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Biomedical subjects

T Matsui

Publications and source records attributed to T Matsui.

At least 163 records · Page 9Linked to original sources
PubMed2001

[Neoadjuvant chemotherapy for advanced epithelial ovarian cancer].

Primary surgical cytoreduction followed by paclitaxel/carboplatin combination chemotherapy currently is the treatment of choice for advanced epithelial ovarian cancer. Aggressive surgery is widely accepted as a valid approach to initial cytoreduction of stage III disease, but suboptimal residual disease following primary surgical resection is one of the most important adverse prognostic factors in these patients. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery for initial management of bulky ovarian cancer, with the goal of improving surgical quality. General acceptance of neoadjuvant chemotherapy as an alternative to primary surgery for patients who are not ideal surgical candidates remains limited, because equivalent or superior survival has not yet been demonstrated in a prospective randomized study. A large-scale, prospective, randomized study is being conducted by the European Organization for Research and Treatment of Cancer (EORTC) Gynecologic Cancer Cooperative Group and Gynecologic Oncology Group (GOG) to compare outcomes (overall and progression-free survival, quality of life, treatment complications) of neoadjuvant chemotherapy/interval debulking surgery versus primary cytoreductive surgery/adjuvant chemotherapy in patients with advanced epithelial ovarian carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Effects of water depth on abdominal [correction of abdominails] aorta and inferior vena cava during standing in water.

During water immersion bradycardia and increase in stroke volume induce by changing in hydrostatic pressure. We hypothesised that the cardiac alterations with immersion are associates with an increase in venous return from lower body. Because the venous return reflects volume of capacitance vein e.g, inferior vena cava. Therefore, we clarified the effects of water immersion on the size in left ventricle, aorta, and vena cava.

Adult↗
PubMed2000

18F-fluorodopa PET study of striatal dopamine uptake in the diagnosis of dementia with Lewy bodies.

Using (18)F-fluorodopa PET and a constant 0.0062 influx rate in the putamen, dementia with Lewy bodies (n = 7) was distinguished from AD (n = 10) with a sensitivity of 86% and a specificity of 100%. A constant 0.0071 influx rate in the caudate yielded a sensitivity of 71% and a specificity of 100% for distinction of the two disorders. Despite a limited sample size, these findings suggest that assessing nigrostriatal dopaminergic function with (18)F-fluorodopa PET may be a useful diagnostic aid in cases of dementia with Lewy bodies while patients are alive.

Aged↗
PubMed2000

Akt-mediated survival of oligodendrocytes induced by neuregulins.

Neuregulins have been implicated in a number of events in cells in the oligodendrocyte lineage, including enhanced survival, mitosis, migration, and differentiation. At least two signaling pathways have been shown to be involved in neuregulin signaling: the phosphatidylinositol (PI)-3 kinase and the mitogen-activated protein kinase pathways. In the present studies, we examined the signaling pathway involved in the survival function of heregulin, focusing on heregulin-induced changes in Akt activity in cultured glial cells, and the consequences of Akt activation in cells in the oligodendrocyte lineage. Heregulin binds erbB receptors, and in our studies, primary cultures of both oligodendrocyte progenitor cells and differentiating oligodendrocytes expressed erbB2, erbB3, and erbB4 receptors. In C6 glioma cells and primary cultures of oligodendrocytes, heregulin induced time- and dose-dependent Akt phosphorylation at Ser(473) in a wortmannin-sensitive manner. To investigate further the signaling pathway for heregulin in glial cells, BAD was overexpressed in C6 glioma cells. In these cells, heregulin induced phosphorylation of BAD at Ser(136). Apoptosis of oligodendrocyte progenitor cells induced by growth factor deprivation was effectively blocked by heregulin in a wortmannin-sensitive manner. Overexpression of dominant negative Akt but not of wild-type Akt by adenoviral gene transfer in primary cultures of both oligodendrocytes and their progenitors induced significant apoptosis through activation of the caspase cascade. The present data suggest that the survival function of heregulin is mediated through the PI-3 kinase/Akt pathway in cells in the oligodendrocyte lineage and that the Akt pathway may be quite important for survival of cells in this lineage.

