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Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 181 records · Page 10Linked to original sources

Induction of rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) following phosphorylation by the nonreceptor tyrosine kinase Src.

Ras-GRF1/CDC25(Mm) has been implicated as a Ras-guanine nucleotide exchange factor (GEF) expressed in brain. Ras-GEF activity of Ras-GRF1 is augmented in response to Ca(2+) influx and G protein betagamma subunit (Gbetagamma) stimulation. Ras-GRF1 also acts as a GEF toward Rac, but not Rho and Cdc42, when activated by Gbetagamma-mediated signals. Tyrosine phosphorylation of Ras-GRF1 is critical for the induction of Rac-GEF activity as evidenced by inhibition by tyrosine kinase inhibitors. Herein, we show that the nonreceptor tyrosine kinase Src phosphorylates Ras-GRF1, thereby inducing Rac-GEF activity. Ras-GRF1 transiently expressed with v-Src was tyrosine-phosphorylated and showed significant GEF activity toward Rac, but not Rho and Cdc42, which was comparable with that induced by Gbetagamma. In contrast, Ras-GEF activity remained unchanged. The recombinant c-Src protein phosphorylated affinity-purified glutathione S-transferase-tagged Ras-GRF1 in vitro and thereby elicited Rac-GEF activity. Taken together, tyrosine phosphorylation by Src is sufficient for the induction of Rac-GEF activity of Ras-GRF1, which may imply the involvement of Src downstream of Gbetagamma to regulate Ras-GRF1.

Cell Line↗

Expression of thyrotropin-releasing hormone (TRH) receptor subtype 1 in mouse pancreatic islets and HIT-T15, an insulin-secreting clonal beta cell line.

Thyrotropin-releasing hormone (TRH), originally isolated as a hypothalamic hormone, has been reported to be present and released from the pancreatic beta cells, affecting pancreatic functions. However, it still remains unclear whether TRH receptor is expressed in the pancreas. In the present study, we characterized TRH receptors (TRHR) in mouse pancreatic islets and HIT-T15 cells, a hamster clonal beta cell line. RT-PCR study showed significant expression of TRHR subtype 1 (TRHR1) mRNA in both mouse pancreatic islets and HIT-T15 (HIT) cells. In contrast, there was no expression of TRHR2 mRNA, a novel subtype of TRHR which is expressed predominantly in the central nervous system. Sequencing analysis demonstrated that TRHR1 of the islets was identical to that in the pituitary, and cloned hamster TRHR1 shared 93.3 % homology with that of the mouse at the nucleic acid level. Northern blot analysis of TRHR 1 mRNA in HIT-T15 cells showed a single strong hybridization signal approximately 3.7 kb in length. Furthermore, Scatchard plot analysis in HIT-T15 cells revealed that the Kd value for MeTRH was 0.63 nM. Significant elevation of intracellular calcium concentration was observed in response to as little as 10 nM TRH , and this was not affected by removal of extracellular calcium. This is the first description indicating the presence of functional TRH receptor subtype 1 in the pancreatic beta cells, and our observations suggested the regulation of pancreatic function by TRH through autocrine or paracrine mechanisms.

Amino Acid Sequence↗

Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure.

BACKGROUND: Experimental studies have shown that adrenomedullin (AM) causes vasodilatation, diuresis, and a positive inotropic effect. In humans, however, whether infusion of AM has beneficial effects in congestive heart failure (CHF) remains unknown. METHODS AND RESULTS: Hemodynamic, renal, and hormonal responses to intravenous infusion of human AM (0.05 microg. kg(-1). min(-1)) were examined in 7 patients with CHF and 7 normal healthy subjects (NL). In NL group, AM significantly decreased mean arterial pressure (-16 mm Hg, P<0. 05) and increased heart rate (+12 bpm, P<0.05). In CHF group, AM also decreased mean arterial pressure (-8 mm Hg, P<0.05) and increased heart rate (+5 bpm, P<0.05), but to a much lesser degree (P<0.05 versus NL). AM markedly increased cardiac index (CHF, +49%; NL, +39%, P<0.05) while decreasing pulmonary capillary wedge pressure (CHF, -4 mm Hg; NL, -2 mm Hg, P<0.05). AM significantly decreased mean pulmonary arterial pressure only in CHF (-4 mm Hg, P<0.05). AM increased urine volume (CHF, +48%; NL, +62%, P<0.05) and urinary sodium excretion (CHF, +42%; NL, +75%, P<0.05). Only in CHF, plasma aldosterone significantly decreased during (-28%, P<0.05) and after (-36%, P<0.05) AM infusion. These parameters remained unchanged in 7 patients with CHF and 6 healthy subjects who received placebo. CONCLUSIONS: Intravenous infusion of AM has beneficial hemodynamic and renal effects in patients with CHF.

