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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 235 records · Page 13Linked to original sources
PubMed1999

Antiproliferative effect of IL-1 is mediated by p38 mitogen-activated protein kinase in human melanoma cell A375.

The role of p38 mitogen-activated protein kinase (MAPK) in IL-1-induced growth inhibition was investigated using IL-1-sensitive human melanoma A375-C2-1 cells and IL-1-resistant A375-R8 cells. In both cells, p38 MAPK was activated by IL-1. A selective inhibitor for p38 MAPK, SB203580, almost completely recovered the IL-1-induced growth inhibition in A375-C2-1 cells. IL-1-induced IL-6 production was also suppressed by SB203580. However, the reversal effect of SB203580 was not due to the suppression of IL-6 production because the SB203580 effect was still observed in the presence of exogenous IL-6. Down-regulation of ornithine decarboxylase (ODC) activity as well as its protein level has been shown to be essential for IL-1-induced growth inhibition. SB203580 also reversed the IL-1-induced down-regulation of ODC activity and intracellular polyamine levels without affecting ODC mRNA levels in A375-C2-1 cells. In IL-1-resistant R8 cells, however, IL-1 only slightly suppressed ODC activity. In A375-C2-1 cells, the mRNA expression level of antizyme (AZ), a regulatory factor of ODC activity, has been shown to be up-regulated by IL-1. IL-1-induced up-regulation of AZ mRNA level was not affected by SB203580. These findings demonstrate that p38 MAPK plays an important role in IL-1-induced growth inhibition in A375 cells through down-regulating ODC activity without affecting the level of ODC mRNA and AZ mRNA. In IL-1-resistant A375-R8 cells, IL-1 signaling pathway is deficient between p38 MAPK activation and down-regulation of ODC activity.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Subendocardial enhancement in gadolinium-diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging in aortic stenosis.

We investigated the usefulness of magnetic resonance imaging (MRI) with gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) in assessing myocardial damage from valvular aortic stenosis (AS). Cardiac catheterization and echocardiography were performed in 17 patients with AS. T1-weighted spin-echo sequence was used to obtain magnetic resonance images of short-axis planes of the left ventricle before and after intravenous Gd-DTPA injection in all patients using a 1.5 Tesla imager. Patients were divided into 2 groups according to the presence or absence of regional myocardial enhancement in the images. The Gd-DTPA-enhanced magnetic resonance images of 7 patients showed circumferential subendocardial enhancement. All patients with enhancement had a history of heart failure and were in New York Heart Association functional class III or IV, whereas patients without enhancement were in New York Heart Association functional class I or II. Patients with enhancement had a smaller aortic valve area (0.28 +/- 0.09 vs 0.38 +/- 0.07 cm2/m2, p <0.05), a higher transvalvular pressure gradient (109 +/- 40 vs 68 +/- 18 mm Hg, p <0.05), greater elevation of left ventricular end-diastolic pressure (22 +/- 11 vs 12 +/- 2 mm Hg, p <0.05), and greater reduction in left ventricular ejection fraction (40 +/- 9 vs 59 +/- 10%, p <0.05). Subendocardial enhancement by Gd-DTPA-enhanced MRI was thus shown to be closely related to the severity of AS. In conclusion, Gd-DTPA-enhanced MRI is a new noninvasive tool that can provide useful information about myocardial damage in AS.

Adult↗
PubMed1999

Detection of DNA abnormalities by arbitrarily primed PCR fingerprinting: amplification of the MDM2 gene in a mediastinum fibrosarcoma.

