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Biomedical subjects

T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 361 records · Page 20Linked to original sources
PubMed1997

[A surgical case of severe Ebstein's anomaly, pulmonary atresia in the neonate: experience of modified Starnes operation].

We report a surgical case of severe Ebstein's anomaly associated with pulmonary atresia in the neonate. The baby had remarkable cardiomegaly (CTR > or = 90%) soon after birth and presented severe respiratory distress. He underwent modified Starnes operation (closure of tricuspid valve using a perforated patch, enlargement of interatrial communication, modified Blalock shunt, and PDA ligation) at the age of 12 days. He survived the procedure and cardiopulmonary failure was improved. However, he died from arrhythmia on the 3rd postoperative day. We think this procedure is useful regard to improvement of cardiopulmonary failure due to this fatal congenital heart disease.

Cardiac Surgical Procedures↗
PubMed1997

Role of cytoprotective mechanisms in the photochemical purging of autologous bone marrow grafts.

The molecular basis of the differential sensitivity of normal hematopoietic stem cells and of leukemia, lymphoma, and neuroblastoma cells to merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) is not yet completely understood. While the capacity to bind dye molecules appears to be the major determinant of a cell's susceptibility of MC540-mediated PDT, we here present evidence that under certain experimental conditions a cell's capacity to repair MC540-mediated photodynamic damage is also an important factor. Two parameters, temperature and intracellular glutathione (GSH) content, were varied to investigate the role of cellular defense mechanisms in the dye-sensitized photoinactivation of normal murine granulocyte/macrophage progenitors (CFU-GM) and K562, L1210, and melphalan-resistant L1210/L-PAM1 leukemia cells. When exposed to MC540 and light at room temperature, the three leukemia cell lines bound similar amounts of dye and accumulated similar amounts of lipid hydroperoxide (LOOH) but differed markedly in their sensitivity to MC540-mediated PDT. Performing MC540-mediated PDT at 4 degrees C instead of at room temperature reduced dye binding and LOOH generation and enhanced cytotoxicity in some but not all cell lines. A brief (< or = 120 minutes) incubation at 37 degrees C immediately following MC540-mediated PDT accelerated the decay of LOOH in all leukemic cell lines and reduced cell kill by about 2 log in both CFU-GM and leukemia cells. The effect of post-PDT incubation at 37 degrees C on LOOH decay was most pronounced in K562 and least pronounced in L1210/L-PAM1 cells, whereas its effect on cell survival was less pronounced in L1210 cells than in the remaining cell types. L1210/L-PAM1 cells whose GSH content had been reduced from 8.2 to 1.6 micrograms/mg protein by incubation with buthionine sulfoximine recovered from potentially lethal photodynamic damage as rapidly as untreated L1210/L-PAM1 cells and more rapidly than wild-type L1210 cells with a GSH content of 4.5 micrograms/mg protein. Thus, with regard to capacity of L1210/L-PAM1 cells to recover from photodynamic damage, the cells' enhanced capacity to synthesize GSH appeared more decisive than intracellular GSH levels per se. Taken together, these data suggest that temperature-dependent cellular defense mechanisms are significant determinants of a cell's susceptibility to MC540-mediated PDT. The data emphasize the need for temperature control during and immediately after the photochemical purging of autologous bone marrow or peripheral blood stem cells.

Animals↗
PubMed1997

[Molecular mechanism of cardiac hypertrophy and dysfunction].

We examined the signal transduction pathway for the development of cardiac hypertrophy induced by high blood pressure. The activities of Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK), MAP kinases (MAPKs) and 90-kDa ribosomal S6 kinase (p90rsk) was examined by passively stretching neonatal rat cardiomyocytes in vitro. Mechanical stretch activated these protein kinases transiently and sequentially: the maximal activation of Raf-1, MAPKK, MAPKs and p90rsk was observed at 2 minutes, 5 minutes, 8 minutes and 10 approximately 30 minutes, respectively. Both angiotensin II (AngII) and endothelin-1 (ET-1) were constitutively secreted from cultured cardiomyocytes, and a significant increase in the concentration was recognized in the culture medium of cardiomyocytes within 10 minutes after stretch. ET-1 mRNA levels were also increased in cardiomyocytes at 30 minutes after stretch. Moreover, ET-1 and AngII synergistically activated Raf-1 and MAPKs in cultured cardiomyocytes. In conclusion, mechanical stretch stimulates secretion and production of AngII and ET-1 in cultured cardiomyocytes, and both vasoconstrictive peptides may play an important role in mechanical stress (high blood pressure)-induced cardiac hypertrophy.

