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Ken Takeuchi

Publications and source records attributed to Ken Takeuchi.

33 records · Page 2Linked to original sources
PubMed2004

Genetic aspects of intestinal permeability in inflammatory bowel disease.

There is a long-standing belief that disruption of the intestinal barrier function may lead to systemic and local intestinal disease. The role of increased intestinal permeability in Crohn's disease is reviewed here. What is not in doubt is that intestinal permeability in patients with Crohn's disease is increased proportional to disease activity; it can be used to predict clinical relapse of disease and prognosis; and a small proportion of first-degree relatives have increased intestinal permeability. This last finding has been subject to much speculation. In particular it has been suggested that it represents a genetically determined abnormality. If so it might play an important pathogenic process in the disease. However this permeability change in relatives does not conform to a classical inheritance pattern and in some studies it is found in the patients' spouses. This suggests an environmental cause for the changes. However proponents of an environmental factor have been singularly inactive in attempting to identify this agent(s). In view of recent research it seems likely that the increased intestinal permeability in relatives of Crohn's patients may be secondary to sub-clinical intestinal inflammation. This inflammation conforms to an inherited additive trait. The genetic basis for this inflammation is being studied.

Crohn Disease↗
PubMed2003

Clinical and serological associations of autoantibodies to GW bodies and a novel cytoplasmic autoantigen GW182.

A novel autoantigen named GW182 was recently identified when the serum from a patient with a sensory ataxic polyneuropathy was used to immunoscreen a HeLa cDNA library. Unique features of the GW182 protein include 39 repeats of glycine (G) and tryptophan (W) residues, binding to a subset of messenger RNA and localization to unique structures within the cytoplasm that were designated GW bodies (GWBs). The goal of the present study was to identify the clinical features of patients with anti-GW182 antibodies and to characterize the B cell anti-GW182 response by defining the epitopes bound by human autoantibodies. The most common clinical diagnosis of patients with anti-GW182 antibodies was Sjögren's syndrome followed by mixed motor/sensory neuropathy, and systemic lupus erythematosus. Of interest, 5 (28%), 9 (50%), and 3 (17%) of the 18 sera that react with GWBs had autoantibodies to the GW182 and the 52 kDa and 60 kDa SS-A/Ro autoantigens, respectively. Epitopes bound by the human autoantibodies were mapped to the GW-rich middle part of the protein, the non-GW rich region, and the C-terminus of GW182 protein. None of the GW182 epitopes had significant sequence similarities to other known proteins. GW182 represents a new category of ribonucleoprotein autoantigens.

Adult↗
PubMed2003

Autocrine motility factor-receptor gene expression in lung cancer.

OBJECTIVE: Autocrine motility factor (AMF) stimulates cell motility via binding its receptor (AMF-R) and AMF-R is engaged in tumor cell motility and the AMF-R gene expression level may define a more aggressive phenotype. In this study, we investigated the expression of AMF-R in lung cancer cells and revealed its roles in the cell motility of a tumor. We detected AMF-R expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) analyses and phagokinetic assay, we studied the correlation between the level of AMF-R gene expression and cell motility. We quantified the expression of AMF-R in 51 patients with NSCLCs to investigate the relationship between AMF-R expression and clinicopathologic factors and prognosis. RESULTS: We found that lung cancer cell lines with higher AMF-R gene expression tended to have larger cell motility than those with lower AMF-R gene expression. The AMF-R gene expression was significantly associated with lymph node metastasis, and stage. The overall survival rate for patients with a high level of AMF-R gene expression with tumors was significantly worse than for those individuals whose tumors had low AMF-R expression. Furthermore, AMF-R expression was significantly related to survival by multivariate analysis. CONCLUSION: These data indicate that AMF-R may contribute to tumor progression and AMF-R gene expression can serve as a useful prognostic marker in NSCLCs.

Aged↗
PubMed2003

Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes.

Apheresis has been recognized both economically and therapeutically as a novel approach for the treatment of inflammatory diseases, and certain others, which respond poorly to drug therapy. This report is about Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device with a volume of 335 mL, filled with about 220 g of cellulose acetate beads of 2 mm diameter as the column adsorptive carriers. Pre- and post-column leukocyte counts have shown that the carriers adsorb about 65% of granulocytes, 55% of monocytes and 2% of lymphocytes from the blood in the column. Additionally, after apheresis, there is a marked decrease in inflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) produced by blood leukocytes, together with down-modulation of L-selectin and the chemokine receptor CXCR3. Adacolumn has been used to treat patients with rheumatoid arthritis, ulcerative colitis and HIV infection. Typical apheresis sessions have been 4-10, at a frequency of one or two sessions per week. Treatment of patients with Adacolumn has been associated with very promising efficacy and safety data. Accordingly, in Japan, Adacolumn has been approved by the Ministry of Health for the treatment of ulcerative colitia. Furthermore, Adacolumn met the required quality and safety standards for medical devices and received an EC certification (CE-mark) from TUV in 1999. However, although Adacolumn carriers are very efficient in depleting excess and activated granulocytes and monocytes/macrophages, the clinical efficacy associated with Adacolumn apheresis cannot be fully explained on the basis of reducing granulocytes and monocytes per se. Hence, a long lasting effect on inflammatory cytokine generation, chemokine activities or immunomodulation is likely, but the precise mechanisms involved are not fully understood yet.

