Biomedical subjects

T Adachi

Publications and source records attributed to T Adachi.

At least 37 records · Page 2Linked to original sources

PubMed2003

Long-term therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor, in spontaneous diabetic GK rats.

The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190+/-19 vs. 250+/-25 mg/dl, P<0.01; 1 h, 212+/-23 vs. 256+/-20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase-isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration.

Alkaline Phosphatase↗

PubMed2003

Mucosal sulfhydryl compounds evaluation by in vivo electron spin resonance spectroscopy in mice with experimental colitis.

BACKGROUND: Sulfhydryl (SH) compounds are essential in maintaining mucosal integrity in the gastrointestinal tract. A decrease in colonic mucosal SH compounds affects the redox status of the mucosa, resulting in vulnerability to further attacks. Therefore, there is a strong need for in vivo evaluation of SH compounds in the colonic mucosa. AIMS: The aim of the current study was to establish a method of evaluating levels of SH compounds in the colonic mucosa of live animals before and after induction of colitis. METHODS: Murine experimental colitis was induced by instillation of trinitrobenzene sulphonic acid (TNBS) dissolved in 50% ethanol into the colon via the anus. For evaluation of mucosal SH compounds in the colon, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL), a stable nitroxide radical, was instilled into the colonic lumen of live mice and the spin clearance rate was measured by L-band electron spin resonance (ESR) spectroscopy. RESULTS: Morphological study showed that mucosal damage was severe one or two days after TNBS instillation. The colonic mucosa started to regenerate at four days, and looked normal at seven days, after induction of colitis. The spin clearance rate of carbamoyl-PROXYL decreased significantly at 0.5, 1, 2, and 4 days after induction of colitis compared with mice before TNBS instillation. Surprisingly, although the colonic mucosa looked normal seven days after TNBS administration, the spin clearance rate still remained significantly slow. The spin clearance rate returned to normal 14 days after induction of colitis. The change in in vivo spin clearance rate was consistent with the time dependent change in mucosal reduced glutathione, a major component of SH compounds. CONCLUSION: The spin clearance rate obtained by L-band ESR spectroscopy in combination with carbamoyl-PROXYL can give an estimate of the level of colonic mucosal SH compounds in live animals and is useful for evaluating the mucosal defence system against oxidative stress.

Animals↗

PubMed2003

Upregulated response to chemokines in oxidative metabolism of eosinophils in asthma and allergic rhinitis.

Reactive oxygen species (ROS) from eosinophils are known to cause tissue damage in allergic inflammation. CC chemokines, especially eotaxin and regulated on activation, normal T-cell expressed and secreted (RANTES), are involved not only in chemotaxis but also in eosinophil activation, such as ROS production. It has been shown that eosinophils from allergic patients are not functionally equivalent to those from normal subjects. In the present study, the characteristics of chemokine-primed ROS production in eosinophils from allergic patients and normal controls were compared. After pretreatment with chemokines, eosinophils were stimulated with calcium ionophore A23187. ROS production by eosinophils was measured using luminol-dependent chemiluminescence. Both RANTES and eotaxin exhibited a priming effect on calcium ionophore-induced ROS production from eosinophils. Despite there being no difference in expression of CC chemokine receptor 3, the priming effect of RANTES and eotaxin was significantly enhanced in eosinophils from the patients. Interleukin-5 further enhanced the priming effect of chemokines in eosinophils from normal subjects, but not those from allergic subjects. The present results suggest an upregulated response to chemokines in eosinophils from allergic patients, and that interleukin-5 can induce a similar phenotype to that found in vivo in allergic patients.

Adolescent↗

PubMed2003

[Video-assisted thoracic surgery for the resection of pulmonary metastases].

