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Biomedical subjects

K Matsui

Publications and source records attributed to K Matsui.

At least 271 records · Page 15Linked to original sources

Fatty acid hydroperoxide lyase is a heme protein.

Fatty acid hydroperoxide lyase (HPO lyase) is an enzyme that cleaves hydroperoxides of polyunsaturated fatty acids to form short chain aldehydes and omega-oxoacids. Spectrophotometric analyses of HPO lyase highly purified from green bell pepper fruits indicate that it is a heme protein. The heme species was revealed to be heme b (protoheme IX) from the absorption spectrum of the pyridine hemochromogen. Although the spectrum highly resembles that of a plant cytochrome P450, allene oxide synthase from flaxseed, CO treatment of the enzyme caused no appearance of a peak at 450 nm, which is an essential diagnostic feature of a cytochrome P450. Internal amino acid sequences determined with peptide fragments obtained from the lyase showed no homology with any reported sequences.

Aldehyde-Lyases↗

A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells.

Necrotizing and crescentic glomerulonephritis (NCGN) is frequently associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA). It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). The purpose of this study was to identify membrane proteins of PMNs, and/or glomerular cells, as additional autoantigenic ANCA targets. When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. Gp130 was purified, and monoclonal and rabbit antibodies (Abs) were produced which showed the same double specificity as the patient's ANCA. Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-associated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti-gp130 Ab yielded a clone derived from h-lamp-2. Gp170/80-110 was localized primarily in granule membranes of resting PMNs, and was translocated to the cell surfaces by activation with FMLP. By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capillaries, rather than in lysosomes, as found for h-lamp-2. Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. Specific reactivity was detected in approximately 90% of cases with active phases of NCGN, and frequently also in combination with autoantibodies specific for PR3 or MPO. Collectively, these data provide evidence that h-lamp-2 in PMNs and a different, structurally related 130-kD membrane protein on the cell surface of renal microvascular endothelial cells are autoantigenic targets for ANCA in patients with active NCGN.

Amino Acid Sequence↗

Chronic active hepatitis and liver cirrhosis in association with combined tamoxifen/tegafur adjuvant therapy.

Two female breast cancer patients who received combined tamoxifen and tegafur as postsurgical adjuvant therapy developed severe hepatotoxicity after being treated for three and eight months, respectively. Shortly after the cessation of the treatment, routine liver tests showed gradual recovery, but liver biopsies revealed chronic active hepatitis in one patient and liver cirrhosis in the other. Four and five years, respectively, after the cessation of the treatment, the results of liver tests were normal and distinct histological improvement was observed in both patients. Because these patients had no viral and immunoserological markers nor any history of alcohol abuse, this study suggested that the tamoxifen and tegafur regimen induced reversible chronic active liver disease.

Adult↗

Hepatitis E probably contracted via a Chinese herbal medicine, demonstrated by nucleotide sequencing.

Hepatitis E is endemic in developing countries and may occur as imported hepatitis in industrialized countries. A 46-year-old Japanese man developed immunoserologically diagnosed acute hepatitis E in Japan 4 months after he had made a trip to China. He had bought a Chinese herbal medicine there, taking it occasionally until approximately 6 weeks prior to the onset of acute hepatitis. Nucleotide sequencing of the 3' terminal region of the viral cDNA amplified from the patient's serum by polymerase chain reaction revealed a high degree of homology (99.8% of 752 nucleotides) with the Chinese strain. Thus, the results of sequencing suggest that his hepatitis E was caused by infection with the Chinese strain, via the Chinese herbal medicine.

Acute Disease↗

Cucumber cotyledon lipoxygenase oxygenizes trilinolein at the lipid/water interface.

The reactivity of cucumber cotyledon lipoxygenase with trilinolein was examined. The activity of the enzyme against linoleic acid rapidly decreased with increasing pH of the assay solution, and essentially no activity could be detected above pH 8.5. The rapid decrease in activity was not the result of an inactiveness of the enzyme at alkaline pH, because with trilinolein, the enzyme showed a broad pH-activity profile, and substantial activity could be detected even at pH 9.0. Rather, the decrease in activity was due to the dissociation of the linoleic acid emulsion into acid-soap aggregates and/or the monomeric form, depending on the ionization of the terminal carboxylic group. This suggests that cucumber cotyledon lipoxygenase acts only on an insoluble substrate at the lipid/water interface but not on a soluble one. High-performance liquid chromatography analyses of the products formed from trilinolein revealed that the enzyme inserted oxygen into the acyl moiety of trilinolein without hydrolysis of the ester bonds. Preincubation of the enzyme with triolein emulsions effectively abolished its activity against trilinolein added afterward. Furthermore, the enzyme was adsorbed on the trilinolein or triolein emulsion droplets in an essentially irreversible manner. A reaction velocity curve of the enzyme with trilinolein showed saturation kinetics. This is thought to be due to a regional substrate deficiency as the reaction proceeds. These lines of evidence indicate that the enzyme, once bound to the lipid/water interface, is unable to break free and bind to other emulsions.