Absorption↗
PubMed2003

Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective, uncontrolled, pilot study.

BACKGROUND AND AIMS: Active ulcerative colitis (UC) is characterized by infiltration of activated granulocytes and monocytes/macrophages (GM) within the large bowel mucosa. GM are major sources of inflammatory cytokines, and in UC they are elevated with increased survival time. We investigated the possibility that reducing the level of these cells might promote remission of active UC. METHODS: Thirty-one patients with active corticosteroid refractory (refractory) UC, mean age of 42 years, duration of UC 6 years, clinical activity index (CAI) of 15, disease activity index (DAI) of 10, and 8 corticosteroid naive patients (naive), mean age of 36 years, duration of UC 2 years, CAI of 11, DAI of 8 were recruited. Each patient was treated with up to 11 cycles of granulocyte and monocyte adsorptive apheresis over 11 weeks by using a 335-mL capacity column filled with cellulose acetate beads that adsorb GM. RESULTS: At week 12, 81% of refractory (CAI, 3; P < 0.001 and DAI, 4; P < 0.001) and 88% of naive (CAI, 1; P = 0.012 and DAI, 3; P = 0.011) patients achieved remission. Early relapse was not a feature, and at 12 months, 26 of 33 patients had maintained their remission. The treatment was well tolerated, and no severe side effects were observed. CONCLUSIONS: The outcome of this study suggests that reduction of circulating granulocytes and monocytes results in alleviation of inflammation and promotes clinical remission in patients with severe active UC that has not responded to intensive corticosteroid treatment. These data suggest that formal controlled studies are warranted.

Adult↗
PubMed2003

[The comparison in double immunodiffusion and western blotting methods of anti-SS-A/B antibodies in patients with Sjögren's syndrome].

OBJECTIVE: To investigate the autoimmune responses against SS-A/B antigens by double immunodiffusion (DID) and western blotting (WB) in primary and secondary Sjögren's syndrome (SS). PATIENTS: Forty-nine patients with primary SS (PSS), 28 patients with secondary SS (SSS) and control group that couldn't be diagnosed as SS were included in this study. RESULTS: In DID analysis, Anti-SS-A antibody was detected in 69% of PSS and 86% of SSS, and anti-SS-B antibody was found in 22% of PSS and 39% of SSS. No significant difference could be demonstrated between PSS and SSS concerning anti-SS-A/B antibodies. Conversely, WB studies disclosed evidences that 18% of PSS and no SSS reacted only with the 52 kD protein, and there was significantly increased in PSS. Sera reacting with the 60 kD antigen were found in 37% of PSS, 71% of SSS, and 75% of SSS with SLE, 63% of SSS with RA. The ratio of SSS, and SSS with SLE were particularly significantly higher than PSS. CONCLUSION: Our results revealed data that there are the difference of reactivity against SS-A/B antigens in WB between PSS and SSS.

Antibodies, Antinuclear↗
PubMed2003

[Clinical significance of faecal calprotectin levels in patients with ulcerative colitis].

AIMS: To assess the clinical significance of faecal calprotectin levels (a neutrophil protein) in patients with ulcerative colitis (UC). METHODS: 25 patients with UC provided stool samples for calprotectin assay and the amount of calprotectin was related to UC disease activity index in each patient. Of 25 patients 4 with prednisolone refractory UC received 10 granulocyte and monocyte adsorption apheresis (GMCAP) sessions of 60 minutes duration, flow rate 30 mL per minute for 10 consecutive weeks. RESULTS: Calprotectin level in consecutive faecal samples from three patients was stable. However, increased calprotectin levels were significantly (p < 0.005) associated with Matts's endoscopic index, reflecting the level of colorectal inflammation. The 4 patients who received GMCAP therapy had a clinical activity index < 2 at week 7, the calprotectin level declined with improving Matts' index. CONCLUSIONS: Assay of faecal calprotectin holds promise as a sensitive biomarker to identify colorectal inflammation.