Arbitrarily primed PCR (AP-PCR) fingerprinting method is easy and useful for analysis of genetic alterations in anonymous chromosomal regions. We applied this technology to analysis of DNA from human primary cancers and found amplification of a DNA fragment in a mediastinum fibrosarcoma. PCR-based analysis of radiation hybrid panels following cloning and nucleotide sequence determination of the fragment revealed that it was derived from a region of chromosome 12q13-q15. In this region, the MDM2 and IFNG genes were noted as known genes that could be involved in human carcinogenesis. Southern blot analysis of genomic DNA of the tumor revealed the amplification of the MDM2 gene together with the fragment locus, but not the IFNG gene. Our results demonstrated that detection of DNA alterations by AP-PCR fingerprinting without any previous knowledge of the genes and subsequent analysis of radiation hybrid panels could lead to easy identification of candidates for genes involved in carcinogenesis.

Base Sequence↗
PubMed1999

A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator.

A protein module called the WW domain recognizes and binds to a short oligopeptide called the PY motif, PPxY, to mediate protein-protein interactions. The PY motif is present in the transcription activation domains of a wide range of transcription factors including c-Jun, AP-2, NF-E2, C/EBPalpha and PEBP2/CBF, suggesting that it plays an important role in transcriptional activation. We show here that mutation of the PY motif in the subregion of the activation domain of the DNA-binding subunit of PEBP2, PEBP2alpha, abolishes its transactivation function. Using yeast two-hybrid screening, we demonstrate that Yes-associated protein (YAP) binds to the PY motif of PEBP2alpha through its WW domain. The C-terminal region of YAP fused to the DNA-binding domain of GAL4 showed transactivation as strong as that of GAL4-VP16. Exogenously expressed YAP conferred transcription-stimulating activity on the PY motif fused to the GAL4 DNA-binding domain as well as to native PEBP2alpha. The osteocalcin promoter was stimulated by exogenous PEBP2alphaA and a dominant negative form of YAP strongly inhibited this activity, suggesting YAP involvement in this promoter activity in vivo. These results indicate that the PY motif is a novel transcription activation domain that functions by recruiting YAP as a strong transcription activator to target genes.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Computer Simulations for the Growth Process of Peanut-Type Hematite Particles.

The growth process of a monodispersed peanut-type hematite particle consisting of much smaller elongated subcrystals has been reproduced by computer simulation. On the basis of the microscopic internal structure, the simulation was performed by replacing the sequential events of surface nucleation and the subsequent growth of each subcrystal in the actual process with an arranged deposition of rectangular segments of fixed dimensions under different conditions in their site-dependent deposition rate and in the flexibility of their tilt angles. The most successful simulation model was obtained on the assumptions of a relatively fast deposition of the segments on the outermost side-surface of the ellipsoidal particle and the flexible tilt angle of each segment depending on the position of a neighboring new segment placed afterward. The result of the simulation strongly supported the previous elucidation of the growth mechanism in terms of the outward bending of adjoining subcrystals by nucleation and growth of a new subcrystal in each space between them. Enhancement of the outward bending of subcrystals by a large amount of sulfate ions adsorbed to the growing subcrystals was also suggested. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Distribution and characterization of immunoreactive prolactin-releasing peptide (PrRP) in rat tissue and plasma.

We established a sensitive and specific two-site enzyme immunoassay (EIA) for prolactin-releasing peptide (PrRP) using two region-specific monoclonal antibodies. We investigated the tissue distribution and the plasma concentration of immunoreactive (ir-) PrRP in rats using this assay. Ir-PrRP was widely distributed in the central nervous system and pituitary gland. The highest concentration of ir-PrRP was found in the hypothalamus. In peripheral tissues, appreciable levels of ir-PrRP were found only in the adrenal gland. The mean plasma concentration of ir-PrRP was 0.13 +/- 0.01 fmol/ml (mean +/- SEM). In reverse-phase and gel-filtration high performance liquid chromatography, hypothalamic ir-PrRP eluted at a position identical to that of PrRP31 and PrRP20. On the other hand, ir-PrRP from the adrenal gland and plasma eluted only at the position of synthetic PrRP31, indicating that molecular forms of ir-PrRP in vivo differed among tissues.

Adrenal Glands↗
PubMed1999

Myocardial oxygenation during high work states in hearts with postinfarction remodeling.

