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Biomedical subjects

Y Ueda

Publications and source records attributed to Y Ueda.

At least 451 records · Page 25Linked to original sources

Free radical scavenging activity of the Japanese herbal medicine toki-shakuyaku-san (TJ-23) and its effect on superoxide dismutase activity, lipid peroxides, glutamate, and monoamine metabolites in aged rat brain.

The free radical scavenging activity of the Japanese herbal medicine, Toki-Shakuyaku-San (TJ-23; TSUMURA & Co., Tokyo, Japan), was examined using electron spin resonance (ESR) spectrometry. TJ-23 scavenged 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), superoxide (O2-), and hydroxyl radicals (.OH) dose-dependently. It also diminished carbon centered radicals (.C) generated by oxidative stress and inhibited thiobarbituric acid-reactive substances (TBARS) formation in mouse cortex homogenate. In addition, the effect of TJ-23 on the concentration of neurotransmitters and TBARS formation, and superoxide dismutase (SOD) activity in the cortex, hippocampus and striatum of the aged rat brain was studied. The concentrations of the metabolites of monoamines, glutamate and glutamine were decreased by 4 weeks of oral administration of TJ-23. The SOD activity of mitochondrial fraction was increased and TBARS formation was significantly suppressed. These results suggest that TJ-23 has an antioxidant action and would have a prophylactic effect against free radical-mediated neurological diseases associated with aging.

3,4-Dihydroxyphenylacetic Acid↗

Warm heart operation in a patient with myotonic dystrophy.

Myotonic dystrophy is the most severe form of myotonic disorder. Hypothermia or hyperkalemia may cause generalized muscle contraction during heart operations. We successfully repaired an atrial septal defect and pulmonary stenosis in a patient with myotonic dystrophy using systemic normothermia with continuous normokalemic coronary perfusion. This is the second reported case of a patient with myotonic dystrophy who underwent a cardiac operation.

Adult↗

Coexpression of preprotachykinin-A, alpha-calcitonin gene-related peptide, somatostatin, and neurotrophin receptor family messenger RNAs in rat dorsal root ganglion neurons.

Syntheses of substance P, somatostatin, and calcitonin gene-related peptide in sensory neurons have been suggested to be regulated by neurotrophic factors retrogradely transported from target tissues. In this study, we re-examined this idea by investigating the coexpression of neurotrophin receptor (trk family proto-oncogene) messenger RNAs, and preprotachykinin-A (a precursor peptide of substance P), alpha-calcitonin gene-related peptide and somatostatin messenger RNAs in lumbar dorsal root ganglion neurons by means of in situ hybridization histochemistry in rats. Approximately 35-40%, 5% and 15-20% of sensory neurons displayed signals for trkA, trkB, and trkC messenger RNAs, respectively. Approximately 28% of dorsal root ganglion neurons were positive for preprotachykinin-A messenger RNA, and were divided into two groups; those labeled strongly and those labeled weakly by in situ hybridization. All the strongly-labeled neurons (78% of preprotachykinin-A-positive cells) expressed trkA messenger RNA at the same time, while the weakly-labeled neurons did not. Thirty-seven per cent of dorsal root ganglion neurons expressed alpha-calcitonin gene-related peptide messenger RNA, and most of these neurons (84%) also expressed trkA messenger RNA. No or few preprotachykinin-A messenger RNA- and/or alpha-calcitonin gene-related peptide messenger RNA-expressing neurons were also positive for trkB or trkC messenger RNAs. Nine per cent of dorsal root ganglion neurons expressed somatostatin messenger RNA, and these neurons lacked all three trk messenger RNAs. Furthermore, most of these neurons (about 90%) showed positive, albeit weak, signals for preprotachykinin-A and alpha-calcitonin gene-related peptide messenger RNAs. The results suggest that expression of preprotachykinin-A and alpha-calcitonin gene-related peptide messenger RNAs is mediated by nerve growth factor via trkA receptor but not by brain-derived neurotrophic factor or neurotrophin-3, and that somatostatin gene transcription is not regulated by any member of the neurotrophin family in rat sensory neurons.

Animals↗

Collateral channels that develop after an acute myocardial infarction prevent subsequent left ventricular dilation.

