Biomedical subjects

K Tsuchida

Publications and source records attributed to K Tsuchida.

At least 19 recordsLinked to original sources

PubMed2006

Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model.

Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.

Animals↗

PubMed2006

Benefical effect of neutrophil elastase inhibitor on renal warm ischemia-reperfusion injury in the rat.

Renal ischemia-reperfusion (I/R) injury is a significant problem in renal transplantation. Neutrophils play an important role in renal I/R injury. Several reports have demonstrated that neutrophil elastase derived from the activated neutrophils might play an important role in this injury. We investigated the effect of a neutrophil elastase inhibitor in renal I/R injury. Male Lewis rats (270-320 g) were used in the model. The right kidney was harvested and the left renal artery and vein were clamped at laparotomy. The kidney was reperfused after 90 minutes of ischemia. Neutrophil elastase inhibitor (ONO-5046: 30 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent neutrophil activation. In the nontreatment I/R group, no hosts survived 4 days. However, after treatment with neutrophil elastase inhibitor, 3 of 10 rats in the I/R group, survived more than 7 days. These results demonstrated that treatment with neutrophil elastase inhibitor ameliorated renal I/R injury.

Animals↗

PubMed2006

Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling.

Activin type II receptors (ActRIIs) including ActRIIA and ActRIIB are serine/threonine kinase receptors that form complexes with type I receptors to transmit intracellular signaling of activins, nodal, myostatin and a subset of bone morphogenetic proteins. ActRIIs are unique among serine/threonine kinase receptors in that they associate with proteins having PSD-95, Discs large and ZO-1 (PDZ) domains. In our previous studies, we reported specific interactions of ActRIIs with two independent PDZ proteins named activin receptor-interacting proteins 1 and 2 (ARIP1 and ARIP2). Overexpression of both ARIP1 and ARIP2 reduce activin-induced transcription. Here, we report the isolation of two isoforms of ARIP2 named ARIP2b and 2c. ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. ARIP2 and its isoforms have one PDZ domain in the NH2-terminal region, and interact with ActRIIA. Although PDZ domains containing GLGF motifs of ARIP2b and 2c are identical to that of ARIP2, their COOH-terminal sequences differ from that of ARIP2. Interestingly, unlike ARIP2, overexpression of ARIP2b or 2c did not affect ActRIIA internalization. ARIP2b/2c inhibit inhibitory actions of ARIP2 on activin signaling. ARIP2 is widely distributed in mouse tissues. ARIP2b/2c is expressed in more restricted tissues such as heart, brain, kidneys and liver. Our results indicate that although both ARIP2 and ARIP2b/2c interact with activin receptors, they regulate ActRIIA function in a different manner.

Activin Receptors, Type II↗

PubMed2006

Inhibitors of the TGF-beta superfamily and their clinical applications.

The transforming growth factor-beta (TGF-beta) superfamily includes TGF-betas, activin, myostatin and bone morphogenetic proteins. Misregulation of the activity of TGF-beta family members is involved in pathogenesis of cancer, muscular dystrophy, obesity and bone and tooth remodeling. Natural inhibitors for the TGF-beta superfamily regulate fine-tuning of activity of TGF-beta family in vivo. In addition to natural inhibitors for the TGF-beta family, soluble forms of receptors for the TGF-beta family, blocking monoclonal antibodies and small chemical TGF-beta inhibitors have been developed. In this review, we summarize recent advances in our understanding of inhibitors for the TGF-beta superfamily and their medical applications.

Animals↗

PubMed2005

Expression of peroxisome proliferator-activated receptor-gamma in renal ischemia-reperfusion injury.