BACKGROUND: Postinfarction left ventricular remodeling (LVR) is associated with reductions in myocardial high-energy phosphate (HEP) levels, which are more severe in animals that develop overt congestive heart failure (CHF). During high work states, further HEP loss occurs, which suggests demand-induced ischemia. This study tested the hypothesis that inadequate myocyte oxygen availability is the basis for these HEP abnormalities. METHODS AND RESULTS: Myocardial infarction was produced by left circumflex coronary artery ligation in swine. Studies were performed in 20 normal animals, 14 animals with compensated LVR, and 9 animals with CHF. Phosphocreatine (PCr)/ATP was determined with 31P NMR and deoxymyoglobin (Mb-delta) with 1H NMR in myocardium remote from the infarct. Basal PCr/ATP tended to be decreased in postinfarct hearts, and this was significant in animals with CHF. Infusion of dobutamine (20 microg x kg-1 x min-1 IV) caused doubling of the rate-pressure product in both normal and LVR hearts and resulted in comparable significant decreases of PCr/ATP in both groups. This decrease in PCr/ATP was not associated with detectable Mb-delta. In CHF hearts, rate-pressure product increased only 40% in response to dobutamine; this attenuated response also was not associated with detectable Mb-delta. CONCLUSIONS: Thus, the decrease of PCr/ATP during dobutamine infusion is not the result of insufficient myocardial oxygen availability. Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability.

Adenosine Triphosphate↗
PubMed1999

Paroxysmal nocturnal hemoglobinuria: An acquired genetic disease.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterized by an intravascular hemolytic anemia. Abnormal blood cells lack a series of glycosylphosphatidylinositol (GPI)-anchored proteins. The lack of GPI-anchored complement regulatory proteins, such as decay-accelerating factor (DAF) and CD59, results in complement-mediated hemolysis and hemoglobinuria. In the affected hematopoietic cells from patients with PNH, the first step in biosynthesis of the GPI anchor is defective. At least four genes are involved in this reaction step, and one of them, an X-linked gene termed PIG-A, is mutated in affected cells. The PIG-A gene is mutated in all patients with PNH reported to date. Here, we review recent advances in the understanding of the molecular pathogenesis of PNH.

Glycosylphosphatidylinositols↗
PubMed1999

Systematic identification, classification, and characterization of the open reading frames which encode novel helicase-related proteins in Saccharomyces cerevisiae by gene disruption and Northern analysis.

Helicase-related proteins play important roles in various cellular processes incuding DNA replication, DNA repair, RNA processing and so on. It has been well known that the amino acid sequences of these proteins contain several conserved motifs, and that the open reading frames (ORFs) which encode helicase-related proteins make up several gene families. In this study, we have identified 134 ORFs that encode helicase-like proteins in the Saccharomyces genome, based on similarity with the ORFs of authentic helicase and helicase-related proteins. Multiple alignment of the ORF sequences resulted in the 134 ORFs being classified to 11 clusters. Seven out of 21 previously uncharacterized ORFs (YDL031w, YDL070w, YDL084w, YGL150c, YKL078w, YLR276c, and YMR128w) were identified by systematic gene disruption, to be essential for vegetative growth. Three (YDR332w, YGL064c, and YOL095c) out of the remaining 14 dispensable ORFs exhibited the slow-growth phenotype at 30 degrees C and 37 degrees C. Furthermore, the expression profiles of transcripts from 43 ORFs were examined under seven different growth conditions by Northern analysis and reverse transcription-polymerase chain reaction, indicating that all of the 43 tested ORFs were transcribed. Interestingly, we found that the level of transcript from 34 helicase-like genes was markedly increased by heat shock. This suggests that helicase-like genes may be involved in the biosynthesis of nucleic acids and proteins, and that the genes can be transcriptionally activated by heat shock to compensate for the repressed synthesis of mRNA and protein.

