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Biomedical subjects

K Matsuo

Publications and source records attributed to K Matsuo.

At least 109 records · Page 6Linked to original sources

Different susceptibility of each L-myc genotype to esophageal cancer risk factors.

To understand the relationship between the L-myc genotypes and esophageal cancer risk, a polymerase chain reaction-based restriction fragment length polymorphism analysis was performed on 91 Japanese patients with esophageal cancer and 241 non-cancer outpatients. No significant difference in the distribution of genotypes was observed between patients and controls; 18.7% LL genotype, 56.0% LS and 25.3% SS among patients, and 24.5%, 55.6% and 19.9%, respectively, among controls. Frequency of the s-allele in patients (0.533) was slightly higher than in controls (0.477), but the difference was not statistically significant. However, the odds ratios (ORs) for smoking or heavy drinking were markedly higher in SS and LS genotypes than in LL genotype; age-sex-adjusted ORs for smoking was 7.57 in the SS genotype, 6.40 in the LS genotype and 1.77 in the LL genotype. Age-sex-adjusted ORs for heavy drinking were 19.78, 18.20 and 7.40, respectively. The age-sex-adjusted ORs for both factors combined were 12.77, 18.45 and 1.44, respectively. These results suggested that the L-myc polymorphism might modify the effects of lifestyle factors on esophageal cancer risk.

Aged↗

Receptor specificities of human respiroviruses.

Through their hemagglutinin-neuraminidase glycoprotein, parainfluenza viruses bind to sialic acid-containing glycoconjugates to initiate infection. Although the virus-receptor interaction is a key factor of infection, the exact nature of the receptors that human parainfluenza viruses recognize has not been determined. We evaluated the abilities of human parainfluenza virus types 1 (hPIV-1) and 3 (hPIV-3) to bind to different types of gangliosides. Both hPIV-1 and hPIV-3 preferentially bound to neolacto-series gangliosides containing a terminal N-acetylneuraminic acid (NeuAc) linked to N-acetyllactosamine (Galbeta1-4GlcNAc) by the alpha2-3 linkage (NeuAcalpha2-3Galbeta1-4GlcNAc). Unlike hPIV-1, hPIV-3 bound to gangliosides with a terminal NeuAc linked to Galbeta1-4GlcNAc through an alpha2-6 linkage (NeuAcalpha2-6Galbeta1-4GlcNAc) or to gangliosides with a different sialic acid, N-glycolylneuraminic acid (NeuGc), linked to Galbeta1-4GlcNAc (NeuGcalpha2-3Galbeta1-4GlcNAc). These results indicate that the molecular species of glycoconjugate that hPIV-1 recognizes are more limited than those recognized by hPIV-3. Further analysis using purified gangliosides revealed that the oligosaccharide core structure is also an important element for binding. Gangliosides that contain branched N-acetyllactosaminoglycans in their core structure showed higher avidity than those without them. Agglutination of human, cow, and guinea pig erythrocytes but not equine erythrocytes by hPIV-1 and hPIV-3 correlated well with the presence or the absence of sialic acid-linked branched N-acetyllactosaminoglycans on the cell surface. Finally, NeuAcalpha2-3I, which bound to both viruses, inhibited virus infection of Lewis lung carcinoma-monkey kidney cells in a dose-dependent manner. We conclude that hPIV-1 and hPIV-3 preferentially recognize oligosaccharides containing branched N-acetyllactosaminoglycans with terminal NeuAcalpha2-3Gal as receptors and that hPIV-3 also recognizes NeuAcalpha2-6Gal- or NeuGcalpha2-3Gal-containing receptors. These findings provide important information that can be used to develop inhibitors that prevent human parainfluenza virus infection.

Animals↗

Conduction left-to-right and right-to-left across the crista terminalis.

A line of block between the vena cava and the crista terminalis (CT) region is important for atrial flutter (AFL), but whether it is fixed or functional is controversial. To test the hypothesis that conduction across the CT normally occurs, but when block occurs in this region it is functional, we analyzed atrial activation during right and left atrial pacing (cycle lengths of 500--130 ms), AFL, and atrial fibrillation in 15 dogs with sterile pericarditis and 7 normal dogs. Electrograms from 396 right, left, and septal atrial sites were simultaneously recorded. Activation across the CT occurred during atrial pacing, AFL, and atrial fibrillation. Activation wave fronts from the right to the left atrium and vice versa traveled over several routes, including Bachmann's bundle and inferior to the inferior vena cava, as well as across the CT. In these models, there is no fixed conduction block across the CT, and when block in the CT region occurs, as during AFL, it is functional.

