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Biomedical subjects

N Ueda

Publications and source records attributed to N Ueda.

At least 181 records · Page 10Linked to original sources

Gingival crevicular interleukin-1 and interleukin-1 receptor antagonist levels in periodontally healthy and diseased sites.

Interleukin-1 (IL-1) molecules, IL-1 alpha and IL-1 beta are cytokines involved in the acute-phase response against infection and in the pathogenesis of periodontal destruction. Administration of exogenous IL-1 receptor antagonist (IL-1ra) is effective in reducing the inflammatory reactions mediated by IL-1. However, the relationship between these three naturally occurring IL-1 molecules and periodontal diseases has been poorly characterized. We investigated the correlation of gingival crevicular IL-1 molecules and the clinical status of patients with different severities of periodontitis. IL-1 alpha, IL-1 beta, IL-1ra and the total IL-1/IL-1ra ratio (IL-1 activity index; IL-1AI) were measured in 75 gingival crevicular fluid (GCF) samples from non-inflamed gingiva sites in 2 healthy subjects and diseased sites in 7 patients with several types of periodontitis. IL-1 alpha, IL-1 beta and IL-1ra were measured by specific non-cross-reactive enzyme linked immunosorbent assay. The probing depth, gingival index and alveolar bone loss of each site was recorded at the time of GCF sampling. The total amount of IL-1 alpha, IL-1 beta and the IL-1AI, but not total IL-1ra, were found to be correlated with alveolar bone loss score. Three IL-1 molecules were also measured in the gingival tissue of patients with periodontitis. A similar progressive decrease of the IL-1AI was detected in gingival tissue with periodontitis. These results suggest that the amounts of both crevicular IL-1 and IL-1AI are closely associated with periodontal disease severity.

Acute-Phase Reaction↗

[Serological differences in Helicobacter pylori].

To study antigenic differences in Helicobacter pylori (H. pylori), we performed immunoblot (IB) analysis with monoclonal antibody, MAb102, and measured the serum antibody titer with captured ELISA method with MAb102 antibody. In IB analysis, specific 54 K antigen was detected in 39 strains derived from patients with gastritis, gastric ulcer, duodenal ulcer, and gastric carcinoma. But only one strain (GC32 strain) isolated from a patient with gastric cancer did not react with MAb102 antibody. In the result of antibody titer with captured ELISA method using other six strains of H. pylori as antigen, H. pylori strains were divided into 3 groups, group R (RD26, T7, and T13 strains), group E (England and MR31 strains), group T (T37 strain). However, four cases belonged to false negative in ELISA method. These cases could have been infected with H. pylori strains such as GC32 strain. These strains did not have 54 K antigen nor 54 K related antigen which is different in its antigenicity from the 54 K antigen of the six strains. Thus the GC35 strain and the strain(s), which infected these four cases, consisted of other group, group N. These results suggested that 54 K antigen is usually stable in many strains, but occasionally different in antigenicity in some strains.

Adult↗

Long-term survivors in biliary atresia--findings for a 20-year survival group.

Recently, there has been remarkable increase in the survival rate in cases of biliary atresia (BA). However, long-term survivors are as yet a small population. Of the total of 152 patients undergoing surgery for BA during the period from 1969 to 1995 in our institution, 39 of them were operated on more than 20 years ago with follow up for all but one of these, who can no longer be accounted for. Six are still alive, 1 male, and 5 females, two cases being of type I BA, and the other 4 of type III and 1 is unaccounted for. The prognosis of these individuals was clinically evaluated. At the present time, none of them is receiving hospital care, but 3 have experienced sequelae. Two patients required partial splenic embolization (PSE), endoscopic infusion sclerotherapy (EIS), and/or gastroesophageal decongestion and splenectomy (Hassab's operation) (Hassab 1967) for hypersplenism and/or portal hypertension. The other has needed hospital care for recurrent cholangitis. Laboratory investigations revealed a serum total bilirubin (TB) of less than 1.0 mg/100 ml in 3 of the 5 patients for which samples could be obtained, between 1.0 and 2.0 mg/100 ml in 1, and in excess of this in the remaining case. The 1-alanine 2 oxoglutarate aminotransferase (ALT) level was within the normal range in only 1, and was mildly to moderately elevated in 4. The white blood cell count (WBC) was less than 3,000/microliter and the platelet count was less than 10 x 10(4)/microliter in 1, and within the normal ranges in the other 4 patients. The results thus indicate that occult and progressive liver damage may occur in long-term survivors of BA.

Adolescent↗

[Effects of oxitropium bromide on exercise and lung function in patients with pulmonary emphysema].