The pathogenesis of ischemia-reperfusion injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Peroxisome proliferator-activated receptor (PPAR)-gamma is considered an important immunomodulatory factor as well as a fatty acid regulator. In this study, we researched the expression of PPAR-gamma in renal ischemia-reperfusion injury of the rat. The right kidney was harvested and left renal artery and vein were clamped under laparotomy. The kidney was reperfused after 90 minutes of ischemia, and rats were sacrificed at 0, 1.5, 3, 5, 12, and 24 hours after reperfusion. PPAR-gamma expression was analyzed by immunohistochemical staining using monoclonal antibody. In normal kidney, PPAR-gamma staining was weak on endothelial cells, including mesangial cells. On the other hand, PPAR-gamma staining was weak on interstitial cells and strong on collecting ducts of medulla. From 1.5 to 5 hours after reperfusion, PPAR-gamma staining was strong on endothelial cells, moderate on interstitial cells, and strong on collecting ducts. Twelve hours after reperfusion, PPAR-gamma staining was weak on endothelial cells, moderate on interstitial cells, and strong on collecting ducts. PPAR-gamma is induced on collecting ducts, interstitial cells, and endothelial cells in a rat model having renal ischemia-reperfusion injury.

Animals↗

PubMed2005

Synergistic activity of activin A and basic fibroblast growth factor on tyrosine hydroxylase expression through Smad3 and ERK1/ERK2 MAPK signaling pathways.

Activin has previously been shown to act as a nerve cell survival factor and to have neurotrophic effects on neurons. However, the role of activin in regulating neurotransmitter expression in the central nervous system and the exact mechanisms involved in this process are poorly understood. In the present study, we report that activin A and basic fibroblast growth factor (bFGF) synergistically increased the protein level of tyrosine hydroxylase (TH), and also greatly increased the TH mRNA level, in both mouse E14 striatal primary cell cultures and the hippocampal neuronal cell line HT22. Activin A and bFGF cooperatively stimulated nuclear translocation of Smad3 and specifically activated ERK1/2, but not p38 or JNK. Interestingly, a specific inhibitor for MEK, U0126, efficiently blocked the induction of TH promoter activity by activin A and bFGF, indicating that activin A collaborated with bFGF signaling to induce the TH gene through selective activation of ERK-type MAP kinase in mouse striatal and HT22 cells. These data suggest that activin A may act in concert with bFGF for the development of TH-positive neurons.

Activins↗

PubMed2004

Queen and worker policing in monogynous and monandrous colonies of a primitively eusocial wasp.

Kin-selection theory predicts that a worker prefers to produce her own sons in a colony with monandry and monogyny because relatedness to her sons (0.5) and nephews (0.375) exceeds that to brothers (0.25). In spite of this prediction, recent studies reveal that workers police each other (mutual-worker egg removal) even in monandrous and monogynous colonies. We conducted field and laboratory studies to evaluate queen and worker policing in queen-right colonies of the primitively eusocial wasp Polistes chinensis antennalis. Genetic studies using microsatellite markers, as well as extensive observations of natural colonies, revealed that both queen and workers removed both queen- and worker-laid eggs in monogynous and monandrous colonies. The queen's eggs survived to hatching more successfully than those of the workers (88.5% versus 1.4%). We discuss the likely factors to explain these worker-policing behaviours.

Animals↗

PubMed2004

Study of peroxisome proliferator-activated receptor (PPAR)-gamma in renal ischemia-reperfusion injury.

Recent studies of ischemia-reperfusion (I/R) injury have focused on the function of neutrophils, the action mechanism of inflammatory cytokines. However, few reports have addressed peroxisome proliferator-activated receptor (PPAR)-gamma. PPAR-gamma is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. It plays a role in both adipocyte differentiation and tumorigenesis. We researched the expression of PPAR-gamma in renal I/R injury of the rat. Male Lewis rats were used. The right kidney was harvested and the left renal artery and vein were clamped at 90 minutes of ischemic time. Rats were killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. PPAR-gamma expression was studied by immunohistostaining. PPAR-gamma expression was observed only on mesangial and endothelial cells of normal kidney. From 1.5 to 3 hours after reperfusion, PPAR-gamma expression gradually became stronger on mesangial and endothelial cells. PPAR-gamma expression was most intense on mesangial cells and endothelial cells at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney and nearly all the tubular epithelial cells were destroyed, but 12 hours after reperfusion PPAR-gamma expression gradually became weaker on mesangial and endothelial cells. PPAR-gamma was expressed in the rat model having renal I/R injury. Several hours after maximal of PPAR-gamma expression, maximal renal I/R injury was observed. These results may indicate a relationship between PPAR-gamma expression and renal I/R injury.

