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Biomedical subjects

T Takagi

Publications and source records attributed to T Takagi.

At least 73 records · Page 4Linked to original sources
PubMed2001

Adrenomedullin reduces ischemic brain injury after transient middle cerebral artery occlusion in rats.

BACKGROUND: The effect of adrenomedullin, a vasodilatory peptide on transient middle cerebral artery (MCA) occlusion was investigated in rats. METHODS: Transient MCA occlusion for 2 hours was made by using the intra-arterial suture method, followed by reperfusion. FINDINGS: An intravenous infusion of adrenomedullin (1 microg/kg/min) from one hour before ischemia to one hour after ischemia significantly reduced the infarct size and improved neurological deficits (p<0.05), without affecting systemic blood pressure or other physiological parameters. The infarct size was reduced with adrenomedullin by 25.4+/-12.7%, 31.3+/-5.8%, 31.6+/-6.1% respectively at the coronal level 6, 8 and 10 mm posterior from the frontal pole. Adrenomedullin also significantly inhibited the increase in myeloperoxidase (MPO) activity in the MCA area of the ischemic hemisphere after 22-hour reperfusion (control: 0.205+/-0.054 unit/g wet tissue, adrenomedullin group: 0.047+/-0.009 unit/g wet tissue, p<0.0001). INTERPRETATION: These data suggest that adrenomedullin reduces acute ischemic brain injury and one of is neuroprotective mechanisms may be derived from inhibition of the infiltration of neutrophils into the ischemic tissue.

Adrenomedullin↗
PubMed2001

New bone formation around porous hydroxyapatite wedge implanted in opening wedge high tibial osteotomy in patients with osteoarthritis.

A porous hydroxyapatite (highly purified synthetic Ca10(PO4)6(OH)2) wedge was inserted into the tibia in 10 knees of 7 patients with osteoarthritis of the knee who underwent high tibial osteotomy. The interface of this HA wedge with bone was histologically examined in undecalcified specimens obtained at the time of hardware removal in all 10 knees, and total incorporation of the HA into bone was observed, with no inflammatory reaction. The proportion of pores that were filled with regenerated bone within 300 microm from the interface was 71.8 +/- 10.1% (mean +/- S.D.), and it was positively correlated with the time from implantation to biopsy. Radiodensity of the HA wedge was measured during the follow-up period, and it did not change significantly within 36 months after osteotomy. Our study concluded that bone ingrowth into the HA block slowly progressed and was correlated with the passage of time.

Aged↗
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

Interferon-associated retinopathy in a uniform regimen of natural interferon-alpha therapy for chronic hepatitis C.

BACKGROUND/AIMS: The development of retinal lesions induced by a uniform regimen of interferon-alpha therapy for chronic hepatitis C was prospectively investigated. METHODS: Eighty-one patients received 6 mega units of natural interferon-alpha intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of interferon-alpha administered was uniformly 478 mega units per patient. Two expert ophthalmologists prospectively examined the patients for retinal lesions before, during and after the therapy. RESULTS: Retinopathy was not found in comparison groups or any of the patients before treatment. In total 34.6% (28/81) of the patients showed cotton-wool spots or minor retinal hemorrhage, or both lesions, during therapy, but these lesions were reversed during or after interferon therapy. The occurrence rates of cotton-wool spots alone, retinal hemorrhage alone and both lesions were 13.6% (11/81), 6.2% (5/81), and 14.8% (12/81), respectively. The appearance of retinopathy did not correlate with patients' background including viral loads and response to the therapy, but was more frequently found in older patients and patients with hypertension and/or diabetes mellitus; disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared 2-4 months after the start of the therapy, and the severity of the lesions did not differ between patients with and without hypertension and/or diabetes mellitus. CONCLUSION: Although it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alpha.

Age Distribution↗
PubMed2001

Murine Schnurri-2 is required for positive selection of thymocytes.