Anticholinergic drugs have been reported to be effective in pulmonary emphysema. We studied the effects of the anticholinergic drug oxitropium bromide on exercise capacity and lung function in patients with this disease. We studied 11 men and 1 women, aged 69.3 +/- 4.5 yrs, in whom chest radiography showed pulmonary emphysema. Before and after the subjects inhaled two puffs of oxitropium bromide, they walked in a corridor for 12 minutes, and the distance they walked and spirometric data were recorded. FVC and FEV1 were significantly higher after inhalation of the drug. FEV1% did not change, and the distance walked increased slightly. We also studied symptoms and peak expiratory flow rate in 37 patients with pulmonary emphysema before and after the start of therapy with inhaled oxitropium bromide. Symptom scores of wheezing and sleep improved, and peak expiratory flows increased significantly. We conclude that inhaled oxitropium bromide can improve lung function and slightly increase exercise capacity in patients with pulmonary emphysema. These effects may be caused by bronchodilation-induced increases in FEV1 and FVC. Monitoring of peak expiratory flow in patients with pulmonary emphysema may be useful for evaluating the clinical effectiveness of oxitropium bromide.

Aged↗

Recent advances in understanding mechanisms of renal tubular injury.

Study of cell death has emerged as an important and exciting area of research in cell biology. In this review, we first discuss two kinds of cell death, apoptosis and necrosis, then describe the evidence suggesting a role of endonuclease activation in renal tubular injury. The pathway that is followed by the cell is dependent on both the nature and the severity of the insults and may evolve from the apoptotic to the necrotic form of cell death. It is also conceivable that there are some common pathways that are shared and regulated in the two modes of cell death. Along these lines, interleukin 1 beta-converting enzyme (ICE) and ICE-like proteases, generally associated with the apoptotic mode of cell death, recently have been shown to be important in hypoxic injury. We describe the studies documenting an important role of endonuclease in renal tubular injury and some of the important mechanisms by which it may be regulated. A large body of evidence supports a role of protooncogenes in the regulation and modification of apoptotic cell death. Many of these protooncogenes and related proteins have been shown to be altered in models of acute renal failure, suggesting their potential importance. Therapeutic opportunities may lie in prevention of cell injury or enhancing recovery by inhibiting endonucleases and ICE and ICE-like proteases as well as by induction of certain oncogenes and related proteins.

Apoptosis↗

[Immunohistochemical study of myofibroblast and S-100 protein positive cells in interstitial pneumonia associated with collagen vascular disease].

Immunohistochemical study was carried out in patients with collagen vascular disease associated with interstitial pneumonia. The subjects were 16 patients, consisting of seven rheumatoid arthritis (RA), five dermatomyositis (DM) and four progressive systemic sclerosis (PSS), in whom the pathological findings were consistent with usual interstitial pneumonia. Immunohistochemical examinations were performed by the ABC method using antibodies to vimentin (vim), alpha-smooth muscle actin (alpha-SMA), and S-100 protein. In fibrosis associated with RA, proliferation of alpha-SMA-positive myofibroblasts was widely observed in all subjects. Myofibroblasts were present also in patients with DM and PSS, but not as notable as in those with RA. Proliferation of vim-positive fibroblasts was observed in patients with idiopathic pulmonary fibrosis (IPF). Diverse S-100 protein positive cells appeared in patients with acute exacerbations of RA, especially when associated with bronchiolitis obliterans organizing pneumonia (BOOP) pattern. S-100 protein positive cells were observed occasionally also in patients with DM and PSS, but they markedly decreased in number, compared to those with RA. They were generally hard to detect in lungs of patients with IPF. These findings suggest that interstitial pneumonia associated with collagen vascular disease can be fairly clearly differentiated from IPF each other, based on the degree of proliferation of myofibroblasts and on the presence of S-100 protein positive cells in number.

Adult↗

Qualitative platelet 12-lipoxygenase abnormality in a patient with essential thrombocythemia.

Quantitative platelet 12-lipoxygenase (12-LOX) deficiency has been reported in some patients with myeloproliferative disorders (MPD). We report here for the first time a novel qualitative abnormality of the 12-LOX enzyme of platelets from a patient with essential thrombocythemia. The anti-12-LOX immunoprecipitates from the patient's platelet homogenates showed a deficiency of 12-LOX activity, but contained normal amount of 12-LOX protein. There was no difference in subcellular localization of the enzyme between the patient's platelets and normal ones. This 12-LOX protein lacking its enzyme activity showed slightly larger electrophoretic mobility than normal one, suggesting a molecular abnormality of the enzyme. However, we could not detect any genetic mutation causing such abnormalities in all exons of 12-LOX gene by sequencing the patient's PCR-amplified DNA. Thus, our results indicate that the deficient activity of this abnormal 12-LOX protein is probably due to a posttranslational modification, and the possibility that platelets of some MPD patients have qualitative abnormality of the 12-LOX enzyme besides quantitative ones.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

[Thermoradiotherapy combined with daily administration of low dose cisplatin for locally advanced laryngeal carcinoma].

