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Biomedical subjects

T Arai

Publications and source records attributed to T Arai.

At least 109 records · Page 6Linked to original sources
PubMed2001

Microsatellite instability of papillary subtype of human gastric adenocarcinoma and hMLH1 promoter hypermethylation in the surrounding mucosa.

Gastric cancer has striking heterogeneity in histological pattern, cellular phenotype, genotype, biomarkers, and biological behavior. We focused on the specific morphological papillary phenotype of gastric adenocarcinoma and attempted to identify its distinct molecular characteristics. In our comparative study, early stage papillary (papillary-dominant) gastric cancer showed a significantly higher and more widespread high-frequency microsatellite instability (MSI-H) than other morphological types. Analysis of mutations in a panel of five putative microsatellite instability (MSI)-associated genes in the MSI-H cases revealed that papillary or papillary-dominant cancer displays a unique profile of mutations compared to profiles previously reported in gastric cancer. Immunohistochemical staining and methylation analysis revealed that silencing of hMLH1 by methylation in its promoter region was responsible for the failure of mismatch repair in papillary-type gastric cancer, whereas aberrant promoter methylation of hMLH1 was not found in any cases without the unique mutator phenotype. Promoter hypermethylation of the hMLH1 genes was found to a lesser degree in the adjacent non-tumor mucosa in four of the 10 cases with tumor having the mutator phenotype. Microsatellite instability itself could not be detected in the adjacent non-tumor mucosa. Inactivation of hMLH1 expression by promoter hypermethylation may be an early event in carcinogenesis of this type of gastric cancer, preceding the development of the clear MSI phenotype of papillary carcinoma.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Low power diode laser treatment using indocyanine green for eradication of esophageal varices.

BACKGROUND AND STUDY AIMS: Endoscopic variceal ligation (EVL) is an alternative to sclerotherapy for the treatment of esophageal varices, but is associated with higher rates of recurrence and subsequent bleeding than sclerotherapy. To prevent recurrence of varices after EVL, we have developed a low-dose diode laser therapy combined with the injection of indocyanine green, which allows enhanced tissue absorption of the laser beam selectively around varices. In this study we investigated the efficacy and safety of this technique. PATIENTS AND METHODS: Eight patients with F2 or F3 esophageal varices were enrolled. At 1 week after EVL, indocyanine green solution (1 mg/ml) was injected submucosally around the remaining varices. A diode laser (power 10 watts) was applied to the surface from the esophagogastric junction to 5 cm above it. The spot size was kept to 5 mm in diameter. RESULTS: Laser irradiation was performed safely, without bleeding from the varices, or perforation. There were no major complications. Endoscopy 1 month later showed F0 forms in seven patients, F1 in one patient, and no red color sign in any patient. No recurrence of varices has been observed in any of the patients during the follow-up period of at least 12 months. CONCLUSION: This technique may provide a simple, safe and effective procedure, as an additional treatment to EVL, for the prevention of recurrence of esophageal varices.

Adult↗
PubMed2001

Removal of digoxin by column for specific adsorption of beta(2)-microglobulin: a potential use for digoxin intoxication.