Amino Acid Sequence↗
PubMed1999

The contributory role of interstitial water in Gd-DTPA-enhanced MRI in myocardial infarction.

We studied the mechanism underlying regional enhancement of myocardial infarction using T1-weighted MRI with gadolinium (Gd)-DTPA. Anterior myocardial infarction (MI) was produced by left anterior descending coronary artery ligation in three groups of rats as follows: 60 minutes occlusion (occlusion group, N = 6), 60 minutes occlusion plus 120 minutes reperfusion (reperfusion group, N = 8), and sham-operated (control, N = 6). In Gd-DTPA-enhanced MRI, MI was demarcated as a hypoenhanced region in the occlusion group and as a homogeneous hyperenhanced region in the reperfusion group. Both Gd-DTPA tissue concentration and tissue water content in the anterior wall were highest in the reperfusion group (P<0.05), a finding suggestive of microscopically observed interstitial edema. The data suggest that regional accumulation of Gd-DTPA in the reperfused group can be explained by increased interstitial water content, contributing to the delayed washout of the water-soluble contrast medium.

Animals↗
PubMed1999

Myocardial ischemia due to vasospasm of small coronary arteries detected by methylergometrine maleate stress myocardial scintigraphy.

BACKGROUND: Recently, several case reports have implicated vasospasm of small coronary arteries in vasospastic angina pectoris. Vasospasm of small coronary arteries was also considered from angiographic findings in patients with atypical chest pain. In Syrian hamster, vasospasm in small coronary arteries was considered to be the cause of dilated cardiomyopathy. HYPOTHESIS: This study was undertaken to determine whether vasospasm in small coronary arteries can be induced by methylergometrine maleate stress thallium-201 (201Tl) myocardial scintigraphy. METHODS: Twenty-five patients with chest pain, all of whom had intact coronary arteries, were studied. After intracoronary methylergometrine maleate injection, coronary arteriograms also looked normal in all cases. Thallium-201 myocardial scintigraphy was carried out immediately after intracoronary methylergometrine maleate injection in four patients with chest pain. In the remaining 21 patients with chest pain, methylergometrine maleate was given intravenously within up to 2 weeks before 201Tl myocardial scintigraphy. RESULTS: In the intracoronary injection study, one patient had chest discomfort after methylergometrine maleate injection, and ST-segment elevation was observed on electrocardiogram (ECG). Of the 21 patients with chest pain, 11 patients felt angina-like chest pain after intravenous injection of methylergometrine maleate, but their ECGs showed no ischemic changes. Stress 201Tl myocardial scintigrams showed methylergometrine maleate-induced perfusion defects with complete redistribution in 3 of 4 patients in the intracoronary injection study and in 12 of 21 patients in the intravenous injection study. These findings suggest that vasospasm in small coronary arteries caused myocardial ischemia in 15 of 25 patients (60%) with chest pain. CONCLUSION: Vasospasm in small coronary arteries may be involved in the myocardial ischemia of some patients with chest pain who do not show any large coronary artery vasospasm.

Adult↗
PubMed1999

An additional dose of cefazolin for intraoperative prophylaxis.

We examined the pancreatic tissue concentrations of cefazolin in ten patients undergoing pancreatectomy, and determined the optimal intraoperative time to deliver a repeat dose of cefazolin. An intravenous bolus dose of 1 g cefazolin was administered at the time of skin incision. Peripheral blood, subcutaneous adipose tissue, and peritoneal samples were obtained intraoperatively every hour for 4 h after the antibiotic was first administered, and pancreatic tissue samples were obtained at the time of pancreatectomy. To determine adequate tissue levels of cefazolin, minimum inhibitory concentrations (MIC) were measured for four bacterial species, namely 360 isolates of methicillin-sensitive Staphylococcus aureus (MSSA), 204 isolates of Klebsiella pneumoniae, 314 isolates of Escherichia coli, and 30 isolates of Streptococcus spp. The antibiotic concentrations in adipose tissue and peritoneum 3 h after the administration of cefazolin were lower than the MIC80 for K. pneumoniae, E. coli, and Streptococcus spp. Most pancreatic tissue samples showed antibiotic concentrations greater than the MIC80 for these bacterial species; however, those from four patients complicated by severe chronic pancreatitis, massive intraoperative bleeding, or obesity showed concentrations lower than the MIC80. Thus, we recommend that a second dose of cefazolin be given 3 h after the first administration to maintain adequate levels of antibiotic activity.