We report the use of video-assisted thoracic surgery (VATS) as a treatment or pulmonary metastases. Between July 1994 and March 2002, 75 patients were treated for metastatic lung tumor by VATS. These patients included 45 males and 30 females with an average age of 60.6 years. Their primary diseases were Colon cancer (38), renal cell carcinoma (12), breast cancer (6), seminoma (3), thyroid carcinoma (3), parotid cancer (2), pharyngeal cancer (2) and the others (9). Tumor size ranged from 6 to 62 mm in diameter. A preoperative high resolution spiral computed tomography (CT) scan was used to locate the nodule in all patients. Ten recurrence cases were performed re-resection by VATS approach with an average period was 22 month. We conclude that VATS is a good candidate for the resection of lung metastases in the selected cases.

Adult↗

PubMed2002

Possible involvement of C-C chemokines in functional augmentation of adhesion molecules in asthmatic patients.

Adhesion molecules and C-C chemokines play an important role in the accumulation of eosinophils in allergic inflammation. In the present study, the expression and function of adhesion molecules on eosinophils from asthmatic patients and involvement of RANTES and eotaxin were examined. Eosinophils isolated by the CD16 negative selection method were stimulated with or without RANTES or eotaxin. Expression of b integrins on eosinophils and the functional adherence to recombinant soluble intercellular adhesion molecule-1 (r-sICAM-1)-coated plates were examined. Compared with normal subjects, eosinophils from asthmatic patients showed increased expression of b2 integrins and functional adherence to r-sICAM-1-coated plates. RANTES and eotaxin augmented the functional adherence of eosinophils without a significant upregulation of b2 integrins. Anti-b2 integrin antibody inhibited the augmentative effect on eosinophil adherence of RANTES and eotaxin. Pertussis toxin, wortmannin, and genistein inhibited chemokine-induced adherence. RANTES and eotaxin are closely related to eosinophil accumulation not only as chemotactic agents but also as augmentative agents for eosinophil adherence through involvement in functional eosinophil adherence to ICAM-1 by a possible qualitative change of b2 integrins. Pertussis toxin-sensitive G proteins, PI3 kinase, and tyrosine kinase are involved in signal transduction leading to activation of b2 integrins on eosinophil following stimulation with RANTES and eotaxin.

Adult↗

PubMed2002

Normalization of cytoplasmic calcium response in pancreatic beta-cells of spontaneously diabetic GK rat by the treatment with T-1095, a specific inhibitor of renal Na+-glucose co-transporters.

Chronic hyperglycemia is known to lead to a progressively further impaired insulin response and to hasten the development of complications in patients with type 2 diabetes, a notion referred as glucose toxicity. T-1095, a derivative of phlorizin, is a newly developed oral hypoglycemic agent that acts as a specific inhibitor of renal Na(+)-glucose co-transporters, reducing circulating blood glucose levels by promoting glucose excretion into urine. The effects of glycemic improvement by T-1095 on secretory function and cytoplasmic calcium response in pancreatic beta-cells were investigated using spontaneously diabetic GK rats. After four weeks of treatment with T-1095 (age 4 to 8 week rats), serum glucose and HbA1c levels were significantly improved (serum glucose level, GK vs. GK T-1095, 277.3 +/- 11.8 vs. 204.7 +/- 6.4 mg/dl; HbA1c level, GK vs. GK T-1095, 6.2 +/- 0.2 vs. 4.8 +/- 0.1 %). Insulin secretion induced by 16.7 mM glucose was also significantly increased in the T-1095-treated group compared to the untreated group. The [Ca(2+)]i response induced by 16.7 mM glucose in GK beta-cells was characterized by the loss of the steep first peak of [Ca(2+)]i elevation, and the lost first peak of [Ca(2+)]i reappeared in T-1095-treated beta-cells in 32 of 34 observations. In T-1095-treated beta-cells, the time lag to peak [Ca(2+)]i levels in the 16.7 mM glucose stimulation was significantly reduced (259.1 +/- 15.3 sec, p < 0.01) compared to untreated GK rats (524.7 +/- 52.9 sec). Thus, improvement of hyperglycemia by T-1095 ameliorates beta-cell function by relieving [Ca(2+)]i response.

