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T Asai

Publications and source records attributed to T Asai.

At least 73 records · Page 4Linked to original sources
PubMed2002

Substitution of Dmo1 with normal alleles results in decreased manifestation of diabetes in OLETF rats.

AIM: Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes in the Otsuka Long Evans Tokushima Fatty (OLETF) rat strain. To evaluate possible metabolic and pathological improvements generated by correction of the Dmo1 genetic pathway, we produced congenic lines, in which both OLETF Dmo1 alleles are replaced by the F344-derived genome. METHODS: Congenic animals were produced by introgressing F344-derived Dmo1 alleles into the OLETF rat. Congenic animals of the fourth generation (BC4) were intercrossed to obtain F1 animals (BC4:F1). Animals of the next generation, BC4:F2, were used for this study. We used 23 BC4:F2 males harbouring homozygous replacement of the OLETF Dmo1 region with the F344-derived genome. Seven animals with OLETF-derived Dmo1 alleles were used as controls. RESULTS: Dmo1-F344/F344 congenic rats showed significant decreases in body weight, abdominal fat weight, serum triacylglycerols, total cholesterol, food consumption and blood glucose after glucose loading (13%, 39%, 45%, 27%, 18% and 27% respectively; p < 0.05) compared with Dmo1-OLETF/OLETF animals. Furthermore, histopathological analysis of the kidney showed that mesangial sclerosis, hyalin deposits and deposition of PAS-positive substance were significantly lower in Dmo1-F344/F344 animals (p < 0.05). CONCLUSION: Improvements in metabolic parameters and histopathological scores show that correction of the Dmo1 genetic pathway in the diabetic and mildly obese OLETF rat strain produces wide-ranging therapeutic effects. Thus, this pathway might represent a new drug target also applicable to humans.

Animals↗
PubMed2002

Mobilization factors of peripheral blood stem cells in healthy donors.

As a source of hematopoietic stem cells for transplantation, the use of peripheral blood stem cells (PBSCs) has become routine and comparable to that of the use of bone marrow. Recently, elderly patients with hematological malignancies also have been allowed to receive minitransplantations with nonmyeloablative conditioning regimens under sufficient PBSC infusion. As a result of these minitransplantations, elderly donors have been chosen increasingly from the siblings of elderly patients. We analyzed factors influencing the condition of CD34+ cells in the first days of collection in 49 healthy donors from July 1995 to January 2001. The median dose of recombinant human granulocyte colony-stimulating factor was 8 microg/kg/day (range 8 - 10) over 3 days. The target number of CD34+ cells used in this study was > or = 3 x 10(6) cells/kg of recipient body weight. The median apheresis volume was 12 L. Except for one 60 year old man, we obtained an adequate number of stem cells. In the regression analysis, a negative correlation was seen between donor age and the number of CD34+ cells/kg of recipient body weight per 12 L volume (Y = aX + b; a = -0.07507; b = 6.629996; r = -0.50985; p = 0.000252). Significantly higher apheresis results were obtained in donors younger than 45 years compared with donors 45 years old and older (p < 0.0227). There were no correlations among the number of CD34+ cells, donor body weight, and the number of leukocytes in peripheral blood on the first day of apheresis.

Adolescent↗
PubMed2002

The laryngeal tube compared with the laryngeal mask: insertion, gas leak pressure and gastric insufflation.

BACKGROUND: We have compared the laryngeal tube and laryngeal mask in 22 patients for the success rate of insertion, gas leak pressure and the incidence of gastric insufflation. METHOD: In a randomized, crossover design, the laryngeal tube and laryngeal mask were inserted in turn after induction of anaesthesia and neuromuscular block. The cuffs were inflated until the intracuff pressure reached 60 cm H(2)O. We measured adequacy of ventilation and the minimum airway pressure at which gas leaked around the cuff. The presence or absence of gastric insufflation was studied at an inflation pressure of 20 cm H(2)O. RESULTS: It was possible to ventilate through the laryngeal tube in 21 patients and through the laryngeal mask in 21 patients. The mean leak pressure for the laryngeal tube (26 (SD 5) cm H(2)O) was significantly greater than that for the laryngeal mask (19 (4) cm H(2)O) (P<0.01; 95% confidence intervals for mean difference: 5.3-10.2 cm H(2)O). Gastric insufflation did not occur when the laryngeal tube was used and was noted in three patients when the laryngeal mask was used. CONCLUSION: The laryngeal tube provides a better seal in the oropharynx than the laryngeal mask.