Adsorption↗

Specific disruption of samAB genes in a 60-megadalton cryptic plasmid of Salmonella typhimurium.

The expression of umuDC operon is required for UV and most chemical mutagenesis in Escherichia coli. The closely related species Salmonella typhimurium has two sets of umuDC-like operons, i.e., umuDCST in the chromosome and samAB in a 60-megadalton cryptic plasmid. In this study, we specifically disrupted the samAB genes to investigate their exact roles in UV mutagenesis in S. typhimurium. The specific gene disruption was carried out by the preligation method. Deletion of samAB did not lower the UV mutability of S. typhimurium TA2659 but rather increased the UV mutability about twofold. The samAB-umuDCST double deletion mutant as well as the umuDCST deletion mutant was UV nonmutable. These results suggest that the samAB genes do not considerably contribute to the UV mutability of S. typhimurium and raise the question of why such quiet umuDC-like genes are present in the cryptic plasmid of S. typhimurium.

Blotting, Southern↗

Distribution pattern of the basement membrane components is one of the significant prognostic correlates in peripheral lung adenocarcinomas.

Clinicopathological variables that might have an effect on prognosis were analyzed in 98 samples of resectable peripheral lung adenocarcinoma. Pathological stage (stage I v stage II, III, or IV; P < .001), degree of central fibrosis (grade 1 or 2 v grade 3 or 4; P < .01), and histological grade (well differentiated v moderately or poorly differentiated; P < .05) were shown to be prognostic factors, whereas any other variable, including patient age at diagnosis, sex, cigarette smoking habits, and tumor histological subtype and cytological type, showed no meaningful correlation with patient length of survival. The distribution pattern of the basement membranes (BMs) was significantly associated with pathological stage (intact v disrupted or absent; P < .001). It was noteworthy that in stage I samples a significant relationship between the distribution pattern of the BMs and patient length of survival was found (intact v disrupted or absent; P < .001), although such a relationship could not be detected when analyzed in samples from the other pathological stages. The distribution pattern of the BMs also was correlated with the presence or absence of lymph node metastasis but not with its extension. There were no meaningful relationships between the distribution pattern of the BMs and any other clinicopathological variables, including degree of central fibrosis, histological grade, etc. The distribution pattern of the BMs in peripheral lung adenocarcinomas might be useful for postoperative therapeutic strategy and could serve as an important prognostic indicator for stage I lesions.

Adenocarcinoma↗

The effect of a naphthalene derivative, TEI-6472, on histamine release and tyrosine phosphorylation in rat basophilic leukemia cells.

It is well known that rat basophilic leukemia cells (RBL-2H3) express high-affinity IgE receptors (Fc epsilon RI) and that the aggregation of these receptors causes the release of chemical mediators. When RBL-2H3 cells are sensitized with IgE antibody and subsequently stimulated by an antigen, significant histamine release and the tyrosine phosphorylation of several proteins are observed. In this study, we examined the effects of a synthetic naphthalene derivative, (7E)-N-(2-carboxyphenyl)-8-(2-naphthyl)-5,6-trans-5,6-methano-7-++ +octenamide (TEI-6472), on the Fc epsilon RI-mediated histamine release from RBL-2H3 cells. Preincubation for 10 min with 100 microM TEI-6472 caused significant inhibition of Fc epsilon RI-mediated histamine release from RBL-2H3 cells. Furthermore, Western blotting analysis using anti-phosphotyrosine antibody showed that Fc epsilon RI-mediated tyrosine phosphorylation of 78 and 92 kDa proteins in RBL-2H3 cells was also significantly inhibited. Tyrosine phosphorylation of these 78 and 92 kDa proteins was not induced by direct activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) and the calcium ionophore A23187. However, the inhibition of histamine release from TEI-6472-treated RBL-2H3 cells was restored by direct activation of PKC. Taken together, these results suggest that tyrosine phosphorylation of the 78 and 92 kDa proteins in RBL-2H3 cells is involved in a signal transduction system for histamine secretion, and that these tyrosine phosphorylations may occur upstream of PKC activation.

Animals↗

Contribution of peroxidation products to oxidative inactivation of rat liver microsomal glucose-6-phosphatase.