OBJECTIVES: We sought to evaluate the effect of collateral channels that develop late after a first anterior myocardial infarction on left ventricular dilation and function. BACKGROUND: Collateral channels in an infarct-related artery may develop long after occlusion of the artery. Well visualized collateral channels that appear immediately after a myocardial infarction reduce infarct size and preserve left ventricular function. However, the functional significance of collateral channels that develop late after myocardial infarction has not been evaluated in terms of left ventricular function. METHODS: We studied 21 patients with a first anterior myocardial infarction and an infarct-related artery that remained totally occluded after reperfusion therapy and did not reopen within 1 month of infarction. No collateral channels were observed during the acute period. Patients were classified into two groups according to the extend of collateral formation 1 month after infarction: group C, patients with well developed collateral channels (n = 11), and group NC, patients with absent or poorly developed collateral channels (n = 10). Infarct size was determined by peak creatine kinase activity and thallium-201 single-photon emission computed tomography. Global and regional left ventricular function and left ventricular volumes were assessed by left ventriculography. These measurements were identical in both groups 1 month after infarction. Left ventricular function was reevaluated after 2.12 +/- 0.79 years (mean +/- SD). RESULTS: There were no significant changes in global and regional left ventricular function between the two groups during the long-term follow-up period. However, the end-diastolic volume index of group NC increased from 71 +/- 14 to 85 +/- 19 ml/m2, whereas that of group C decreased from 64 +/- 18 to 59 +/- 12 ml/m2. This important change during the long-term follow-up period resulted in a significant difference (p = 0.0006) in the end-diastolic volume index between the groups 2 years after onset (p = 0.002), whereas 1 month after infarction the difference was not significant (p = 0.36). A similar pattern was observed for the end-systolic volume index (group C: 38 +/- 16 to 35 +/- 14 ml/m2; group NC: 45 +/- 12 to 58 +/- 18 ml/m2, p = 0.018). The power of the tests to detect the observed differences showing nonsignificant results ranged from 0.05 to 0.38, whereas the power of the tests indicating a significant difference in end-diastolic and end-systolic volume indexes was >0.88. CONCLUSIONS: Collateral channels that develop after a myocardial infarction do not reduce the infarct size or prevent left ventricular dilation within 1 month of infarction. In contrast, such collateral channels prevent subsequent ventricular dilation and the deterioration of left ventricular function over 2 years. However, our results may have been biased because of the small number of patients.

Aged↗

Changes in calcium transient and left ventricular function during positive inotropic stimulation and myocardial ischemia in indo-1-loaded beating guinea pig heart.

To elucidate the issues such as excitation-contraction coupling and myocardial ischemia, it is necessary to measure intracellular free Ca2+ concentration and mechanical function of hearts perfused via the normal arterial circulation. For this purpose, we simultaneously measured Ca(2+)-dependent indo-1 fluorescence and left ventricular (LV) pressure on a beat-to-beat basis in Langendorff guinea-pig hearts, and investigated the changes in Ca2+ transient and LV function during inotropic stimulation and myocardial ischemia. The indo-1 fluoresence ratio and LV developed pressure increased the perfusate [Ca2+] increased from 1.6 to 3.2 mmol/L, and there was a good correlation between Ca2+ transient and LV contractility. Digoxin (10(-6) mol/L) and milrinone (10(-5) mol/L) increased LV contractility with a concomitant increase in Ca2+ transient, and the relative increase of Ca2+ transient produced by milrinone was much more than that by digoxin. The reduction of coronary perfusion pressure from 80 to 40 mm Hg decreased LV contractility with an increase in indo-1 fluorescence ratio. These results suggest that Ca2+ responsiveness of contractile apparatus declines during inotropic stimulation by milrinone and during myocardial ischemia. Thus, this experimental technique is useful to investigate the interrelation of Ca2- regulation and LV function during a variety of pharmacological and physiologic perturbations.

Animals↗

Monocyte/macrophage response to beta 2-microglobulin modified with advanced glycation end products.

