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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 163 records · Page 9Linked to original sources

Cardiac performance after deep hypothermic circulatory arrest in chronically cyanotic neonatal lambs.

OBJECTIVES: It is controversial whether immature cyanotic hearts are more susceptible to ischemic injury than normoxemic hearts. Acutely induced alveolar hypoxic stress before cardiopulmonary bypass has been used as a model of cyanosis and is reported to worsen recovery of immature hearts after subsequent ischemic insult by means of a free radical injury mechanism. Because of concerns about the relevance of acute alveolar repair to the chronic cyanosis encountered clinically, we assessed the effects of chronic cyanosis without alveolar hypoxia, acute alveolar hypoxia, and normoxemia on recovery of cardiac function after deep hypothermic circulatory arrest. METHODS: A chronic cyanosis model was created in 8 lambs by an anastomosis between the pulmonary artery and the left atrium (cyanosis group). Eight lambs underwent sham operation (control). One week later, the animals underwent cardiopulmonary bypass with 90 minutes of deep hypothermic circulatory arrest at 18 degrees C. Another 8 lambs underwent 45 minutes of hypoxic ventilation before bypass, with arterial oxygen tension being maintained at 30 mm Hg (acute hypoxia group). Cardiac index, preload recruitable stroke work, and tau were measured. Malondialdehyde and nitrate-nitrite, nitric oxide metabolites, were also measured in the coronary sinus. Myocardial antioxidant reserve capacity at 2 hours of reperfusion was assessed by measuring lipid peroxidation in left ventricular tissue samples incubated with t-butylhydroperoxide at 37 degrees C. RESULTS: Oxygen tension was 35 +/- 3 mm Hg in the acute hypoxia group versus 93 +/- 7 mm Hg in the control group. In the acute hypoxia group the recovery of cardiac index, preload recruitable stroke work, and tau were significantly worse than that found in both the control and cyanosis groups. Preload recruitable stroke work at 2 hours of reperfusion was slightly but significantly lower in the cyanosis group than in the control group. The postischemic level of nitric oxide metabolites was significantly lower in the acute hypoxia group than in the cyanosis and control groups. However, malondialdehyde levels in the coronary sinus and myocardial antioxidant reserve capacity were not significantly different among the groups. CONCLUSION: Recovery of left ventricular function after deep hypothermic circulatory arrest in neonatal lambs with chronic cyanosis was slightly worse than that found in acyanotic animals. Acute hypoxia before bypass was associated with significantly worse recovery of left ventricular function, and the mechanism of injury may be related to an impairment of nitric oxide production. Free radical injury does not appear to explain any differences among cyanotic, acyanotic, and acutely hypoxic animals in recovery of left ventricular function after ischemia.

Analysis of Variance↗

Molecular mechanism of activation and superactivation of Ret tyrosine kinases by ultraviolet light irradiation.

The catalytic activities of Ret tyrosine kinases as the products of oncogene RET with multiple endocrine neoplasia type 2A (Ret-MEN2A) or 2B (Ret-MEN2B) mutations and the hybrid gene from c-RET and RFP (Rfp-Ret) were higher than those of c-Ret. We demonstrated that ultraviolet light (UV) irradiation induced activation of c-Ret and superactivation of genetically mutated, and thereby constitutively activated, Ret-MEN2A, Ret-MEN2B, and Rfp-Ret. We found that small proportions of c-Ret and Ret-MEN2B and a large proportion of MEN2A were dimerized due to disulfide bonds and that high kinase activity resided in these fractions. The UV-induced activation of c-Ret and superactivation of Ret-MEN2A and Ret-MEN2B were then shown to be closely associated with promotion of the disulfide bond-mediated dimerization of the Ret proteins. Furthermore, we showed that a large proportion of Rfp-Ret was dimerized or polymerized and that almost all kinase activities resided in the highly polymerized but not dimerized fraction. The UV-induced superactivation of Rfp-Ret was also found to be closely associated with promotion of polymerization but not with dimerization of Rfp-Ret. Further experiments revealed that UV induced intracellular dimerization and activation of the extracellular domain-deleted mutant Ret (Ret-PTC-1). Most importantly, the levels of basal kinase activity and dimerization of Ret-TPC-1-C376A, in which cysteine 376 in the tyrosine kinase domain of Ret-TPC-1 was replaced with alanine, were low and were not increased by UV irradiation. These results suggest that the cysteine at this position works as the primary target of dimerization of Ret proteins inside the cell for both the maintenance of the basal kinase activity and its promotion by UV, possibly in co-operation with the cysteine(s) in the extracellular domain of Ret-MEN2A and Rfp-Ret, which is the target of dimerization and polymerization outside the cell. The potential biological significance of the UV-mediated superactivation of mutant Ret through the newly proposed mechanism in oncogenesis is discussed.