A key step in T cell development involves the positive selection of cells that recognize antigen presented by self-major histocompatibility complex. Yet, the signals that are activated by T cell receptor engagement and lead to cell survival remain unclear. We show here that mice lacking the transcription factor Schnurri-2 (Shn-2), a large metal-finger protein, had severely defective positive selection of CD4+ and CD8+ cells. Drosophila Shn acts as a cofactor of Smad homolog and is required for Decapentaplegic signaling. Vertebrates have at least three Shn orthologs (Shn-1, Shn-2 and Shn-3), which are thought to act as nuclear targets in the bone morphogenetic protein-transforming growth factor-beta-activin signaling pathways. These data raised the possibility that the Smad-Shn-2 complex is involved in the thymic selection of T cells.

Activins↗
PubMed2001

Serum nm23-H1 protein as a prognostic factor for indolent non-Hodgkin's lymphoma.

Standard chemotherapy has been ineffective for improving the poor 10-year survival rate of patients with indolent lymphoma. However, a wider choice of therapeutic modalities has become recently available, including immunotherapy with monoclonal antibodies and allogeneic peripheral blood stem cell transplantation. Accordingly, a sensitive prognostic indicator is required to identify high-risk patients and to help design new therapeutic approaches for them. We previously reported that the serum nm23-H1 protein level was an independent prognostic factor for aggressive lymphoma. The present study was performed to assess the clinical implications of this protein on indolent lymphoma and whether it can be used to classify the aggressiveness of the disease in order to assist in the individualization of therapy. A total of 130 patients with indolent lymphoma were enrolled in this multicenter study. The serum nm23-H1 protein level was significantly higher in patients with indolent lymphoma than in a normal control group. In addition, indolent lymphoma patients with higher nm23-H1 levels had worse overall and progression-free survival rate than those with lower nm23-H1 levels. Therefore, nm23-H1 in serum may be useful for identifying a distinct group of patients at high risk.

Adolescent↗
PubMed2001

Domain-domain interactions of HtpG, an Escherichia coli homologue of eukaryotic HSP90 molecular chaperone.

In the present study, we investigated the domain structure and domain-domain interactions of HtpG, an Escherichia coli homologue of eukaryotic HSP90. Limited proteolysis of recombinant HtpG, revealed three major tryptic sites, i.e. Arg7-Gly8, Arg336-Glu337 and Lys552-Leu553, of which the latter two were located at the positions equivalent to the major cleavage sites of human HSP90alpha. A similar pattern was obtained by papain treatment under nondenaturing conditions but not under denaturing conditions. Thus, HtpG consists of three domains, i.e. Domain A, Met1-Arg336; domain B, Glu337-Lys552; and domain C, Leu553-Ser624, as does HSP90. The domains of HtpG were expressed and their interactions were estimated on polyacrylamide gel electrophoresis under nondenaturing conditions. As a result, two kinds of domain-domain interactions were revealed: domain B interaction with domain A of the same polypeptide and domain C of one partner with domain B of the other in the dimer. Domain B could be structurally and functionally divided into two subdomains, the N-terminal two-thirds (subdomain BI) that interacted with domain A and the C-terminal one-third (subdomain BII) that interacted with domain C. The C-terminal two-thirds of domain A, i.e. Asp116-Arg336, were sufficient for the binding to domain B. We finally propose the domain organization of an HtpG dimer.

Amino Acid Sequence↗
PubMed2001

Pioglitazone, a specific PPAR-gamma ligand, inhibits aspirin-induced gastric mucosal injury in rats.

BACKGROUND: Neutrophils activation and tumour necrosis factor-alpha (TNF-alpha) induction play a critical role in aspirin-induced gastric mucosal injury. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of inflammatory responses. The aim of the present study was to determine whether pioglitazone, a specific PPAR-gamma ligand, can ameliorate aspirin-induced gastric mucosal injury in rats, and whether the agent can inhibit the increase in neutrophil accumulation associated with TNF-alpha expression. METHODS: Aspirin-induced injury was produced by the intragastric administration of aspirin (200 mg/kg) and HCl (0.15 N, 8.0 mL/kg). Pioglitazone was given to the rats by gastric intubation 1 h before the aspirin administration. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. The gastric concentration of TNF-alpha and the expression of TNF-alpha mRNA was determined by ELISA and reverse transcriptase-polymerase chain reaction. RESULTS: The intragastric administration of acidified aspirin induced hyperemia and haemorrhagic erosions in rat stomachs. The increase in the total gastric erosive area after aspirin administration was significantly inhibited by treatment with pioglitazone in a dose-dependent manner. The increases in thiobarbituric acid-reactive substances and myeloperoxidase activity after aspirin administration were both significantly inhibited by pre-treatment with pioglitazone (10 mg/kg). The gastric content of TNF-alpha increased and the expression of TNF-alpha mRNA was up-regulated after aspirin treatment. However, the peak TNF-alpha mRNA expression 1 h after aspirin administration was inhibited by pioglitazone. CONCLUSION: Based on these data, the beneficial effects of pioglitazone on aspirin-induced gastric mucosal injury may be attributed to its anti-inflammatory properties.

