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Biomedical subjects

M Matsuo

Publications and source records attributed to M Matsuo.

At least 19 recordsLinked to original sources
PubMed2005

Selective inhibition of TNF-alpha-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib.

We have reported that the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ('Iressa', ZD1839), suppressed intrahepatic metastasis of hepatocellular carcinoma CBO140C12 cells. In this study, we focused on the tumour necrosis factor-alpha (TNF-alpha) signalling pathways. Real-time reverse transcription-polymerase chain reaction showed that TNF-alpha mRNA was expressed in large quantities in the implanted tumour. Gefitinib inhibited EGF- but not hepatocyte growth factor (HGF)-induced activation of mitogen-activated protein kinase (MAPK) cascades, suggesting selectivity of the inhibitor. However, gefitinib inhibited the TNF-alpha-induced activation of MAPKs and Akt. In addition, TNF-alpha-induced metastatic properties including adhesion to fibronectin, mRNA expression of integrin alpha v, production of matrix metalloproteinase-9 and invasion were inhibited by gefitinib without affecting cell proliferation. Furthermore, the TNF-alpha-induced responses except for NF-kappaB activation were blocked by metalloprotease inhibitors, suggesting that gefitinib inhibited the transactivation of EGFR induced by TNF-alpha. These results suggest that the TNF-alpha signalling pathway is a possible target of gefitinib in suppressing the intrahepatic metastasis of hepatocellular carcinoma.

Animals↗
PubMed2005

Molecular genetic analysis of QTLs for ferulic acid content in dried straw of rice (Oryza sativa L.).

Phenolic acids are secondary metabolic organic compounds produced by plants and often are mentioned as allelochemicals. This study was conducted to determine the genetic basis controlling the ferulic acid content of rice straw in a recombinant inbred (RI) population derived from a cross between a japonica variety, Asominori, with a higher content of ferulic acid, and an indica variety, IR24, with a lower content, using 289 RFLP markers. Continuous distributions and transgressive segregations of ferulic acid content were observed in the RI population, which showed that ferulic acid content in rice straw was quantitatively inherited. Single marker analysis and composite interval mapping identified three quantitative trait loci (QTLs) for ferulic acid content with LOD values of 2.03 (chromosome 3), 3.16 (chromosome 6), and 3.06 (chromosome 7); all three had increased additive effects (13.5, 18.3, and 18.1 microg g(-1)) from the Asominori parent and accounted for 5.5, 16.9, and 12.8% of total phenotypic variation, respectively. This is the first report on the identification of QTLs associated with ferulic acid and their chromosomal localization on the molecular map of rice. The tightly linked molecular markers that flank the QTLs might be useful in breeding and selection of varieties with higher phenolic acid content.

Chromatography, Gas↗
PubMed2005

Screening for Menkes disease using the urine HVA/VMA ratio.

Menkes disease is a disorder of copper transport that results in early death. Early therapy with parenteral copper-histidine has been shown to markedly improve outcomes. However, early diagnosis is difficult because patients are asymptomatic in early infancy. In Menkes disease, impaired activity of dopamine beta-hydroxylase, a copper-dependent enzyme, leads to increased urine ratios of homovanillic acid/vanillylmandelic acid (HVA/VMA). Urine HVA/VMA ratios ranged from 4.1 to 69.7 among 15 patients with Menkes disease, whereas only 0.18% of controls had ratios greater than 4.0. Thus, the urine HVA/VMA ratio is a useful screening method for Menkes disease.

Alleles↗
PubMed2005

Two-step models to predict binding affinity of chemicals to the human estrogen receptor alpha by three-dimensional quantitative structure-activity relationships (3D-QSARs) using receptor-ligand docking simulation.