Animals↗

Expression and role of vascular endothelial growth factor in liver regeneration after partial hepatectomy in rats.

Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, which is essential for both healing of injured tissue and proliferation of carcinoma cells. In this study we elucidated the expression and role of VEGF in rat liver regeneration after partial hepatectomy. VEGF expression was mainly detected in periportal hepatocytes and reached a maximal level 48-72 hr after partial hepatectomy by both immunohistochemistry and in situ hybridization. Similarly, immunohistochemistry for Ki-67 showed that the proliferative activity of sinusoidal endothelial cells was highest in the periportal area and reached a maximal level 72 hr after partial hepatectomy. Moreover, neutralization of VEGF significantly inhibited proliferative activity of hepatocytes (p<0. 0001), as well as sinusoidal endothelial cells (p<0.001), at 48 and 96 hr after partial hepatectomy. Conversely, injection of VEGF significantly promoted proliferative activity of hepatocytes (p<0. 0001) as well as sinusoidal endothelial cells (p<0.0005) at 48 hr after partial hepatectomy. These results suggest that VEGF promotes proliferation of hepatocytes through reconstruction of liver sinusoids by proliferation of sinusoidal endothelial cells. Furthermore, these data point to a new therapeutic strategy, the use of VEGF and other hepatocyte growth factors in fulminant or severe acute hepatitis.

Animals↗

Effect of long-term, low-dose acyclovir suppressive therapy on susceptibility to acyclovir and frequency of acyclovir resistance of herpes simplex virus type 2.

We have examined the susceptibility to acyclovir and frequency of acyclovir-resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive therapy (200 mg/day) for 1-9 years and 15 patients naive to acyclovir. Suppressive therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of acyclovir, were subjected to the acyclovir susceptibility test, and 155 clones isolated in the presence of acyclovir were analysed for the mechanisms of resistance to acyclovir. There were no significant differences in the susceptibility to acyclovir, the frequency of acyclovir-resistant virus and the ratio of thymidine kinase-deficient viruses in acyclovir-resistant viruses between the two groups. The frequency of acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with genital herpes with or without acyclovir-suppressive therapy. Thus, the low dose of acyclovir suppressive therapy did not affect the susceptibility to acyclovir or increase the frequency of acyclovir-resistant viruses in the genital lesions.

Acyclovir↗

Anti-androgenic activity of Myricae Cortex--isolation of active constituents from bark of Myrica rubra.

The aqueous ethanol extract of Myricae Cortex (bark of Myrica rubra Sieb. et Zucc., Myricaceae) showed in vitro testosterone 5alpha-reductase inhibitory activity and in vivo anti-androgenic activity using growth of flank organ in castrated Syrian hamsters and/or hair regrowth after shaving in testosterone-treated C57Black/6CrSlc mice. Three constituents, myricanone, myricanol, and myricetin were identified as the main active principles.

5-alpha Reductase Inhibitors↗

Study on anti-Oketsu activity of rhubarb II. Anti-allergic effects of stilbene components from Rhei undulati Rhizoma (dried rhizome of Rheum undulatum cultivated in Korea).

Methanol extract (RM-ext) obtained from the dried rhizome of Rheum undulatum was screened for activity in experimental models of type I allergy. RM-ext exhibited the inhibition on 48-h homologous passive cutaneous anaphylaxis (PCA) in rats and an antigen-induced histamine release from rat peritoneal mast cells. Among nine stilbenes isolated from RM-ext, seven inhibited the histamine release. Rhapontigenin (compound 1), piceatannol (2) and piceatannol 3'-beta-D-glycoside (6) with oral administration showed the inhibition on PCA. Compounds 1 and 2 exhibited the inhibitory effect on sheep red blood cell-induced delayed-type hyper sensitivity (SRBC-DTH) of type IV allergic model. These results indicated that the rhizome of Rheum undulatum inhibits the allergic reactions and that these inhibitory effects may be partially attributable to the stilbenes mentioned above.