Animals↗
PubMed2001

Zymosan enhances the immune response to DNA vaccine for human immunodeficiency virus type-1 through the activation of complement system.

In the present study, the adjuvant effect of zymosan on human immunodeficiency virus type-1 (HIV-1)-specific DNA vaccine and the mechanism of this enhancement were studied in a murine model. We coinoculated zymosan with our candidate HIV-1 specific DNA vaccine (pCMV160IIIB) into skeletal muscles of BALB/c mice. Higher levels of both humoral immune response and HIV-specific delayed-type hypersensitivity (DTH) response were observed when zymosan was coinoculated with pCMV160IIIB compared with that obtained using pCMV160IIIB alone. HIV-specific cytotoxic T lymphocyte (CTL) activity was also enhanced. This enhancing activity was suppressed when coinoculated to the fifth complement (C5)-deficient DDD and AKR mice. The enhanced activity was also suppressed when anti-C3 antibody was inoculated to mice intramuscularly. There was significant induction of immunoglobulin G2a (IgG2a) and interferon-gamma (IFN-gamma) in pCMV160IIIB vaccine with zymosan. These results suggest that zymosan-mediated DNA vaccination enhances helper T cell (Th) 1-mediated immunity. The effect is suggested to be based on the consequences of its recruitment and activation of macrophages, dendritic cells or antigen-presenting cells (APC) through complement activation, especially through the alternative pathway. Taken together, these results suggest that zymosan can be an effective immunological adjuvant in DNA vaccination against HIV-1.

AIDS Vaccines↗
PubMed2001

Involvement of p21(WAF1/Cip1), p27(Kip1), and p18(INK4c) in troglitazone-induced cell-cycle arrest in human hepatoma cell lines.

Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates cell growth and differentiation. Recent evidence has suggested that PPARgamma ligands had anti-tumor effects through inhibiting cell growth and inducing cell differentiation in several types of malignant neoplasm. In the present study, we investigated: 1) the expression of PPARgamma in both human hepatoma cell lines and 5 resected human hepatocellular carcinoma (HCC) tissues; 2) the growth-inhibitory effect of troglitazone, a PPARgamma ligand, on those hepatoma cells; and 3) the molecular mechanisms of troglitazone-induced cell-cycle arrest. Five hepatoma cell lines, HLF, HuH-7, HAK-1A, HAK-1B, and HAK-5, were used. The mRNA expression levels of PPARgamma, p21(WAF1/Cip1), and p27(Kip1) were determined by real-time quantitative reverse transcription-polymerase chain reaction. The expression of cell cycle-regulating proteins, such as p21, p27, p18(INK4c), cyclin E, and pRb, was examined using Western blotting. PPARgamma was constitutively expressed in all the cell lines and the HCC tissues used in this study. A cytostatic effect of troglitazone was found in those cell lines, and this inhibition of cell growth was dosage-dependent. G0/G1 arrest was apparently demonstrated in flow cytometric analysis in HLF, HAK-1A, HAK-1B, and HAK-5, all of which showed an increased expression of p21 protein. However, HuH-7, lacking p21 protein expression, did not demonstrate clear arrest in the cell-cycle analysis. HLF, which was deficient in the protein product of the retinoblastoma tumor-suppressor gene (pRb), responded most profoundly to troglitazone, showing an increased expression in not only p21, but also in p27 and in p18. These findings suggested that p21, p27, and p18 might be involved in troglitazone-induced cell-cycle arrest in human hepatoma cells.