We applied thermoradiotherapy combined with daily administration of low dose cisplatin (CDDP) to five patients with locally advanced laryngeal carcinoma. The total response rate (CR + PR) was 100% after irradiation of 30 or 40 Gy. One case showed CR, and the larynx could be preserved by adding a full dose of irradiation. CDDP administration was discontinued in two cases due to renal dysfunction or thrombopenia, but other cases tolerated the therapy without severe side effects. Total laryngectomy and bilateral neck dissection was carried out in four cases after irradiation of 30 or 40 Gy. Removed larynxes were prepared for light microscopic observations of the serial sections. One of the four specimens revealed a CR histologically. The combination of thermoradiotherapy with low dose CDDP showed a remarkable effect on reduction of tumor size and cytotoxicity of tumor cells. This might contribute to saving the larynx of patients with locally advanced laryngeal carcinoma.

Aged↗

Effect of vitamin E on expression of cyclooxygenase-2 in lipopolysaccharide-stimulated rat macrophages.

To clarify the role of vitamin E (alpha-tocopherol) for the induction of cyclooxygenase-2 (COX-2) in rat macrophages stimulated by lipopolysaccharide (LPS), vitamin E-enriched macrophages were prepared by intraperitoneal injection of vitamin E for 6 days at a rate of 5 mg per day. The production of PGE2 was increased in dose- and time-dependent manners by addition of LPS in both control and vitamin E-enriched peritoneal macrophages. The maximum effect of LPS was observed in 12 h at concentration of 5 micrograms/ml. By analyzing COX-2 mRNA level by Northern blot and COX-2 enzyme mass and phosphotyrosine by Western blot, it was revealed that the increase of PGE2 production reflected the induction of COX-2 expression through activation of tyrosine kinase. Vitamin E failed to inhibit PGE2 production in LPS-stimulated macrophages; however, genistein, a tyrosine kinase inhibitor, completely inhibited the production at 100 microM. These results suggest that vitamin E does not inhibit COX-2 expression via LPS-mediated tyrosine kinase signal transduction pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Incidence of p53 and Ha-ras gene mutations in chemically induced rat mammary carcinomas.

To determine whether p53 alterations, which are frequent in human breast cancers, are also common in rat mammary tumors, we examined 40 tumors from 24 rats treated with 7,12-dimethylbenz[a]anthracene (DMBA) and 34 tumors from 14 rats treated with N-nitroso-N-methylurea (NMU) (an N-nitroso compound). DMBA and NMU are known genotoxic mutagens. The entire coding regions of the p53 and Ha-ras genes were examined for mutations by polymerase chain reaction single-strand conformational polymorphism analysis and by direct sequencing. One of the 40 DMBA-induced mammary tumors had a p53 mutation, a single-base substitution (AGC-->GGC) at codon 307, resulting in an amino-acid change from Ser to Gly. No mutations were found in NMU-induced tumors. The incidence of Ha-ras gene mutation was 79% (27 of 34) at codon 12 in the NMU group and 23% (nine of 40) at codon 61 in the DMBA group. Thus, p53 mutation, in contrast to Ha-ras mutation, did not seem to be a prerequisite for carcinogenesis in chemically induced rat mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Immunohistochemical detection of truncated APC protein in sporadic human colorectal adenomas and adenocarcinomas.

Mutations of the APC gene frequently occur in sporadic forms of colorectal adenomas and adenocarcinomas. Phenotypically, the vast majority of these mutations result in the truncation of the APC protein. To demonstrate the defective APC gene product in human colorectal tumors, rabbit region-specific antisera raised against the APC protein of amino acid sequences between 371 and 390 (SPI) and between 1821 and 1840 (SP3) were used to exhibit the truncated APC protein. In all, 86 lesions from 67 cases of sporadic adenoma and adenocarcinoma were examined; abnormal staining patterns were distinguished in 43 lesions (50%); the incidence of abnormalities was not significantly different between adenomas and carcinomas. The majority, 75% exhibited epitopic change with the SPI-positive and SP3-negative phenotype (type P1), and 25% exhibited neither of these phenotypes (type P2). The staining pattern in all lesions was uniform, and studies of carcinomas arising in adenomas showed the same pattern of staining. These findings supported the view that the APC lesion is a very early event in colorectal carcinogenesis. Furthermore, this simple immunohistochemical approach demonstrated that different adenomas from the same patient showed different staining patterns.

