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Biomedical subjects

M Tanji

Publications and source records attributed to M Tanji.

At least 19 recordsLinked to original sources
PubMed1999

Hypoxia up-regulates telomerase activity via mitogen-activated protein kinase signaling in human solid tumor cells.

Solid tumor cells are often exposed to hypoxia in vivo, which has been suggested to promote genetic instability in those cells. Telomere elongation by telomerase is implicated in chromosome stabilization in immortal cells. Here we found that hypoxia enhanced telomerase activity in the solid tumor A2780 and HT-29 cells but not in the leukemia U937 cells. The telomerase activation correlated with activation of mitogen-activated protein kinase (MAPK) and c-fos expression. The MEK1 inhibitor PD98059 repressed telomerase activation in the hypoxic cells. Consistently, a dominant negative MEK1 inhibited telomerase activation by hypoxia. Finally, we found a good correlation between telomerase activation and resistance to apoptotic cell death under hypoxic conditions. These findings indicate that hypoxia up-regulates telomerase activity via MAPK cascade signaling especially in solid tumor cells and suggest that solid tumor cells might enhance the telomerase activity as a stress response against genotoxicity induced by hypoxia.

Apoptosis↗
PubMed1999

The leukemic oncogene tal-2 is expressed in the developing mouse brain.

tal-1 (T-cell acute leukemia-1; also known as SCL) and tal-2 genes belong to a family of basic helix-loop-helix transcription factors and were originally isolated from the breakpoints of chromosomal translocations in human T-cell leukemia cell lines. tal-1 is expressed not only in hematopoietic cells but also in several endothelial structures and the central nervous system during development. On the other hand, the detailed function and the sites of expression of tal-2 have remained obscure. We cloned the tal-2 cDNA from a mouse embryonic cDNA library and examined its expression pattern in the mouse, comparing with that of tal-1. In situ analyses revealed that tal-2 transcripts are detected at embryonic day 12.5 in the following regions; 1) the diencephalon-the zona limitans intrathalamica and the pretectum, 2) the mesencephalon-the tectum, and the anterior and posterior tegmentum, 3) the metencephalon-the isthmus and the anterior pons. In the diencephalon and the mesencephalon, the expression sites of tal-2 gene were similar to those of tal-1, and its expression was stronger than that of tal-1. In the metencephalon, tal-2 expression was observed in the anterior pons, whereas tal-1 transcripts were detected in the entire pons, and showed stronger expression than tal-2. The tal-2 messages were barely detectable in the brain at birth. These results suggest that tal-1 and tal-2 are involved in the development of specific areas of the central nervous system.

Amino Acid Sequence↗
PubMed1996

Cerebral metabolic recovery from deep hypothermic circulatory arrest after treatment with arginine and nitro-arginine methyl ester.

BACKGROUND: Recent studies suggest that nitric oxide is important in the pathogenesis of ischemic brain injury and also has a role in controlling cerebrovascular tone. This study examines the net effects of nitric oxide on cerebral metabolic recovery after deep hypothermic circulatory arrest. METHODS: Two-week-old piglets were supported by cardiopulmonary bypass and cooled to 15 degrees C followed by 1 hour of deep hypothermic circulatory arrest, 45 minutes of reperfusion and rewarming, and then 3 hours of normothermic perfusion. Groups of 10 piglets received one of four treatments before bypass; L-nitro-arginine methyl ester, inhibitor of nitric oxide synthesis, 10 mg/kg intravenously; L-arginine, to enhance nitric oxide synthesis, 30 mg/kg intravenously before bypass and then 10 mg/kg per minute during the first hour of reperfusion; a combination of L-nitro-arginine methyl ester plus L-arginine at these same doses; and no pretreatment (controls). Cerebral high-energy phosphates and pH were measured by magnetic resonance spectroscopy in half the animals. Cerebral blood flow, metabolic rates for oxygen and glucose, and the oxidation/reduction state of cytochrome aa3 and oxygenated and deoxygenated hemoglobin measured by near-infrared spectroscopy were assessed in the other half of the piglets. RESULTS: L-nitro-arginine methyl ester significantly increased cerebral vascular resistance and markedly reduced recovery of high-energy phosphates, pH, and oxidation state of cytochrome aa3, L-arginine increased cerebral blood flow, cerebral glucose and oxygen consumption, and recovery of cytochrome aa3 oxidation and high-energy phosphates. L-Arginine did not reverse completely the effects of L-nitro-arginine methyl ester on cerebral metabolic recovery. CONCLUSION: In a piglet model of deep hypothermic circulatory arrest, L-nitro-arginine methyl ester has a deleterious effect and L-arginine has a beneficial effect on cerebral metabolic recovery. The deleterious metabolic effects of L-nitro-arginine methyl ester are only partially reversed by L-arginine. This fact suggests that there may be mechanisms in addition to inhibition of nitric oxide synthesis contributing to the neurotoxicity of L-nitro-arginine methyl ester in this model.