Amino Acid Sequence↗

Optimal propofol plasma concentration during upper gastrointestinal endoscopy in young, middle-aged, and elderly patients.

BACKGROUND: Suitable propofol plasma concentrations during gastroscopy have not been determined for suppressing somatic and hemodynamic responses in different age groups. METHODS: Propofol sedation at target plasma concentrations from 0.5 to 4.0 microgram/ml were performed randomly in three groups of patients (23 per group) who were undergoing elective outpatient gastroscopy: ages 17-49 yr (group 1), 50-69 yr (group 2), and 70-89 yr (group 3). Plasma propofol concentration in which 50% of patients do not respond to these different stimuli were determined by logistic regression: verbal command (Cp50ls), somatic response to gastroscopy (Cp50endo), and gag response to gastroscopy (Cp50gag). Hemodynamic responses were also investigated in the different age groups. RESULTS: Cp50ls concentrations were 2.23 microgram/ml (group 1), 1.75 microgram/ml (group 2), and 1.40 microgram/ml (group 3). The Cp50endo values in groups 1 and 2 were 2.87 and 2.34 microgram/ml, respectively, which were significantly higher than their respective Cp50ls values. Cp50endo value in group 3 was 1.64 microgram/ml, which was close to its Cp50ls value. Because of a high degree of interpatient variability, Cp50gag could not be defined. Systolic blood pressure response decreased with increasing propofol concentrations. CONCLUSIONS: The authors determined the propofol concentration necessary for gastroscopy and showed that increasing age reduces it. Propofol concentration that suppresses somatic response induces loss of consciousness in almost all young patients.

Adolescent↗

Tumor necrosis factor gene polymorphism in chronic sinusitis.

OBJECTIVES: It is likely that genetic factors play a role in the etiology of chronic sinusitis, and airway inflammation is an important pathological feature in chronic sinusitis. We hypothesized that individuals with greater inflammatory responses may be more likely to acquire the disease. Polymorphisms of the tumor necrosis factor (TNF) genes have been described, and certain inflammatory diseases are reportedly associated with certain alleles of TNF genes. The purpose of this study is to examine whether there is an association between some alleles of TNF genes and chronic sinusitis. STUDY DESIGN: Thirty-eight Japanese patients with intractable chronic sinusitis were selected on the basis of the following criteria: 1) persistent mucous or mucopurulent nasal discharge and/or postnasal dripping for longer than 3 years and 2) opacification in bilateral maxillary sinuses and ethmoid cells on plain radiographic films. METHODS: Both tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) gene polymorphisms were analyzed by polymerase chain reaction (PCR) with restriction fragment length polymorphisms in these patients and 35 healthy control subjects. RESULTS: A significantly higher frequency (P < .05) of TNFB*2 allele of TNF-beta gene polymorphism was observed in patients with chronic sinusitis (74%) compared with control subjects (56%). There was no association between alleles of TNF-alpha and chronic sinusitis. CONCLUSION: We concluded that TNF-beta gene polymorphism may form a component of the genetic predisposition to chronic sinusitis in Japanese patients.

Adolescent↗

Calcium concentration and artificial precipitates in human pancreatic juice.