Angiotensin II↗
PubMed1997

Short-term hemodialysis treatment in dogs and cats with total uretic obstruction.

This study evaluated the single-pass system for the short-term dialysis treatment of dogs and cats with experimental renal failure. The hemodialyzer was equipped with a thin and highly permeable Cuprophan membrane. Four animals (two dogs and two cats) with total uretic obstruction were dialyzed twice in a one-week period. The vascular access by venipuncture of external jugular vein delivered more than 5 ml/min/kg/body weight of blood repeatedly, even for the cats. The evaluation of the effects of the blood flow, dialysate flow and ultrafiltration pressure revealed that the blood flow was the most important factor for effective dialysis. A 300 ml/min dialysate flow provided enough clearance of blood urea nitrogen and creatinine. The ultrafiltration pressure played an important role in ensuring that the fluid removal was constant. Laboratory studies revealed a 50.0% (range 42.0 to 59.3%) reduction of blood urea nitrogen, a 48.7% (range 42.5 to 58.7%) reduction of creatinine, and a 49.8% (range 34.3 to 66.2%) reduction of inorganic phosphate during the dialysis treatment. No dialysis disequilibrium syndrome was shown by the clinical signs. We conclude that this short-term dialysis using a single-pass system for small animals was sufficiently applicable to dogs and cats, and that the optimal duration of the dialysis was 2 hours.

Animals↗
PubMed1997

[Successful treatment with intermittent administration of etoposide for an adult case with recurrent hemophagocytic syndrome, developed in association with chronic EB virus infection related lymphoid hyperplasia in the small intestine].

A 28-year-old man complaining of melena accompanied by high grade fever was previously operated on for two small ulcerative, infiltrative lesions of the small bowel at another hospital in April, 1992. In the resected small intestines an immunohistochemical study was positive for EBV encoded RNA (EBER). It is assumed that Epstein-Barr (EB) virus infection has contributed to the small bowel lesions. In March, 1993, he was diagnosed as having chronic EB virus infection. In October, 1993, he was transferred to our hospital for further examination of high grade fever, rapidly worsening thrombocytemia and severe liver disfunction. Mature histiocytes with hemophagocytosis were detected in the bone marrow and he was diagnosed as having hemophagocytic syndrome (HPS) due to reactivation of chronic EB virus infection. Although treatment by corticosteroids, acyclovir and gamma globulin was not effective administration of etoposide induced remission of the disease. In December, 1993 and January, 1994 HPS recurred, but etoposide was again effective in alleviating the disease. To prevent recurrence of HPS after we discharge the patient, intermittent administration of small doses of etoposide was started. Since then HPS has not recurred, and the drug was eventually discontinued in November, 1995. Our case suggested that Etoposide could change the fulminant course of EB virus-associated HPS and that it is effective to sustained remission.

Adult↗
PubMed1997

[Nutritional support in terminal patients--evaluation of 109 cases receiving home parenteral nutrition].

For end-stage patients with malignant disease, home parenteral nutrition (HPN) is an effective and useful treatment in terms of pain control and nutritional support. Therefore, these patients are able to spend their final days at home with their family. In 1990, we started the treatment and have been experienced 109 cases. In this report, we evaluate these cases and which condition or circumstance are necessary to perform HPN for the terminal patients.

Adult↗
PubMed1997

Autoregulation of human cardiac homeobox gene CSX1: mediation by the enhancer element in the first intron.

Csx/Nkx-2.5 is a murine homeobox gene expressed predominantly in cardiocytes and their progenitor cells. The highly lineage-restricted expression pattern of Csx/Nkx-2.5 gene suggests the existence of a positive autoregulatory loop in the transcriptional regulation of Csx/Nkx-2.5. The first intron of CSX1, a human homolog of Csx/Nkx-2.5 gene, had two potential CSX1-binding sequences. Activity of the CSX1 minimal promoter in cultured cardiac myocytes was significantly increased by placing the 3' half of the CSX1 first intron downstream of the reporter gene, suggesting that this region functions as a positive enhancer element. Transient transfection experiments in nonmuscle cells demonstrated that the reporter construct containing the CSX1 minimal promoter and the 3' half of the CSX1 first intron was strongly transactivated by overexpression of CSX1, whereas the CSX1 minimal promoter alone was not. Together these results suggest that the highly lineage-restricted expression of CSX1 is accomplished by autoactivation, which may be mediated by the enhancer element in the first intron.