Adrenomedullin↗

Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation.

Signals triggered by diverse receptors modulate the activity of Rho family proteins, although the regulatory mechanism remains largely unknown. On the basis of their biochemical activity as guanine nucleotide exchange factors (GEFs), Dbl family proteins are believed to be implicated in the regulation of Rho family GTP-binding proteins in response to a variety of extracellular stimuli. Here we show that GEF activity of full-length proto-Dbl is enhanced upon tyrosine phosphorylation. When transiently coexpressed with the activated form of the non-receptor tyrosine kinase ACK1, a downstream target of Cdc42, Dbl became tyrosine-phosphorylated. In vitro GEF activity of Dbl toward Rho and Cdc42 was augmented following tyrosine phosphorylation. Moreover, accumulation of the GTP-bound form of Rho and Rac within the cell paralleled ACK-1-dependent tyrosine phosphorylation of Dbl. Consistently, activation of c-Jun N-terminal kinase downstream of Rho family GTP-binding proteins was also enhanced when Dbl was tyrosine-phosphorylated. Collectively, these findings suggest that the tyrosine kinase ACK1 may act as a regulator of Dbl, which in turn activates Rho family proteins.

Animals↗

A Model for Simultaneous Homogeneous and Heterogeneous Nucleation in the Case of Slow Reaction Rate.

Our previous model for simultaneous homogeneous and heterogeneous nucleation, which was successfully tested for silver particle generation by a chemical reduction method, is extended to the case of slow reaction rate. Nucleation in a system containing seed particles in the case where the reaction rate is slow occurs according to the following rule: homogeneous nucleation is predominant when n(p)/n(0)(*),>1 (n(p) is the seed number concentration, and n(0)(*) the number concentration of homogeneously nucleated particles without seed particles), and heterogeneous nucleation is predominant when n(p)/n(0)(*)<1. This theoretical prediction is in good agreement with the experimental results obtained for zinc sulfide particles generated by homogeneous precipitation. Copyright 2000 Academic Press.

Journal Article↗

Analysis of Ras-dependent signals that prevent caspase-3 activation and apoptosis induced by cytokine deprivation in hematopoietic cells.

In hematopoietic cells, Ras has been implicated in signaling pathways that prevent apoptosis triggered by deprivation of cytokines, such as interleukin-3 (IL-3). However, the mechanism whereby Ras suppresses cell death remains incompletely understood. We have investigated the role of Ras in IL-3 signal transduction by using the cytokine-dependent BaF3 cell line. Herein, we show that the activation of the pro-apoptotic protease caspase-3 upon IL-3 removal is suppressed by expression of activated Ras, which eventually prevents cell death. For caspase-3 suppression, the Raf/extracellular signal-regulated kinase (ERK)- or phosphatidylinositol 3-kinase (PI3-K)/Akt-mediated signaling pathway downstream of Ras was required. However, inhibition of both pathways did not block activated Ras-dependent suppression of cell death-associated phenotypes, such as nuclear DNA fragmentation. Thus, a pathway that is independent of both Raf/ERK and PI3-K/Akt pathways may function downstream of Ras, preventing activated caspase-3-initiated apoptotic processes. Conditional activation of c-Raf-1 also suppressed caspase-3 activation and subsequent cell death without affecting Akt activity, providing further evidence for a PI3-K/Akt-independent mechanism.

Animals↗

Bladder-pumping therapy for the treatment of low-capacity or low-compliance bladders.