Binding of chemicals to the estrogen receptor (ER) is known to be a key mode of action of endocrine disruption effects. In this study, combined quantitative structure-activity relationship (QSAR) models from discriminant and multilinear regression (MLR) analyses, termed a two-step model, were developed. These were used to predict the binding potency to human ERalpha of four chemical groups, namely alkylphenols, phthalates, diphenylethanes and benzophenones. These groups are considered to be important chemical classes of ER-binders. The descriptors investigated were calculated following the simulation of docking between the receptor and ligand. Discriminant analysis in the first step of a two-step model was applied to distinguish binders from non-binders. It had a concordance, following leave-one-out (LOO), of greater than 87% for all chemical classes. Binders were defined as chemicals whose IC50 was reliably measured in a competitive binding assay. The MLR analysis in the second step was performed for the quantitative prediction of the binding affinity of chemicals that were previously discriminated as binders. The q2 values for alkylphenols and diphenylethanes were 0.75 and 0.74, respectively. However good MLR relationships were not obtained for phthalates and benzophenones as the observed binding affinities of chemicals in these categories were weak and in a too narrow range.

Benzene Derivatives↗
PubMed2005

Cystic adenomyosis with florid glandular differentiation mimicking ovarian malignancy.

We report a case of cystic adenomyosis, presenting as a huge exophytic cystic mass with florid glandular differentiation. MR findings of the mass mimicked ovarian carcinoma associated with endometriosis. The presence of signal voids bridging the uterus and tumour should suggest a mass of uterine origin. Hyperintense protuberance in a hypointense loculus on T(2) weighted images may suggest benign disease. However, surgical exploration and resection is still required to exclude an ovarian malignancy.

Adult↗
PubMed2005

An ultrasonographic classification for diverse clinical symptoms of pediatric nutcracker phenomenon.

AIMS: The nutcracker phenomenon (NCP) is the significant compression of the left renal vein (LRV) by the aorta and superior mesenteric artery (SMA), and found in the patients with so-called idiopathic renal bleeding, orthostatic proteinuria and severe orthostatic intolerance. The purpose of this study is to investigate clinical implications among these disorders possibly related to the NCP. MATERIAL AND METHODS: We analyzed 93 pediatric patients (56 with idiopathic renal bleeding, 14 with massive orthostatic proteinuria and 23 with severe orthostatic intolerance), and the findings of 64 patients were compared on both digital subtraction angiography (DSA) and ultrasonography (US) to obtain a new US classification of the NCP with seven grades. RESULTS: US grades of the NCP were well-correlated with DSA findings (rs = 0.797, p < 0.0001). LRV stenosis was a typical finding in patients with idiopathic renal bleeding. LRV occlusion was observed in 70% for severe orthostatic intolerance, and in contrast in 18% and 14% for idiopathic renal bleeding and massive orthostatic proteinuria, respectively. Collateral veins on color Doppler US as well as a mirror image of the SMA in the aorta on conventional US were found as subsidiary signs of LRV occlusion. Extreme dilatation of the LRV was present in 44% for massive orthostatic proteinuria and in 7% for idiopathic renal bleeding (p < 0.0001). CONCLUSIONS: Anew US classification is useful for the diagnosis of the NCP in diverse clinical symptoms.

Adolescent↗
PubMed2005

Rescue of dystrophin mRNA of Duchenne muscular dystrophy by inducing exon skipping.

Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease, and its victims usually succumb in their twenties. Many studies, including investigations into gene-replacement therapy, have been conducted in a search for a treatment for DMD, and the most promising treatment to date is rescue of mutant dystrophin mRNA by induction of exon skipping. On the basis of results from the molecular analysis of dystrophin Kobe, we propose a treatment for DMD in which antisense oligonucleotides induce exon skipping to edit out-of-frame dystrophin mRNA into in-frame, thereby converting severe DMD to a milder form. Here we review the progress of development of this alternative treatment, with a special focus on dystrophin Kobe.

Dystrophin↗
PubMed2004

Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity.

BACKGROUND AND METHODS: Many missense mutations in the voltage-gated sodium channel subunit gene SCN1A were identified in patients with generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI), although GEFS+ is distinct from SMEI in terms of clinical symptoms, severity, prognosis, and responses to antiepileptic drugs. The authors analyzed the localization of missense mutations in SCN1A identified in patients with GEFS+ and SMEI to clarify the phenotype-genotype relationships. RESULTS: Mutations in SMEI occurred more frequently in the "pore" regions of SCN1A than did those in GEFS+. These SMEI mutations in the "pore" regions were more strongly associated than mutations in other regions with the presence of ataxia and tendency to early onset of disease. The possibility of participation of ion selectivity dysfunction of the channel in the pathogenesis of SMEI was suggested by a mutation in the pore region (R946C) identified in a SMEI patient. CONCLUSIONS: There was a significant phenotype-genotype relationship in generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy of infancy with SCN1A missense mutations. More severe sodium channel dysfunctions including abnormal ion selectivity that are caused by mutations in the pore regions may be involved in the pathogenesis of SMEI.