Animals↗

Racemization kinetics of meluadrine tartrate in aqueous solution.

The kinetics of racemization of meluadrine tartrate in aqueous solution was investigated by HPLC, over the pH range of 1.2 to 12 at 40, 60 and 80 degrees C. The racemization was followed by measuring both the residual (R)-enantiomer and formed (S)-enantiomer of meluadrine. The pH-racemization rate profile of meluadrine showed a minimum racemization rate constant between pH 4 and 6, and the rate constant increased rapidly with decreasing pH below pH 3. In the basic region, the racemization rate constant showed a maximum at around pH 9. Four pathways of racemization of meluadrine are proposed, depending on the dissociation state of the phenolic and amino groups. The calculated racemization rate-pH profile agreed well with the observations. The values of activation energy (95-115 kJ/mol) suggest that a similar quinoid intermediate is involved throughout the pH range examined. The objective of this study is to clarify the racemization mechanism of benzylalcohol derivative with phenoric group. This study offers fundamental knowledge for the other benzylalcohol derivatives, which have similar moiety structure.

Adrenergic beta-2 Receptor Agonists↗

The right ventricular outflow tract as an unusual location for an implantable defibrillator electrode in a patient with arrhythmogenic right ventricular dysplasia.

A 41-year-old woman with arrhythmogenic right ventricular dysplasia (ARVD) underwent the implantation of an implantable cardioverter-defibrillator (ICD), in which the defibrillator electrode was unusually located in the right ventricular (RV) outflow tract. Although fractionated electrograms were demonstrated in the RV apex, which is the usual site for ICD electrodes, normal electrograms were recorded in the RV outflow tract during an electrophysiologic study. An electrode with a screw-in tip was used to fix the implant in the RV outflow tract and obtain successful defibrillation. If normal electrograms are recorded in the RV outflow tract, the site may prove to be an alternative location for an ICD electrode even for ARVD patients.

Adult↗

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease.

The present study was undertaken to investigate whether human chorionic gonadotropin (hCG) beta-core fragment (hCG beta cf) was directly produced by gestational trophoblastic tumors. Immunoreactivity of hCG beta cf was demonstrated in the extracts as well as in the culture media of hydatidiform mole tissues. It was also present in the extracts of choriocarcinoma tissues, and its molar concentration exceeded that of intact hCG. The presence of hCG beta cf was then confirmed by gel chromatography and Western blot analysis. Immunohistochemistry showed localization of hCG beta cf immunoreactivity to the syncytiotrophoblasts and scattered cells in the stroma of mole tissue, and to syncytiotrophoblastic cells in choriocarcinoma. Immunoreactivity of hCG beta cf was also detected in the sera of the patients with gestational trophoblastic disease, although the hCG beta cf/hCG ratio was less than one hundredth of that in the tissue extracts. Serial measurement of serum hCG beta cf levels after mole evacuation showed that they declined much more rapidly than those of hCG and became undetectable in the patients with subsequent spontaneous resolution, while hCG beta cf remained or became detectable before the rise of hCG was observed in the patients with subsequent persistent trophoblastic disease. Taken together, these results suggest that hCG beta cf is directly produced by gestational trophoblastic tumors, and monitoring of hCG beta cf in the serum after mole evacuation may be useful for early prediction of subsequent development of postmolar persistent trophoblastic disease.

Animals↗

Intercellular adhesion molecule-1 in patients with idiopathic interstitial pneumonia.

