Effect of olprinone hydrochloride on cerebral blood flow in patients after cardiac surgery].

This study was designed to investigate the effect of olprinone hydrochloride on cerebral blood flow in ten patients after cardiac surgery by transcranial Doppler sonography (TCD). We assessed cerebral blood flow in the middle cerebral artery by transtemporal approach and in the carotid siphon by transorbital approach. We measured the mean blood flow velocity in the left middle cerebral artery (Vmca) and the left carotid siphon (Vlca) and calculated the pulsatility index in the left middle cerebral artery (PImca) and the left carotid siphon (PIlca) using 2 MHz transcranial Doppler ultrasound system (DWL Multidop-P). After baseline measurement, the olprinone hydrochloride loading dosage was increased from 0.15 to 0.3 microgram.kg-1.min-1 every 60 minutes. The mean blood flow velocity was measured at each point. Vmca and Vlca significantly increased, and PImca and PIlca significantly decreased at the infusion rate of 0.3 microgram.kg-1.min-1. There were significant linear correlations between CI and Vmca, CI and Vlca, SVRI and Vmca, as well as SVRI and Vlca. Dose-response relationships were observed in CI, SVRI, Vmca, and Vlca. In conclusion, we demonstrated that olprinone hydrochloride led to an increase of cerebral blood flow in the patients after cardiac surgery.

Aged↗

HLA class II alleles in Japanese patients with inflammatory bowel disease.

The association of various HLA class II loci with Crohn's disease (CD) and ulcerative colitis (UC) has yet to be fully elucidated. To determine whether there is an association of HLA class II genes (DR, DQ and DP alleles) with inflammatory bowel disease (IBD), HLA class II genes for polymorphisms were analyzed at the DNA level in 111 patients with CD, 81 with UC and 525 healthy controls by the polymerase chain reaction-sequence specific oligonucleotide probe method. Allele and haplotype frequencies were compared between these populations. Results were as follows: 1) the presence of DQB1*0402 (RR=3.90, Pc=0.0001) was positively associated with CD; 2) the presence of DRB1*1502 (RR=4.51, P<1X10(-8)), DRB5*0102 (RR=4.70, Pc<1x10(-8)), DQA1*0103 (RR=3.72, Pc=1x10(-5)), DQB1*06011 (RR=3.78, PC=1x10(-5)), DPA1*0201 (RR=3.23, Pc=0.0001) and DPB1*0901 (RR=4.83, PC<1x10(8)) was positively associated and that of DRB4*0101 (RR=0.20, Pc<1X10(-8)) and DQA1*0302 (RR=0.34, Pc=0.001) negatively associated with UC; 3) haplotype analysis showed a positive association between the presence of DRB1*0410-DQA1*0302-DQB1*0402 and DRB1*0802-DQA1*0401-DQB1*0402 with CD, and a negative association between the presence of DRB1*1502-DQA1*0103-DQB1*06011 and CD, there was no association of DRB1*08032-DQA1*0103-DQB1*06011 with CD; and 4) in UC, a positive association with the presence of DRB1*1502-DQA1*0103-DQB1*06011 was found, but DRB1*08032-DQA1*0103-DQB1*06011 was not associated with it. In conclusion, in CD in the Japanese population, HLA-linked disease susceptibility alleles appear to be DQB1*0402 and DRB1*1502, a disease resistance allele. In UC, DRB1*1502 appears to be a disease susceptibility allele.

Adolescent↗

Contribution of major histocompatibility complex genes to susceptibility and resistance in Helicobacter pylori related diseases.

BACKGROUND/AIM: Although there have been numerous reports concerning the virulence factors of isolates for investigating the pathogenesis of Helicobacter pylori infection, few studies have been carried out regarding the association of HLA class II genes of the host with H. pylori related diseases. Two published studies have only analysed the HLA DQ locus alone. The aim of this study was thus to determine the association of HLA class II genes (DR, DQ and DP) with H. pylori related diseases using the DNA typing method. METHODS: Fifty-eight patients with H. pylori positive gastric ulcers, 44 patients with H. pylori positive duodenal ulcers, 45 patients with H. pylori positive gastritis and 34 healthy subjects without H. pylori infection were typed for HLA class II genes by means of DNA typing with the polymerase chain reaction-sequence specific oligonucleotide probes method. RESULTS: A negative association with DRB1*1501, DQA1*01021 and DQB1*0602 alleles was noted in all three of the patient groups studied. Compared with the healthy controls, a positive association with DPA1*0201 (P= 0.032) and DPB1*0901 (P=0.005) in gastric ulcers, a positive association with DRB1*0405 (P=0.022) and DQB1*0401 (P=0.044) in duodenal ulcers, and a positive association with DPB1*0901 (P=0.016) in gastritis were observed. A haplotype analysis showed that the association of alleles with H. pylori related disease was with the haplotype rather than with either of the alleles individually. After correction for multiple comparisons, all the significant associations obtained between H. pylori related diseases and HLA class II genes disappeared. CONCLUSIONS: The interplay between host immunogenetic factors, bacterial virulence factors and environmental conditions may thus play a more important role in the outcome of H. pylori infection than immunogenetic factors alone.