Adolescent↗
PubMed2001

Endothelin-1 gene variant associates with blood pressure in obese Japanese subjects: the Ohasama Study.

A recent report based on the results of 2 epidemiological studies, the Etude Cas-Temoin de l'Infarctus Myocarde (ECTIM) and the Glasgow Heart Scan Study, revealed that a G/T polymorphism with an amino acid substitution (Lys-->Asn) at codon 198 in exon 5 of the endothelin-1 gene (ET-1) is associated with blood pressure in overweight people. They suggested that G/T polymorphism of ET-1 strongly interacted with body mass index (BMI) in the determination of BP levels. To examine interaction among G/T polymorphism of ET-1, BMI, and BP, we performed an association study in a general Japanese population. Subjects (n=1250) were recruited from Ohasama, a cohort in a rural community of northern Japan. DNA was extracted from buffy coat of participants, and G/T polymorphism of ET-1 was determined by the TaqMan probe polymerase chain reaction method, a powerful tool for semiautomatic genotype determination of a large number of samples. Frequency of T (Asn 198) allele in Japanese (27%) was slightly but significantly higher than in whites (24%). Baseline characteristics (age, BMI, systolic and diastolic BP, and antihypertensive treatment) of all subjects were not significantly different according to the genotype of G/T polymorphism. However, in obese subjects (> or =25 kg/m(2)) diastolic BPs were significantly associated with G/T polymorphism of ET-1. After adjustment for confounding factors, significant association remained; for overweight subjects, diastolic BP level in those with T allele (GT + TT) was 1.8 mm Hg (P=0.04) higher than in those with GG genotype. That similar results were obtained from subjects of different races suggests that the Lys198Asn polymorphism of ET-1 is involved in determination of BP levels in obese subjects.

Asian People↗
PubMed2001

Additive effects of nicorandil on coronary blood flow during continuous administration of nitroglycerin.

OBJECTIVES: We examined whether patients with ischemic heart disease (IHD) should be treated with nicorandil, an adenosine triphosphate-sensitive potassium channel opener, in addition to the regular use of nitrates. BACKGROUND: It has been reported that nicorandil possibly has additive effects on nitroglycerin (NTG) treatment for angina, but the mechanism is not clear. METHODS: We directly measured anterograde coronary blood flow (CBF) with a Doppler guide wire to examine the effects of intravenous administration of NTG (0.3 mg) and nicorandil (6 mg) during continuous administration of NTG at a sufficient dose (25 microg/min) in subjects with normal and stenotic coronary arteries. RESULTS: Additional systemic administration of NTG decreased anterograde CBF (normal -19.7%; stenotic -21.2%). In contrast, nicorandil increased anterograde CBF in both normal (54.6%) and stenotic (89.6%) coronary arteries, without the coronary steal phenomenon. There was a tendency toward nicorandil-dilated diameters in the patients with stenotic arteries (p = 0.06). There were no effects of additional administration on pulmonary artery wedge pressure. There was no difference in changes in heart rate and mean aortic blood pressure between NTG and nicorandil therapy. CONCLUSIONS: These results suggest that in patients treated with nitrates, additional administration of nicorandil is more useful, in terms of increasing CBF, than additional administration of nitrates. Adjunctive use of nicorandil with nitrates may provide the further benefit of myocardial protection and may improve the prognosis of patients with IHD.

Aged↗
PubMed2001

Targeting and anti-tumor efficacy of liposomal 5'-O-dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine in mice lung bearing B16BL6 melanoma.

2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (CNDAC) is a potent anti-cancer agent, and we previously observed that liposomal formulation of 5'-O-dipalmitoylphosphatidyl derivative of CNDAC (DPP-CNDAC) is desirable for targeting. For targeting to pulmonary cancer, we investigated the in vivo behavior of liposomes containing DPP-CNDAC by a non-invasive method using positron emission tomography. Liposomes composed of DPP-CNDAC and cholesterol (DPP-CNDAC/CH liposomes) were markedly accumulated in mice lung bearing B16BL6 melanoma. In metastatic pulmonary cancer model, DPP-CNDAC/CH liposomes significantly reduced the lung colonization in a dose-dependent manner. The activity was significantly superior to conventional liposomal formulation or soluble CNDAC. These results suggest that DPP-CNDAC/CH liposomes are useful for metastatic pulmonary cancer.

Animals↗
PubMed2001

Case report: a normal capnogram despite esophageal intubation.