This study focuses on a possible role of intercellular adhesion molecule-1 (ICAM-1) in interstitial pulmonary diseases. We determined a soluble form of ICAM-1 in serum and bronchoalveolar lavage fluid (BALF) using ELISA in patients with usual interstitial pneumonia (UIP), bronchiolitis obliterance organizing pneumonia (BOOP), or nonspecific interstitial pneumonia (NSIP). In addition, we investigated the expression of ICAM-1 in the lung tissues of these patients by means of immunohistochemical staining. Serum levels of soluble ICAM-1 were significantly higher in patients with UIP or NSIP than in healthy subjects, and were also high in patients with BOOP. The soluble ICAM-1 in BALF tended to be higher in patients with UIP, BOOP, or NSIP than in normal subjects. A significant correlation was seen between soluble levels of ICAM-1 in serum and BALF. In the immunostaining of ICAM-1 of the lung tissues, ICAM-1 expression was more pronounced in patients with UIP than in those with BOOP or NSIP. The increased expression of ICAM-1 was seen in type II alveolar epithelium and vascular endothelium in patients with interstitial pneumonia. A positive correlation was observed between the degree of ICAM-1 expression in the lung tissues and the BALF levels of soluble ICAM-1. The expression of ICAM-1 in type II alveolar epithelium suggests that ICAM-1 plays a specific role in the fibrotic process of the lung, and that the measurement of soluble ICAM-1 in sera and BALF could be a useful marker for evaluating the progression of fibrosis.

Adult↗

The role of fibronectin in bronchoalveolar lavage fluid of asthmatic patients.

Allergic and chronic inflammation of the airway is regarded as the main pathogenesis of bronchial asthma, in which adhesion of inflammatory cells requires the expression of adhesion molecules. Thus, to clarify the role of fibronectin (FN) in the airway inflammation of bronchial asthma, FN levels in plasma and bronchoalveolar lavage fluid (BALF) from bronchial asthmatics were determined. FN concentrations in plasma and BALF were measured by enzyme-linked immunosorvent assay (ELISA) in 17 asthmatic patients and 10 healthy controls to elucidate the role of FN in allergic inflammation. The mean FN/albumin (Alb) level in the BALF of asthmatic patients was 2.973 micrograms/mg, which was significantly higher than that of healthy controls (0.727 microgram/mg). Non-atopic asthmatics showed a significantly higher level of FN in their BALF in comparison with atopic asthmatics, although the ratio of FN to albumin showed no significant difference. FN levels in BALF correlated significantly with total cell density (r = 0.71, P < 0.05) and alveolar macrophage density (r = 0.64, P < 0.05). FN levels in plasma did not correlate with those in BALF. In conclusion, increased FN in BALF, which was produced locally in the airways of asthmatic patients, is actively involved in the regulation of allergic inflammation.

Adult↗

Plasma fibronectin in asthmatic patients and its relation to asthma attack.

This study investigated the relation between asthma attacks and levels of plasma fibronectin (FN) and serum eosinophilic cationic protein (ECP) in patients with bronchial asthma in order to clarify the role of FN in the airway inflammation of bronchial asthma. Plasma levels of FN were significantly higher (P < 0.025) in patients with bronchial asthma than in healthy controls. They were also significantly higher (P < 0.05) in non-atopic asthmatics than in atopic asthmatics. Furthermore, plasma FN was lower during the attack than the non-attack stage (P < 0.025), and a significant increase of plasma FN was noted (P < 0.05) in asthmatics who had more severe and more frequent attacks. Serum levels of ECP were significantly higher during the attack than the non-attack stage (P < 0.005). An increase of plasma FN in the non-attack stage after attacks showed a significant correlation (P < 0.05) with a decrease of serum ECP. These observations clearly indicate that the decrease in plasma FN associated with attacks is closely related to aggravation of airway inflammation, and that the increase in plasma FN in the non-attack stage reflects chronic airway inflammation. These results suggest that the fluctuation in plasma levels of FN may be one of the factors affecting allergic inflammation and attacks in bronchial asthma.

Acute Disease↗

Substrate phage as a tool to identify novel substrate sequences of proteases.

Combinatorial phage peptide libraries have been used to identify the ligands for specific target molecules. These libraries are also useful for identification of the specific substrates of various proteases. A substrate phage library has a random peptide sequence at the N-terminus of the phage coat protein and an additional tag sequence that enables attachment of the phage to an immobile phase. When these libraries are incubated with a specific enzyme, such as a protease, the uncleaved phage is excluded from the solution with tag-binding macromolecules. This provides a novel approach to define substrate specificity. The aim of this review is to summarize recent progress on the application of the substrate phage technique to identify specific substrates of proteolytic enzymes. As an example, some of our own experimental data on the selection and characterization of substrate sequences for thrombin, a serine protease, and membrane type-1 matrix metalloproteinase (MT1-MMP) will be presented. Using this approach, the canonical consensus substrate sequence for thrombin was deduced from the selected clones. As expected from the collagenolytic activity of MT1-MMP, a collagen-like sequence was identified in the case of MT1-MMP. A more selective substrate sequence for MT1-MMP was identified during a substrate phage screen. The delineation of the substrate specificity of proteases will help to elucidate the enzymatic properties and the physiological roles of these enzymes. Comprehensive screening of very large numbers of potential substrate sequences is possible with substrate phage libraries. Thus, this approach allows novel substrate sequences and previously unknown target molecules to be defined.