Aged↗
PubMed1999

The effectiveness of perineal rectosigmoidectomy for the treatment of rectal prolapse in elderly and high-risk patients.

We report herein on the follow-up of ten consecutive patients who underwent perineal rectosigmoidectomy, and discuss the indications, surgical technique, and outcomes of this procedure. The median age of the patients was 79 years, with a range of 26 to 85 years, and eight patients had complicating medical conditions. Of five patients who underwent this procedure for a recurrent prolapse after another type of perineal procedure, four had previously undergone the Thiersch operation combined with the Gant-Miwa technique. The mean length of the excised rectum and sigmoid colon was 22.1 cm. Pain was minimal or absent in all patients and oral intake was commenced after 2 days. There were no mortalities, but anastomotic leakage occurred in one patient. The mean follow-up period was 3.5 years. Only one patient developed recurrent rectal prolapse 24 months after the operation. Of seven patients who underwent concomitant levatoroplasty for incontinence, five became fully continent within 3 weeks after the operation, while the remaining two improved after 2 months. We propose that perineal rectosigmoidectomy is indicated for patients who have suffered an early recurrence of prolapse after another transperineal repair; elderly or high-risk patients with incontinence; male patients; and patients with an incarcerated or gangrenous prolapsed rectal segment.

Adult↗
PubMed1999

Surgical approaches for pancreatic ascites: report of three cases.

Pancreatic ascites can occur in association with the rupture of a pseudocyst or the disruption of a pancreatic duct during the natural course of chronic pancreatitis. We report herein the successful treatment of three patients with pancreatic ascites by performing a surgical procedure after 4-6 weeks of total parenteral nutrition (TPN) proved ineffective. The principles of our surgical procedure for pancreatic ascites are as follows: (1) minimum pancreatic tissue is resected; (2) surgical intervention to repair leaking sites is not necessary; (3) pancreatic duct drainage is facilitated by an intestinal Roux-en-Y loop; (4) An external drainage tube is inserted through the Roux-en-Y loop into the main pancreatic duct. All three patients who underwent our surgical procedure had a good outcome. Although the mean follow-up time is still only 18.3 months, their condition has improved, with no evidence of recurrent ascites. Thus, our surgical procedure should be considered as an appropriate treatment for pancreatic ascites because it can be applied for all types of leakage, including leakage from the posterior wall of pancreas; it preserves pancreatic function, especially endocrine function; and it enables preservation of the spleen.

Aged↗
PubMed1999

Cranial MRI of neurologically impaired children suffering from neonatal hypoglycaemia.

BACKGROUND: Metabolic disturbances such as anoxia and hypoglycaemia are important in causing maldevelopment of the neonatal brain. While there have been some pathology studies of the effects of neonatal hypoglycaemia on brain development, reports of MRI findings in such infants have been rare. OBJECTIVES: To describe the MRI findings in neurologically handicapped children who had suffered from neonatal hypoglycaemia and to evaluate the relationship between the neurological impairment and neonatal hypoglycaemia. MATERIALS AND METHODS: We retrospectively evaluated the MRI findings in eight full-term infants with neonatal symptomatic hypoglycaemia who later exhibited neurological handicap. The age at which the MRI scans were obtained ranged from 9 months to 8 years 10 months (mean 4 years 1 month, median 4 years). RESULTS: The most striking findings were prolonged T1 weighting and T2 weighting in the parieto-occipital periventricular deep white matter in six patients, suggesting abnormal or delayed myelination. Dilatation of the lateral ventricles, especially of the trigones, was observed in five patients in whom the distance between the posterior horns of the lateral ventricles and the adjacent sulci was reduced. The volume of white matter relative to grey matter was reduced in two patients. In addition, four patients exhibited cerebral cortical atrophy, mainly in the occipital lobe. CONCLUSIONS: These findings suggest that neonatal hypoglycaemia may cause delayed or abnormal myelination, especially in the parieto-occipital, periventricular, deep white matter, and may cause cerebral cortical atrophy, especially in the occipital lobe.

