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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 559 records · Page 31Linked to original sources
PubMed1995

[Atrial late potential by P wave-triggered signal-averaged electrocardiogram and paroxysmal atrial fibrillation].

Atrial fibrillation (AF), which is rather a common disease has a high risk of developing systemic embolism and stroke. Accordingly it can be significant for us to predict a patient at risk for AF during sinus rhythm Recently signal averaged ECG triggered by P wave has been expected to detect atrial late potential (ALP), which is thought to coincide with fractionated ECG significantly recorded directly from atrial muscle of a patient with paroxysmal AF. Although many time-domain ALP indices have been proposed, those excepting filtered P duration remain controversial with their diagnostic criteria having not yet been established, many studies agree as to the prolongation of filtered P duration, as observed for patients with AF. Although, also recently, frequency domain method has been applied to ALP for FFT analysis with the view of detecting ALP possibly undetectable by time domain method, no results better than the above method have been obtained, and further examination is hoped for.

Atrial Fibrillation↗
PubMed1995

Detection of right ventricular infarction by gadolinium DTPA-enhanced magnetic resonance imaging.

We investigated the usefulness of gadolinium-enhanced magnetic resonance (Gd-MR) imaging for diagnosis of right ventricular (RV) infarction in 14 patients with acute inferior infarction. Myocardial perfusion images with thallium 201 and technetium 99m pyrophosphate (dual single-photon emission computed tomography: dual SPECT) and haemodynamic data were obtained on admission. Patients were classified into three groups based on dual SPECT and Gd-MR findings: no accumulation in the right ventricle (negative, Type 1), posterior RV infarction (Type 2) and anterior and posterior RV infarction (Type 3). No patients exhibited the haemodynamic criteria for RV infarction (a mean right atrial pressure above 10 mmHg and a ratio of mean right atrial pressure to pulmonary artery wedge pressure above 0.8). Dual SPECT identified RV infarction in eight patients (three Type 2 and five Type 3, 57% of the total). Gd-MR imaging also identified eight patients (57%) as positive (five Type 2 and three Type 3). Our results showed that Gd-MR imaging was not only useful for diagnosis of RV infarction, but also equal to dual SPECT in sensitivity and specificity, and superior to it as regards acquisition time and assessing the spatial anatomy of heart. In conclusion, Gd-MR imaging is superior to dual SPECT for detection of RV infarction.

Aged↗
PubMed1995

User interface design and evaluation for electronic medical record system.

A user interface for an electronic medical record system (EMRS) is proposed. A pen-based device adopted for data input and the GUI windows layout simulate conventional paper forms, so that doctors can quickly grow accustomed to the EMRS. A comparison study shows the proposed interface does not significantly delay the examination, even when used in hospitals with many outpatients.

Ambulatory Care↗
PubMed1995

The effects of leukotrienes C4 and D4 on ciliary activity of human paranasal sinus mucosa in vitro.

The effects of leukotrienes C4 and D4 on ciliary activity of human paranasal sinus mucosa were investigated in vitro. Normal mucosa was surgically obtained from human paranasal sinuses and incubated in the form of tissue culture. Ciliated cells were magnified under an inverted microscope, and ciliary activity was photoelectrically measured. LTD4 progressively inhibited ciliary activity, and showed a more potent effect on ciliary activity compared to LTC4. The concentrations of LTC4 and LTD4 in the incubation medium were determined by radioimmunoassay when the mucosa was incubated with 10(-8) M LTC4. The concentration of LTD4 gradually increased and after 90 min reached the maximum of 0.71 x 10(-8) M, while that of LTC4 was reduced to about 10% of its initial concentration within 60 min. These results suggested the possible conversion of LTC4 to LTD4 on the mucosa, and that LTC4 can inhibit ciliary activity by means of LTD4.

Cilia↗
PubMed1994

Forced expression of antizyme abolishes ornithine decarboxylase activity, suppresses cellular levels of polyamines and inhibits cell growth.

Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. It is a short-lived protein and negatively regulated by its products, polyamines. Its degradation is accelerated by the binding of antizyme, an ODC-inhibitory protein induced by polyamines. To evaluate the physiological importance of antizyme we examined the effect of forced expression of antizyme on cellular ODC and polyamine levels and cell growth. Antizyme almost completely abolished the induction of ODC by growth stimuli. This may have been caused by antizyme-induced rapid degradation of newly synthesized ODC, since the half-life of ODC complexes with antizyme was less than 5 min. Forced expression of antizyme caused reductions of cellular putrescine and spermidine levels, and inhibited cell growth, which was partially restored by the addition of putrescine. These observations suggested a critically important role of antizyme in polyamine metabolism.