The walls of low-capacity or low-compliance bladders are thought to be less elastic than normal. Pumping of the bladder was found to disrupt collagen-fiber bundles in the rat bladder wall, offering the promise of potential clinical application. This result prompted us to use bladder-pumping therapy to soften the bladder wall in patients with low-capacity or low-compliance bladders to restore bladder elasticity. CO(2) gas or air, at a volume below the maximum bladder capacity (</=200 mL), was repeatedly pumped in and out of the bladder through a catheter under caudal anesthesia in 26 patients with low-capacity or low-compliance bladders and without uninhibited bladder contractions, who presented with urinary frequency or incontinence. A respirator was used to control the pumping at 0.5 cycles/s for a duration of 15 minutes. No serious adverse effects were encountered during or after the procedure. Overall subjective improvement was noted 4 weeks after the procedure in 11 of 18 patients with a low capacity bladder (<300 mL) and in five of eight patients with a low-compliance bladder (<20 mL/cm H(2)O). The procedure significantly increased the maximum bladder capacity, single voided volume, and average urinary flow rate after 4 weeks. In the responding patients, subjective improvement lasted from 3 months to over 6 years. Bladder-pumping therapy is an easy and safe procedure and exerts a beneficial effect for a long period, in patients with low-capacity or low-compliance bladders and without uninhibited bladder contractions. Neurourol. Urodynam. 19:19-28, 2000.

Adolescent↗

Peroxide reductase activity of NADH dehydrogenase in the presence of an endogenous 20-kDa component of an alkaliphilic Bacillus.

The membrane-bound NADH dehydrogenase of an alkaliphilic Bacillus YN-1 involved in the respiratory chain exhibits reductase activity for hydrogen peroxide and cumene hydroperoxide in the presence of the 22-kDa component (AhpC) from Amphibacillus xylanus (Koyama et al. Biochem. Biophys. Res. Commun. 247, 659-662). In this study, AhpC-like polypeptide with an apparent molecular mass of 20 kDa was isolated from the cell-free extract of YN-1. The NADH dehydrogenase exhibited reductase activity for cumene hydroperoxide in the presence of the purified AhpC-like component from YN-1. It is likely that the NADH dehydrogenase is not only involved in the respiratory chain, but also functions for scavenging peroxide in the presence of its own endogenous AhpC component. The enzyme expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST) showed the NADH dehydrogenase activity as high as the native enzyme from YN-1. While the fusion protein was unable to reduce cumene hydroperoxide in the presence of AhpC-like protein from YN-1, the protein obtained by the cleavage treatment of the fusion protein to release GST exhibited the reductase activity as much as the native enzyme.

Bacillus↗

Primary intestinal T-cell lymphoma resembling lymphomatous polyposis: report of a case.

We report an interesting case of primary intestinal T-cell lymphoma (ITL) resembling lymphomatous polyposis (LP) in a 24-year-old man. The neoplasm macroscopically showed numerous small polyps throughout the colon and microscopically showed diffuse proliferation of small-sized tumor cells with occasionally cleaved or irregularly shaped nuclei. The tumor cells were immunohistochemically positive for CD3, CD8, TIA-1, and CD56, and a polymerase chain reaction study showed a single band, indicating monoclonal rearrangement of the T-cell receptor beta gene. The phenotypic features in the current case are consistent with those of ITL derived from cytotoxic CD56+ CD8+ intraepithelial lymphocytes. This is the second documented case of primary ITL with a morphologic pattern of LP.

Adult↗

Phlegmonous colitis: a specific and severe complication of chronic hepatic disease.

Phlegmonous colitis (PC) is an acute infectious entity caused by bacteria. In this study, we reviewed 8,822 autopsy cases and found 13 cases of PC (0.15%). PC affected 2.43% of patients with hepatic cirrhosis or subacute liver atrophy, both of which were considered to be due to hepatitis viral infection. Before autopsy, none of the cases studied was suspected to involve PC, irrespective of the immediate cause of patient death. Thirteen autopsy cases showed some or all of the following pathohistologic characteristics: (1) involvement of the cecum (9 cases, 76.9%), (2) phlegmonous inflammatory changes and edema in the submucosa (100%), (3) bacterial infection (100%), (4) no microscopically detectable mucosal injuries (12 cases, 92.3%), and (5) acute serositis (peritonitis) (2 cases, 15.4%). These results suggest that PC is an unrecognized, but fatal complication of patients with some hepatic diseases and that PC has pathohistologic characteristics in common with previously reported spontaneous bacterial peritonitis in animal models. PC probably arises due to spontaneous infection in patients with hepatic cirrhosis.

Adult↗

Propofol injection pain is not alleviated by pretreatment with flurbiprofen axetil, a prodrug of a nonsteroidal antiinflammatory drug.