Animals↗

PubMed2002

Effects of xenon on acetylcholine release in the rat cerebral cortex in vivo.

BACKGROUND: We have reported previously the effects of several anaesthetics on cholinergic activity in the central nervous system (CNS). In this study, we report the effects of xenon on cholinergic cell activity. METHODS: Using in vivo brain microdialysis, we measured acetylcholine (ACh) release in the rat cerebral cortex in vivo during xenon anaesthesia. RESULTS: Xenon induced an initial increase in ACh release, followed by a gradual decrease. The level of Ach release at 40 min of xenon administration was significantly higher than the control. CONCLUSIONS: Xenon activates CNS cholinergic cell activity followed by development of acute tolerance.

Acetylcholine↗

PubMed2002

Necrotising encephalitis in the Yorkshire terrier: a case report and literature review.

A four-year-old, spayed female Yorkshire terrier was presented with a two-month history of lameness in the left forelimb, circling and falling. A magnetic resonance imaging (MRI) examination 11 days after presentation revealed dilation of the right lateral ventricle. Following euthanasia, which was performed about 10 months after the onset of clinical signs, there was gross evidence of degeneration and cavitation of the cerebrum and dilation of the lateral ventricle on the right side. Microscopically, cavitation and necrosis were observed in the white and grey matter of the right cerebrum and there was abundant gemistocytic and fibrillary astrocytosis. Haemorrhage and marked perivascular cuffing with mononuclear cells were found in the mesencephalon. Inflammatory lesions consisting of lymphocytic infiltration and glial proliferation were also present in the dorsal funiculus of the cervical spinal cord. This case was diagnosed as necrotising encephalitis in the Yorkshire terrier (NEYT) with involvement of the spinal cord. NEYT is a chronic progressive neurological disorder, resulting from widespread, destructive non-suppurative inflammation of the central nervous system of unknown cause. In the past decade, 12 cases have been documented in adult to aged Yorkshire terriers. Computed tomography and MRI can detect the characteristic multifocal cavitations and ventriculomegaly, facilitating premortem diagnosis.

Animals↗

PubMed2002

Mechanical and magnetic properties of nickel-dispersed tetragonal zirconia nanocomposites.

Effects of Ni dispersions on microstructure and mechanical properties have been studied for Y2O3-stabilized tetragonal zirconia (Y-TZP)/Ni nanocomposites with Ni dispersion up to 10 vol%. Composites were successfully fabricated by reducing and hot-pressing Y-TZP/NiO powder mixtures. Fracture strength was significantly improved from 1.5 GPa for monolithic Y-TZP to 1.9 GPa for nanocomposites with a small addition of Ni (1-2 vol%). Magnetic properties of Y-TZP/Ni nanocomposites were also investigated. Magnetization curves of Y-TZP/Ni nanocomposites showed typical hysteresis loops of soft magnetic materials, whereas coercivity was much larger than that of pure Ni metal. A new function arising from magnetomechanical effects of metallic Ni is also discussed for the present nanocomposites.

Compressive Strength↗

PubMed2002

[Total aortic arch replacement for distal aortic arch aneurysm with adhered left lung: report of a case].

A 76-year-old man with a history of pleuritis and a cerebral infarct underwent a total arch replacement for an aneurysm of the distal aortic arch. Computed tomography revealed a true aneurysm having a maximum diameter of 70 mm as well as pleural thickening and calcification. Total arch replacement with selective cerebral perfusion was performed through median sternotomy and left thoracotomy. The myocardial ischemic time was shortened by reperfusion from the right axillary artery after the anastomosis of the proximal ascending aorta and the brachiocephalic artery. After the other branches of the arch were anastomosed, a distal anastomosis through the left thoracotomy was then performed using the pull-through method, enabling minimal decortication of the adhered lung. Our surgical procedure for distal arch aneurysm with adhered lung involves the addition of a left thoracotomy, but the reduction in the myocardial ischemic time and lung injury are of benefit.