Animals↗
PubMed1997

[Can 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) evaluate the renal function without blood sampling?: consensus report from multicenter study].

A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.

Adolescent↗
PubMed1997

Structure model and physicochemical properties of the C-U mismatch pair in the double stranded RNA in solution.

Structure of the C-U mismatch pair was reported only in crystal but none in solution. Here we have studied the structure and physicochemical properties of the C-U mismatch pair in a double stranded RNA in solution. RNA oligomers r(CGACUCAGG) and r(CCUGCGUCG) form a double stranded structure with the C-U pair. The arrangement of the C-U pair derived from the model building based on nOe gives a similar structural feature to that in crystal. The modeling reveals that the amino-proton of cytidine and the keto-oxygen of uridine are located within hydrogen bonding distance, and the imino proton of uridine is exposed to bulk water. From the melting experiment which monitors chemical shifts of non-exchangeable protons, the melting of all the base-pairs including the C-U pair occurs simultaneously. This suggests the possibility where the C-U mismatch pair is stacked on the neighboring base-pairs in the double helix until the duplex is denatured to single strands.

Base Composition↗
PubMed1996

Protein kinase C, but not tyrosine kinases or Ras, plays a critical role in angiotensin II-induced activation of Raf-1 kinase and extracellular signal-regulated protein kinases in cardiac myocytes.

Angiotensin II (AngII) induces cardiac hypertrophy through activating a variety of protein kinases. In this study, to understand how cardiac hypertrophy develops, we examined AngII-evoked signal transduction pathways leading to the activation of extracellular signal-regulated protein kinases (ERKs), which are reportedly critical for the development of cardiac hypertrophy, in cultured cardiac myocytes isolated from neonatal rats. Inhibition of protein kinase C (PKC) with calphostin C or down-regulation of PKC by pretreatment with a phorbol ester for 24 h abolished AngII-induced activation of Raf-1 and ERKs, and addition of a phorbol ester conversely induced a marked increase in the activities of Raf-1 and ERKs. Pretreatment with two chemically and mechanistically dissimilar tyrosine kinase inhibitors, genistein and tyrphostin, did not attenuate AngII-induced activation of ERKs. In contrast, genistein strongly blocked insulin-induced ERK activation in cardiac myocytes. Although pretreatment with manumycin, a Ras farnesyltransferase inhibitor, or overexpression of a dominant-negative mutant of Ras inhibited insulin-induced ERK activation, neither affected AngII-induced activation of ERKs. Overexpression of a dominant-negative mutant of Raf-1 completely suppressed ERK2 activation by AngII, endothelin-1, and insulin. These results suggest that PKC and Raf-1, but not tyrosine kinases or Ras, are critical for AngII-induced activation of ERKs in cardiac myocytes.

Angiotensin II↗
PubMed1996

Effects of locally administered desipramine on myocardial interstitial norepinephrine levels.

We investigated whether locally administered neuronal uptake blockade with desipramine (DMI) modified basal myocardial interstitial norepinephrine (NE) levels and stimulation-induced NE responses. Using the dialysis technique, dialysates were sampled from the midwall of the left ventricle in anesthetized cats. Dialysate NE concentrations, as an index of myocardial interstitial NE level, were measured by high performance liquid chromatography. Through the dialysis probe, local administration of DMI (10(-4) mol/l) increased the dialysate NE level from 24.6 +/- 12.2 to 127.8 +/- 37.4 and from 11.9 +/- 5.4 to 64.9 +/- 28.7 pg/ml regardless of whether stellate ganglia were intact or transected. The arterial pressure and heart rate responses to electrical stimulation of the stellate ganglia were not altered by DMI. Control nerve stimulation increased dialysate NE concentrations to 214.5 +/- 100.0 and 57.5 +/- 22.0 pg/ml at 5 Hz and 2 Hz, respectively. During local administration of DMI, nerve stimulation-induced NE response increased to 997.5 +/- 202.0 at 5 Hz and to 436.0 +/- 68.5 pg/ml at 2 Hz. We conclude that local administration of DMI caused marked rises in basal myocardial interstitial NE concentrations and responses to cardiac sympathetic activation.