Age of Onset↗
PubMed2004

Compound and rotational damping in warm deformed rare-earth nuclei.

The gamma decay in the quasicontinuum from selected configurations of the rotational nucleus 163Er has been measured with the EUROBALL array. A new analysis technique has allowed for the first time to directly measure the compound and rotational damping widths Gamma (micro) and Gamma (rot). Values of Gamma (micro) approximately 20 keV and Gamma (rot) approximately 200 keV are obtained in the spin region I approximately 30-40 variant Planck's over 2pi, in good agreement with microscopic cranked shell model calculations. A dependence of Gamma (micro) and Gamma (rot) on the K-quantum number of the nuclear states is also presented.

Journal Article↗
PubMed2004

Identification of temperature-sensitive dnaD mutants of Staphylococcus aureus that are defective in chromosomal DNA replication.

The DnaD protein in Gram-positive bacteria is thought to be essential for the initiation step in DNA replication. In the present study, we characterized two Staphylococcus aureus mutants whose temperature-sensitive growth phenotype could be complemented by a plasmid carrying the dnaD gene. These mutants each had a single amino acid substitution in the DnaD protein and showed decreased DNA synthesis at restrictive temperature. Analyses of the origin to terminus ratio by Southern blotting, and of origin numbers per cell by flow cytometry, revealed that, at the restrictive temperature, one mutant continued ongoing DNA replication but failed to initiate DNA replication. The other mutant, in contrast, could not complete ongoing DNA replication and proceeded to degrade the chromosome. However, if protein synthesis was inhibited, the second mutant could complete DNA replication. These results suggest that DnaD protein is necessary not only for the initiation step, but also to avoid replication fork blockage. Moreover, both mutants were sensitive to mitomycin C, a drug that induces DNA damage, suggesting that the DnaD protein is also involved in DNA repair.

Amino Acid Substitution↗
PubMed2004

Clinicopathological study of vesicoureteral reflux (VUR)-associated pyelonephritis in renal transplantation.

We retrospectively studied the occurrence of vesicoureteral reflux (VUR)-associated pyelonephritis using renal biopsies obtained from the transplanted kidneys, and correlated the histological changes with clinical parameters. Out of a total of 131 renal biopsies performed between 1990 and 2001 on renal transplant patients at the department of Urology of Nagasaki University Graduate School of Biomedical Sciences, 12 patients showed pyuria more than twice in a single year. Seven of these 12 patients were available for determining VUR by voiding cystourethrography (VCUG). Cystoureterography demonstrated VUR in three of seven studied patients with pyuria. A histopathological examination revealed dilatation of both proximal and distal tubules in renal biopsies of transplant patients with VUR, compared to renal biopsies of transplant patients without VUR, or non-transplanted patients with thin membrane disease. One of the patients with VUR showed advanced features of chronic pyelonephritis in four consecutive biopsies at different time points, suggesting a late stage of reflux nephropathy in the transplanted kidney. We conclude from our study that the occurrence of VUR-related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.

Adult↗
PubMed2004

Analysis of the survival motor neuron and neuronal apoptosis inhibitory protein genes in Malay patients with Spinal Muscular Atrophy.

In Malaysia, Spinal Muscular Atrophy (SMA) is diagnosed based on clinical observation with or without muscle biopsy. Molecular analyses of the SMA-related genes have not been available so far. In this preliminary study, we searched for homozygous deletion of Survival Motor Neuron (SMN1) and Neuronal Apoptosis Inhibitory Protein (NAIP) genes in Malay patients with SMA and found homozygous deletion of SMN1 exon 7 and 8 in all the patients while homozygous deletion of NAIP exon 5 was detected in only our type 1 patients but not in the type 3 patient. To the best of our knowledge, these are the first SMA cases diagnosed at the molecular level in Malaysia.