Aged↗

PubMed2002

[Corrective surgery for pectus excavatum in patients with Marfan syndrome].

OBJECTIVE: Among 1,967 patients who underwent corrective surgery for pectus excavatum in our department between January 1980 and December 2001, 33 patients diagnosed as having Marfan syndrome were evaluated. We evaluated the clinical problems and outcome of the 33 patients. RESULTS: The outcome of corrective surgery for pectus excavatum in the 26 patients who underwent a single technique surgery was generally good. Pectus excavatum was complicated by a total of 25 cases of cardiovascular disorder in 14 of 33 (42%) patients. Six patients underwent corrective surgery for pectus excavatum and cardiovascular disorders simultaneously. Three patients also had disorders of lung, which included spontaneous pneumothorax in 2 patients and progressive emphysematous cyst in 1 patient. The 2 patients with spontaneous pneumothorax underwent resection of bullae together with corrective surgery of pectus excavatum, while the patient with progressive emphysematous cyst underwent resection of bullae in a separate surgery after correction of pectus excavatum. Cardiovascular disorders were aggravated in 6 of the 20 patients who could be follow up. A total of 4 (20%) patients died long after surgery. CONCLUSIONS: We corrected pectus excavatum in 33 patients with Marfan syndrome, and obtained favorable outcomes. The postsurgical outcome depends on progression of lesions of the heart and large vessels, and it is essential to monitor such lesions carefully.

Adolescent↗

PubMed2001

The functional role of rho and rho-associated coiled-coil forming protein kinase in eotaxin signaling of eosinophils.

The CC chemokine eotaxin plays a pivotal role in local accumulation of eosinophils. Very little is known about the eotaxin signaling in eosinophils except the activation of the mitogen-activated protein (MAP) kinase family. The p21 G protein Rho and its substrate Rho-associated coiled-coil forming protein kinase (ROCK) regulate the formation of stress fibers and focal adhesions. In the present study, we studied the functional relevance of Rho and ROCK in eosinophils using the ROCK inhibitor (Y-27632) and exoenzyme C3, a specific Rho inhibitor. Eotaxin stimulates activation of Rho A and ROCK II in eosinophils. Exoenzyme C3 almost completely inhibited the ROCK activity, indicating that ROCK is downstream of Rho. We then examined the role of Rho and ROCK in eosinophil chemotaxis. The eotaxin-induced eosinophil chemotaxis was significantly inhibited by exoenzyme C3 or Y-27632. Because extracellular signal-regulated kinase (ERK)1/2 and p38 MAP kinases are activated by eotaxin and are critical for eosinophil chemotaxis, we investigated whether Rho and ROCK are upstream of these MAP kinases. C3 partially inhibited eotaxin-induced phosphorylation of ERK1/2 but not p38. In contrast, neither ERK1/2 nor p38 phosphorylation was abrogated by Y-27632. Both C3 and Y-27632 reduced reactive oxygen species production from eosinophils. We conclude that both Rho and ROCK are important for eosinophil chemotaxis and reactive oxygen species production. There is a dichotomy of downstream signaling pathways of Rho, namely, Rho-ROCK and Rho-ERK pathways. Taken together, eosinophil chemotaxis is regulated by multiple signaling pathways that involve at least ROCK, ERK, and p38 MAP kinase.

ADP Ribose Transferases↗

PubMed2001

Nitric oxide and its decomposed derivatives decrease the binding of extracellular-superoxide dismutase to the endothelial cell surface.

Extracellular-superoxide dismutase (EC-SOD) is bound to the vascular endothelial cell surface with an affinity for heparan sulfate proteoglycan. The binding of EC-SOD to the human umbilical vein endothelial cell (HUVEC) and bovine aortic endothelial cell surface proteoglycans was significantly decreased by the incubation with S-nitroso-N-acetyl-DL-penicillamine (SNAP) and +/- -N-[(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexene-1-yl]-3-pyridine carboxamide (NOR4), potent nitric oxide (NO) donors. NO derived from lipopolysaccharide-stimulated J774 A-1 cells also decreased the binding of EC-SOD to HUVEC, and this decrease was blocked by N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor. SNAP and NOR4 also decreased the binding of EC-SOD to immobilized heparin. Furthermore, the decomposed derivatives of NO donors and sodium nitrite decreased the binding of EC-SOD. These observations suggest that excess NO produced in the inflammatory conditions decreases the binding of EC-SOD to the vascular endothelial cell surface, which results in a loss of the ability to protect the endothelial cell surface from oxidative stress.