BACKGROUND: A beta(2)-microglobulin adsorption column used for the treatment of dialysis-related amyloidosis removes serum beta(2)-microglobulin by recognition of lipophilic residue in the protein. No data are available for the adsorption of the highly lipophilic drug digoxin. METHODS: In vivo clearance of digoxin with the beta(2)-microglobulin column was measured by a single use of the column in 8 patients receiving hemodialysis with a therapeutic level of digoxin. In vitro adsorption was evaluated by use of incubation with adsorbent of the column and digoxin or ranitidine, a hydrophilic drug. Clearance with the beta(2)-microglobulin column was further compared with that obtained by use of activated charcoal in the dogs intoxicated with digoxin. RESULTS: Digoxin concentration was reduced from 1.11 +/- 0.25 ng/mL to 0.57 +/- 0.15 ng/mL at 240 minutes after initiation of hemoperfusion with the column in the patients. Digoxin clearance with the beta(2)-microglobulin column was about 145 +/- 20 mL/min, with a blood flow rate of 160 to 220 mL/min (80% of plasma flow rate). Eighty-five percent of digoxin was adsorbed in vitro, and the capacity of the beta(2)-microglobulin column was not saturated until a toxic level was reached (50 ng/mL). This value was higher than that obtained with use of charcoal. In dogs with digoxin intoxication, digoxin clearance was 38.9 +/- 1.5 mL/min, with a blood flow rate of 50 mL/min (95% of plasma flow rate), which was almost twice as that achieved with charcoal. The degree of thrombocytopenia and leukopenia was small with use of the beta(2)-microglobulin column. CONCLUSION: These data suggested that the beta(2)-microglobulin column selectively adsorbs digoxin. This column is a promising tool for the treatment of digoxin intoxication, especially in patients undergoing hemodialysis.

Adsorption↗
PubMed2001

Use of chemically extracted muscle grafts to repair extended nerve defects in rats.

Nerve regeneration, measured as axonal outgrowth, Schwann cell migration, macrophage invasion, and neovascularisation, was compared after repair of a 15 mm gap in rats' sciatic nerves using autologous muscle grafts made acellular either by freezing and thawing or by chemical extraction. Both extracted and freeze-thawed acellular muscle grafts could be used to bridge the defect. However, axons and Schwann cells, as shown by immunohistochemical staining for neurofilaments and S-100 protein, respectively, grew faster into the extracted muscle grafts than into the freeze-thawed acellular muscle grafts and somewhat more axons were observed in the former graft. There were no significant differences between the two graft types with respect to neovascularisation as showed by staining for endothelial alkaline phosphatase, and limited differences concerning invasion of macrophages (ED1 and ED2) as detected by immunocytochemistry. The results showed that chemically extracted muscle grafts could be used to bridge an extended nerve defect and that such grafts in some aspects were superior to freeze-thawed muscle grafts for extended gaps.

Alkaline Phosphatase↗
PubMed2001

Transient right phrenic nerve palsy associated with central venous catheterization.

An 85-yr-old woman with advanced sigmoid colon cancer developed right phrenic nerve palsy following central venous catheterization for preoperative nutritional and fluid balance improvement. The central venous catheter was successfully placed via the left subclavian vein at the first attempt. Blood returned freely through the catheter. The chest x-ray film taken immediately after the catheterization showed the proper placement of the catheter, but it revealed a significant right hemidiaphragmatic elevation indicating phrenic nerve palsy. A chest computed tomography scan and bronchoscopy were normal. As the patient did not complain of dyspnoea and vital signs were normal, tumour resection was performed. The operative and postoperative course was uneventful. The chest x-ray film after the surgery still showed the elevation of the right hemidiaphragm. It resolved completely within 3 days of withdrawing the central venous catheter by 3 cm on the fourth postoperative day. We concluded the likely cause of the phrenic nerve palsy was that the catheter tip impinged upon the thin venous wall and compressed the phrenic nerve running alongside the superior vena cava.

Aged↗
PubMed2001

Blockade of central histaminergic H2 receptors aggravates ischemic neuronal damage in gerbil hippocampus.