Animals↗
PubMed1996

The primary structure of the major pepsinogen from the gastric mucosa of tuna stomach.

The complete primary structure of the major component of tuna pepsinogens was determined by conventional protein chemistry methods. It was composed of a prosegment of 37 residues and a pepsin moiety of 323 residues, having a relative molecular mass of 39,364. The essential aspartyl residues in the active site and the three disulfide bonds common to other pepsinogens were conserved; however, several unique substitutions and/or deletions characteristic of tuna pepsinogen were found at various positions, especially in the prosegment and subsite regions, as compared with the sequences of other pepsinogens, which may affect the rate of activation of the zymogen, and/or the catalytic function and substrate specificity of the enzyme. Tuna pepsinogen is the least acidic among pepsinogens. The sequence identity between tuna pepsinogen and other pepsinogens ranged from 45 to 52%. A phylogenetic tree based on the primary structures suggested that tuna pepsinogen diverged from the pepsinogen A and prochymosin groups in an early period of pepsinogen evolution.

Amino Acid Sequence↗
PubMed1996

[Total cavopulmonary connection using a knitted dacron prosthesis impregnated with gelatin (GELSEAL) as an intracardiac conduit].

It is important to find a suitable vascular prosthesis as an intracardiac conduit for a total cavopulmonary connection because of the need for long-term patency. A 7-year-old girl with a double outlet of right ventricle, hypoplastic left ventricle, pulmonary atresia and single atrium with azygos connection underwent a total cavopulmonary connection using a knitted dacron prosthesis impregnated with gelatin (GELSEAL) as an intracardiac conduit. Her postoperative course was uneventful. GELSEAL is soft, easy to hand and effective at preventing blood loss. The conduit is also expected to have long-term patency because of good healing with thin and uniform pseudointimal formation. However, long-term patency especially in the right side of the heart is still unknown. She should be followed with close anticoagulant therapy and careful observation.

Anastomosis, Surgical↗
PubMed1996

[A case of congenital tricuspid regurgitation associated with atrial septal defect and peripheral pulmonary stenosis].

This report describes a 5-year-old girl with congenital tricuspid regurgitation associated with an atrial septal defect and peripheral pulmonary stenosis. The girl was diagnosed with the heart murmur at birth and recently developed the cardiomegaly. Cardiac echocardiography and catheterization showed severe tricuspid regurgitation, an atrial septal defect of the secundum type and peripheral pulmonary stenosis. In the operative findings, the tricuspid annulus was dilated to 33 mm in diameter, and leaflets were attached normally to the antomic annulus. There was a large cleft of the anterior leaflet of the tricuspid valve. Suture of the cleft and annuloplasty of the tricuspid valve, suture closure of the atrial septal defect and patch dilatation of peripheral pulmonary stenosis were successfully performed. Including this case, 19 other cases with congenital tricuspid regurgitation undergoing surgery were reported to date.

Child, Preschool↗
PubMed1995

Regulation of Raf-1 kinase activity by the 14-3-3 family of proteins.