Androstadienes↗
PubMed2000

Glycogen synthase kinase-3beta is a negative regulator of cardiomyocyte hypertrophy.

Hypertrophy is a basic cellular response to a variety of stressors and growth factors, and has been best characterized in myocytes. Pathologic hypertrophy of cardiac myocytes leads to heart failure, a major cause of death and disability in the developed world. Several cytosolic signaling pathways have been identified that transduce prohypertrophic signals, but to date, little work has focused on signaling pathways that might negatively regulate hypertrophy. Herein, we report that glycogen synthase kinase-3beta (GSK-3beta), a protein kinase previously implicated in processes as diverse as development and tumorigenesis, is inactivated by hypertrophic stimuli via a phosphoinositide 3-kinase-dependent protein kinase that phosphorylates GSK-3beta on ser 9. Using adenovirus-mediated gene transfer of GSK-3beta containing a ser 9 to alanine mutation, which prevents inactivation by hypertrophic stimuli, we demonstrate that inactivation of GSK-3beta is required for cardiomyocytes to undergo hypertrophy. Furthermore, our data suggest that GSK-3beta regulates the hypertrophic response, at least in part, by modulating the nuclear/cytoplasmic partitioning of a member of the nuclear factor of activated T cells family of transcription factors. The identification of GSK-3beta as a transducer of antihypertrophic signals suggests that novel therapeutic strategies to treat hypertrophic diseases of the heart could be designed that target components of the GSK-3 pathway.

Animals↗
PubMed2000

Diphenyleneiodonium prevents reactive oxygen species generation, tyrosine phosphorylation, and histamine release in RBL-2H3 mast cells.

Mast cells play a central role in immediate allergic reactions mediated by immunoglobulin E. It has recently been reported that mast cells generate intracellular reactive oxygen species (ROS) in response to stimulation with divergent physiologically relevant stimulants. However, the physiological role of ROS is poorly understood. Here we demonstrate that mast cell model rat basophilic leukemia (RBL-2H3) cells generate ROS in response to antigen and the calcium-ionophore A23187 via activation of diphenyleneiodonuim (DPI)-sensitive enzyme and that blockade of ROS generation by DPI suppresses histamine release induced by either stimulant. Increased tyrosine phosphorylation of pp125(FAK) and a 77-kDa protein coprecipitating specifically with the kinase occurred in parallel with the secretion, and blockade of ROS generation by DPI also suppressed the tyrosine phosphorylation of both proteins. These findings suggest that ROS generated by a flavoenzyme-dependent mechanism may be involved in histamine release through the pp125(FAK) pathway.

Animals↗
PubMed2000

Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain.

Radixin is a member of the ezrin/radixin/moesin (ERM) family of proteins, which play a role in the formation of the membrane-associated cytoskeleton by linking actin filaments and adhesion proteins. This cross-linking activity is regulated by phosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) in the downstream of the small G protein Rho. The X-ray crystal structures of the radixin FERM domain, which is responsible for membrane binding, and its complex with inositol-(1,4, 5)-trisphosphate (IP3) have been determined. The domain consists of three subdomains featuring a ubiquitin-like fold, a four-helix bundle and a phosphotyrosine-binding-like domain, respectively. These subdomains are organized by intimate interdomain interactions to form characteristic grooves and clefts. One such groove is negatively charged and so is thought to interact with basic juxta-membrane regions of adhesion proteins. IP3 binds a basic cleft that is distinct from those of pleckstrin homology domains and is located on a positively charged flat molecular surface, suggesting an electrostatic mechanism of plasma membrane targeting. Based on the structural changes associated with IP3 binding, a possible unmasking mechanism of ERM proteins by PIP2 is proposed.

Amino Acid Sequence↗
PubMed2000

Epigallocatechin gallate inhibits histamine release from rat basophilic leukemia (RBL-2H3) cells: role of tyrosine phosphorylation pathway.