OBJECTIVE: Histaminergic H2 antagonists have been reported to provoke central nervous system dysfunction in humans. They also aggravate ischemic neuronal damage in experimental animals. Because energy failure and glutamate release are crucial factors in ischemic neuronal damage, the effects of ranitidine on energy state and the extracellular concentration of glutamate were investigated in gerbil brain. DESIGN: Prospective, randomized, controlled animal study. SETTING: University animal laboratory. SUBJECTS: Male Mongolian gerbils. INTERVENTIONS: The changes in the direct-current potential shift in the hippocampal CA1 area produced by transient forebrain ischemia for 2.5 mins were compared in gerbils pretreated with saline or ranitidine (10 nmol) intracerebroventricularly. The histologic outcome was evaluated 7 days after ischemia by observing the delayed neuronal death in these animals. In a second study, brain concentrations of adenosine 5'-triphosphate after various durations of decapitation ischemia were determined, and the effect of ranitidine was evaluated. In a third experiment, changes in the extracellular concentrations of excitatory amino acids during forebrain ischemia were examined by a microdialysis procedure. MEASUREMENTS AND MAIN RESULTS: The forebrain ischemia produced a sudden shift in the membrane potential 62 +/- 5 secs (mean +/- sd, n = 6) after the start of ischemia. The preischemic administration of ranitidine facilitated onset of depolarization (38 +/- 8 secs; p <.01). The histologic outcome was aggravated by ranitidine (p <.01). Decapitation ischemia reduced brain adenosine 5'-triphosphate concentration rapidly. Ranitidine facilitated the ischemic reduction in adenosine 5'-triphosphate, and the value after 1 min was 55% of that in the corresponding saline group (p <.01). Ranitidine enhanced the ischemic increase in the glutamate concentration, and the peak value in the ranitidine group was 316% of that in the saline group (p <.05). CONCLUSION: The deleterious effect of ranitidine on ischemic neuronal damage may involve the increase in the extracellular concentration of glutamate and facilitation of energy depletion in an anaerobic state.

Adenine Nucleotides↗
PubMed2001

Calcium concentration and pH of the periapical environment after applying calcium hydroxide into root canals in vitro.

The purpose of the present study was to determine both calcium concentration and pH in the periapical region after application of 1 of 4 different calcium hydroxide preparations into experimental root canals. Fifty root canal models were divided into five groups: group 1--calcium hydroxide was mixed with distilled water at a powder/water weight ratio of 38%; group 2--calcium hydroxide was mixed with distilled water at 44%; group 3--calcium hydroxide was mixed with distilled water at 50%; group 4--calcium hydroxide powder only was used; and group 5-the control group, in which nothing was applied to the canals. All samples were immersed in distilled water maintained at 37 degrees C. Calcium concentration and pH of the distilled water were measured after 3 days, 7 days, and then at weekly intervals up to 15 wk, during which time the storage medium was renewed after each measurement. Calcium concentration and the change in pH of the distilled water were statistically quicker and greater in groups 1 to 3 (mixture groups) than group 4 (powder only) (p < 0.05). The highest calcium concentration (peak Ca2+ release) was observed after 3 days for the mixture groups, whereas that for the powder only group was found at 7 days. Peak pH change was found after 14 days for the mixture groups, whereas that for the powder only group was found at 49 days. After peaking, all groups showed a decline of the pH over time. These results suggest that the time required for optimum intracanal activity when using calcium hydroxide mixtures is at least 2 wk.

Analysis of Variance↗
PubMed2001

Determining the temperature distribution of a model vessel wall under pulsed laser irradiation: an experimental attempt to measure fibrous cap thickness and detect temperature elevation in atherosclerotic lesions.

In order to measure the temperature of atherosclerotic plaques, we developed a method to determine the temperature distribution of vessel walls using a three-layer phantom agar model. Under pulsed-laser irradiation, the thickness of upper layer corresponding to fibrous cap overlying the middle layer corresponding to atherosclerotic lesion could be calculated. The temperature was calculated from measured temperature changes under pulsed-laser irradiation.

Aorta↗
PubMed2001

The role of the mora in the timing of spontaneous Japanese speech.

This study investigates whether the mora is used in controlling timing in Japanese speech, or is instead a structural unit in the language not involved in timing. Unlike most previous studies of mora-timing in Japanese, this article investigates timing in spontaneous speech. Predictability of word duration from number of moras is found to be much weaker than in careful speech. Furthermore, the number of moras predicts word duration only slightly better than number of segments. Syllable structure also has a significant effect on word duration. Finally, comparison of the predictability of whole words and arbitrarily truncated words shows better predictability for truncated words, which would not be possible if the truncated portion were compensating for remaining moras. The results support an accumulative model of variance with a final lengthening effect, and do not indicate the presence of any compensation related to mora-timing. It is suggested that the rhythm of Japanese derives from several factors about the structure of the language, not from durational compensation.