We studied the role of the increase in the calcium concentration in pure pancreatic juice of alcoholic noncalcified chronic pancreatitis. Pure pancreatic juice was obtained endoscopically. The pancreatic juice from patients with chronic pancreatitis was adjusted to pH 7.5; then the calcium concentration was adjusted to 0.4, 2.9, 5.4, or 10.4 mmol/L. Artificial precipitates were produced by incubation of the samples at 37 degrees C for 6 hours. Proteins in the artificial precipitates were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the protein patterns were compared with the patterns of natural protein plugs from patients with chronic pancreatitis. The amount of the precipitate increased as the added calcium increased. The protein patterns of SDS-PAGE of the artificial precipitates were similar to those of protein plugs. Albumin, a-amylase, lipase, trypsinogen, and chymotrypsinogen were identified by immunoblotting both in the precipitate and in the protein plug. The increased calcium concentrations in pancreatic juice induced the formation of precipitates whose protein composition was similar to that of protein plugs. An increased calcium concentration in human pancreatic juice may play an important role in the pathogenesis of protein plugs.

Adult↗

Recovery of pathogenic measles virus from cloned cDNA.

Reverse genetics technology so far established for measles virus (MeV) is based on the Edmonston strain, which was isolated several decades ago, has been passaged in nonlymphoid cell lines, and is no longer pathogenic in monkey models. On the other hand, MeVs isolated and passaged in the Epstein-Barr virus-transformed marmoset B-lymphoblastoid cell line B95a would retain their original pathogenicity (F. Kobune et al., J. Virol. 64:700-705, 1990). Here we have developed MeV reverse genetics systems based on the highly pathogenic IC-B strain isolated in B95a cells. Infectious viruses were successfully recovered from the cloned cDNA of IC-B strain by two different approaches. One was simple cotransfection of B95a cells, with three plasmids each encoding the nucleocapsid (N), phospho (P), or large (L) protein, respectively, and their expression was driven by the bacteriophage T7 RNA polymerase supplied by coinfecting recombinant vaccinia virus vTF7-3. The second approach was transfection with the L-encoding plasmid of a helper cell line constitutively expressing the MeV N and P proteins and the T7 polymerase (F. Radecke et al., EMBO J. 14:5773-5784, 1995) on which B95a cells were overlaid. Virus clones recovered by both methods possessed RNA genomes identical to that of the parental IC-B strain and were indistinguishable from the IC-B strain with respect to growth phenotypes in vitro and the clinical course and histopathology of experimentally infected cynomolgus monkeys. Thus, the systems developed here could be useful for studying viral gene functions in the context of the natural course of MeV pathogenesis.

Animals↗

Sendai virus blocks alpha interferon signaling to signal transducers and activators of transcription.

We demonstrate here that Sendai virus (SeV) blocks alpha interferon (IFN-alpha) signaling to signal transducers and activators of transcription (STATs) in HeLa cells. IFN-alpha-stimulated tyrosine phosphorylation of STATs and subsequent formation of the IFN-stimulated gene factor 3 transcription complex were inhibited in SeV-infected cells, resulting in inefficient induction of IFN-stimulated gene products. None of the components of the signaling pathway-type I IFN receptor subunits Jak1, Tyk2, Stat1, Stat2, and p48-was degraded. Moreover, tyrosine phosphorylation of Jak1 in response to IFN-alpha was unaffected at the early phase of infection, suggesting that oligomerization of the receptor subunits proceeded normally. In contrast to Jak1, IFN-alpha-stimulated tyrosine phosphorylation of Tyk2 was partially inhibited. Therefore, this partial inhibition of activation of Tyk2 probably contributes to the subsequent failure in the activation of STATs.

Cytokines↗

Protective effect of lafutidine against indomethacin-induced intestinal ulceration in rats: relation to capsaicin-sensitive sensory neurons.