Brain↗
PubMed1999

Sequence determination and phylogenetic analysis of RNA-dependent RNA polymerase (RdRp) of the porcine enterovirus 1 (PEV-1) Talfan strain.

The nucleotide sequence of the region including the RNA-dependent RNA polymerase (RdRp) of the porcine enterovirus 1 (PEV-1) Talfan strain was determined. Amino acid identities of Talfan RdRp with those of other picornaviruses were significantly lower than those seen among the viruses of the same genus of picornaviruses. The phylogenetic analysis of RdRp indicated that picornaviruses were divided into 8 clusters, in which Talfan was genetically distinct from other picornaviruses in contrast to the current taxonomy. In this study, we propose that PEV-1 Talfan be regarded as a new genus for the family Picorna- viridae.

Amino Acid Sequence↗
PubMed1999

Myocardial oxygenation at high workstates in hearts with left ventricular hypertrophy.

BACKGROUND: High cardiac workloads produced by catecholamine infusion result in loss of myocardial phosphocreatine (PCr) and accumulation of inorganic phosphate (Pi) which are more prominent in heart with left ventricular hypertrophy (LVH) than in normal hearts. Since ischemia can cause changes in phosphorylated compounds similar to those during catecholamine stimulation, this study tested the hypothesis that the exaggerated depletion of PCr and accumulation of Pi during high workloads in LVH is the result of impaired myocyte oxygenation. METHODS AND RESULTS: 31P- and 1H-NMR spectroscopy were used to determine myocardial high energy phosphate levels and myoglobin desaturation, respectively, in eight normal dogs and nine dogs with LVH produced by ascending aortic banding. The mean LV weight/body weight ratio was approximately twice normal in the LVH group. Infusion of dobutamine (15 and 30 micrograms/kg/min), and dobutamine + dopamine (each 20 micrograms/kg/min) caused progressive similar increases in the heart rate x systolic LV pressure product to a maximum of 57.4 +/- 3.3 x 10(3) in normal and 63.9 +/- 2.7 x 10(3) in LVH animals, while myocardial oxygen consumption increased from 0.09 +/- 0.01 to 0.24 +/- 0.04 in normals and from 0.10 +/- 0.02 to 0.25 +/- 0.03 ml/min/g in LVH. PCr/ATP ratios during basal conditions were lower in LVH hearts (1.73 +/- 0.10, 1.61 +/- 0.09 and 1.51 +/- 0.09 in subepicardium, midwall and subendocardium, respectively) as compared with normals (2.24 +/- 0.09, 2.01 +/- 0.08 and 1.89 +/- 0.07; each p < 0.01 normal vs. LVH). Catecholamine infusions caused dose-related decreases in PCr/ATP and appearance of Pi which was more marked in LVH than in normal hearts. 1H-NMR spectroscopy did not detect deoxymyoglobin in either normal or LVH hearts even during the highest workloads. In contrast, occlusion of the anterior descending coronary artery resulted in a large deoxymyoglobin signal. CONCLUSIONS: Increases of cardiac work produced by catecholamine stimulation resulted in greater decreases of PCr and greater increases of Pi in hypertrophied than in normal hearts. These abnormalities were not the result of inadequate intracellular oxygen availability and consequently cannot be ascribed to demand ischemia.

Adenosine Triphosphate↗