Some tea polyphenolic compounds including (-)-epigallocatechin gallate (EGCG) have been shown to inhibit histamine release from mast cells through poorly understood mechanisms. By using a mast cell model rat basophilic leukemia (RBL-2H3) cells we explored the mechanism of the inhibition. EGCG inhibited histamine release from RBL-2H3 cells in response to antigen or the calcium-ionophore A23187, while (-)-epicatechin (EC) had little effect. Increased tyrosine phosphorylation of several proteins including approximately 120 kDa proteins occurred in parallel with the secretion induced by either stimulation. EGCG also inhibited tyrosine phosphorylation of the approximately 120-kDa proteins induced by either stimulation, whereas EC did not. The tyrosine kinase-specific inhibitor piceatannol inhibited the secretion and tyrosine phosphorylation of these proteins induced by either stimulation also. Further analysis showed that the focal adhesion kinase pp125(FAK) was one of the approximately 120-kDa proteins. These findings suggest that EGCG prevents histamine release from mast cells mainly by inhibiting tyrosine phosphorylation of proteins including pp125(FAK).

Animals↗
PubMed2000

Alpha2-macroglobulin gene polymorphisms show racial diversity and are not associated with Alzheimer's disease.

Two genetic markers of the plasma protein alpha2-macroglobulin, a 5 bp deletion/insertion at the 5' splice site of exon 18 (A2MI) and the GTC/ATC (VaIIO00IIe) in exon 24 (A2M2), may have roles in the development of Alzheimer's disease (AD). Genotyping and linkage analysis of these markers in 426 Japanese sporadic AD patients, 85 autopsy-confirmed Caucasian AD cases, and, as controls, 382 Japanese and 65 Caucasians who were cognitively normal and 140 Japanese Parkinson's disease patients showed racial diversity in the frequencies and relationship of the two markers. Comparison of genotype and allele frequencies, stratification of the samples by the presence of the apolipoprotein E epsilon4 allele, and logistic regression analysis revealed no association of these markers with AD in either racial group.

Aged↗
PubMed2000

Prospects for gene therapy for heart failure.

Heart failure represents an enormous clinical challenge in need of effective therapeutic approaches. The possibility of gene therapy for heart failure merits consideration at this time because of improvements in vector technology; cardiac gene delivery; and, most importantly, our understanding of the molecular pathogenesis of heart failure. We will first review recent advances in cardiac gene delivery in animal models and then examine several targets being considered for therapeutic intervention. In this context, gene transfer provides not only a potential therapeutic modality but also an important tool to help validate specific targets. Several interventions, particularly those enhancing sarcoplasmic calcium transport, show promise in animal models of heart failure and in myopathic cardiomyocytes derived from patients. However, bridging the gap between these basic investigative studies and clinical gene therapy remains a formidable task. Early experiments in rodents will need to be extended to large-animal models with clinical-grade vectors and delivery systems to assess both efficacy and safety. On the basis of a foundation of rigorous science and a growing understanding of heart failure pathogenesis, there is reason for cautious optimism for the future.

Animals↗
PubMed2000

Snake venom proteases affecting hemostasis and thrombosis.

The structure and function of snake venom proteases are briefly reviewed by putting the focus on their effects on hemostasis and thrombosis and comparing with their mammalian counterparts. Up to date, more than 150 different proteases have been isolated and about one third of them structurally characterized. Those proteases are classified into serine proteases and metalloproteinases. A number of the serine proteases show fibrin(ogen)olytic (thrombin-like) activities, which are not susceptible to hirudin or heparin and perhaps to most endogenous serine protease inhibitors, and form abnormal fibrin clots. Some of them have kininogenase (kallikrein-like) activity releasing hypotensive bradykinin. A few venom serine proteases specifically activate coagulation factor V, protein C, plasminogen or platelets. The venom metalloproteinases, belonging to the metzincin family, generally show fibrin(ogen)olytic and extracellular matrix-degrading (hemorrhagic) activities. A few venom metalloproteinases show a unique substrate specificity toward coagulation factor X, platelet membrane receptors or von Willebrand factor. A number of the metalloproteinases have chimeric structures composed of several domains such as proteinase, disintegrin-like, Cys-rich and lectin-like domains. The disintegrin-like domain seems to facilitate the action of those metalloproteinases by interacting with platelet receptors. A more detailed analysis of snake venom proteases should find their usefulness for the medical and pharmacological applications in the field of thrombosis and hemostasis.