Animals↗

PubMed2003

Cyclooxygenase-1 and -2 in human testicular tumours.

In this study, we investigated the expression of cyclooxygenase (COX)-1 and -2 in human testicular cancer (TC) and normal testis (NT) tissues, as well as the effects of COX ligands on viability and proliferation. Tumour specimens were obtained from 72 patients with TC and 20 patients with NT. RT-PCR and immunohistochemical methods were used to determine COX expression. While COX expression was not noted in any of the NT tissues, a marked expression was observed in the TC samples. The extent and intensity of immunoreactive COX-1 and -2 polypeptides in the TC tissues was statistically greater than the expression in the NT tissues. The synthetic COX inhibitors inhibited the growth of the TC cells. Both COX-1 and COX-2 are induced in testicular cancer, and these results indicate that both COX-1 and COX-2 are essential for the growth of TC cells.

Adult↗

PubMed2003

Transfer of cholesterol and diacylglycerol from lipophorin to Bombyx mori ovarioles in vitro: role of the lipid transfer particle.

The objective of this study was to characterize the transfer of diacylglycerol (DAG) and cholesterol from larval Bombyx mori lipophorin to ovarioles. Transfer studies were carried out by incubating pupal ovarioles (5-day) with [(3)H]-cholesterol and [(3)H]-DAG-labeled lipophorin under different conditions. Transfer of both cholesterol and DAG exhibited hyperbolic dependency on lipophorin concentration with apparent Km values of 0.83 +/- 0.17 mg/ml and 0.74 +/- 0.16 mg/ml, respectively. Pretreatment of ovarioles with anti-lipid transfer particle (LTP) IgG significantly inhibited transfer of labeled DAG to ovarioles (75%) and not cholesterol. Injection of B. mori pupae (day 4) with anti-LTP IgG significantly affected the weight (65%), number of eggs (49%), amount of lipid (74%), and protein (65%) of the adult ovaries. Matured eggs had a very faint yellow color and deformed shape compared to controls. The inhibitory effect demonstrates the active role LTP plays in growth of ovaries, development, and oogenesis. The effect on vitellogenin shortage on egg development and maturation was determined by implanting ovaries in male recipients that lack vitellogenin. An 80% decline in egg production was observed. However, the mature eggs were normal in shape, color, and lipid content. Thus, restricting lipid or protein delivery to developing ovaries would dramatically affect choriogenesis.

Animals↗

PubMed2003

[Torsion of the middle lobe after right upper lobectomy of the lung; report of a case and the review of the Japanese literatures].

We report a case of torsion of the residual right middle lobe of the lung, following right upper lobectomy for lung cancer. A 71-year-old man who had medical treatment for emphysema was admitted with a lung tumor on chest computed tomography. The tumor was diagnosed as pulmonary adenocarcinoma by transbronchial biopsy. Right upper lobectomy with mediastinal lymph node dissection, and partial resection of the right lower lobe were performed. On the following day, chest X-ray showed an opacification in the right upper lung field, which gradually increased. Bronchoscopic examination revealed a stenotic middle lobe bronchus. Torsion of the middle lobe was suspected, and rethoracotomy was performed on the second postoperative day. The middle lobe was torsed 90-degree counterclockwise around its bronchovascular pedicle. A middle lobectomy was performed secondary to severe congestion. The patient was discharged in good condition on the 11th postoperative day. In reviewing the literatures including this case, 13 of 16 torsions occurred after right upper lobectomy of the lung. Thirteen patients had rethoracotomy, 10 of them underwent resection of the rotated lung. Simple detorsion was carried out in 3 patients, and 1 of them developed cerebral infarction. Lung torsion was reported to be potentially life-threatening. Therefore, fixation of a remaining lobe should be performed. Exploratory thoracotomy should be performed without delay, if lung torsion is suspected.