BACKGROUND/AIM: We examined the prophylactic effect of lafutidine, a novel histamine H(2)-receptor antagonist [(+/-)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2-pyr idyl]oxy- (Z)-2 butenyl]acetamide], on indomethacin-induced small intestinal ulcers in rats and investigated the relation of this action to capsaicin-sensitive sensory neurons. METHODS AND RESULTS: Subcutaneously administered indomethacin (10 mg/kg) provoked ulceration in the small intestine, mainly the jejunum and ileum, accompanied by increases in myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well as the enterobacterial numbers invading the mucosa. Intestinal ulcerogenic response to indomethacin was prevented by 16,16-dimethyl prostaglandin E(2) (10 microg/kg, p.o.) and capsaicin (10 mg/kg, p.o. ) as well as ampicillin (800 mg/kg, p.o.), but not omeprazole (100 mg/kg, p.o.). Likewise, lafutidine (1-10 mg/kg, p.o.), but not cimetidine (100 mg/kg, p.o.), reduced the occurrence of intestinal ulcers in response to indomethacin in a dose-dependent manner, and a significant effect was observed at 3 mg/kg or greater. The protective action of lafutidine as well as capsaicin was almost totally abolished by chemical ablation of capsaicin-sensitive sensory neurons. Both lafutidine and capsaicin significantly suppressed the increases in MPO and iNOS activities as well as enterobacterial numbers in the mucosa. These agents also significantly enhanced mucus secretion in the small intestine. CONCLUSION: These results suggest that lafutidine protects the small intestine against ulceration via stimulation of capsaicin-sensitive sensory neurons. This action may be attributable to inhibition of enterobacterial invasion in the intestinal mucosa, probably by increasing the mucus secretion.

16,16-Dimethylprostaglandin E2↗

Effect of ecabet disodium, a novel locally-acting antiulcer drug, on epithelial restitution following injury by hypertonic NaCl in bullfrog stomach in vitro.

BACKGROUND: The antiulcer drug ecabet 2Na (12-sulfodehydroabietic acid disodium salt) exhibits a gastroprotective activity, mainly through a local action, involving endogenous prostaglandins (PGs) and nitric oxide (NO). In the present study, we examined the effect of ecabet on the epithelial restitution of the bullfrog gastric mucosa in vitro following injury by hypertonic NaCl. METHODS: Bullfrog fundic mucosa was mounted in an Ussing chamber. The tissue injury was induced by exposure of the mucosa to 1.25 M NaCl for 5 min, and transmucosal potential difference (PD) and electrical resistance (R) were measured during a 4-hour test period. Ecabet (3-30 mg/ml) was added to the luminal solution for 10 min before or after NaCl, while 16,16-dimethyl PGE(2) (dmPGE(2): 1x 10(-6) M) or NOR-3 (a NO donor: 1 x 10(-4) M) was added to the nutrient solution 10 min before NaCl. RESULTS: Mucosal application of 1.25 M NaCl caused an immediate reduction of PD and R, followed by a gradual normalization, reaching about 70% of the pre-exposure levels within 4 h. Ecabet, added before NaCl, significantly expedited the recovery of PD and R in a concentration-dependent manner; this effect was mimicked by posttreatment with ecabet and significantly mitigated by prior addition of indomethacin (1 x 10(-5) M) or N(G)-nitro-L-arginine methyl ester (L-NAME: 1 x 10(-3) M). The epithelial restitution was also significantly promoted by serosal application of either dmPGE(2) or NOR-3. The mucosal exposure to ecabet significantly increased the luminal release of PGE(2) and NO metabolites, the effects being attenuated by indomethacin and L-NAME, respectively. The mucous secretion was increased by ecabet as well as dmPGE(2) and NOR-3, and the effect of ecabet was significantly suppressed by both indomethacin and L-NAME. The inhibitory effects of L-NAME on the ecabet action were all significantly antagonized by concurrent addition of L-arginine. CONCLUSION: These results suggest that ecabet significantly expedited the restitution following gastric surface cell injury, and this action is mediated by endogenous NO as well as PGs and may be functionally associated with an increase of mucous secretion.

Abietanes↗

Chronic unilateral ureteral obstruction represented as renin-dependent hypertension.

A 50-year-old woman developed renin-dependent hypertension immediately after accidental unilateral ureteral ligation during hysterectomy, and the hypertension lasted for 5 months. Surgical release of the obstruction was carried out 157 days after the ligation. Then, her blood pressure was normalized. However, the obstructed kidney showed intensive tubulointerstitial fibrosis and functional recovery was not obtained. This case suggests that the renin-angiotensin system may be upregulated in human kidney during unilateral ureteral obstruction for a long duration.

Atrophy↗

Role of neutrophil elastase in endotoxin-induced mucus hypersecretion in rat nasal epithelium.