Animals↗

PubMed2001

Reduced sarco/endoplasmic reticulum Ca(2+) uptake activity can account for the reduced response to NO, but not sodium nitroprusside, in hypercholesterolemic rabbit aorta.

BACKGROUND: Hypercholesterolemia (HC) impairs acetylcholine-induced relaxation but has little effect on that caused by the NO donor sodium nitroprusside (SNP), suggesting that acetylcholine releases less NO from the endothelium in HC. The relaxation to authentic NO gas, however, is also impaired in HC aortic smooth muscle, indicating an abnormal smooth muscle response. NO relaxes arteries by both cGMP-dependent and -independent mechanisms, and the response involves calcium (Ca(2+)) store refilling via the sarco/endoplasmic reticulum calcium ATPase (SERCA). We studied the involvement of cGMP and SERCA in the smooth muscle response to NO and SNP in HC rabbit aorta. METHODS AND RESULTS: A selective guanylyl cyclase inhibitor, 1H-[1,2,4]-oxadiazole-[4,3-a]quinoxalin-1-one, eliminated SNP-induced relaxation but only partially blocked NO-induced relaxation in both normal and HC aorta. The residual relaxation to NO was still less in HC and, in both normal and HC aorta, was abolished by concomitant administration of the SERCA inhibitor cyclopiazonic acid (CPA). In contrast, CPA did not affect SNP-induced relaxation in either normal or HC aorta. SERCA activity measured by (45)Ca(2+) uptake was markedly decreased in HC, although SERCA2 protein expression did not change significantly. CONCLUSIONS: These data suggest that NO-induced relaxation but not that to SNP is partially mediated by cGMP-independent Ca(2+) uptake into sarco/endoplasmic reticulum and that reduced sarco/endoplasmic reticulum Ca(2+) pump function can account for the impaired response to NO in HC.

Acetylcholine↗

PubMed2001

Overexpression of EC-SOD suppresses endothelial-cell-mediated LDL oxidation.

Reactive oxygen species have been proposed to play important roles in atherosclerosis. To investigate the protective role of extracellular superoxide dismutase (EC-SOD), its inhibition of endothelial-cell-mediated LDL oxidation was examined. We constructed the recombinant adenovirus AxCAEC-SOD expressing human EC-SOD by CAG promoter. Infection of endothelial cells with AxCAEC-SOD resulted in EC-SOD protein secretion in a dose-dependent manner and a decrease of endothelial-cell-derived superoxide production. Moreover, it was proven to coexist with heparan sulfate by immunohistochemical staining. Endothelial-cell-mediated LDL oxidation enhanced by ferric-sodium EDTA was inhibited by 47% in TBARS formation by AxCAEC-SOD infection. In agarose gel electrophoresis, AxCAEC-SOD decreased the negative charge of oxidized LDL by 50% and suppressed fragmentation of apolipoprotein B. These results suggested that human EC-SOD localized in the extracellular space and reduced endothelial-cell-mediated LDL oxidation. In subendothelial space, EC-SOD bound on heparan sulfate might suppress LDL oxidation through reduction of superoxide anion.

Animals↗

PubMed2001

SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates.