Adenocarcinoma↗

PubMed2003

Outcome of directly observed therapy for tuberculosis in Yokohama City, Japan.

BACKGROUND: Yokohama City is currently developing directly observed treatment (DOT) in its programme, and requires guidance on types of DOT appropriate for local conditions. OBJECTIVE: To assess the effectiveness of DOT for tuberculosis treatment in a retrospective study under operational conditions in Yokohama City. METHODS: We included 80 patients with sputum-positive tuberculosis, 39 enrolled in DOT and 41 self-administered patients. The study was done at the National Hospital for Chest Diseases and the Community Clinic, which provide tuberculosis services with a standard daily short-course regimen. The main outcome measures were cure and treatment completion. RESULTS: The cure or treatment completion rate for the DOT and self-administered groups were respectively 87.2% and 68.3%. In a multivariate logistic regression model, cure or treatment completion was significantly associated with out-patient DOT (OR 4.04, 95%CI 1.22-13.33, P = 0.022). CONCLUSION: DOT was shown to be significantly superior to the self-administered regimen. However, our results were from an impoverished population with city-sponsored apartments and supplementary benefits. Further research will be needed to know the effectiveness of DOT in the general population.

Antitubercular Agents↗

PubMed2002

[Thoracoscopic pericardial fenestration for persistent pericardial effusion after radiotherapy for esophageal cancer; report of a case].

We performed thoracoscopic pericardial fenestration for persistent pericardial effusion after radiotherapy for esophageal cancer. An 85-year-old man who had radiation therapy (70.2 Gy) for esophageal cancer was admitted for shortness of breath. Chest computed tomography showed a pericardial effusion. During the 6 months prior to this admission, the patient had undergone percutaneous pericardial drainage 3 times for cardiac tamponade. We performed thoracoscopic partial pericardiectomy with creation of a pleuropericardial window via one access port. Histopathologically, no malignant cells were found in either the resected pericardium or the pericardial effusion. Therefore, we believe the persistent pericardial effusion was secondary to radiotherapy. There was no recurrence of the pericardial effusion for 7 months postoperatively. In summary, thoracoscopic pericardial fenestration is useful in both the diagnosis and treatment of persistent pericardial effusion.

Aged↗

PubMed2001

Appican, the proteoglycan form of the amyloid precursor protein, contains chondroitin sulfate E in the repeating disaccharide region and 4-O-sulfated galactose in the linkage region.

Chondroitin sulfate (CS)-D and CS-E, which are characterized by oversulfated disaccharide units, have been shown to regulate neuronal adhesion, cell migration, and neurite outgrowth. CS proteoglycans (CSPGs) consist of a core protein to which one or more CS chains are attached via a serine residue. Although several brain CSPGs, including mouse DSD-1-PG/phosphacan, have been found to contain the oversulfated D disaccharide motif, no brain CSPG has been reported to contain the oversulfated E motif. Here we analyzed the CS chain of appican, the CSPG form of the Alzheimer's amyloid precursor protein. Appican is expressed almost exclusively by astrocytes and has been reported to have brain- and astrocyte-specific functions including stimulation of both neural cell adhesion and neurite outgrowth. The present findings show that the CS chain of appican has a molecular mass of 25-50 kDa. This chain contains a significant fraction (14.3%) of the oversulfated E motif GlcUA beta 1-3GalNAc(4,6-O-disulfate). The rest of the chain consists of GlcUA beta 1-3GalNAc(4-O-sulfate) (81.2%) and minor fractions of GlcUA beta 1-3GalNAc and GlcUA beta 1-3GalNAc(6-O-sulfate). We also show that the CS chain of appican contains in its linkage region the 4-O-sulfated Gal structure. Thus, appican is the first example of a specific brain CSPG that contains the E disaccharide unit in its sugar backbone and the 4-O-sulfated Gal residue in its linkage region. The presence of the E unit is consistent with and may explain the neurotrophic activities of appican.

