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Biomedical subjects

K Yokota

Publications and source records attributed to K Yokota.

At least 109 records · Page 6Linked to original sources

Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in bladder cancer.

BACKGROUND: Matrix metalloproteinase-2 (MMP-2), which degrades the extracellular matrix or the basement membrane, has an essential role in tumor invasion and metastasis. To evaluate the roles of MMP-2, its inhibitor (tissue inhibitor of metalloproteinase-2 [TIMP-2]), and its activator (membrane-type matrix metalloproteinase-1 [MT1-MMP]) in tumor invasion or as a prognostic factor in patients with bladder carcinoma, the authors investigated the expression of MMP-2, TIMP-2, and MT1-MMP in patients with bladder carcinoma. METHODS: Tissues obtained from 41 patients with bladder carcinoma were used for analysis. Expression of MMP-2, TIMP-2, MT1-MMP, and glyceraldehyde-3-phosphate dehydrogenase was examined by reverse transcriptase-polymerase chain reaction analysis. Correlations between the levels of MMP-2, TIMP-2, and MT1-MMP expression and histologic findings or patient outcome were evaluated. RESULTS: Expression of MMP-2 and TIMP-2 was significantly higher in muscle invasive pT2< or = bladder tumors than in pT1a tumors (MMP-2: P < 0.0005; TIMP-2: P < 0.005). Moreover, high levels of MMP-2 and TIMP-2, as well as MT1-MMP expression, all were strongly associated with decreased survival (MMP-2: P < 0.0001; TIMP-2: P < 0.0001; and MT1-MMP: P < 0.005). Even within the radically cystectomized muscle invasive pT2< or = tumor group, patients with a high expression of any of these three genes had a worse prognosis than those with low expression (MMP-2: P < 0.05; TIMP-2: P < 0.05; and MT1-MMP: P = 0.0641). CONCLUSIONS: MMP-2 and TIMP-2 are believed to contribute to the invasive properties of bladder carcinoma. The authors report that expression of MMP-2, TIMP-2, and MT1-MMP are useful prognostic indicators in patients with bladder carcinoma and may be helpful in designing treatment protocols.

Aged↗

Classification of Clostridium butyricum based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and pulsed-field gel electrophoresis.

Eleven strains of Clostridium butyricum collected from different sources were analysed by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and pulsed-field gel electrophoresis (PFGE). The strains could be classified into four groups based on their banding profiles of the proteins extracted from the cells on SDS-PAGE. Group I consisted of seven strains, and these strains were further divided into five subgroups by PFGE. The strains belonging to groups II, III, and IV on SDS-PAGE were also classified into the same II to IV groups by PFGE. These data indicate that grouping of the strains of C. butyricum can be performed by employing both SDS-PAGE and PFGE.

Journal Article↗

The significance of specific IgG4 antibodies to methyltetrahydrophthalic anhydride in occupationally exposed subjects.

BACKGROUND: A definitive role for allergen-specific IgG4 as either an anaphylactic or a blocking antibody, or both, remains controversial. OBJECTIVE: A population of 148 workers from two condenser plants (A and B) using epoxy resin with methyltetrahydrophthalic anhydride (MTHPA) was studied to evaluate the significance of MTHPA-specific IgG4 antibody. METHODS: The workers were evaluated through questionnaire and serological investigations. RESULTS: Ninety-seven (66%) of the currently exposed workers had positive MTHPA-specific IgE. IgE-sensitized workers in each plant had significantly more eye and nose complaints than unsensitized workers (P < 0.03). As the result of multiple logistic analysis, specific IgE antibodies was the most important predictor of work-related symptoms and its effect was greater than that of specific IgG4 (odds ratio 16.7 and 3.68, respectively). These indicate an IgE-mediated mechanism in most cases of work-related symptoms associated with MTHPA exposure. However, it cannot be denied that specific IgG4 is an anaphylactic antibody. Furthermore, IgE-sensitized workers in these plants displayed work-related symptoms despite the presence of specific IgG4. The frequency of positive specific IgG4 in continuously exposed workers was significantly (P < 0.02) higher in plant A than in plant B, reflecting the difference of the MTHPA levels between the two plants. In plant A, the frequency of positive specific IgG4 was significantly (P < 0.002) higher in continuously exposed workers than in intermittently exposed workers. Multiple regression analysis also confirmed that plant and exposure style contributed significantly (P < 0.01) to the determination of specific IgG4 levels. CONCLUSION: These results suggest that work-related eye and nasal symptoms are likely to be IgE-mediated, and that specific IgG4 may reflect the intensity of MTHPA exposure and may not act as a blocking antibody.