We recently found that acidic beta 2-microglobulin (beta 2m), a major isoform of beta 2m in amyloid fibrils of patients with dialysis-related amyloidosis (DRA), contained early Amadori products and advanced glycation end products (AGEs) formed nonenzymatically between sugar and protein. Further analysis revealed that acidic beta 2m induces monocyte chemotaxis and macrophage secretion of bone-resorbing cytokines, suggesting the involvement of acidic beta 2m in the pathogenesis of DRA. Acidic beta 2m, however, is a mixture of heterogeneous molecular adducts due to various types of modification. In the present study, we investigated the modification responsible for the biological activity of acidic beta 2m toward monocytes/macrophages. The presence of a fair amount of beta 2m species with deamidation was detected in acidic beta 2m isolated from urine of non-diabetic long-term hemodialysis patients, but deamidated beta 2m had no biological activity. In contrast, normal beta 2m acquired the activity upon incubation with glucose in vitro. Among the glycated beta 2m, the pigmented and fluorescent beta 2m that formed after a long incubation period, that is, AGE-modified beta 2m, exhibited biological activity, whereas beta 2m modified with Amadori products, major Maillard products in acidic beta 2m, had no such activity. These findings suggest that AGEs, although only a minor constituent of acidic beta 2m, are responsible for monocyte chemotaxis and macrophage secretion of cytokines, implicating the contribution of AGEs to bone and joint destruction in DRA.

Adult↗

Production of the third and fourth component of complement (C3, C4) by smooth muscle cells.

Production of the third and fourth components of complement (C3, C4) by smooth muscle cells was investigated by using normal human aortic smooth muscle cells (AoSMC), human smooth muscle cell line (G402) and vascular smooth muscle cells obtained from human umbilical cord vein (UVSMC). AoSMC spontaneously produced both C3 and C4 at 15 ng/10(6) cells/72 hr and 22 ng/10(6) cells/72 hr, respectively, and both were enhanced by interferon-gamma (IFN-gamma). Although phorbol 12-myristate 13-acetate (PMA) and tumour necrosis factor-alpha (TNF-alpha) enhanced C3 production, C4 production was reduced by these agents. On the other hand, G402 produced C4 but not C3 in a dose-dependent manner when cultured with IFN-gamma. UVSMC produced only a small amount of C3 and C4 compared with AoSMC or G402. C3 and C4 produced by AoSMC were confirmed to be identical with their human serum counterparts as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and measurement of haemolytic activity. Northern blotting analysis showed that the expression of mRNA of C3 and C4 was enhanced by TNF-alpha and IFN-gamma, respectively, in AoSMC. Our findings suggest the importance of smooth muscle cells as a source of components of complement in vascular diseases including vasculitis.

Aorta↗

Detection and sequencing of Norwalk-like viruses from stool samples in Japan using reverse transcription-polymerase chain reaction amplification.

Norwalk-like viruses were detected in Japan in 12% (26/209) of patients with nonbacteria and nonrotavirus gastroenteritis in an outpatient clinic of a hospital from 1991 to 1994 by reverse transcription-polymerase chain reaction. They were also present in 7% (26/378) of total samples including those from rotavirus-positive gastroenteritis patients. In addition, the viruses were recovered in samples from 15 of 17 patients which were collected during outbreaks of gastroenteritis in various places in Japan by the same method. The DNA sequence of the polymerase region from patients at the hospital (sporadic cases) showed that two subgenogroups, similar to UK1-6 in genogroup G1 and to UK1-1 in genogroup G2 (Ando et al, J Clin Microbiol, 1995, 33: 64-71) exist in Japan. The latter was more frequently found.

Base Sequence↗

Signal transduction properties of the T cell activation monoclonal antibody panel: ubiquitous increase in cellular substrate tyrosine phosphorylation in the absence of detectable calcium mobilization.

A panel of coded monoclonal antibodies (mAbs) submitted to the T cell section of the Vth International Workshop and Conference on Human Leukocyte Differentiation Antigens was examined for the ability to induce cellular activation. Intracellular calcium levels were examined by loading resting T cells with the Ca(+2)-specific dye Indo-1, incubating the cells with Ab, cross-linking with goat anti-mouse Ab and analyzing by flow cytometry. Only 11 out of 68 Abs induced a detectable rise in Ca+2; two of these Abs induced a substantial rise in Ca+2. In resting T cells, 63 of 68 Abs induced increased tyrosine phosphorylation of substrates compared to negative control. Approximately half of the Abs that induced tyrosine phosphorylation induced substrates different from those seen following treatment of cells with anti-CD3 Ab. All mAbs that induced a rise in Ca+2 also induced increased tyrosine phosphorylation. These experiments show a distinct difference in the ability of cross-linked Ab to induce changes in tyrosine phosphorylation and intracellular free Ca+. Furthermore, these results indicate that transient increases in cellular substrate phosphorylation may have questionable biologic significance in T cells.