Exposure of rat liver microsomes to ascorbic acid/Fe(2+) caused decreases in the membrane-bound glucose-6-phosphate (G-6-Pase) activity and the protein thiols after a short lag period (4 min). Under the same conditions, the production of thiobarbituric acid-reactive substances and fluorescent products was also initiated from 4 min after the start of the treatment, although conjugated diene was formed immediately on incubation of the microsomes with ascorbic acid/Fe(2+). After centrifugation of the treated microsomes, the fluorescent products and the enzyme activity remained in the membrane fraction. The results of kinetic studies of the enzyme activity indicated that ascorbic acid/Fe(2+)-induced inhibition of the enzyme activity is mainly due to an increased Km value for the substrate. A decreased activity of the microsomal G-6-Pase was also observed when the microsomes were incubated with aldehydes such as malondialdehyde, n-heptaldehyde, acetaldehyde, and trans-2-nonenal. However, loss of protein thiols was detected only upon treatment of the microsomes with trans-2-nonenal. Glucose-6-phosphate (G-6-P)effectively prevented ascorbic acid/Fe(2+)- or trans-2-nonenal-induced inhibition of the enzyme activity, but the substrate failed to protect the protein thiols in both systems. The results of fluorescence anisotropy measurements of diphenylhexatriene-labeled microsomes suggested that changes in the lipid dynamics are not directly related to peroxidation- mediated inhibition of the enzyme activity. Based on these results, a possible reason for the inhibition of the microsomal G-6-Pase activity associated with ascorbic acid/Fe(2+) treatment is discussed.

Aldehydes↗

Relationship between the pharmacokinetics of irinotecan and diarrhea during combination chemotherapy with cisplatin.

Two phase I trials of irinotecan (CPT-11) in combination with cisplatin were conducted. In both cases, the dose-limiting toxicities were leukopenia and/or diarrhea. During these trials the pharmacokinetics of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were investigated to evaluate the relationship between pharmacokinetic parameters and diarrhea, since this is an unpredictable and severe toxicity of combination chemotherapy using CPT-11 and cisplatin. Twenty-three previously untreated patients with advanced lung cancer were evaluated in the pharmacokinetic study. Ten patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 60 mg/m2. The other 13 patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 80 mg/m2 with the granulocyte colony-stimulating factor support (2 micrograms/kg x 16 days). CPT-11 was given as a 90-min intravenous infusion on days 1, 8, and 15. Cisplatin was given on day 1. The pharmacokinetics of CPT-11 and SN-38 were analyzed on day 8 during the first course of treatment. The maximum tolerated dose of CPT-11 was 90 mg/m2 in both phase I trials. The severity of diarrhea was best correlated with the peak plasma concentration of SN-38 among the pharmacokinetic parameters tested. In addition, patients with a plasma SN-38 level > 12.4 ng/ml at 1.75 h after the start of CPT-11 infusion had a higher incidence of Eastern Cooperative Oncology Group grade 3-4 diarrhea than those with a lower SN-38 level (P = 0.0003). Stepwise logistic regression analysis identified the SN-38 concentration as a significant contributor to the development of diarrhea (P = 0.0021). We conclude that there is a clear relationship between the SN-38 concentration and diarrhea during chemotherapy with CPT-11 plus cisplatin.

Adult↗

Immunosuppression induced by Salmonella infection is correlated with augmentation of interleukin-2 receptor alpha chain expression in murine splenic lymphocytes.

In a previous study, we observed that the suppression of T-cell proliferation induced by Salmonella cell-free extract was associated with augmentation of IL-2 receptor (IL-2R) alpha chain expression. In this study, we also observed this kind of augmentation of IL-2R alpha in Salmonella-infected mice. Phytohaemagglutinin (PHA)-stimulated proliferation of murine spleen cells was significantly suppressed when the mice were infected with Salmonella typhimurium. However, expression of the alpha chain but not the beta chain of IL-2R in lymphocytes was augmented by the infection. Analysis of the IL-2R-positive cell-population showed that the augmentation of IL-2R alpha was not specific to certain cell subpopulations. Furthermore, the inhibition of PHA-stimulated murine spleen cell proliferation and the augmentation of IL-2R alpha expression induced by the infection in lymphocytes was completely reversed by treatment with anti-interferon-gamma monoclonal antibody (anti-IFN-gamma Ab). These results suggest that the suppression of T-cell proliferation induced by Salmonella infection was associated with augmentation of IL-2R alpha expression in an IFN-gamma production-dependent manner in the same way as the suppression of T-cell proliferation induced by Salmonella cell-free extract.

Animals↗

A cell-free Salmonella typhimurium extract induces inhibition of tyrosine phosphorylation in murine splenic T-lymphocytes.