In the present study, hypertrophic and metaplastic changes of goblet cells were induced in rat nasal epithelium by intranasal instillation of endotoxin or elastase. A significant increase in the amount of intraepithelial mucosubstance was observed after 24 hours during 3 days of instillation. The elastase-induced mucus production was not inhibited in neutrophil-depleted rats, but the endotoxin-induced change was significantly inhibited. Intranasal instillation of the neutrophil elastase inhibitor ONO-5046 partially inhibited the endotoxin-induced mucus production. Epithelial mucus secretion was evaluated by the temporary decrease in the amount of intraepithelial mucosubstance. The endotoxin-induced mucus secretion peaked 3 to 6 hours after intranasal instillation, coinciding with the peak of the intraepithelial neutrophil infiltration. The elastase-induced mucus secretion peaked 1 to 3 hours after intranasal instillation; intraepithelial neutrophil infiltration was not induced by elastase. These results indicate that neutrophil elastase is an important mediator of the intraepithelial mucus synthesis and secretion induced by endotoxin.

Animals↗

Word deafness after resection of a pineal body tumor in the presence of normal wave latencies of the auditory brain stem response.

We studied the case of a 48-year-old woman who had resection of a pineal body tumor in terms of postoperative audiological function. Postoperative magnetic resonance imaging disclosed partial inferior colliculi destruction and medial geniculate body degeneration. A pure tone audiogram revealed only moderate sensorineural hearing loss, but her speech perception was totally impaired. The binaural sound localization function was also impaired. The auditory brain stem response (ABR) showed waves I, III, and V to have normal latencies. The amplitude of wave III was larger than that of wave V. These results support the view that the waves of the ABR are elicited from multiple sources in the auditory brain stem nuclei and tracts. This case suggests a substantial role for the inferior colliculus and medial geniculate body in the processing of speech perception and sound localization.

Astrocytoma↗

Reverse redistribution of thallium-201 myocardial single photon emission tomography and contractile reserve.

The present study investigated the contractile reserve of myocardium exhibiting reverse redistribution (RRD) of thallium-201 (201Tl) after acute myocardial infarction. Forty patients experiencing their first acute myocardial infarction underwent resting 201Tl single-photon emission computed tomography (SPECT) and low-dose (5-10 microgxkg(-1)xmin(-1)) dobutamine stress echocardiography (DSE) within 4 weeks after the onset of infarction. The left ventricle was divided into 13 segments for analysis. The severity of defects in 201Tl SPECT and the extent of wall motion abnormality in DSE were visually assessed and scored. The sum of each defect score and wall motion score of infarct-related segments were defined as total defect score (TDS) and total wall motion score (TWM), respectively. Quantitative analysis of 201Tl uptake was also performed. Resting 201Tl SPECT revealed RRD in 16 patients (group RRD), fixed defect (FIX) in 23 patients (group FIX), and redistribution in one. There was a significant difference in improvement of TWM between rest and stress in TWM in both the RRD and FIX groups (p<0.0001, each case). The improvement of TWM with dobutamine was significantly greater in RRD than in FIX (1.6+/-1.0 vs 0.6+/-0.7, p=0.001). There was a positive correlation between the magnitude of RRD and improvement of TWM with dobutamine (r=0.48, p=0.002). Myocardium exhibiting RRD on 201Tl SPECT in patients with acute myocardial infarction has greater contractile reserve than that exhibiting a fixed defect.

Adult↗

Effects of metabolically ischemic, but viable, myocardium on QT dispersion in patients with acute myocardial infarction: a study with resting I-123-BMIPP/thallium-201 myocardial single-photon emission computed tomography.

In chronic Q-wave myocardial infarction, QT dispersion is closely correlated with infarct size, but this correlation has not been evaluated for acute myocardial infarction (AMI). The effects of abnormal fatty acid metabolism on QT dispersion were examined in 123 patients with AMI who underwent resting iodine-123-15-iodophenyl 3-methyl pentadecanoic acid (BMIPP)/thallium-201(201Tl) myocardial single photon emission computed tomography (SPECT) and electrocardiographic analysis in the subacute phase. The relationship between BMIPP and 201Tl was defined as match when the total defect score for BMIPP was equal to or smaller than that for 201Tl, and as mismatch when the total defect score for BMIPP was larger than that for 201Tl. Twenty-six patients (21%) demonstrated BMIPP-201Tl match and 97 (79%) demonstrated mismatch. Infarct size was closely correlated with QT dispersion (r=0.67, p<0.001) in patients with BMIPP-201Tl match, but weakly correlated (r=0.30, p<0.005) in patients with BMIPP-201Tl mismatch. For small infarctions, QT dispersion was significantly larger in patients with BMIPP-201Tl mismatch than in those with BMIPP-201Tl match (62+/-24 ms vs 41+/-18 ms, p=0.03), but did not differ between the 2 groups for large infarctions. This study shows that QT dispersion is influenced by infarct size and by the presence of metabolically ischemic but viable myocardium in patients with AMI.