Adult↗

Semi-quantitative analysis of telomerase activity in exfoliated human urothelial cells and bladder transitional cell carcinoma.

OBJECTIVE: To determine the utility of detecting telomerase activity in transitional cell bladder cancer, using the telomeric repeat amplification protocol (TRAP) assay, and thus provide a test for the detection and monitoring of bladder cancer, especially low-grade tumours. PATIENTS, SUBJECTS AND METHODS: Telomerase activity was assayed in bladder cancer tissues and the exfoliated urothelial cells from 29 patients with bladder cancer, 10 with benign disease, and in 10 healthy subjects using the TRAP assay. The levels were assessed semiquantitatively by calculating the ratio to an internal telomerase assay standard. RESULTS: Telomerase activity was very low in the exfoliated urothelial cells from all healthy subjects and patients with benign disease, with a mean (SD) ratio of 0.25 (0.03) and 0.33 (0.04), respectively. A threshold ratio of 0.4 was calculated as the mean +/- 2 SD of the telomerase activity level of the exfoliated urothelial cells from patients with benign disease. Using this threshold, telomerase activity was negative in exfoliated urothelial cells from all benign cases (100% specificity) and positive in all 26 bladder cancer tissue samples assayed. In tumour tissue, telomerase activity was not associated with tumour grade, size or stage. Telomerase activity in exfoliated urothelial cells from patients with bladder cancer was positive in 25 of 29 samples (86% sensitivity). The sensitivity of telomerase activity in exfoliated cells was seven of nine in G1, 10 of 12 in G2 and all eight G3 tumours; the corresponding sensitivity for voided urine cytology in G1, G2 and G3 tumours was two of nine, six of 12 and six of eight, respectively. CONCLUSION: These results indicate that telomerase activation occurs as an early step in carcinogenesis and the semi-quantitative analysis of telomerase activity in exfoliated urothelial cells could be a minimally invasive and useful method for detecting bladder cancer, even in low-grade tumours.

Aged↗

The association between serum levels of Th cytokines and rhinoconjunctivitis caused by methyltetrahydrophthalic anhydride.

BACKGROUND: There are few epidemiologic studies on the association between serum levels of T helper (Th) cytokines and allergic symptoms caused by sensitizing agents. METHODS: A population of 147 workers from two condenser plants using epoxy resin with methyltetrahydrophthalic anhydride (MTHPA) underwent a questionnaire survey and serologic investigations. Total and MTHPA-specific IgE levels were measured by the Pharmacia CAP System, and serum levels of interleukin (IL)-4, IL-13, and interferon-gamma (IFN-gamma) by enzyme immunoassay. RESULTS: A significant association was found between work-related eye and nasal symptoms and a range of atopic characteristics, including the frequency of positive specific IgE, specific and total IgE levels, and IL-4 levels. A positive correlation was observed between levels of IL-4 and IL-13 (r=0.42). Furthermore, multiple logistic analysis revealed significant contributions of specific IgE and IL-13 to the work-related symptoms. A similar but nonsignificant association was also found for IL-4 (P=0.07). On the other hand, a multiple regression model with specific IgE levels as a dependent variable showed a significant association with total IgE, but not with IL-4, IL-13, and IFN-gamma. CONCLUSIONS: These results suggest that work-related eye and nasal symptoms are closely related to specific IgE antibodies, and that allergic responses, mediated by IgE, to MTHPA may lead to a shift in the balance between Th1 and Th2 cells.

Adult↗

Effect of rebamipide, a novel antiulcer agent, on Helicobacter pylori adhesion to gastric epithelial cells.

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to human gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in the prevention of H. pylori infection. Experiments were performed to evaluate the effect of rebamipide, a novel antiulcer agent, on H. pylori adhesion to gastric epithelial cells. MKN-28 and MKN-45 cells, derived from human gastric carcinomas, were used as target cells. Ten H. pylori strains isolated from patients with chronic gastritis and gastric ulcer were used in the study. We evaluated the effect of rebamipide on H. pylori adhesion to MKN-28 and MKN-45 cells quantitatively using our previously established enzyme-linked immunosorbent assay. The adhesion of H. pylori to MKN-28 and MKN-45 cells was significantly inhibited by pretreatment of these cells with 100 microg of rebamipide per ml. However, the adhesion was not affected by the pretreatment of H. pylori with rebamipide. On the other hand, the viabilities of H. pylori, MKN-28 cells, and MKN-45 cells were not affected by rebamipide. Our studies suggest that rebamipide inhibits the adhesion of H. pylori to gastric epithelial cells.