We have identified the beta (beta) isoform of the 14-3-3 family of proteins as an activator of the Raf-1 protein kinase. 14-3-3 was isolated in a yeast two-hybrid screen for Raf-1 kinase domain binding proteins. Purified bovine brain 14-3-3 interacted specifically with both c-Raf-1 and the isolated Raf-1 kinase domain. Association was sensitive to the activation status of Raf-1; 14-3-3 bound to unactivated Raf-1, but not Raf-1 activated by protein kinase C alpha or Ras and Lck. The significance of these interactions under physiological conditions was demonstrated by co-immunoprecipitation of Raf-1 and 14-3-3 from extracts of quiescent, but not mitogen-stimulated, NIH 3T3 cells. 14-3-3 was not a preferred Raf-1 substrate in vitro and did not significantly affect Raf-1 kinase activity in a purified system. However, in cell-free extracts 14-3-3 acted as a Ras-independent activator of both c-Raf-1 and the Raf-1 kinase domain. The same results were obtained in vivo using transfection assays; 14-3-3 enhanced both c-Raf-1- and Raf-1 kinase domain-stimulated expression of AP-1- and NF-kappa B-dependent reporter genes and accelerated Raf-1 kinase domain-triggered differentiation of PC12 cells. We conclude that 14-3-3 is a latent co-activator bound to unactivated Raf-1 in quiescent cells and mediates mitogen-triggered but Ras-independent regulatory effects aimed directly at the kinase domain.

14-3-3 Proteins↗
PubMed1995

The role of experimental aluminum intoxication in allogeneic immunoresponse.

To evaluate the immunological properties of aluminum (Al) in experimental Al intoxication in rats, we performed heart transplantation and in vitro experiments. Lewis (Lew) rats were intoxicated with intraperitoneal injections of AlCl3. heart transplants were performed using Brown-Norway (BN) rats as donors. Isotransplants and normal Lew were used as controls. No differences in survival were observed. Unidirectional mixed lymphocyte cultures (MLC) and Concanavalin A (Con A)-stimulated cultures were prepared using spleen cells from normal and Al-intoxicated Lew rats. No differences were found in unidirectional MLC. Intoxicated cells showed a less intense response to con A than did normal cells. In conclusion, we could not detect an immunosuppressive role of Al intoxication in experimental cardiac transplantation or in MLC. However, the depressed Con A blastogenic response of Al-intoxicated cells may reflect an immunological role yet to be defined.

Aluminum↗
PubMed1994

Activation of protein kinase C by purified bovine brain 14-3-3: comparison with tyrosine hydroxylase activation.

In the course of the purification of 14-3-3 protein (14-3-3) we found that 14-3-3 isolated from bovine forebrain activates protein kinase C (PKC), rather than the previously reported protein kinase C inhibitory activity (KCIP). We have characterized the 14-3-3 activation of PKC. The physical properties of purified PKC activator are the same as those previously reported for 14-3-3 and KCIP; i.e., (1) it is composed of subunits of molecular weight 32,000, 30,000, and 29,000; (2) it is homogeneous with respect to molecular weight, as judged by native gradient-gel electrophoresis, with a molecular weight of 53,000; and (3) it is composed of at least six isoforms when analyzed by reverse-phase HPLC. The concentration dependence of PKC activation by 14-3-3 is in the same range as that shown previously for KCIP inhibition of PKC, and as that required for 14-3-3 activation of tyrosine hydroxylase; a maximal stimulation of two- to three-fold occurs at 40-100 micrograms/ml. 14-3-3's activation of PKC is sensitive to alpha-chymotrypsin digestion but is not heat labile. Activation is specific to PKC; at least two other protein kinases, cyclic AMP- and calcium/calmodulin-dependent protein kinases, are not activated. The activation of PKC by 14-3-3 is independent of phosphatidylserine and calcium and, as such, is an alternative mechanism for the activation of PKC that obviates its translocation to membranes.

14-3-3 Proteins↗
PubMed1994

[A case of left ventricular outflow tract obstruction after repair of ostium primum defect].