Amino Acid Sequence↗

Possible risk reduction in esophageal cancer associated with MPO -463 A allele.

Myeloperoxidase (MPO), an enzyme found in lysosomes of phagocytes, causes hydroxy radicals linked to DNA damage and activation of smoking related carcinogens. A -463 G/A polymorphism in the promoter region of the MPO gene results in reduced gene expression, which would imply lower susceptibility of esophageal cancer in mutant carriers. We conducted case-control study to test this hypothesis. Cases were 91 patients with esophageal cancer and controls were 241 non-cancer outpatients. MPO genotypes were examined by PCR-RFLP. The allele frequency for MPO -463A was found to be 8.2% for cases and 10.5% for controls. The age, sex, smoking and drinking status adjusted odds ratio for all subjects for MPO -463 GG/GA as compared to the AA was 0.61 (95% CI: 0.28-1.32). The adjusted odds ratio for the GG/GA genotype was significantly low (0.15; 0.03-0.76, P=0.022) for those aged 61 years or older who had a significantly higher odds ratio for smoking than younger subjects. No difference was observed in disease risk when prevalent and incident cases were compared. Although there are limitations for interpretation of this study because of prevalent case-control study and partial statistical significance, these results suggest that MPO -463 A allele reduce the risk of esophageal cancer.

Adult↗

Smoking habit and interleukin lB C-31T polymorphism.

Recent studies suggest that smoking habit may relate to genetic traits. This study examines the association with a polymorphism (C-31T) of interleukin 1B (IL-1B), which encodes IL-1beta, a multifunctional pro-inflammatory cytokine. Since the T allele makes a TATA box, the allele is thought to be responsible for a higher potency of IL-1B expression, indicating that individuals harboring the T allele are prone to inflammation. The study subjects were two different populations; 241 non-cancer outpatients (118 males and 123 females) at a cancer hospital and 462 examinees (127 males and 335 females) of a health checkup program provided by a local government. Current smokers were 36.4% for the male outpatients, 9.8% for the female outpatients, 38.6% for the male examinees, and 5.6% for the female examinees. The sex-age-adjusted odds ratios of current smokers were calculated for the genotypes with the T allele relative to the CC genotype by an unconditional logistic model. The estimate was 0.45 (95% confidence interval, 0.21-0.97) for the outpatients, and 0.83 (0.42-1.61) for the examinees. Although not significant for the examinees, the observed associations suggest that this polymorphism may influence smoking behavior through an inflammatory response of the respiratory tract to cigarette smoke.

Adult↗

Adjustment of prognostic effects in prevalent case-control studies on genotype.

Since genotypes are unchangeable, adjustment of prognostic effects in prevalent case-control studies may produce an unbiased estimate of odds ratio (OR) for disease occurrence. In this paper, the prognostic effects on OR is demonstrated, then three approaches to examine and/or adjust the OR are presented. The demonstration shows that the prognostic effects are larger in diseases with poor prognosis than in those with better prognosis. Genotypes increasing disease risk and fatality rate are underestimated, while those increasing the risk and improving prognosis are overestimated. The simplest approach to examine the OR derived from prevalent case-control studies is to conduct stratified analysis according to the interval between diagnosis and study enrollment. When the stratified analysis finds no substantial difference in the estimate, the OR reflects mainly the relative risk for disease occurrence. The proportion of genotype among putative cases at diagnosis can be estimated from prevalent cases by a logistic model, producing the OR adjusted for the interval from diagnosis. An incomplete-data case-control design is also applicable to adjust the prognostic effects. An actual prevalent case-control study on breast cancer is used to demonstrate the three approaches. They are useful to compensate the disadvantage of prevalent case-control studies.

Adult↗