Alanine↗

Analysis of immunoglobulin A antibodies to Helicobacter pylori in serum and gastric juice in relation to mucosal inflammation.

Helicobacter pylori is a major etiologic agent in gastroduodenal disorders. In this study, immunoglobulin A (IgA) antibodies to H. pylori antigens were evaluated in serum and gastric juice specimens obtained from patients with gastritis or peptic ulcers by utilizing antibody capture enzyme-linked immunosorbent assays (ACELISAs). Urease alpha subunit (UA), urease beta subunit (UB), the 66-kDa heat shock protein (HSP), and the 25-kDa protein (25K) were used as antigens for the ACELISAs. The antibody titers of the ACELISAs reflect the ratio of H. pylori-specific IgA to total IgA. The ratio is stable, although the antibody concentration fluctuates in gastric juice. By using ACELISAs it was possible to evaluate quantitatively not only serum IgA antibodies but also gastric juice secretory IgA (S-IgA) antibodies. In both serum IgA and gastric juice S-IgA ACELISAs, the titers of antibody to HSP and 25K were remarkably correlated with the histologic grade of gastritis, whereas those to UA and UB were not strongly correlated with histologic grade. Thus, it is useful for estimating the histologic grade of gastritis to quantify serum IgA and gastric juice S-IgA antibodies to HSP and 25K.

Adolescent↗

Detection of Helicobacter pylori associated antigen and heat shock protein 60 on follicular dendritic cells in the germinal centres of low grade B cell lymphoma of gastric mucosa associated lymphoid tissue (MALT).

AIMS: To investigate the localisation of Helicobacter pylori antigens and the expression of human heat shock proteins (HSP) in stomachs affected by MALT lymphoma. METHODS: Surgically resected stomachs from 24 patients with MALT lymphoma were immunostained with anti-H pylori rabbit antibodies (ORP-1 and ORP-2) and anti-human HSP60 mouse monoclonal antibodies (mAb) (LK-1 and LK-2). RESULTS: Follicular dendritic cells of germinal centres in the stomachs affected by MALT lymphoma were immunostained with anti-H pylori polyclonal antibodies and with anti-human HSP60 mAb, as were the epithelial cells. None of the lymph node samples reacted. CONCLUSIONS: Human HSP60, which cross reacts with anti-H pylori polyclonal antibodies, is often expressed on follicular dendritic cells in gastric MALT lymphoma tissues and may be aetiologically relevant to lymphomagenesis of MALT lymphoma.

Antigens, Bacterial↗

Further study on the two pivotal parts of Hlg2 for the full hemolytic activity of staphylococcal gamma-hemolysin.

Staphylococcal gamma-hemolysin consists of LukF of 34 kDa and Hlg2 (or H gamma II) of 32 kDa, which cooperatively lyse human and rabbit erythrocytes. Our previous data showed that the 5-residue segment K23R24L25A26I27 of Hlg2 is pivotal for the hemolytic activity [Nariya, H. and Kamio, Y., Biosci. Biotechnol. Biochem., 59, 1603-1604 (1997)]. Here, we identify an additional amino acid residue in Hlg2 necessary for the full gamma-hemolysin activity by measuring the toxin activity of Hlg2 mutants in the presence of LukF. The data obtained showed that Arg217 of Hlg2 is an additional pivotal amino acid residue besides the KRLAI segment for the full Hlg2-specific function in gamma-hemolysin. We also report evidence that the Hlg2 mutants showing a low or null hemolytic activity in the presence of LukF towards human erythrocytes had low or no binding activity to the cells, resulting in failure of formation of the ring-shaped pore-forming complex on the erythrocytes.

Animals↗

Antibody and cytokine responses in Helicobacter pylori-infected various mouse strains.

Helicobacter pylori (H. pylori) infection in the stomach is etiologically closely associated with chronic active gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. In this study, we examined the antibody responses and cytokine profiles of three strains of mice (BALB/c, C3H/He, and C57BL/6) infected with H. pylori. Following this, correlations between host-immune reactions and intensity of inflammation were analyzed. H. pylori (ATCC43504) was intragastrically administered once a week to the mice from 4 weeks of age, and they were sacrificed at the ages of 4 and 7 months. In these mice, we examined the histology of the stomach, antibody titers against H. pylori, and serum levels of cytokines (IL-4, IL-10, TNF-alpha, IL-2 and Interferon-gamma). In BALB/c mice, inflammation of the stomach was minimal. Inflammation was observed in 63.6% of C57BL/6 mice and 33.3% of C3h/He mice. In C57BL/6 and C3H/He mice, all the cytokines tended to increase. In contrast, BALB/c mice were inactive in cytokine production except for IL-2. Two C3H/He mice developed severe inflammation with lymph follicles; one showed a response largely typical of Th-1, and the other showed a response largely typical of Th-2. Although a definite correlation was not shown between Th-1/Th-2 response evaluated by cytokine production and intensity of inflammation, it appears that in H. pylori-induced inflammation both cell-mediated (Th-1) and humoral (Th-2) immunity play a role in pathogenesis.