PURPOSE: To report a case of accidental esophageal intubation which could not be detected by capnography. CLINICAL FEATURES: A 43-yr-old man with osteogenic sarcoma of the mandible underwent mandibulectomy, radical neck dissection, reconstruction of the mandible and radiation therapy. He was scheduled for revision surgery to the mandible. He had a limited mouth opening and neck movement after operation and radiation. After the cuffed oropharyngeal airway (COPA) was inserted, anesthesia was induced with sevoflurane, and fibreoptic nasotracheal intubation attempted, but it was impossible to insert the fibrescope into the trachea because of a deformed larynx. While equipment for tracheostomy was prepared, one last attempt was made to insert the tube blindly into the trachea. The capnograph showed apparently normal carbon dioxide waveforms, and the reservoir bag inflated and deflated regularly. However, immediately after inflation of the cuff of the tracheal tube the reservoir bag movement stopped and CO(2) waveforms disappeared. Fibreoptic bronchoscopy showed that the tube was in fact in the esophagus. It was then noticed that the patient was still breathing spontaneously through the cuffed airway. The patient was awakened and tracheostomy performed. It was considered that egress of the expired gas was partially prevented by the cuffed airway, pooled in the oral cavity, aspirated down the esophagus during inspiration (likely to be due to negative intrathoracic pressure) and pushed out through the tube during expiration; inflation of the cuff prevented the gas entering the esophagus. CONCLUSION: Under such exceptional circumstances, apparently normal carbon dioxide waveforms were observed despite esophageal intubation in a spontaneously breathing patient.

Adult↗
PubMed2001

Glycation cross-links inhibit matrix metalloproteinase-2 activation in vascular smooth muscle cells cultured on collagen lattice.

AIMS/HYPOTHESIS: Extracellular matrix glycation has been proposed to contribute to the arterial stiffness observed in aging and diabetes. We examined whether matrix protein glycation regulates the proleolytic process through the manipulation of matrix metalloproteinases (MMPs) activation, using collagen fibrils model. METHODS: Vascular smooth muscle cells were cultured on control or glycated collagen fibrils. Matrix metalloproteinase-2 activation and the production of tissue inhibitors of metalloproteinase (TIMPs) were measured in the conditioned medium by using gelatin zymography and immunoblotting. Membrane type 1 matrix metalloproteinase (MT1-MMP) expression was also measured in cell lysates. RESULTS: When smooth muscle cells were cultured on collagen fibrils, pro-MMP-2 processing to active form was observed in the conditioned medium in coincidence with the increased MT1-MMP expression and the suppressed TIMP-2 production. Culturing smooth muscle cells on glycated collagen fibrils inhibited MMP-2 activation and attenuated MT1-MMP expression without the alteration of TIMP-2 production compared with control fibrils, indicating the possible mechanism of the suppression of MT1-MMP expression for the inhibition of MMP-2 activation on glycated collagen fibrils. Inclusion of aminoguanidine, an inhibitor of cross-linking formation, during collagen glycation restored the MMP-2 activation, suggesting the role of cross-links on the inhibition of MMP-2 activation. CONCLUSION/INTERPRETATION: These observations suggest that glycation-induced cross-linking formation in interstitial collagen contributes to arterial stiffness in aging and diabetes through the manipulation of matrix metalloproteinase activation along with the reduction of the susceptibility to proteolytic enzymes.

Cell Adhesion↗
PubMed2001

Rho-Rho kinase is involved in smooth muscle cell migration through myosin light chain phosphorylation-dependent and independent pathways.

Although Rho, a small GTPase, has been demonstrated to play an important role in the smooth muscle contraction and relaxation, little is known about the involvement of Rho protein in smooth muscle cell (SMC) migration. In this study the role of Rho-Rho kinase pathway was examined in SMC migration induced by platelet-derived growth factor (PDGF) and lysophosphatidic acid (LPA). C3 transferase, a specific inhibitor of Rho, blocked SMC migration induced by PDGF and LPA. Y-27632, a specific inhibitor of Rho kinase, a direct target molecule of Rho, inhibited PDGF and LPA-induced SMC migration in a concentration dependent manner. Although rapid increase in myosin light chain (MLC) phosphorylation in SMC treated with LPA was observed, no enhanced MLC phosphorylation was detected in response to PDGF. Y-27632 suppressed LPA-induced as well as basal level of MLC phosphorylation. ML-9, a specific inhibitor of myosin light chain kinase (MLCK), inhibited PDGF and LPA-induced SMC migration without the suppression of MLC phosphorylation at 5 min incubation, suggesting that MLCK may contribute to SMC migration via mechanism other than MLC phosphorylation. These results suggest that Rho-Rho kinase pathway is implicated in SMC migration and that different signaling pathways downstream of Rho-Rho kinase may be involved in LPA and PDGF-induced SMC migration. MLC phosphorylation via Rho-Rho kinase pathway appears to be implicated in LPA-dependent SMC migration. Whereas PDGF-mediated SMC migration is independent of increased MLC phosphorylation and other target molecules downstream of Rho-Rho kinase seem to be involved.