In a previous study, we observed that suppression of T-cell proliferation induced by Salmonella infection is associated with inhibition of tyrosine phosphorylation in T-cells, and that a cell-free Salmonella typhimurium LT2 extract (LT2 extract) also suppressed mitogen-induced T-cell proliferation. In the present study, therefore, we attempted to clarify whether the T-cell suppression induced by LT2 extract involved inhibition of tyrosine phosphorylation in T-cells. Western blotting using anti-phosphotyrosine antibodies showed that the mitogen-induced tyrosine phosphorylation of 120-, 106-, 94-, 76-, 68-, 57- and 36-kDa proteins in murine splenic T-cells was inhibited by treatment with LT2 extract. These results suggest that the suppression of T-cell proliferation induced by LT2 extract is also associated with inhibition of tyrosine phosphorylation in T-cells.

Animals↗

[The survey of prevalence of Lyme borreliosis in forestry workers in Saitama prefecture].

Forestry workers in Saitama Prefecture are in high occupational risk to Lyme borreliosis transmitted by ticks. We surveyed the incidence of tick bites and the prevalence of antibodies against Borrelia burgdorferi in 80 forestry workers. ELISA with the antigen from B. burgdorferi sensu stricto B31 as well as Borrelia garinii HP3 and Borrelia japonica HO14 isolated in Japan was used for the detection of antibodies. Antibody-positive cases against B31, HP3 and HO14 was 3.8, 23.8 and 13.8%, respectively. Antibody-positive cases by ELISA were subjected to Western blotting with the antigens from three borrelias. Finally, 20.0% of the workers were antibody-positive by specific antibodies, anti-OspA antibody. The correlation between ELISA and Western blotting was better when HP3 was used as an antigen. One out of 30 normal control individuals was positive in ELISA with HP3 antigen, but negative in Western blotting. Thirty percent of the workers had a history of tick bites, and these cases had no characteristic symptoms of Lyme borreliosis. However, the rate of tick bites in antibody-positive cases was significantly higher than that in antibody-negative cases. These results suggested that the forestry workers in Saitama are very likely to be infected with Lyme borreliosis transmitted by ticks.

Adolescent↗

Naturally occurring 5-lipoxygenase inhibitors. VI. Structures of ardisiaquinones D, E, and F from Ardisia sieboldii.

New 1,4-benzoquinone derivatives, ardisiaquinones D(2), E(4), and F(5) along with the known ardisiaquinones A(1) and B(3) have been isolated from the leaves of Ardisia sieboldii (Myrsinaceae) and shown to be 5-lipoxygenase inhibitors. Their structures have been elucidated by spectroscopic analysis and chemical degradation. The degree of inhibition of 5-lipoxygenase activity by the ardisiaquinones and some derivatives of ardisiaquinone A is reported.

Animals↗

A unique case of renovascular hypertension caused by combined renal artery disease.

We present a unique case of renovascular hypertension due to combined renal artery disease in a 22-year-old woman. Renal angiography revealed renal artery stenosis with poststenotic dilatation and an aneurysm due to fibromuscular dysplasia in the left kidney, and a congenital arteriovenous fistula in the right kidney. The results of a captopril test and plasma renin sampling demonstrated that the renin-angiotensin-aldosterone system was stimulated in both kidneys, accounting for the hypertension in this patient. Almost all cases of renovascular hypertension are due to only one underlying renal artery disease. This is the first case of renovascular hypertension associated not only with renal artery stenosis and an aneurysm due to fibromuscular dysplasia, but also with a congenital arteriovenous fistula.

Adult↗

Significance of serum neuron-specific enolase as a predictor of relapse of small cell lung cancer.

We conducted a prospective study to evaluate the significance of serum neuron-specific enolase (NSE) as a predictor of relapse of small cell lung cancer (SCLC). Patients entered into the study were drawn from those who had shown a complete or partial response to first-line chemotherapy with a concurrent decline in the NSE level to less than 10 ng/ml. When the serum NSE level increased to more than 15 ng/ml, the patient was restaged on the basis of clinical, radiological, and bronchoscopic examinations. During the period from August 1988 to December 1990, 57 patients with SCLC were enrolled and followed up until May 1992. Of these patients, 45 had clinical relapses, and 14 (31%) of them showed a clear elevation of the serum NSE level prior to the clinical recognition of relapse. Although one false-positive case was noted, this involved only a transient elevation of the NSE level. In patients who showed increased NSE levels, the relapses occurred in more difficult to detect silent sites such as the adrenal gland, liver, and deep lymph nodes. In addition, the percentage of patients demonstrating high NSE levels who were able to benefit from salvage chemotherapy was higher than for those who did not (RHO < 0.05). Our results indicate that serial NSE measurements are useful for the early prediction of SCLC relapse and should help to facilitate early administration of salvage chemotherapy for affected patients.

Adult↗