Adenocarcinoma↗

Altered carbohydrate composition in colorectal adenomas and carcinomas: histochemical characterization of N-acetylgalactosamine, L-fucose, and o-acetylated sialic acid.

Changes of surface sugar residues in the large intestinal mucosa may be associated with malignant transformation and may be of importance in differentiating borderline lesions. To compare these changes in normal mucosa, adenomas, and carcinomas of the large intestine, we investigated modifications of carbohydrate composition, such as those of N-acetyl-galactosamine (GalNac), L-fucose, and o-acetylated sialic acid, by histochemical staining with Dolichos biflorus agglutinin (DBA) and Ulex europaeus agglutinin-1 (UEA-1) lectins, and with Culling's periodic acid-thionin Schiff/potassium hydroxide/periodic acid-Schiff (PAT/KOH/PAS), respectively. For stable staining, the sections stained with DBA and UEA-1 were pretreated with potassium hydroxide and neuraminidase. We conclude that the pattern of the two lectin stainings in carcinomas is quite different from that in normal mucosa and adenomas, and that it shows the carcinomatous features in some cases of adenoma with severe atypia (borderline lesions). In contrast, PAT/KOH/PAS staining demonstrates differences between normal mucosa and adenomas rather than differences between adenomas and carcinomas.

Acetylgalactosamine↗

Decreased cerebrospinal fluid levels of substance P in Machado-Joseph disease.

To clarify the mechanism of brain impairment in Machado-Joseph disease (MJD), we measured the cerebrospinal fluid (CSF) levels of substance P in 7 patients (mean age 45.7 +/- 12.09 years) with this disease. Four patients had type I and three had type II disease. Findings were compared with those obtained in 14 age-matched controls, 8 patients with Parkinson's disease, 7 patients with multiple system atrophy, and 6 patients with myopathy. The CSF level of substance P was significantly (p = 0.0000) lower in the patients with MJD, being 44.5% of the control value. However, the mean CSF levels of substance P in the patients with Parkinson's disease, multiple system atrophy, or myopathy did not differ significantly from that in the control subjects. The alteration in the CSF level of substance P may be related to the neurological impairment observed in MJD.

Adult↗

Subcellular distribution of protein kinase C in the living outer hair cell of the guinea pig cochlea.

Immunohistochemical staining using isoform-specific antibodies and intracellular localization using fluorescent probes for protein kinase C (PKC) were evaluated in the cochlear outer hair cell (OHC). Among three isoforms of classic PKC, PKC alpha was selectively stained in the fixed OHC as well as inner hair cells under a surface preparation method. Two types of fluorescent probes to detect subcellular localization of PKC were observed with a confocal laser scanning microscopy in the present study, fim-1 diacetate which binds to the ATP-competitive catalytic domain of PKC and Bodipy FL C12-phorbol acetate which binds to specific site localized to the first cysteine-rich loop of the C1 region in the regulatory domain. High fluorescence intensity of both dyes was observed in subcuticular and subsynaptic regions, infracuticular network, and along the lateral wall. The displacement experiments to evaluate binding specificity were performed by incubating Bodipy FL C12-phorbol acetate in the presence of 10 microM phorbol 12-myritate 13-acetate (PMA) and the fluorescence was totally disappeared. For the acute treatment of phorbol ester, cells were preincubated with 1 microM PMA 30 min before loading with fim-1 diacetate. The brightest area in the plasma membrane became much larger as compared with untreated cells, which suggests a dramatic translocation of PKC to the plasma membrane. The biological functions involving PKC in the OHC are discussed.

Adenosine Triphosphate↗

Enzymes for anandamide biosynthesis and metabolism.

Anandamide is an endogenous ligand for cannabinoid receptors. We tried to isolate and purify "anandamide amidohydrolase' which hydrolyzes anandamide to arachidonic acid and ethanolamine. The enzyme activity was found in the microsomal fraction of porcine brain homogenate. The enzyme was solubilized in 1% Triton X-100, and partially purified by hydrophobic chromatography to a specific activity of about 0.3 mumol/min per mg protein (37 degrees C). Apparent K(m) for anandamide was about 60 microM. The enzyme reacted also with ethanolamides of linoleic, oleic, and palmitic acids at lower rates. This enzyme preparation also converted arachidonic acid to anandamide in the presence of 250 mM concentration of ethanolamine. Several lines of evidence including experiments using various inhibitors suggested that the anandamide synthase and amidohydrolase activities were derived from a single enzyme protein.

Animals↗