PURPOSE: The effects of nonsteroidal antiinflammatory drugs (NSAIDs) on pain from propofol injection are controversial, partially because NSAIDs themselves cause injection pain. We evaluated the effects of flurbiprofen axetil (LFP), a prodrug of an NSAID, on pain induced by intravenous propofol injection, because LFP produces little pain on injection. METHODS: A randomized, double-blind, controlled trial was undertaken in patients who were assigned to one of three groups ( n = 50 in each). Patients received either 5 ml of saline followed approximately 10 min later by propofol mixed with 0.4 ml of saline, LFP (50 mg, 5 ml) i.v. followed by propofol mixed with 0.4 ml of saline, or 5 ml of saline followed by propofol mixed with lidocaine (40 mg, 0.4 ml). Verbal rating scores for injection pain were assessed every 10 s during propofol administration at a rate of 0.05 mg.kg(-1).s(-1). RESULTS: None of the patients complained of pain during injection of LFP or saline. Admixture of lidocaine, but not of LFP, significantly reduced the incidence of pain and the severity of pain scores during propofol injection ( P = 0.0017 and P < 0.001, respectively). CONCLUSION: Lidocaine, but not LFP, is effective for controlling pain induced by propofol injection. This result suggests that NSAIDs have little effect on pain from propofol injection.

Clinical Trial↗

Enhanced secretion of cardiac hepatocyte growth factor from an infarct region is associated with less severe ventricular enlargement and improved cardiac function.

OBJECTIVES: We hypothesized that the hepatocyte growth factor (HGF) may play a cardioprotective role in human myocardial infarction (MI). BACKGROUND: The HGF is a novel, multifunctional growth factor implicated in wound healing, angiogenesis and promotion of cell survival. Recent animal studies have demonstrated the existence of an HGF system in the heart, where it is activated in response to myocardial ischemia and reperfusion. METHODS: We studied 40 patients with acute myocardial infarction (AMI), who underwent coronary reperfusion therapy upon admission. Approximately four weeks later, left ventricular (LV) catheterization was repeated to determine the LV ejection fraction (EF), end-diastolic volume index (EDVI) and pressure (EDP). The levels of HGF and brain natriuretic peptide (BNP) were measured by collecting blood samples from cardiac veins draining the infarcted region (MI region) and those draining the noninfarcted region (non-MI region). The ratio of the HGF level in the MI region to that in the non-MI region (= MI/non-MI ratio) was calculated in each patient as an index of the MI-related HGF secretion. The MI/non-MI ratio for BNP was also calculated. RESULTS: The MI/non-MI ratio for HGF correlated inversely with LVEDP (r = -0.644, p < 0.0001) and LVEDVI (r = -0.843, p < 0.0001) and positively with LVEF (r = 0.763, p < 0.0001). These correlations were completely opposite in direction from those for BNP and LVEDP (r = 0.678, p < 0.0001), LVEDVI (r = 0.783, p < 0.0001) and LVEF (r = -0.805, p < 0.0001). These findings indicate that cardiac HGF acts in contrast to BNP, a biochemical marker for the development of LV remodeling. CONCLUSIONS: Enhanced secretion of cardiac HGF from the MI region is associated with an attenuation of ventricular enlargement and an improvement in cardiac function. The HGF system may modulate the process of ventricular remodeling and thus have important clinical implications.

Biomarkers↗

Evaluation of the cardiovascular responses to fiberoptic orotracheal intubation with television monitoring: comparison with conventional direct laryngoscopy.

STUDY OBJECTIVE: To evaluate and compare cardiovascular responses to a new method of orotracheal intubation incorporating TV monitoring, with conventional orotracheal intubation via rigid blade laryngoscopy. DESIGN: Prospective single-blind study. SETTING: Operating room of a medical college hospital. PATIENTS: 90 ASA physical status I and II surgical patients requiring general anesthesia and orotracheal intubation. INTERVENTIONS: Patients were randomly allocated to two groups, one for the new intubation method and the other for conventional intubation using a rigid laryngoscope. In the new method, an anesthesiologist inserted an endotracheal tube alone into the trachea via TV monitoring through the bronchoscope, which was inserted by an assistant through the mouth to the middle larynx. The patient's trachea was intubated without extreme stretching of laryngeal tissues or deep insertion of the tip of the bronchoscope. In the conventional method, orotracheal intubation was performed with rigid direct laryngoscopy. MEASUREMENTS: Noninvasive blood pressure (BP) and heart rate (HR) were measured before arrival at the operating room, and before and after orotracheal intubation. MAIN RESULTS: Although this method was expected to be a minimally invasive fiberoptic intubation technique, the patients showed significant increases in BP and HR. No significant differences between the two groups were observed in cardiovascular responses immediately after intubation: the systolic BP, 169.5 +/- 28.3 versus 167.0 +/- 23.1 mmHg, and HR, 100.2 +/- 18.2 versus 98.8 +/- 16.6 bpm. CONCLUSIONS: Insertion of an endotracheal tube may itself be the most invasive stimulus during intubation procedures.