Amyloid beta-Protein Precursor↗

PubMed2001

Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383.

We have reported previously that the PTEN COOH-terminal 33 amino acids play a role in the maintenance of PTEN protein stability (Tolkacheva and Chan, Oncogene, 19: 680-689, 2000). By site-directed mutagenesis, we identified two threonine residues within this COOH-terminal region at codon 382 and 383 that may be targets for phosphorylation events. Interestingly, PTEN mutants rendered phosphorylation-incompetent at these two sites, T382A/T383A, and were found to have drastically reduced expression in cultured cells. The enhanced degradation of PTEN was most likely mediated by the proteosome-dependent pathway, we have evidence that PTEN was polyubiquitinated. More interestingly, the non-phosphorylated forms of PTEN displayed significantly greater binding affinity than the wild-type protein to a previously identified PTEN interacting partner, MAGI-2/ARIP1. On the basis of all these data, we propose that PTEN recruitment to the cell-cell junction may be regulated through the phosphorylation of its COOH terminus.

3T3 Cells↗

PubMed2001

Intracellular and extracellular control of activin function by novel regulatory molecules.

Activin signal transduction is regulated through multiple mechanisms. We have identified novel regulatory proteins that control activin functions either intracellularly or extracellularly. As intracellular molecules, PSD-95/Dlg/ZO-1 (PDZ) proteins that specifically associate with activin type II receptors (ActRIIs) were identified. We have named the molecules as activin receptor-interacting proteins (ARIPs). ARIP1 has two WW domains and five PDZ domains, associates not only with ActRIIs but also with Smads, and controls activin functions intracellularly in neuronal cells. Another ARIP we have found has only one PDZ domain, and is likely to be involved in intracellular trafficking and sorting of activin receptor complexes in the cell. As an extracellular regulatory protein, we have identified a novel follistatin-like protein, named follistatin-related gene (FLRG). Like follistatins, FLRG binds activins and bone morphogenetic proteins (BMPs) and controls their functions extracellularly. The mode of association of follistatin and FLRG with activins and their expression patterns are different, suggesting the distinct functions of follistatin and FLRG in vivo.

Activin Receptors↗

PubMed2001

Synthesis of linear-type chondroitin clusters having a C8 spacer between disaccharide moieties and enzymatic transfer of D-glucuronic acid to the artificial glycans.

Newly designed linear-type glycoclusters were synthesized which involve a chondroitin repeating disaccharide ligand and a hydrophobic octyl ether spacer. The spacer mimics the corresponding disaccharide unit. Repeating elongation of the pseudo-tetrasaccharide that was derived from the common cluster unit [-->8)-octyl-(1-->3)-beta-D-Gal-NAc-(1-->4)-beta-D-GlcA-(1-->] allowed the syntheses of up to the pseudo-decasaccharide analog of chondroitin. An enzymatic D-GlcA transfer at the non-reducing end of the synthesized artificial glycans by GlcATase II was observed.

Carbohydrate Sequence↗

PubMed2001

Lipid storage and mobilization in insects: current status and future directions.

In this paper we review the current status of research on fatty acid absorption and conversion to diacylglycerol in the midgut. We further discuss how diacylglycerol may leave the midgut and associate with lipophorin in hemolymph. We review the present understanding of the role of the lipid transfer particle and lipophorin receptors in lipid delivery between lipophorin and tissues. Finally, we discuss recent studies on the mobilization of diacylglycerol from the fat body in response to adipokinetic hormone. Several suggestions for exciting areas of future research are described.

Absorption↗