Adult↗

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↗

Importance of left anterior descending coronary artery curvature in determining cross-sectional plaque distribution assessed by intravascular ultrasound.

We assessed the relation between the circumferential distribution of coronary atherosclerotic plaques and the structure of the epicardial coronary arteries in patients with coronary artery disease using intravascular ultrasound in vivo. Coronary atherosclerosis preferentially formed at the inner arc of the curved coronary vessels, and greater vessel curvatures were associated with greater distributions of atherosclerotic lesions along the inner coronary artery wall.

Adult↗

Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation without causing inhibition of platelet aggregation or altering hemostatic parameters after angioplasty in rat.

An antibody was raised in rabbits against SFFLRNPSEDTFEQF peptide, which is an NH2-terminal peptide of the thrombin-cleaved rat thrombin receptor. In vitro, the antibody inhibited rat smooth muscle cell proliferation but had no effect on rat platelet aggregation or clotting time. These data indicate that the antibody is a specific blocker of the thrombin receptor-signaling pathway in rat smooth muscle cells but does not work as a blocker in rat platelets, suggesting the existence of a second thrombin receptor in the platelets. Using an in vivo balloon catheter-induced injury model in rats, we examined the effect of the anti-rat thrombin receptor IgG on intimal smooth muscle cell accumulation 2 weeks after angioplasty. Analysis of the ratio of intimal to medial cross-sectional areas showed that injection of immune IgG resulted in 43.7% and 53.1% reduction (P<0.01) of neointimal smooth muscle cell accumulation compared with saline and nonimmune IgG treatment, respectively. Moreover, the injection of immune IgG caused a significant decrease of thrombin receptor mRNA expression and also 40.5% and 43.0% decreases (P<0.01) of the proliferating cell nuclear antigen (PCNA) index in the intima compared with the PCNA index after saline and nonimmune IgG treatment, respectively. The suppression of the PCNA index was also observed in the immune IgG-treated group at an early stage after angioplasty. These results suggest that thrombin receptor activation is involved in the proliferation and accumulation of neointimal smooth muscle cells induced by balloon injury.

Angioplasty↗

Analysis of human T-cell antigen receptor variable beta gene usage following vaccination with recombinant HBsAg.

We analyzed the TcR Vbeta gene usage before and after vaccination with the hepatitis B vaccine since changes in the TcR Vbeta gene families would be considered to provide preliminary evidence of a mechanism to prevent HBV infection. Six healthy adult volunteers received immunizations. TcR Vbeta usage, T-cell proliferation, and HLA class II alleles were examined in peripheral blood mononuclear cells (PBMC) both before and after vaccination. Furthermore, TcR Vbeta usage in postimmunization PBMC was also compared with PBMC cultured with recombinant HBsAg (rHBsAg). The level of in vitro T-cell proliferation in the presence of rHBsAg increased significantly (P < 0.01) in PBMC isolated after vaccinations. Increases in the different TcR Vbeta genes were also observed in each individual following vaccinations, regardless of the similarity in their HLA alleles. Specific HBV-related antigen-responsive T cells were induced after HB vaccination, without any common restriction for the TcR Vbeta gene families. The mechanism that helps prevent HBV infection was thus found to involve multiclonal alterations in the TcR Vbeta repertoire.

Adult↗

Effect of additional general anesthesia with propofol, midazolam or sevoflurane on stress hormone levels in hysterectomy patients, receiving epidural anesthesia.

Hormonal responses after surgery are characterized by increased pituitary-adrenal axis hormones. We undertook this study to determine whether the choice of anesthesia influences stress hormone levels. Twenty-three adult females scheduled for hysterectomy for benign disease under general anesthesia were randomly assigned to one of three groups: epidural/propofol anesthesia (Group P), epidural/midazolam anesthesia (Group M), and epidural/sevoflurane anesthesia (Group S). The concentrations of ACTH and cortisol in group P and group M were significantly less than that of group S at 60 min after the incision. The concentrations of beta-endorphin and aldosterone in group P and group M were significantly less than that of group S at 60 min after the incision and after extubation. We conclude that combined epidural and general anesthesia with propofol or midazolam has a greater suppressive effect than sevoflurane on the stress response of the pituitary-adrenal axis during hysterectomy.