Adult↗
PubMed2001

Vitamin D receptor gene polymorphism detected by digestion with Apa I influences the parathyroid response to extracellular calcium in Japanese chronic dialysis patients.

BACKGROUND: To play its physiological role, 1,25(OH)2D3 must bind to a specific vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR gene polymorphism influences the parathyroid function in patients with end-stage renal disease (ESRD). In the present study, we have investigated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca2+ in the dialysate. METHODS: 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Genomic DNA was extracted from peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then alleles were classified into genotype A (undigested allele) and genotype a (digested allele). Extracellular ionized calcium ([Ca2+]e), serum phosphate, and intact parathyroid hormone (PTH) were measured before and after each hemodialysis (HD) session with dialysates having different concentrations of Ca2+ (1.5 or 1.25 mmol/l). The significance of differences in statistical analyses was defined within confidence limits of 5.0%. RESULTS: The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly higher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was significantly higher (p = 0.0112) in group aa (50.2 +/- 9.4%) than in group AA+Aa (19.7 +/- 7.2%). There were no significant differences between the two groups in [Ca2+]e nor in serum phosphorus (Pi) before and after HD with either dialysate. Group AA+Aa and group aa did not show statistically significant differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis period. CONCLUSIONS: The study results showed that the patients in group aa were more sensitive to changes in [Ca2+]e than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca2+]e, which in turn may influence onset and progression of hyperparathyroidism in ESRD patients.

Alleles↗
PubMed2001

Temperature measurement for energy-efficient ablation by thermal radiation with a microsecond time constant from the corneal surface during ArF excimer laser ablation.

Measurement of the temperature of the corneal surface during photorefractive keratectomy (PRK) is thought to be useful for monitoring the corneal ablation process, since the photothermal process has been proposed as the major mechanism of ArF excimer laser ablation. For temperature measurement, we measured thermal radiation from the corneal surface during ArF excimer laser ablation using a mercury-cadmium-telluride detector with a 1-micros time constant. To investigate the effects of temperature on ablation depth, the ablation depth of the cornea was measured by microscopy. When corneal ablation was initiated at the fluence of 65 mJ/cm2, the corneal surface temperature rose to 60-70 degrees C. The energy required for a unit-depth ablation (degrees C/microm) was lowest at 120 micro C. Monitoring of transient temperature during PRK provides important information on energy-efficient ablation, which may enable rapid and safe corneal incisions.

Animals↗
PubMed2001

Microsatellite instability in transforming growth factor-beta 1 type II receptor gene in alveolar lining epithelial cells of idiopathic pulmonary fibrosis.

It has been reported that transforming growth factor (TGF)-beta, which plays an integral role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), suppresses proliferation of alveolar epithelial cells in vitro. Although hyperplastic lesions of alveolar lining epithelial cells (ALECs) are characteristic pathologic features of IPF, the mechanism of their involvement in the pathogenesis has not yet been extensively studied. On the assumption that the hyperplastic ALECs have escaped from the growth-inhibitory effects of TGF-beta, we searched for mutations in the microsatellite of the TGF-beta receptor type II (T beta RII) gene. To detect a deletion in the polyadenine tract in exon 3 of the T beta RII gene, cells were isolated by microdissection from lung sections of IPF patients, and DNA was extracted from these cells and amplified by high-fidelity polymerase chain reaction. A total of 121 sites of hyperplastic ALECs from 11 IPF patients were analyzed, and a one-base-pair deletion was detected in nine sites from five patients. The mutation was also detected in smooth muscle-like cells of the thickened pulmonary artery. In some tissue areas where the deletion was detected, low T beta RII expression was confirmed by immunohistochemical staining. These data suggest that microsatellite instability in the T beta RII gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low incidence, and that this genetic disorder might play a partial role in the pathologic changes of IPF.