CDC2-CDC28 Kinases↗
PubMed2001

Endoscopic recurrence of esophageal varices is associated with the specific EUS abnormalities: severe periesophageal collateral veins and large perforating veins.

BACKGROUND: Endoscopic ultrasonography (EUS) with a 20 MHz ultrasound (US) catheter probe can clearly demonstrate esophageal collateral veins. The presence of large periesophageal collateral veins has been correlated with large esophageal varices in patients with portal hypertension. The correlation between the size of esophageal collateral veins and endoscopic recurrence of esophageal varices in patients with portal hypertension who had undergone endoscopic injection sclerotherapy was investigated. Furthermore, whether EUS findings could predict the variceal recurrence was retrospectively studied. METHODS: Thirty-eight patients who had undergone endoscopic injection sclerotherapy were examined every 3 to 4 months with endoscopy and US catheter probe for a period of 2 years. Recurrence of esophageal varices was determined by endoscopic findings of either new varix formation or appearance of red color sign. Esophageal collateral veins were identified by US catheter probe as peri-esophageal collateral veins (adjacent to the esophageal wall) and para-esophageal collateral veins (separated from the esophageal wall) along with perforating veins; and they were graded as severe and mild type by US catheter probe. RESULT: Ten of the 38 patients (26.3%) had endoscopic recurrence at a mean of 10.9 months after endoscopic injection sclerotherapy. In patients with endoscopic recurrences, EUS findings included a significantly (p < 0.001) higher incidence of severe type peri-esophageal collateral veins, a significantly larger number of perforating veins (p < 0.001) and a significantly larger diameter of perforating veins (p < 0.001) compared with patients without recurrence (8 of 10, 80% vs. 2 of 28, 7.1%; 1.30 vs. 0.21; 2.00 vs. 0.32 mm, respectively). The presence of veins at the esophagogastric junction did not correlate with recurrence. CONCLUSION: Severe type peri-esophageal collateral veins and large perforating veins of the esophagus detected by EUS in patients treated by endoscopic injection sclerotherapy signify recurrence of esophageal varices and predict endoscopic recurrence of varices in subsequent months.

Collateral Circulation↗
PubMed2001

Up-regulation of CD44 in rheumatoid chondrocytes.

The adhesion molecule CD44 is thought to play an important role in the inflammatory process. To identify the expression of CD44 in articular chondrocytes in rheumatoid arthritis (RA), monoclonal anti-CD44 antibodies were immunohistochemically used to react with articular cartilage specimens of 15 patients with RA, 9 with osteoarthritis (OA), and 6 with femoral neck fracture (FF). The proportion of CD44-positive chondrocytes in RA was 93 +/- 2% (N=16), which was significantly higher than that in OA (59 +/- 7%, N=9, p<0.001) and FF (46 +/- 5%, N=6, p<0.001). Among CD44 isoforms examined, the hemopoietic form was dominant in chondrocytes in RA. Therefore, up-regulation of CD44 on chondrocytes may play a significant role in cartilage degeneration in RA.

Arthritis, Rheumatoid↗
PubMed2001

Automated extraction of information on protein-protein interactions from the biological literature.

MOTIVATION: To understand biological process, we must clarify how proteins interact with each other. However, since information about protein-protein interactions still exists primarily in the scientific literature, it is not accessible in a computer-readable format. Efficient processing of large amounts of interactions therefore needs an intelligent information extraction method. Our aim is to develop an efficient method for extracting information on protein-protein interaction from scientific literature. RESULTS: We present a method for extracting information on protein-protein interactions from the scientific literature. This method, which employs only a protein name dictionary, surface clues on word patterns and simple part-of-speech rules, achieved high recall and precision rates for yeast (recall = 86.8% and precision = 94.3%) and Escherichia coli (recall = 82.5% and precision = 93.5%). The result of extraction suggests that our method should be applicable to any species for which a protein name dictionary is constructed. AVAILABILITY: The program is available on request from the authors.

Electronic Data Processing↗
PubMed2001

Knowledge representation of signal transduction pathways.