Signaling through the B cell antigen receptor (BCR) is negatively regulated by the SH2 domain-containing protein-tyrosine phosphatase SHP-1, which requires association with tyrosine-phosphorylated proteins for activation. Upon BCR ligation, SHP-1 has been shown to associate with the BCR, the cytoplasmic protein-tyrosine kinases Lyn and Syk, and the inhibitory co-receptors CD22 and CD72. How SHP-1 is activated by BCR ligation and regulates BCR signaling is, however, not fully understood. Here we demonstrate that, in the BCR-expressing myeloma line J558L mu 3, CD72 expression reduces the BCR ligation-induced phosphorylation of the BCR component Ig alpha/Ig beta and its cytoplasmic effectors Syk and SLP-65. Substrate phosphorylation was restored by expression of dominant negative mutants of SHP-1, whereas the SHP-1 mutants failed to enhance phosphorylation of the cellular substrates in the absence of CD72. This indicates that SHP-1 is efficiently activated by CD72 but not by other pathways in J558L mu m3 cells and that inhibition of SHP-1 specifically activated by CD72 reverses CD72-induced dephosphorylation of cellular substrates in these cells. Taken together, BCR-induced SHP-1 activation is likely to require inhibitory co-receptors such as CD72, and SHP-1 appears to mediate the negative regulatory effect of CD72 on BCR signaling by dephosphorylating Ig alpha/Ig beta and its downstream signaling molecules Syk and SLP-65.

B-Lymphocytes↗

PubMed2001

Inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cAMP-induced differentiation of rat C6 glial cell line.

Dioxin is suspected to cause adverse effects on the development of the central nervous system (CNS). To investigate the neurotoxic effects of dioxin on the differentiation of astrocytes, rat C6 glial cell line was used as a model, because these cells are induced to express astrocyte markers and to change the cell morphology toward an astrocytic phenotype by increasing intracellular cAMP levels. When C6 cells were simultaneously exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and N(6),O(2')-dibutylyl cAMP (dbcAMP), the expression of cytochrome P-450 1A1 (CYP1A1) was dramatically increased, and the expression of aryl hydrocarbon receptor (AhR) was moderately decreased in a dose-dependent manner. In addition, extension of astrocytic processes was inhibited by 1 nM TCDD that did not reduce cell viability. TCDD also inhibited the induction of glial fibrillary acidic protein (GFAP) expression in a dose-dependent manner, until the end of a 72-hr exposure period. This inhibition was restored by the addition of an antagonist of AhR, alpha-naphthoflavone. These results indicate that TCDD inhibits astrocytic differentiation of C6 cells, which may be mediated by an AhR-dependent pathway.

Amino Acid Sequence↗

PubMed2001

Relative quantitation of p53 and MDM2 gene expression in leiomyosarcoma; real-time semi-quantitative reverse transcription-polymerase chain reaction.

To investigate the etiology of leiomyosarcoma, we examined abnormalities of p53 and its regulation in 13 cases of leiomyosarcoma using fresh tumor specimens. We estimated p53 and MDM2 mRNA level and MDM2 gene amplification using a real-time semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) based on the TaqMan fluorescence method. We also used immunohistochemistry (IHC) for p53 and MDM2 protein overexpression, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing to detect p53 mutation. Eight of the 13 cases (62%) showed an overexpression of p53 protein on IHC and eight of 13 cases (62%) had p53 gene point mutations. Five of the 13 cases (38%) showed positive staining for MDM2 protein and only one case (7.7%) demonstrated MDM2 gene amplification. The relative p53 mRNA level of the tumors compared with normal tissue ranged from 1.14 to 12.19 arbitrary units (AU), and the MDM2 mRNA level ranged from 1.06 to 17.17 AU. The mRNA level in the p53-positive cases was higher than in the negative cases (positive: 7.70 AU on average; negative: 3.38 AU on average; P=0.0344). However, there was no significant correlation between the MDM2 mRNA level and other factors, such as p53 IHC, p53 mutation status, p53 mRNA level and MDM2 IHC. Our results indicate that p53 abnormalities are major events and that an increasing level of p53 mRNA is associated with an overexpression of p53 protein in leiomyosarcoma and they may play an important role in the tumorigenesis in this tumor.

Adult↗