Adult↗
PubMed2001

Inactivation of rat cytochrome P450 2D enzyme by a further metabolite of 4-hydroxypropranolol, the major and active metabolite of propranolol.

Repetitive administration of propranolol (PL) in rats decreases the activities of cytochrome P450 (CYP) 2D enzyme(s) in hepatic microsomes. We examined the properties of 4-hydroxypropranolol (4-OH-PL) as an inactivator of rat liver microsomal CYP2D enzyme(s) using bunitrolol (BTL) 4-hydroxylation and PL 5- and 7-hydroxylations as indices of CYP2D enzyme activity. Rat microsomal BTL 4-hydroxylase activity was inhibited by the addition of 4-OH-PL to the incubation medium. The inhibition was greater after preincubation of microsomes with 4-OH-PL in the presence of NADPH than in its absence. The type of inhibition kinetics of BTL 4-hydroxylase by 4-OH-PL was changed from a competitive type to a noncompetitive type by the preincubation. The inhibition of rat liver microsomal PL 5- and 7-hydroxylases by 4-OH-PL was blocked efficiently by co-incubation with quinine, a typical inhibitor of rat CYP2D enzyme(s), or to a lesser extent by BTL. However, quinidine, a diastereomer of quinine, did not significantly protect against the enzyme inactivation. The protective capacities of the substrate and inhibitors reflected their affinities for rat CYP2D enzyme(s). BTL hydroxylase was not affected by either 1,4-naphthoquinone or 1,4-dihydroxynaphthalene which are possible metabolites of 4-OH-PL. These results provide further evidence to support the notion that PL is biotransformed by rat CYP2D enzyme(s) to 4-OH-PL, which is further oxidized to a chemically reactive metabolite in the active site. The inactivation of CYP is likely the result of covalent binding of the reactive species to an amino acid residue of the active site.

Adrenergic beta-Antagonists↗
PubMed2001

Effect of herb supplement on hepatic enzyme activities in ddY mice.

Plasma glucose and lipid concentrations and hepatic enzyme activities were measured in male ddY mice supplemented with the herb, Echevaria glauca, to examine the effect of herbal treatment. In mice supplemented with the herb, plasma triglyceride (TG) and free fatty acid (FFA) concentrations decreased and hepatic glycolytic enzyme and glutathione peroxidase (GSHpx) activities increased significantly compared with those in the non-treated control mice. These increases in hepatic enzyme activities were not fully dose-dependent, however the higher dose and longer duration with herb supplement induced increases in the enzyme activities. It was found that dietary herb supplement caused an acceleration of hepatic function, judged by increased activities of glycolytic enzyme and GSHpx in ddY mice.

Administration, Oral↗
PubMed2001

Sequence of the Clostridium thermocellum mannanase gene man26B and characterization of the translated product.

The man26B gene of Clostridium thermocellum strain F1 was found in pKS305, which had been selected as a recombinant plasmid conferring endoglucanase activity on Escherichia coli. The open reading frame of man26B consists of 1,773 nucleotides encoding a protein of 591 amino acids with a predicted molecular weight of 67,047. Man26B is a modular enzyme composed of an N-terminal signal peptide and three domains in the following order: a mannan-binding domain, a family 26 mannanase domain, and a dockerin domain responsible for cellulosome assembly. We found that this gene was a homologue of the man26A gene of C. thermocellum strain YS but that there were insertion or deletion mutations that caused a frame-shift mutation affecting a stretch of 26 amino acids in the catalytic domain. Man26B devoid of the dockerin domain was constructed and purified from a recombinant E. coli, and its enzyme properties were examined. Immunological analysis indicated that Man26B was a catalytic component of the C. thermocellum F1 cellulosome.

Amino Acid Sequence↗