Animals↗

Glomerulonephritis with predominant paramesangial IgG deposition.

The new clinicopathological entity, immunoglobin G (IgG)-associated mesangial proliferative glomerulonephritis (GN), has been reported recently, but serial renal biopsies were not performed in the cases reported. The findings of three serial renal biopsies in a pediatric case with IgG-associated GN and paramesangial deposits are reported. Microscopic hematuria was found incidentally at the age of 8 years and the hematuria often worsened transiently during periods of upper respiratory infections. The patient was treated mainly with dipyridamole. The third biopsy showed that both paramesangial hemispherical deposits and predominant mesangial IgG deposits had increased, while mesangial cell proliferation had markedly decreased. These serial biopsy findings suggest that IgG-associated GN with microscopic hematuria and slight proteinuria may be characterized by a relatively benign histological and clinical course, as described in recent reports.

Child↗

[Diagnosis and clinical manifestations of diarrheal virus infections in Maizuru area from 1991 to 1994--especially focused on small round structured viruses].

Rotavirus (44.7%), adenovirus (5.6%), small round structured viruses such as astrovirus (9.8%) and Norwalk like virus (6.9%) were detected by latex agglutination and reverse transcription polymerase chain reaction amplification from 378 stool samples in an outpatient clinic of Pediatrics in Maizuru area from 1991 to 1994. 70.0% were found from 6 months to 2 years old and 91.0% were detected from January to April. Serotype 1 astrovirus and group 2 Norwalk like virus were mainly found in all serotypes in each virus. Diarrhea, vomiting, nausea, fever, cough and rhinorrhea, and severity of diseases were examined in each case. Fever is significantly found in patients with rotavirus. Sporadic cases with small round structured viruses were recognized in the outpatient clinic of pediatrics.

Adenoviridae↗

[Bacteriological studies of travellar's diarrhoea. 5) Analysis of enteropathogenic bacteria at Osaka Airport Quarantine Station from January 1992 through September 3rd, 1994].

During the last 2 years and 8 months before the closure of Osaka Airport Quarantine Station (from Jan. 1992 to Sep. 3, 1994), a total of 7,421,909 overseas travellers were quarantined. 15,919 reported themselves of suffering from diarrhoea. Bacteriological examination of a total of 6,031 individuals' stools were performed. 1) Various enteropathogenic bacteria were isolated from 31.2% of the stools examined. Isolated species were as follows: Plesiomonas shigelloides, 1,127 cases (59.9%); Vibrio parahaemolyticus, 293 cases (15.6%); Salmonella spp., 262 cases (13.9%); Shigella spp., 235 cases (12.5%); Aeromonas sobria, 93 cases (4.9%); V. cholerae non-O1, 69 cases (3.7%). 2) The enteropathogenic bacteria were isolated through out the year without any seasonal variation. 3) The major regions where the travellers were infected with the pathogens are as follows: V. cholerae non-O1 (NAG Vibrio) and enteropathogenic Escherichia coli, South-East and South-West Asia; Vibrio other than NAG, South-East and East Asia; Shigella, widely distributed but especially in India; P. shigelloides and Salmonella, widely distributed. 4) 2 strains of toxigenic (cholera toxin-producing) V. cholerae O139 were isolated from patients who had visited Indonesia and Thailand, respectively. 5) In 320 cases (17%), plural enteropathogenic bacteria were isolated from single patients, suggesting a high frequency of the mixed infections. 6) Among Shigella strains, S. sonnei were isolated the most, followed by S. flexneri (24.7%), S. boydii (8.8%) and S. dysenteriae (2.9%). 7) Among Salmonella serovers, Salmonella Enteritidis was isolated the most frequently (39 cases, 14.1%). 8) 218 (91.6%) of 238 Shigella strains and 103 (37.6%) of 276 Salmonella strains were resistant to one or more drugs tested (SM.CP.TC.KM.ABPC.NA.OFLX). 9) All of the 22 V. cholerae O1 strains were Ogawa, E1 Tor. Among them, 19 were toxigenic strains and 3 were non-toxigenic. 10) O4:K8 was the most frequently isolated serover of V. paraemolyticus. 87.4% of all V. parahaemolyticus strains were positive with thermostable direct hemolysin (TDH) gene, and 12.6% of them were positive with TDH-related hemolysin (TRH) gene by DNA-probe methods.