Animals↗
PubMed1994

Mutations of the adenomatous polyposis coli gene in the mutation cluster region: comparison of human pancreatic and colorectal cancers.

We analyzed the adenomatous polyposis coli (APC) tumor-suppressor gene as one of the possible genes mutated in human pancreatic carcinomas. DNAs from 39 surgical specimens were subjected to single-strand conformation polymorphism analysis of polymerase chain reaction products and the mutation cluster region (MCR) of the gene was examined. We also examined the same region of DNAs from 27 surgical specimens of sporadic colon carcinomas and detected mutations in 11 carcinomas (41%). This mutation frequency in colon carcinomas was similar to those reported previously. Using this system, we detected a mutated APC gene in one of 39 pancreatic carcinomas. The results indicated that mutation of the MCR in the APC gene is involved in genesis of some of human pancreatic carcinomas, but its frequency is much lower than in colorectal carcinomas.

Adenomatous Polyposis Coli↗
PubMed1994

[Ability of subtraction and dynamic MR imaging to detect breast tumors: comparison with ultrasonography and mammography].

We evaluated the ability of subtraction and dynamic MR imaging to accurately detect breast tumors. Sixty-five breast carcinomas and 24 fibroadenomas were examined by an SE pulse sequence using a 0.2 Tesla unit. Subtraction MR images were obtained every minute during dynamic study with Gd-DTPA. Almost all breast tumors were seen as very bright masses, and the margin of the mass was clearly demonstrated on subtraction MR images. Breast carcinomas and fibroadenomas showed characteristic time-intensity curves on dynamic study, Time-intensity curves of the early peak type and plateau type were seen in 97% of breast carcinomas, while the gradually increasing type was seen in 92% of fibroadenomas. The detectability of breast carcinoma was 98% by MRI, 98% by ultrasonography, and 87% by mammography. That of fibroadenoma was 95% by MRI, 91% by ultrasonography and 60% by mammography. Sensitivity and specificity for breast carcinoma were 98% and 92% for MRI and 97% and 71% for ultrasonography. For fibroadenoma, they were 96% and 98% for MRI and 89% and 92% for ultrasonography.

Adolescent↗
PubMed1994

Antizyme protects against abnormal accumulation and toxicity of polyamines in ornithine decarboxylase-overproducing cells.

Exposure of ornithine decarboxylase (ODC; L-ornithine carboxy-lyase, EC 4.1.1.17)-overproducing mouse FM3A cells to micromolar levels of spermine or spermidine caused abnormal accumulation and toxicity of polyamines. This was apparently due to the inefficiency of negative feedback control of polyamine transport by polyamines in ODC-overproducing cells. Since antizyme is the only protein thus far recognized that can interact with ODC, depletion of free antizyme was regarded as the reason for the abnormal accumulation of polyamines. Accordingly, ODC-overproducing cells were transfected with pMAMneoZ1 possessing rat antizyme cDNA under the control of a glucocorticoid-inducible promoter. In the transfected cells, the addition of dexamethasone caused an increase in the amount of antizyme with an apparent molecular mass of 27 kDa, a decrease in the amount of ODC, a decrease in the polyamine transport activity, and the recovery of growth inhibition or cell death. The results indicate that antizyme can regulate not only the amount of ODC but also the activity of polyamine transport.

Animals↗
PubMed1994

Deletions of chromosome 13q, mutations in Retinoblastoma 1, and retinoblastoma protein state in human hepatocellular carcinoma.