Adult↗

Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action.

Novel benzimidazole derivatives were synthesized and their pharmacological activities were examined. These compounds showed a good suppressive action on histamine release from rat peritoneal mast cells produced by antigen-antibody reaction, an antagonistic action on guinea pig ileum contraction caused by histamine, an inhibitory action on 5-lipoxygenase in rat basophilic leukemia-1 (RBL-1) cells, and a preventive action on NADPH dependent lipid peroxidation induced by Fe3+-ADP in rat liver microsomes. In addition, 1-[2-[2-(4-Hydroxy-2,3,5-trimethylphenoxy)ethoxy]-ethyl]-2-(4-meth yl-1-homopiperazino)-1H-benzimidazole difumarate (BOM1006) exhibited a dose dependent suppressive action on 48 h homologous passive cutaneous anaphylaxis (PCA) reaction in rats orally administered the drug.

Animals↗

Stress responses during laparoscopy with CO2 insufflation and with mechanical elevation of the abdominal wall.

STUDY OBJECTIVE: To compare the intensity of stress responses caused by laparoscopy combined with CO2 insufflation (CI) with those caused by mechanical elevation of the abdominal wall (MEA). DESIGN: Prospective study (Canadian Task Force classification I). SETTING: Tertiary care university hospital. PATIENTS: Thirty-one women. Intervention. Laparoscopy, 16 with CI and 15 with MEA. MEASUREMENTS AND MAIN RESULTS: Circulating levels of norepinephrine, epinephrine, cortisol, and interleukin (IL)-6 were compared in the two groups. Arterial partial pressure of CO2 (PaCO2) did not increase during laparoscopy by either method. Plasma norepinephrine and epinephrine levels increased after extubation in the MEA group but not in the CI group. Circulating cortisol levels in both groups increased during laparoscopy; mean intraoperative levels were higher in the CI group. Serum IL-6 levels increased after extubation in the MEA but not the CI group. Mean heart rate increased during laparoscopy in both groups, whereas blood pressure increased only in the CI group. More patients in the MEA group required postoperative analgesia. CONCLUSION: Laparoscopy with MEA caused more pronounced adrenosympathetic and cytokine responses than that with CI when PaCO2 was maintained within the range of normocapnia.

Carbon Dioxide↗

Intracranial low-grade chondrosarcoma with hyperostosis of the skull: a case report.

We describe a case of intracranial chondrosarcoma in a 46-year-old woman. The preoperative diagnosis was meningioma as plain radiography and computed tomography of the head revealed a tumor with discrete calcifications predominantly in the right frontoparietal region and hyperostosis of the inner table of the skull overlying the tumor. However, the tumor was histologically composed of cartilaginous tissue without meningiomatous differentiation and the final diagnosis was a low-grade chondrosarcoma based on its histological appearance and size, together with the radiologic images. Intracranial chondrosarcoma occurring above the skull base is extremely rare and 19 cases were found in our literature review. Intracranial chondrosarcoma showing hyperostosis of the skull has not been reported in the cases. The discussion includes its differential diagnosis, origin, and clinical behavior.

Chondrosarcoma↗

Low density lipoprotein receptor-related protein gene polymorphisms and risk for late-onset Alzheimer's disease in a Japanese population.

Low density lipoprotein (LDL) receptor-related protein (LRP) gene polymorphisms located in the 5' region and in exon 3, and the apolipoprotein E (APOE) genotype were determined in 100 Japanese patients affected by late-onset Alzheimer's disease (AD). We matched 246 controls for age and found no association between the polymorphism located in the 5' region of the LRP gene. The distribution of LRP exon 3 genotypes and alleles did not differ between AD and the control groups. However, the frequency of T allele in the Alzheimer's group having APOE-epsilon4 was lower than that in the control group having APOE-epsilon4, but it was only marginally significant (p = 0.022). Age of onset was significantly younger in the patients with CC genotype than those carrying the T allele (p = 0.03), and this trend was more evident among non-APOE-epsilon4 carriers (p = 0.008). These results support the possibility that ApoE and LRP may contribute to the development of AD.

Age of Onset↗