Diarrhea↗

[Analysis of HCV infection in patients with hemophilia].

Second generation antibodies of HCV, HCV-RNA, genotype and data of liver function were investigated with the purpose of better understanding the condition of the 32 hemophiliac patients currently in our hospital. The results being: 1) The positivity ratio of second generation antibodies was 96.9% and a negative example occurred in only one infant born in 1990. 2) In the positive example of second generation antibodies, HCV-RNA positivity was 77.4%, which is extremely high result. 3) There are several kinds of genotypes, such as type I, type II, type II + III and type III. Type I is most commonly found in the younger generation. The possibly for this presence was suggested to be from imported blood products. 4) There were few findings of liver disorder in cases of HCV-RNA negative patients. Meanwhile, the presence of liver disorder was found in about 70% HCV-RNA patients. There is evidence of correlation between the level disorder and age of the patient. In general, initial infection for hemophiliac patients takes place early in life. Compared to non-hemophilia hepatitis C patients, the liver disorder occurs at all ages but is becoming more prevalent younger patients. Although not common, there were occasionally a few cases of liver disorder turning into cirrhosis of the liver in patients in their 30's.

Adolescent↗

Decrease in oxygen cost of contractility during hypocapnic alkalosis in canine hearts.

Ca2+ sensitization of contractile machinery could theoretically enhance the mechanoenergetics of the heart. We studied the effects of alkalosis with Ca2+ sensitization on mechanoenergetics within the framework of the relationships of left ventricular pressure-volume area (PVA; a measure of the total mechanical energy), myocardial oxygen consumption per beat (VO2), and the contractility index [E(max) (slope of end-systolic pressure-volume relation)] in 10 excised, cross-circulated canine hearts. Alkalosis was stably maintained without hypoxia (mean pH 7.66). Alkalosis increased E(max) without changing the slope of the VO2-PVA relation, a reflected contractile efficiency. The incremental ratio of unloaded VO2 to E(max) in alkalosis was significantly lower than that in Ca2+ sensitization (0.0012 +/- 0.0010 vs. 0.0062 +/- 0.0030 ml O2 . mmHg-1 . ml . beat-1 . 100 g LV-2; P < 0.01). Basal metabolism under KCl arrest was unchanged by alkalosis, indicating the decreased energy cost of the excitation-contraction coupling by alkalosis. Compared with the control, alkalosis increased E(max) during the Ca2+ infusion of various concentrations without any further increase in unloaded VO2. Thus we demonstrated a decreased oxygen cost of contractility during alkalosis, presumably due to Ca2+ sensitization.

Alkalosis, Respiratory↗

Pharmacokinetics of indomethacin ester prodrugs: gastrointestinal and hepatic toxicity and the hydrolytic capacity of various tissues in rats.

In order to develop a potential prodrug of indomethacin (IM) which causes less irritation to the gastrointestinal mucosa, the ester prodrugs [butyl ester (IM-BE) and octyl ester (IM-OE)] of IM were synthesized and evaluated for their ulcerogenic activity and hepatic injury after oral administration in rats. Additionally, the kinetics of hydrolysis of the prodrugs were examined to characterize the tissues or organs capable of hydrolyzing the ester bonds. The plasma levels of IM after the oral administration of IM-OE and IM-BE were comparatively low compared with those after IM, with a small bioavailability (2.1 and 15.0%, respectively). Ulcerogenic activity and hepatic injury, expressed by decreased hepatic microsomal enzyme activities, were hardly seen after repeated oral administration of the prodrugs, in contrast with the severely irritating effects of IM alone. Hydrolysis of the prodrugs was adequately described by first-order kinetics. IM-BE was relatively rapidly hydrolyzed in plasma, skin and whole blood, but the hydrolysis in the intestinal mucosa and liver was very slow. The hydrolytic rates for IM-OE were exceedingly small or negligible. These results indicate that the main part of IM-BE and IM-OE administered orally might not be hydrolyzed to IM in the gastrointestinal tract, and that the ester prodrugs themselves were absorbed through the mucosa; also, that the hydrolysis of ester bonds would be carried out mainly in the circulatory system. Consequently, IM-BE seems to be an ideal prodrug of IM.

Administration, Oral↗