Twenty-one tumors from 18 patients (two independent tumors were obtained from each of three patients) with hepatocellular carcinomas were examined for loss of heterozygosity (LOH) at loci on chromosome 13q, using 15 polymorphic nucleotide sequences of microsatellites as genetic markers. The results revealed LOH in a common region between the centromeric D13S127 locus (13q12.2-q14.1) and the telomeric D13S137 (13q14.3) locus, including the RB1 locus, in nine of 21 tumors. Immunohistochemical staining of paraffin-embedded tumor sections indicated loss of retinoblastoma (RB) protein expression in all tumors showing LOH except one. Absence of RB protein expression was also observed in three of 12 tumors without LOH. Single-strand conformation polymorphism analysis of polymerase chain reaction products using primers flanking all 27 exons of the RB1 gene, as well as nucleotide sequencing, revealed tumor-specific small deletions of the RB1 coding region in the remaining RB1 allele of two tumors having LOH at the RB1 locus with concomitant loss of RB protein expression. Our results indicate that the loss of a region of chromosome 13q including the RB1 locus significantly (P < 0.006) correlates with loss of RB protein in hepatocellular carcinomas. However, tumor-specific mutations of the RB1 gene were detected in only two of 13 tumors with LOH and/or lack of RB protein expression, indicating that analysis of the RB1 status at the protein level in these tumors may be more sensitive than the actual mutational analysis.

Base Sequence↗
PubMed1994

Conversion of epidermal growth factor (EGF) into a stimulatory ligand for A431-cell growth by herbimycin A by decreasing the level of expression of EGF receptor.

We examined effect of the tyrosine kinase inhibitor herbimycin A on A431 human epidermoid carcinoma cells which over-express epidermal growth factor (EGF) receptor. Herbimycin A inhibited the autophosphorylation of EGF-stimulated receptors in intact cells both time- and dose-dependently. The inhibition was found to be due to a decrease in the level of expression of the receptor amount, because herbimycin A equally decreased the receptor quantity and EGF-stimulated receptor kinase activity in intact cells, but did not exhibit a direct inhibitory effect on EGF receptor kinase activity in vitro. The decrease of the level of EGF receptor was also confirmed by 125I-EGF binding to herbimycin A-treated cells, and Scatchard analysis showed that the decrease in the receptor number occurred in the major population of the low-affinity binding ones, whereas the number with high-affinity binding was unaffected. Interestingly, although the proliferation of A431 cells was inhibited by EGF, herbimycin A converted EGF into a stimulatory ligand for cell growth, as determined by both cell number and DNA synthesis. These findings indicated that herbimycin A decreased the level of expression of EGF receptor by a mechanism other than inactivation of the receptor kinase and reversed the transformed phenotype of A431 cells to a normal one in the proliferative response to EGF.

Benzoquinones↗
PubMed1994

Accelerated degradation of 160 kDa epidermal growth factor (EGF) receptor precursor by the tyrosine kinase inhibitor herbimycin A in the endoplasmic reticulum of A431 human epidermoid carcinoma cells.

The effect of herbimycin A on the biosynthesis of epidermal growth factor (EGF) receptor was examined in human epidermoid carcinoma A431 cells. Cells were pulse-labelled with [35S]methionine, and EGF receptor biosynthesis was quantified by immunoprecipitation using a monoclonal anti-(EGF receptor) antibody. In the presence of herbimycin A, an immature 160 kDa EGF receptor precursor accumulated in 1 h and disappeared completely in 4 h. Pulse-labelled 160 kDa receptor precursor in the absence of herbimycin A, however, was converted normally into a 170 kDa one by chase with herbimycin A. Herbimycin A affected neither the synthesis of the secreted form of EGF receptor devoid of cytoplasmic domain, nor that of the transferrin receptor in A431 cells. The herbimycin A-induced degradation of 160 kDa EGF receptor precursor was not inhibited by an inhibitor of lysosomal enzymes, NH4Cl. Endoglycosidase H digestion of the 160 kDa precursor converted it into the deglycosylated 130 kDa precursor peptide. These results suggested that herbimycin A selectively acted on the EGF receptor precursor during the synthesis of the 160 kDa form, probably on the cytoplasmic domain, to form an aberrant molecule which was subjected to rapid degradation in the endoplasmic reticulum.

Benzoquinones↗
PubMed1994

ATP- and antizyme-dependent endoproteolysis of ornithine decarboxylase to oligopeptides by the 26 S proteasome.