Amides↗
PubMed2001

Plant mitogen-activated protein kinase signaling cascades.

Mitogen-activated protein kinase (MAPK) cascades have emerged as a universal signal transduction mechanism that connects diverse receptors/sensors to cellular and nuclear responses in eukaryotes. Recent studies in plants indicate that MAPK cascades are vital to fundamental physiological functions involved in hormonal responses, cell cycle regulation, abiotic stress signaling, and defense mechanisms. New findings have revealed the complexity and redundancy of the signaling components, the antagonistic nature of distinct pathways, and the use of both positive and negative regulatory mechanisms.

Adaptation, Physiological↗
PubMed2001

Purification and identification of major soluble 40-kDa antigenic protein from Entamoeba histolytica: its application for serodiagnosis of asymptomatic amebiasis.

One of the major soluble antigenic proteins of Entamoeba histolytica was purified to homogeneity and identified on a molecular basis. Its recombinant protein was expressed in Escherichia coli as a fusion protein with Shistosoma japonicum glutathione S-transferase. Apparent molecular weight of the purified antigenic protein was estimated to be 40-kDa and molecular-based analysis indicated that the purified protein was NADP+-dependent alcohol dehydrogenase (EhADH1). The application of the purified protein for the serodiagnosis of amebiasis was evaluated using an enzyme-linked immunosorbent assay applied to sera obtained from patients with amebiasis and healthy human controls. The purified protein was well recognized by the sera from asymptomatic amebiasis humans (22/22, 100%), whereas, it was less recognized by the sera from symptomatic amebiasis patients (5/16, 31%) with amebic colitis or liver abscess. To confirm the antigenicity of EhADH1, the recombinant glutathione S-transferase-EhADH1 fusion protein was also evaluated by the enzyme-linked immunosorbent assay using the same sera. The recombinant protein was also recognized by the sera from asymptomatic amebiasis humans (14/22, 64%) and less recognized by the sera from symptomatic amebiasis patients (2/16, 13%). These results suggest that the purified protein is applicable antigen for serodiagnostic screening of asymptomatic amebiasis humans.

Animals↗
PubMed2001

Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain.

Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using marker-assisted speed congenic protocols, enforced by selective removal of other QTL regions (QTL-marker-assisted counterselection), to efficiently transfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into the OLETF background. In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. We conclude that single-allele correction of an impaired genetic pathway can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Alleles↗
PubMed2001

Tracheal intubation through the intubating laryngeal mask in patients with unstable necks.

BACKGROUND: In patients with unstable necks, the neck should be stabilized during induction of anaesthesia, but this may make tracheal intubation difficult. Awake intubation may produce straining, which could be detrimental to the unstable neck. METHODS: We studied 20 patients with unstable necks to examine the efficacy of insertion of the intubating laryngeal mask under conscious sedation (to minimize the possibility of losing a patent airway and to facilitate fibrescope-aided intubation) followed by tracheal intubation through the laryngeal mask after induction of anaesthesia (to reduce stress response to intubation). After the patient had been sedated with midazolam (up to 5 mg) and fentanyl (up to 100 microg), the intubating laryngeal mask was inserted. General anaesthesia was then induced with sevoflurane and tracheal intubation attempted. RESULTS: In all patients, tracheal intubation through the laryngeal mask succeeded without airway obstruction. Neither insertion of the mask under conscious sedation nor tracheal intubation after induction of anaesthesia caused straining, and only two patients moved upper extremities at intubation. Insertion of the laryngeal mask did not significantly alter blood pressure or heart rate. Tracheal intubation significantly increased blood pressure and heart rate, but the increase was considered to be small. CONCLUSIONS: In the patient with an unstable neck with a low risk of pulmonary aspiration, insertion of the intubating laryngeal mask while the patient is sedated may minimize difficulty in obtaining a patent airway before tracheal intubation and may facilitate a fibrescope-aided tracheal intubation; subsequent induction of anaesthesia before tracheal intubation may minimize stress response to intubation.

Adult↗