We report a 3-year-old girl with left ventricular outflow tract obstruction after repair of ostium primum defect. The girl had closure of an ostium primum defect performed at the age of 1 year. Two years later, she developed left ventricular hypertrophy with systolic ejection murmur. Echocardiography showed discrete stenosis of the left ventricular outflow tract. Cardiac catheterization showed a peak systolic gradient of 63 mmHg across the left ventricular outflow tract. At the reoperation, the fibrous tissue was excised and myectomy was done. After the operation the peak systolic gradient across the left ventricular outflow tract disappeared. Since there is a possibility of occurrence of the left ventricular outflow tract obstruction after repair of atrioventricular septal defect, long term follow up is mandatory.

Child, Preschool↗
PubMed1993

[Left main coronary artery stenosis following aortic valve replacement using a solid coronary perfusion catheter: report of two cases].

We experienced two cases of iatrogenic left main coronary artery stenosis (IOCS) following double (aortic and mitral) valve replacement (DVR). The solid coronary perfusion catheter may attribute IOCS, with grave consequence. There have been no IOCS since the time we exchanged a solid catheter for a soft one. One case, she was successfully treated percutaneous transluminal coronary angioplasty (PTCA), because she developed angina pectoris about 5 years after PTCA. But she developed angina pectoris again and angiographically left main coronary was severe stenotic. So she was undergone aorto coronary bypass grafting (CABG) to the left anterior descending. The other case, he developed angina pectoris about 3 months after DVR. He was treated with PTCA. Angiographically left mine coronary artery stenosis reduced 50% from 90%. Generally the treatment of IOCS is CABG, but we performed PTCA for 2 patients. Because we thought it was very hazardous for us to perform them open heart surgery. When it is very hazardous to perform patients open heart surgery, they need to be performed PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1992

Gastric procathepsin E and progastricsin from guinea pig. Purification, molecular cloning of cDNAs, and characterization of enzymatic properties, with special reference to procathepsin E.

Procathepsin E and progastricsin were purified from the gastric mucosa of the guinea pig. They were converted to the active form autocatalytically under acidic conditions. Each active form hydrolyzed protein substrates maximally at around pH 2.5. Pepstatin inhibited cathepsin E very strongly at an equimolar concentration, whereas the inhibition was much weaker for gastricsin. Molecular cloning of the respective cDNAs permitted us to deduce the complete amino acid sequences of their pre-proforms; preprocathepsin E and preprogastricsin consisted of 391 and 394 residues, respectively. Procathepsin E has unique structural and enzymatic features among the aspartic proteinases. Lys at position 37, which is common to various aspartic proteinases and is thought to be important for stabilizing the activation segment, was absent at the corresponding position, as in human procathepsin E. The rate of activation of procathepsin E to cathepsin E is maximal at around pH 4.0. It is very different from the pepsinogens and may be correlated with the absence of Lys37. Native procathepsin E is a dimer, consisting of two monomers covalently bound by a disulfide bridge between 2 Cys37. Interconversion between the dimer and the monomer was reversible and regulated by low concentrations of a reducing reagent. Although the properties of the dimeric and monomeric cathepsins E are quite similar, a marked difference was found between them in terms of their stability in weakly alkaline solution: monomeric cathepsin E was unstable at weakly alkaline pH whereas the dimeric form was stable. The generation of the monomer was thought to be the process leading to inactivation, hence degradation of cathepsin E in vivo.

Amino Acid Sequence↗
PubMed1992

[Two operated cases of mitral stenosis (MS) associated with left atrial ball thrombus].

Mitral stenosis associated with left atrial ball thrombus is rare. Removal of left atrial ball thrombus and mitral valve replacement was performed in two patients successfully. The rate of thromboembolism was high in patient who has left atrial ball thrombus. Also, sudden death was reported in these cases due to incarceration of ball thrombus in the mitral orifice (hole-in-one thrombus). We concluded that we should operate the MS associated with left atrial ball thrombus as soon as possible.

Female↗