Adult↗

A reverse flow-metabolism mismatch pattern: a new marker of viable myocardium with greater contractility during dobutamine stress than myocardium with a flow-metabolism mismatch pattern.

Few studies have investigated the contractility of myocardium with a reverse flow-metabolism pattern; that is, greater uptake of nitrogen- 13-ammonia (NH3) than fluorine- 18-fluorodeoxyglucose (FDG) on positron emission tomography (PET). This study examined the contraction thickening represented by count increase in ECG-gated FDG-PET of myocardium with a reverse flow-metabolism pattern during low-dose dobutamine stress. Fifty-four patients with myocardial infarction were studied. Relative NH3 and FDG uptake (%NH3, %FDG) and %count increase were measured in 216 apical and 216 lateral segments on ECG-gated FDG-PET. The %count increase during low-dose dobutamine stress was greater in myocardium with a reverse flow-metabolism mismatch pattern than in myocardium with a flow-metabolism mismatch pattern (35.9+/-25.7% vs 24.6+/-15.9%, p=0.0221 in apical segments, and 38.4+/-22.6% vs 27.6+/-18.4%, p=0.0040 in lateral segments) despite smaller %FDG. A reverse flow-metabolism mismatch pattern should be noted as a new marker of viable myocardium with greater contractility during dobutamine stress than myocardium with a flow-metabolism mismatch pattern.

Aged↗

Enhancement of peptone-induced gastric acid secretion in streptozotocin-induced diabetic rats.

We compared the acid secretory response to peptone in normal and streptozotocin-induced diabetic rats. Animals were injected with streptozotocin and used after 5 weeks of diabetes with blood glucose levels of >350 mg/dl. Under urethane anesthesia, 2 ml peptone solution (2-8%) was instilled in the stomach through an acute fistula every 30 min. Peptone increased acid secretion in a concentration-dependent manner in normal rats, the maximal response being obtained at 8%. Likewise, the increased acid response was observed in diabetic rats, yet the maximal response observed at 4% was significantly greater than that in normal rats. In both cases, this response was inhibited potently by famotidine as well as YM-022 (a CCKB antagonist) and partially inhibited by atropine. Peptone increased luminal histamine and plasma gastrin levels in both normal and diabetic rats, and the former response was significantly greater in diabetic animals. The altered acid secretion and histamine output in diabetic rats were reverted by insulin treatment. Pentagastrin- but not histamine-induced acid secretion was also increased in diabetic rats. We conclude that peptone-induced acid secretion is increased in diabetic conditions. This phenomenon is insulin-dependent and associated with an enhanced release of histamine but not with an increased sensitivity of the parietal cells.

Animals↗

Bioelectrical impedance analysis in the clinical management of a pregnant woman undergoing dialysis.

We report a case of successful pregnancy in a woman who was initially diagnosed with renal failure in mid-pregnancy. She was started on hemodialysis, and her fluid balance was serially monitored with bioelectrical impedance analysis. Her body weight decreased and bioelectrical impedance values increased, along with resolution of pulmonary edema in the process of the removal of excessive fluid retention with hemodialysis. The bioelectrical impedance values decreased immediately after the usual dose of oral ritodrine was administered, partly because producing sodium and water retention by ritodrine were enhanced in the setting of fluid imbalances. This decrease preceded the onset of pulmonary edema, while no changes were noted in maternal body weight before hemodialysis. These results suggest that the serial measurement of bioelectrical impedance values enables more reliable and earlier detection of abnormal water retention in pregnant women undergoing dialysis than the effect of body weight changes.

Adult↗