Adrenal Cortex Hormones↗

Megakaryocytopoietic activity of a truncated variant of mouse thrombopoietin.

Thrombopoietin (TPO) is a hemopoietic cytokine that specifically stimulates the growth and development of megakaryocytes. In addition to full-length TPO (corresponding to TPO-1), cDNAs of three truncated variants (TPO-2 to 4) have been isolated. However, whether or not these variants have biological activities has not been clarified presumably because of poor secretion into extracellular milieu. To examine the biological significance of the shortest variants, TPO-4, we prepared two fusion cDNAs of TPO-1 and TPO-4, each of which was combined with the finger-growth factor-kringle 1 (FGK1) domains of tissue plasminogen activator (tPA) as a tag and transfected them into baby hamster kidney (BHK) cells. An immunodetection assay for FGK1 antigen revealed that the amount of secreted TPO-4-FGK1 fusion protein was about 2% of that of TPO-1-FGK1. These fusion proteins after affinity purification had comparable activities on a molar basis in both megakaryocyte colony stimulating activity towards mouse bone marrow cells and growth promotion activity towards the TPO-responsive cell line UT-7/GM. These results indicate that the TPO-4 is biologically active in vitro, although its primary structure of the C-terminal half after the 111th amino acid residues is completely different from authentic TPO-1 due to frame shift.

Animals↗

[Anesthetic management for a patient with pure autonomic failure].

Pure autonomic failure is characterized by orthostatic hypotension, sweating disorder, urinary incontinence, and syncope. A 64 year-old man with pure autonomia failure was scheduled for suprapubic prostatectomy. We monitoring direct arterial pressure and inserted pulmonary artery catheter prior to the induction of anesthesia. General anesthesia was induced with diazepam 10 mg, fentanyl 0.3 mg, and vecuronium 8 mg for tracheal intubation. Anesthesia was maintained with sevoflurane (0.2-1.5%), 60% nitrous oxide in oxygen supplemented with intermittent epidural anesthesia. During anesthesia, blood loss was immediately replaced with banked blood because autonomic failure could not compensate hypovolemia well. Epidural anesthesia in this patient was considered to cause less hypotension than in patients with normal autonomic function. Therefore, we think epidural anesthesia is a useful anesthesia method for patients with pure autonomic failure. The emergence from anesthesia was smooth and no complications were seen during the perioperative period.

Anesthesia, Epidural↗

[Anesthesia management for a patient with pulmonary eosinophilic granuloma associated with bilateral pneumothorax--general anesthesia with positive pressure ventilation].

Pulmonary eosinophilic granuloma (PEG) is a rare fibroinflammatory disorder and is characterized by a mixed interstitial infiltrate of eosinophils, lymphocytes and Langerhans cells. We experienced anesthetic management for a patient with PEG associated with bilateral pneumothorax. Anesthesia was maintained with epidural anesthesia and general anesthesia using positive pressure ventilation. At first we ventilated with a low airway pressure, but recognized an increase in endtidal CO2. Then we switched to a high airway pressure (= 22 cmH2O) and decreased the concentration of carbon dioxide. No new air leaks were observed by ventilating with the high airway pressure. It was concluded that in anesthetic management for PEG we must be careful about the airway pressure during operation.

Adult↗

Anti-atherosclerotic effect of E5324, an inhibitor of acyl-CoA:cholesterol acyltransferase, in Watanabe heritable hyperlipidemic rabbits.

E5324, n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy]-6- methylphenyl]urea, a novel and potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), was evaluated for its anti-atherosclerotic and lipid-lowering effects in Watanabe heritable hyperlipidemic (WHHL) rabbits. At 3 months of age, 40 male WHHL rabbits were divided into 4 groups. The rabbits were fed a standard rabbit chow (control group), or standard rabbit chow containing E5324 (0.1% or 0.02%) or 1% probucol for 16 weeks. Even the high dose of E5324 did not lower the plasma total cholesterol levels throughout the experiment. Probucol slightly reduced the plasma cholesterol levels, and showed anti-atherosclerotic activity, i.e., reductions of atherosclerotic plaque formation and cholesterol content in the aorta. Although E5324 did not lower plasma cholesterol, atherosclerotic plaque formation in the aortic arch and thoracic aorta was reduced (by about 34% and 41%, respectively, at the high dose; P < 0.05). Cholesterol content in the aortic arch and thoracic aorta was also reduced (by about 59% and 62% at the high dose, respectively) compared with the control. These results suggest that E5324 acts directly on the arterial wall through ACAT inhibition, and prevents the progression of atherosclerosis in WHHL rabbits.

Analysis of Variance↗