Adrenergic Uptake Inhibitors↗
PubMed1996

Elevation of either axoplasmic norepinephrine or sodium level induced release of norepinephrine from cardiac sympathetic nerve terminals.

Using dialysis technique, prominent accumulation of norepinephrine (NE) in the myocardial interstitial space was observed under two different conditions: (1) local administration of a monoamine oxidase inhibitor (pargyline, 1, 10 mM), (2) local administration of a Na, K-ATPase inhibitor (ouabain, 10, 100 microM). Further, pretreatment with a vesicle uptake inhibitor (reserpine, 10 microM) augmented these responses. Either condition independently caused endogenous NE release and a brisk increase in dialysate NE levels might occur as a consequence of non-exocytotic release of NE.

Animals↗
PubMed1996

Down-regulation of telomerase activity is an early event in the differentiation of HL60 cells.

Telomerase has been shown to be essential for unlimited cell proliferation and has been linked to immortality. However, still very little is known about the mechanism by which this enzyme is activated or inactivated. To investigate its regulation, we closely monitored telomerase activity during HL60 cell differentiation induced by either 1 alpha,25-dihydroxyvitamin D3 or all-trans retinoic acid. To that effect, we used a new combination of TRAP assay and SPA, which provides reproducible data for the quantitation and detection of variations in enzyme activity. We thereby observed that the decrease in telomerase activity after induction of differentiation by either of these agents is an early event of the differentiation process rather than its consequence, and that it is independent of the growth arrest pathway. It is neither due to a reduced expression of its RNA component nor to the appearance of a telomerase inhibitor in differentiating cells but is parallel to an increase in p21 and Rb mRNA expression.

Base Sequence↗
PubMed1996

Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have different ionization states in the complex formed with the asymmetric drug KNI-272.

In order to improve the design of HIV-1 protease inhibitors, it is essential to understand how they interact with active site residues, particularly the catalytic Asp25 and Asp125 residues. KNI-272 is a promising, potent HIV-1 protease inhibitor (K(i) approximately 5 pM), currently undergoing phase 1 clinical trials. Because KNI-272 is asymmetric, the complex it forms with the homodimeric HIV-1 protease also lacks symmetry, and the two protease monomers can have distinct NMR spectra. Monomer specific signal assignments were obtained for amino acid residues in the drug binding site as well as for six of the eight Asp residues in the protease/KNI-272 complex. Using these assignments, the ionization states of the Asp carboxyl groups were determined from measurements of (a) the pD dependence of the chemical shifts of the Asp carboxyl carbons and (b) the H/D isotope effect upon the Asp carboxyl carbon chemical shifts. The results of these measurements indicate that the carboxyl of Asp25 is protonated while that of Asp125 is not protonated. These findings provide not only the first experimental evidence regarding the distinct protonation states of Asp25/125 in HIV-1 protease/drug complexes, but also shed light on interactions responsible for inhibitor binding that should form the basis for improved drug designs.

Amino Acid Sequence↗
PubMed1996

Molecular basis of a hereditary type I protein S deficiency caused by a substitution of Cys for Arg474.

The molecular basis for a hereditary type I protein S (PS) deficiency was investigated. DNA sequence analysis in the proband showed a novel missense mutation substituting Cys (TGT) for Arg474 (CGT) that is a highly conserved amino acid residue among the related proteins. This missense mutation cosegregated with the type I PS deficiency in this family. Transient expression studies showed that the secretion of the recombinant Cys-mutant PS was markedly decreased compared with that of the recombinant wild-type PS, reproducing the observed phenotype of type I deficiency. Stable expression and pulse-chase experiments demonstrated an intracellular degradation and an impaired secretion of the recombinant Cys-mutant PS. Furthermore, the substitution of Arg474 by Ala or Glu, but not by Lys, markedly reduced the secretion of the recombinant PS mutants in transient expression studies, suggesting that a positively charged basic amino acid might be needed at residue 474 and might play a key role in the protein structure and conformation of the sex hormone binding globulin-homology domain of the PS molecule. We postulate that the loss of the highly conserved Arg474 might be responsible for the type I PS deficiency inherited in this family.

Androgen-Binding Protein↗