Animals↗

[Quantitative analysis of telomerase activity in exfoliated urothelial cells for the diagnosis of bladder carcinoma].

Voided urine cytology is the most common non-invasive examination for the detection and monitoring of bladder cancer. However, the result is not satisfactory, especially for low grade tumors. Activity of telomerase can be detected in most tissues of bladder carcinoma using the telomeric repeat amplification protocol (TRAP) assay. We analyzed the quantitative telomerase activity in exfoliated urothelial cells, and evaluated the values for early diagnosis of bladder carcinoma. We performed a quantitative analysis using a hybridization protection assay (HPA) based on TRAP assay. Telomerase activity was significantly higher level in exfoliated urothelial cells from patients with bladder cancer than all of healthy cases and patients with benign disease (p < 0.0001). The cut off value was calculated as mean + 2SD of the telomerase activity level of the exfoliated urothelial cells from healthy cases. Using this cut off value, telomerase activity was positive in 26 of 41 in exfoliated urothelial cells from bladder cancer patients(63.4% sensitivity), and negative in 63 of 69 in exfoliated urothelial cells from healthy cases and patients with benign disease (91.3% specificity). The sensitivity of telomerase activity in exfoliated cells was higher than urinary cytology, especially in low grade tumors. Our results indicate that quantitative analysis of telomerase activity in exfoliated urothelial cells could become minimum invasive and useful method for detection of bladder carcinoma.

Humans↗

[Cough variant asthma among patients with chronic persistent cough and its clinical outcome].

Thirty-nine patients with chronic persistent cough continuing more than eight weeks were examined regarding to their airway responsiveness to methacholine challenge using the Astograph (TCK-6100H, Chest Corp. Japan). Of these, twenty-three individuals (59%) had airway hyperresponsiveness, leading to diagnose as having cough variant asthma (CVA). Patients with CVA had a higher percentage of eosinophils in peripheral blood and a lower forced expiratory volume in one second than those in non-CVA group. Furthermore, four patients (17%) developed the classic signs and symptoms of asthma, whereas 7 cases (30%) resolved their cough without further treatment and 12 cases (52%) continued to have CVA. These data suggested that a significant proportion of patients with chronic persistent cough had CVA and some of them may develop to classic wheezing asthma.

Asthma↗

Modification of Helicobacter pylori adhesion to human gastric epithelial cells by antiadhesion agents.

Helicobacter pylori is a major etiological agent in gastroduodenal disorders. H. pylori adhesion to human gastric mucosa is the initial step of H. pylori colonization. Inhibition of H. pylori adhesion is thus a therapeutic target in preventing H. pylori infection. We have previously established a method using the enzyme-linked immunosorbent assay to analyze quantitatively H. pylori adhesion to gastric epithelial cells. This method is suitable for screening antiadhesion agents. Some mucoprotective agents are proved to have antiadhesion effects in vitro, and they may modify H. pylori adhesion. This evidence gives us a useful clue to analyze the molecular mechanism of H. pylori adhesion to mucosa. Furthermore, in clinical trials, these mucoprotective agents enhanced the eradication rate when administered with antibiotics. In conclusion, the antiadhesion agents may have potential as therapeutic regimens against H. pylori infection.

Bacterial Adhesion↗

Effect of ecabet sodium on Helicobacter pylori adhesion to gastric epithelial cells.

Helicobacter pylori is a major etiological agent in gastroduodenal disorders, with the adhesion of H. pylori to gastric epithelial cells being the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in preventing H. pylori infection. We evaluated the effect of ecabet sodium, an antiulcer agent, on H. pylori adhesion to gastric epithelial cells, using our previously established enzyme-linked immunosorbent assay. The adhesion of H. pylori was significantly inhibited by ecabet sodium in a dose-dependent manner. Our studies suggest that ecabet sodium inhibits the adhesion of H. pylori to gastric epithelial cells.

Abietanes↗