MOTIVATIONS: Signal transduction is the common term used to define a diverse topic that encompasses a large body of knowledge about the biochemical mechanisms. Since most of the knowledge of signal transduction resides in scientific articles and is represented by texts in natural language or by diagrams, there is the need of a knowledge representation model for signal transduction pathways that can be as readily processed by a computer as it is easily understood by humans. RESULTS: A signal transduction pathway representation model is presented. It is based on a compound graph structure and is designed to handle the diversity and hierarchical structure of pathways. A prototype knowledge base was implemented on a deductive database and a number of biological queries are demonstrated on it.

Amino Acid Motifs↗
PubMed2001

Abnormal axonal inward rectifier in streptozocin-induced experimental diabetic neuropathy.

In order to explore the pathophysiology of diabetic neuropathy, we studied serial changes of axonal excitability in 20 adult Wistar rats with streptozocin-induced diabetes using the technique of threshold electrotonus (TE). After persistent hyperglycaemia had developed, rats were divided into two groups: nine were fed a diet containing aldose reductase inhibitor (Epalrestat 30 mg/kg/day) (ARI(+) group) and 11 were fed a diet without the inhibitor (ARI(-) group). Eight normal control rats of similar age (NC group) were also studied. We monitored membrane properties of motor axons in the tail for 3 months using TE to measure the changes in excitability induced by subthreshold polarizing currents while recording compound muscle action potentials (CMAPs) in the tail muscle. The ARI(-) group showed a significant increase in CMAP latency 1 month after streptozocin injection, and by 3 months there was significantly lower excitability after hyperpolarization for 100 ms compared with the NC group. A similar change in TE was reproduced by injection of caesium chloride, an inhibitor of inward rectification. By contrast, the ARI(+) group exhibited no significant change in TE or latency at 3 months, although they showed significant body weight loss and hyperglycaemia. These findings indicate that inward rectification is reduced in an experimental model, as in human diabetes, and that blocking the polyol pathway with an ARI prevents this reduction. Reduced inward rectification potentiates conduction block caused by activity-dependent hyperpolarization and may underlie the decreased vibratory sensation seen in the early stage of diabetic neuropathy.

Action Potentials↗
PubMed2001

En bloc laminoplasty performed with threadwire saw.

OBJECTIVE: To introduce a method for a simple, nonexpansive laminoplasty that can be performed with a threadwire saw (T-saw) after en bloc laminotomy has been performed. The method can be applied along the entire spinal region, including the thoracic and lumbar spine. METHODS: An en bloc laminotomy of trapezoid shape at the cross section is performed bilaterally at the junctional area of the lamina and facet joint with a thin, flexible T-saw, while preserving the supraspinous, interspinous, and interlaminar ligaments. After the intradural procedure has been performed, the laminar flap is replaced in its original site and fixed with 1-0 nylon sutures, resulting in the complete reconstruction of the posterior supporting elements of the spinal column. RESULTS: En bloc laminoplasty was performed on 16 patients via a T-saw; most of the patients had intradural spinal tumors. The patients did not need their spinal canals to be enlarged after the intradural procedure had been performed. The follow-up period ranged from 2 to 40 months (mean +/- standard error, 22.6 +/- 3.4 mo). The laminoplasty was performed from the upper cervical to the sacral regions, although the most frequently operated level was the lower thoracic level. Two-level laminoplasty was performed in 12 patients, and three-level laminoplasty was performed in four. The laminoplasty was done safely and without any complications, except in one patient, who experienced thoracic root injury from a T-saw that was accidentally inserted anterior to the roots. No spinal column deformity or sinking of the replaced laminar flap was noted during the follow-up period; patients were assessed at follow-up via radiographs or computed tomographic scans. Computed tomographic scans obtained later indicated that bony fusion occurred at the cutting edges 1.0 to 4.0 months after surgery (mean, 1.90 +/- 0.34 mo). CONCLUSION: Simple en bloc laminoplasty performed with a T-saw is a useful, safe procedure that can be used to reconstruct the posterior spinal elements throughout the whole spinal region after the intradural procedure has been performed.

Adult↗