Adolescent↗
PubMed2003

Clinical significance of antibodies to TS1-RNA in patients with mixed connective tissue disease.

OBJECTIVE: To investigate the clinical significance of anti-TS1-RNA antibodies in patients with mixed connective tissue disease (MCTD). METHODS: Anti-TS1-RNA antibodies were detected by immunoprecipitation using 32P-UTP labeled TS1-RNA as the antigen source. In total, 104 patients with MCTD, 30 with Sjögren's syndrome, 30 with systemic lupus erythematosus (SLE), 25 with systemic sclerosis, 23 with polymyositis or dermatomyositis, and 10 with rheumatoid arthritis were examined. Specificity of anti-TS1-RNA antibodies was analyzed by immunoprecipitation using HeLa cell extracts. RESULTS: The frequency of anti-TS1-RNA antibodies was 31.7% in patients with MCTD, significantly higher than in SLE (p < 0.05). In anti-TS1-RNA positive patients, the incidence of hypertension and proteinuria and the frequency of anti-Sm and anti-dsDNA antibodies associated with SLE were higher than those of anti-TS1-RNA negative patients. Clinical features of SS such as sicca complex, the serum level of IgA, and anti-SSA antibodies were also elevated. The frequency of anti-TS1-RNA antibodies was significantly higher in SLE patients with anti-U1-RNP antibodies (p < 0.01); however, anti-TS1-RNA positive sera did not precipitate the specific RNA including U1 RNA in immunoprecipitation using HeLa cell extracts. In longitudinal studies, the level of anti-TS1-RNA antibodies changed in parallel with disease activity. CONCLUSION: We found that the level of anti-TS1-RNA antibodies was possibly correlated with the disease activity of lupus-like clinical features in patients with MCTD.

Adult↗
PubMed2003

Relationships between autoantibody responses to deletion mutants of Ki antigen and clinical manifestations of lupus.

OBJECTIVE: To determine the relationships between subtypes of anti-Ki antibodies and clinical manifestations of systemic lupus erythematosus. METHODS: The cDNA encoding full-length bovine Ki antigens or N- or C-terminal fragments were produced by polymerase chain reaction, and the fragments of Ki antigen were expressed as GST fusion proteins. Immunoreactivities of anti-Ki antibodies were tested by Western blotting. RESULTS: Of 60 sera reactive with full-length Ki antigen (KiF), 21 sera recognized only KiF. KiC5, a fragment containing the last 69 C-terminal amino acids, was recognized by 23 sera. Since no significant difference was observed in prevalence of reactivities between fragments from KiC2 to KiC5, a domain within the last 69 C-terminal amino acids was suggested to be the most common antigenic domain expressed among the GST fusion proteins. All 11 sera reacting with a fragment containing the initial 81 N-terminal amino acids also recognized all other fragments. A domain homologous to SV40 nuclear localization signal was required for N-terminal recognition by 8 sera. Reactivity to the last 69 C-terminal amino acids and the initial 81 N-terminal amino acids showed specificities to systemic lupus erythematosus without and with Sjögren's syndrome, respectively. Sicca was significantly more prevalent in patients whose sera reacted with both N- and C-terminal fragments, while prevalence of anti-SSA/Ro antibody was low. CONCLUSION: Ki antigen contains multiple epitopes recognized by autoimmune sera. Autoantibody profiles revealed distinctive immune responses, associated with certain clinical subtypes.

Autoantibodies↗
PubMed2002

Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus.

OBJECTIVE: To analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation. METHODS: PCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK-PCNA) were purified using anti-PCNA serum AK. The reactions to these antigens of 10 anti-PCNA-positive and 40 anti-PCNA-negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme-linked immunosorbent assays (ELISAs). RESULTS: With one exception (serum OK), anti-PCNA-positive sera reacted exclusively with only the 34-kd polypeptide. In contrast, 14 of 40 anti-PCNA-negative sera reacted with multiple proteins within PCNA complexes. Most anti-PCNA-positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK-PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58-kd polypeptide and the 34-kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes. CONCLUSION: Intermolecular-intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.

Antibodies, Monoclonal↗
PubMed2002

Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole.