Previously we reported that ornithine decarboxylase (ODC) is degraded ATP-dependently by the 26 S proteasome in the presence of antizyme (AZ), an ODC inhibitor (Murakami, Y., Matsufuji, S., Kameji, T., Hayashi, S., Igarashi, K., Tamura, T., Tanaka, K., and Ichihara, A. (1992) Nature 360, 597-599). Here we examined the cleavage of ODC by the 26 S proteasome. When ODC purified from ODC-overproducing cells was incubated with the 26 S proteasome and with AZ fused with maltose-binding protein (MBP) in the presence of ATP, ODC was degraded specifically without appreciable breakdown of MBP-AZ. The major degradation products of ODC, which were separated by high performance liquid chromatography on a reverse-phase column, were identified by N-terminal amino acid sequencing. The 26 S proteasome generated a variety of short peptides of 5-11 amino acid residues derived from regions throughout the ODC sequence. No detectable amounts of free amino acid residues were produced, indicating endoproteolytic degradation of ODC by the 26 S proteasome. Their major sites for cleavage of ODC by the 26 S proteasome were on the carboxyl sides of neutral/hydrophobic amino acid residues, but a few were on those of acidic or basic amino acid residues. These results demonstrate that the 26 S proteasome causes exhaustive endoproteolysis of the naturally occurring short-lived protein ODC in a multicatalytic and ATP-dependent manner.

Adenosine Triphosphate↗
PubMed1994

Functional regions of ornithine decarboxylase antizyme.

Degradation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis, is accelerated by the binding of antizyme, an ornithine decarboxylase inhibitory protein induced by polyamines. In the present study, we examined the effects of a series of deletion mutants of rat antizyme. The results indicated that two regions of antizyme, one internal (amino acids 122-144) and the other near the C-terminus (amino acids 211-218) are necessary for its binding to ornithine decarboxylase and inhibition of its activity, and an additional internal region (amino acids 88-118, especially 113-118) is necessary for its destabilization.

Animals↗
PubMed1994

Glu318 and Thr319 mutations of cytochrome P450 1A2 remarkably enhance homolytic O-O cleavage of alkyl hydroperoxides. An optical absorption spectral study.

Interactions of putative distal mutants of cytochrome P450 1A2 (P450 1A2) with hydroperoxides were studied with optical absorption spectroscopy. The Soret absorption at 393 nm of the wild-type P450 1A2 decreased by adding H2O2, tert-butyl hydroperoxide (TBHP), and cumyl hydroperoxide (CHP), whereas the absorption decrease was accompanied by the appearance of a new band around 423 nm for Glu318 and Thr319 mutants with similar treatments. Spectral simulation based on Gaussian analyses and visible bands indicate that H2O2- and TBHP-induced intermediates' spectra of the wild type are close to that of Compound I of horseradish peroxidase, whereas TBHP- and CHP-induced intermediates' spectra of the mutants are close to that of Compound II of horseradish peroxidase. Based on kinetic parameters of the spectral changes, it is suggested that: 1) TBHP and CHP mainly form porphyrin+.FeIV = O due to heterolytic O-O scission in the wild type, while forming porphyrinFeIV = O for the mutants owing to homolytic O-O scission; and 2) heterolytic O-O scission of H2O2 is not changed by the mutations. Heterolytic/homolytic cleavage ratios for the P450 1A2 reactions with CHP obtained from product analysis were consistent with those obtained from spectral changes.

Alcohols↗
PubMed1994

Differential roles of Glu318 and Thr319 in cytochrome P450 1A2 catalysis supported by NADPH-cytochrome P450 reductase and tert-butyl hydroperoxide.

The kinetic values for 7-ethoxycoumarin (7-EC) hydroxylation have been obtained in both the NADPH-cytochrome P450 reductase- and tert-butyl hydroperoxide (TBHP)-supported systems for several Glu318 and Thr319 mutants of cytochrome P450 1A2. The results with the reductase-supported system suggest that Glu318 is important for both substrate binding and catalysis, whereas Thr319 is critical for neither, although the size of the residue at position 319 influences catalytic activity. In contrast, neither Glu318 nor Thr319 appears to be important for catalytic turnover in the TBHP-supported system despite the fact that the size of the amino acid at position 319 affects the binding of TBHP and 7-EC in opposite manners. The roles of these two distal amino acids in the cytochrome P450 1A2-catalyzed oxidation of 7-EC therefore differ for the reactions supported by cytochrome P450 reductase and TBHP.

Amino Acid Sequence↗
PubMed1994

Micromachined electroporation system for transgenic fish.

Luciferase gene was introduced into fertilized eggs of medaka by a localized electric field between thin film electrodes formed on a glass plate. Miniaturization of the electrodes enabled us to apply a localized electric field to the animal pole of the fertilized egg. Biochemical luminescence and an electrophoresis pattern showed expression and integration of the gene, respectively. The presented system had a higher ratio of gene introduction than the conventional electroporation method.

Animals↗