Amino Acid Sequence↗
PubMed2000

Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase.

BACKGROUND: Senescent hearts are characterized by diastolic dysfunction and a decrease in sarcoplasmic reticulum (SR) Ca(2+)-ATPase protein (SERCA2a). METHODS AND RESULTS: To test the hypothesis that an increase in SERCA2a could improve cardiac function in senescent rats (age 26 months), we used a catheter-based technique of adenoviral gene transfer to achieve global myocardial transduction of SERCA2a in vivo. Adult rat hearts aged 6 months and senescent rat hearts infected with an adenovirus containing the reporter gene beta-galactosidase were used as controls. Two days after infection, parameters of systolic and diastolic function were measured in open-chest rats. Cardiac SERCA2a protein and ATPase activity were significantly decreased in senescent hearts compared with adult rats (Delta -30+/-4% and -49+/-5%) and were restored to adult levels after infection with Ad.SERCA2a. At baseline, left ventricular systolic pressure and +dP/dt were unaltered in senescent hearts; however, diastolic parameters were adversely affected with an increase in the left ventricular time constant of isovolumic relaxation and diastolic pressure (Delta +29+/-9% and +38+/-12%) and a decrease in -dP/dt (Delta -26+/-11%). Overexpression of SERCA2a did not significantly affect left ventricular systolic pressure but did increase +dP/dt (Delta +28+/-10%) in the senescent heart. Overexpression of SERCA2a restored the left ventricular time constant of isovolumic relaxation and -dP/dt to adult levels. Infection of senescent hearts with Ad.SERCA2a markedly improved rate-dependent contractility and diastolic function in senescent hearts. CONCLUSIONS: These results support the hypothesis that decreased Ca(2+)-ATPase activity contributes to the functional abnormalities observed in senescent hearts and demonstrates that Ca(2+) cycling proteins can be targeted in the senescent heart to improve cardiac function.

Adenoviridae↗
PubMed2000

Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure.

In human and experimental models of heart failure, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling. The disturbances in calcium metabolism have been shown to contribute significantly to the contractile dysfunction observed in heart failure. We investigated whether increasing SERCA2a expression can improve ventricular function in an animal model of heart failure obtained by creating ascending aortic constriction in rats. After 19-23 wk of banding during the transition from compensated hypertrophy to heart failure (documented by >25% decrease in fractional shortening), rats were randomized to receive either an adenovirus carrying the SERCA2a gene (Ad.SERCA2a, n = 13) or beta-galactosidase (Ad.betagal, n = 14) by using a catheter-based technique. The failing hearts infected with Ad. betagal were characterized by a significant decrease in SERCA2a expression and a decrease in SERCA2a activity compared with nonfailing sham-operated rats (n = 11). In addition, these failing hearts had reduced left-ventricular systolic pressure, maximal rate of left-ventricular pressure rise and decline (+dP/dt, -dP/dt), and rate of isovolumic relaxation (tau). Overexpression of SERCA2a restored both SERCA2a expression and ATPase activity to nonfailing levels. Furthermore, rats infected with Ad.SERCA2a had significant improvement in left-ventricular systolic pressure, +dP/dt, -dP/dt, and rate of isovolumic relaxation (tau) normalizing them back to levels comparable to sham-operated rats. In this study, we show that in an animal model of heart failure where SERCA2a protein levels and activity are decreased and severe contractile dysfunction is present, overexpression of SERCA2a in vivo restores both systolic and diastolic function to normal levels.

Adenoviridae↗