BACKGROUND AND OBJECTIVES: The acid-inhibitory effect of lansoprazole depends on differences in cytochrome P450 (CYP) 2C19 genotypes. We assessed whether therapeutic effects of lansoprazole on gastroesophageal reflux disease (GERD) depended on the CYP2C19 genotype status in relation to the grade of GERD. METHODS: A total of 65 patients with GERD (grades A-D) completed treatment with lansoprazole, by taking 30 mg orally once a day for 8 weeks. The CYP2C19 genotype status of patients was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Before and after treatment, esophageal endoscopy was performed. GERD was considered to be cured on the basis of endoscopic findings at the end of treatment. Plasma lansoprazole levels could be determined at 3 hours after the last 30-mg dose of lansoprazole in the 27 genotyped patients. RESULTS: Cure rates for GERD depended significantly on the CYP2C19 genotype status, as well as the grade of GERD before treatment. Cure rates in the homozygous extensive, heterozygous extensive, and poor metabolizer groups were 45.8%, 67.9%, and 84.6%, respectively. Cure rates in the groups with GERD grade A, grade B, and grade C or D were 85.0%, 60.0%, and 45.0%, respectively. The cure rate in patients with the homozygous extensive metabolizer genotype of CYP2C19 with a GERD grade of C or D was very low (16.7%). Plasma lansoprazole levels in patients with the homozygous extensive metabolizer genotype were the lowest of the 3 groups. CONCLUSIONS: CYP2C19 genotype status, as well as the grade of GERD before treatment, is one of the determinants for the success or failure of treatment of GERD with lansoprazole. The low cure rate in patients with the homozygous extensive metabolizer genotype appeared to be a result of these patients having the lowest plasma lansoprazole levels among the 3 genotype groups.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

Anti-TS1-RNA: characterization of novel antibodies against sequence-specific RNA by random RNA selection in patients with Sjögren's syndrome.

OBJECTIVE: To define a novel RNA epitope recognized by serum from a patient with Sjögren's syndrome (SS) from a randomized RNA epitope library and investigate the epitope reactivity of the anti-RNA antibodies in patients with various connective tissue diseases. METHODS: Serum from a patient with SS was used to select ligands from a library of RNA oligomers with a central region of 25 degenerate nucleotides. Bound RNA was recovered by reverse transcription, PCR amplification, and subcloning. The relationship between the antibodies to the selected RNA and disease specificity was studied using immunoprecipitation. RESULTS: From the random RNA library, several unique RNA sequences were obtained. Sera from 32 of 61 patients with SS (52.5%) precipitated with one of the selected RNA (TS1-RNA), whereas sera from 8 of 41 patients with systemic lupus erythematosus (19.5%) and 3 of 25 patients with rheumatoid arthritis (12.0%) precipitated. Although the frequency of reactivity to the TS1-RNA was higher in anti-SSA/Ro positive sera, the presence of either native or recombinant SSA/Ro antigen showed no detectable competition, and no apparent sequence homology was found between the TS1-RNA and hY RNA. CONCLUSION: These data suggest that anti-TS1-RNA is a novel antibody against sequence-specific RNA in many patients with SS.

Antibodies, Antinuclear↗
PubMedDate not supplied

Autocrine motility factor receptor gene expression and cell motility in lung cancer cell lines.

The cell motility of tumor cells is an integral component of tumor invasion and metastasis. Autocrine motility factor (AMF) stimulates cell motility via a receptor (R)-mediated signal pathway. We studied the correlation between level of AMF-R gene expression by reverse transcription-polymerase chain reaction and cell motility by phagokinetic track assay with or without AMF in lung cancer cell lines. Lung cancer cell lines with higher AMF-R gene expression tended to have greater cell motility than those with lower AMF-R gene expression with or without AMF. Most of lung cancer cell lines showed significantly increased motility with the stimulation of AMF. We conclude that the presence of higher AMF-R gene expression and tumor cell motility via receptor in response to the stimulation of AMF could be an important aspect in the invasion and metastasis of lung cancer cell lines.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

Immunohistochemical detection of eosinophilic infiltration in pulmonary adenocarcinoma.

OBJECTIVES: Tumor-associated eosinophils play an important role in the biological behavior of cancer. We have detected eosinophilic infiltration immunohistochemically in tissue specimens from patients with pulmonary adenocarcinoma and assessed its association with the prognosis. MATERIALS AND METHODS: Utilizing the monoclonal antibody for EG2 thought to be a specific marker for eosinophils, the authors quantified eosinophil infiltration immunohistochemically in patients with pulmonary adenocarcinoma to investigate the relationship between EG2- positive cell counts and the prognosis. RESULTS: A significant difference in the rate of patient survival was detected between patients whose tumors had high EG2-positive cells and patients whose tumors had low EG2-positive cells overall (p=0.0086). Multivariate analysis also showed that eosinophils were significantly related to survival (p=0.044). CONCLUSION: These data indicate that eosinophilic counts utilizing the monoclonal antibody EG2 serve as a useful independent prognostic marker in pulmonary adenocarcinoma.

Adenocarcinoma↗