Cyclic AMP Response Element-Binding Protein↗
PubMed2003

Dynamics of microbial populations and strong selection for Cycloclasticus pugetii following the Nakhodka oil spill.

Microbial population changes were monitored immediately after the Nakhodka oil spill accident in January 1997 at the heavily oil-contaminated Mikuni coast along the Sea of Japan. The total cell number was almost stable for one year at 2-5 x 10(5) cells mL(-1), while the relative occurrence of culturable heterotrophs and degraders of oil components such as C-heavy oil, kerosene, and n-tetradecane varied, showing a maximum (>50% of the total) immediately following the accident. Gene amplification and phylogenetic analysis of a dilution culture using C-heavy oil as the sole carbon and energy source revealed that one of the predominant oil degraders at the oil-contaminated coast in 2 weeks after the accident closely resembled the aromatic hydrocarbon decomposer Cycloclasticus pugetii. Microbial community composition in oil-contaminated seawater was estimated at the molecular level using newly developed oligonucleotide probes, probe wash-off curve estimation, and quantitative fluorescence dot-blot hybridization techniques. At two different oil-polluted sites, harbor and intertidal regions, the C. pugetii group was estimated to make up 23-25% of the total Bacteria population, followed by the aliphatic hydrocarbon decomposer Alcanivorax borkumensis, which formed 4-7% of the Bacteria. In incubation experiments using floated oil slick and indigenous microbes collected at the harbor, oil degradation activities were enhanced by the addition of both organic and inorganic nutrients. Significant decreases were found in aromatic and aliphatic hydrocarbon fractions: 54-60% and 22-24% in 2 weeks to 68-77% and 23-32% in 2 months, respectively.

Base Sequence↗
PubMed2003

Analysis of dystrophin mRNA from skeletal muscle but not from lymphocytes led to identification of a novel nonsense mutation in a carrier of Duchenne muscular dystrophy.

Dystrophin mRNA expressed in peripheral lymphocytes of individuals with X-linked Duchenne muscular dystrophy (DMD) has been used as a source material for mutation analysis. Here we present the first report of failure of isolation of nonsense dystrophin mRNA in lymphocytes but success in skeletal muscle in a female carrier of DMD. The mutation responsible for dystrophin-negative muscle fibers of the carrier was analysed by direct sequencing of the reverse transcription PCR product of dystrophin mRNA. In her peripheral lymphocytes, no nucleotide change was detected in the 14 kb long mRNA. Remarkably, a novel nucleotide change of C1682T in exon 12, changing glutamine codon to stop codon (Q492X) was found to be present in her skeletal muscle. This change was heterozygous. Analysis of her genomic DNA disclosed heterozygous C and T nucleotides at nt 1682, confirming the genomic origin of the nonsense mutation. Although dystrophin cDNA prepared from lymphocytes was sequenced again after subcloning, mutation-retaining clone could not be isolated. This lymphocyte-specific disappearance of nonsense mRNA strongly suggested tissue-specific skewing of X-inactivation. However, both paternal and maternal dystrophin alleles were shown to be equally expressed in lymphocytes as well as in muscle, indicating no skewing of X-inactivation in lymphocytes. We concluded that the dystrophin mRNA of the DMD carrier was destabilized in lymphocytes. Our results indicated that analysis of mRNA in lymphocytes is not enough for exact carrier diagnosis of Duchenne muscular dystrophy.

Adult↗
PubMed2003

Early-enhancing non-neoplastic lesions on gadolinium-enhanced MRI of the liver.

AIM: To assess the frequency, cause, and significance of early-enhancing, non-neoplastic (EN) lesions on gadolinium-enhanced magnetic resonance imaging (MRI) of the liver performed for the detection of malignant hepatic tumours. MATERIALS AND METHODS: From September 1997 to September 2000, we reviewed the images of 125 patients, suspected of having hepatic tumours, in whom (1) gadolinium-enhanced triphasic dynamic gradient-recalled-echo (GRE) imaging in addition to unenhanced T1- and T2-weighted MRI was performed, (2) conventional angiography and combination computed tomography (CT) hepatic arteriography and CT during arterial portography were performed within 2 weeks of the MRI, and (3) definitive surgery within 2 weeks of the MRI or follow-up study by means of intravenously contrast-enhanced CT or MRI in 10 months or more was performed. Angiographic studies were correlated to determine the underlying causes of the EN lesions. RESULTS: We found 78 EN lesions in 36 patients (29%), ranging in size from 4 and 50 mm (mean, 12.2 mm). From the MR reports, our radiologists had prospectively diagnosed EN lesions as probable malignant tumours in eight (10%), possible malignant tumours in 36 (46%), and probable non-neoplastic lesion in 34 (44%). EN lesions were found in 27 of 81 (33%) cirrhotic patients and in nine of 44 (20%) non-cirrhotic patients. Fifty-one EN lesions (65%) were located along the liver edge. The shape was circular in 42 (54%), oval in 14 (18%), irregular in 12 (15%), wedge-shaped in seven (9%), and fan-shaped in three (4%). Twenty EN lesions (26%) appeared slightly hyperintense on T2-weighted images. The causes were non-neoplastic arterio-portal shunting in 48 (62%), cystic venous drainage in four (5%), rib compression in four (5%), aberrant right gastric venous drainage in two (3%), and unknown in 20 (26%). CONCLUSION: Over half the number of EN lesions were caused by non-neoplastic arterio-portal shunting, occasionally showing slight hyperintensity on T2-weighted images. On MR images the non-neoplastic nature of the EN lesion was often ascertained. Radiologists should not overcall EN lesions as malignant as the patients involved would be inappropriately considered inoperable. In problematic cases, further investigation with angiographic CT or follow-up imaging studies should be performed.

Aged↗
PubMed2003

Dexamethasone accelerates catabolism of leukotriene C4 in bronchial epithelial cells.

Leukotriene (LT)C4, a potent chemical mediator in bronchial asthma, is metabolised to the less active LTE4 via LTD4 in two consecutive reactions catalysed by enzymes of the glutamyl transpeptidase and dipeptidase families. The activities of these catabolic enzymes may be influenced by glucocorticosteroids. This study was conducted to examine whether this inactivation of LTC4 is affected by dexamethasone (DEX) in transformed human bronchial epithelial cells and normal human bronchial epithelial cells. After incubation with DEX for 0-5 days, cells were resuspended in the presence of exogenous LTC4, and conversion of LTC4 to LTE4 was measured using high-performance liquid chromatography. Gamma-glutamyl transpeptidase (GGT) and GGT-related enzyme (GGTRE) messenger ribonucleic acid (mRNA) expression were examined using reverse transcriptase-polymerase chain reaction analysis, and GGT activity by enzyme assay. Conversion to LTE4 was accelerated by DEX pretreatment. GGTRE but not GGT mRNA expression was enhanced after incubation with DEX. The results indicate that dexamethasone transcriptionally upregulates the activity of gamma-glutamyl transpeptidase-related enzyme in human bronchial epithelial cells, which accelerates inactivation of leukotriene C4 via conversion to leukotriene E4. This is a novel mechanism of glucocorticosteroids in human bronchial epithelial cells.

Analysis of Variance↗
PubMed2003

Combined treatment with nafamostat mesilate and aspirin prevents heparin-induced thrombocytopenia in a hemodialysis patient.

We report on the management of a 36-year-old hemodialysis patient with heparin-induced thrombocytopenia (HIT, type II) and clot formation in extracorporeal circulation. Platelet aggregation test and measurement of anti-platelet factor 4/heparin complex antibody by enzyme-linked immunosorbent assay revealed to us that our patient had developed HIT. Instead of heparin, we used nafamostat mesilate (NM) as an anticoagulant during hemodialysis, but could not completely prevent HIT-induced thrombocytopenia or clot formation in the extracorporeal circuit. Combined use of NM and aspirin completely inhibited platelet aggregation, decrease in platelet count and clot formation in the extracorporeal circuit.

Adult↗