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Biomedical subjects

Kiyoshi Maeda

Publications and source records attributed to Kiyoshi Maeda.

At least 37 records · Page 2Linked to original sources

Association between catechol-O-methyltransferase functional polymorphism and male suicide completers.

Suicide has been suggested to involve catecholaminergic dysfunction and to be related to genetics. Catechol-O-methyltransferase (COMT) 158Val/Met polymorphism (GenBank Accession No. Z26491) is a polymorphism of the gene encoding COMT, a major enzyme in catecholamine inactivation. The COMT 158Val/Met polymorphism affects COMT activity, that is, the alleles encoding Val and Met are associated with relatively high and relatively low COMT activity, respectively. In this study, we hypothesized that the COMT 158Val/Met polymorphism is associated with suicide. The study population consisted of 163 suicide completers (112 males and 51 females). We found that the genotype distribution of the COMT 158Val/Met polymorphism was significantly different between male suicide completers and male controls (p=0.036), while the frequency of the Val/Val genotype, a high-activity COMT genotype, was significantly less in male suicide completers than in male controls (OR: 0.52; 95% CL: 0.31-0.89; p=0.016). However, this was not the case in females. Our results suggest that the Val/Val genotype is a protective factor against suicide in males.

Adult↗

Inhibition and mechanism of action of a protease inhibitor in human pancreatic cancer cells.

OBJECTIVES: Tumor-associated trypsinogen (TAT), urokinase-type plasminogen activator (u-PA), matrix metalloproteinase-2 (MMP-2), and MMP-9 each play a dominant role in the degradation of extracellular matrix (ECM) during the invasion process of pancreatic cancer. Transforming growth factor beta1 (TGF-beta1) is a multifunctional poly-peptide that regulates cell growth and differentiation, ECM deposition, cellular adhesion properties, angiogenesis, and also immune functions. We previously reported that TGF-beta1 up-regulated vascular endothelial growth factor (VEGF) production and protease production of MMP-2 and of u-PA in the highly metastatic pancreatic cancer cell lines SW1990 and CAPAN-2. In this study, we examined the inhibitor effects of a protease inhibitor, gabexate mesilate (GM), on cell invasion, cell proliferation, growth factor production, and ECM degradation. We also examined the effect of GM on the production of growth factor and ECM degradation by these cell proteases and enzymatic activities. RESULTS: GM down-regulated the invasiveness and liver metastasis potential of SW1990 and CAPAN-2 cells, but it did not affect the proliferation of these cells. GM inhibited not only the enzymatic activities of TAT and u-PA but also the production of MMP-2, and u-PA, all of which have been known to be secondarily down-regulated by TGF-beta1. CONCLUSIONS: These findings suggested that GM has very good potential for use in the treatment against invasion and metastasis of pancreatic cancer.

Adenocarcinoma↗

Novel missense polymorphism in the regulator of G-protein signaling 10 gene: analysis of association with schizophrenia.

Dysfunction of neuronal signal transduction via G-protein has previously been speculated to be involved in the pathophysiology of schizophrenia. Regulator of G-protein signaling (RGS) is a protein that acts as a GTPase-activator for Galpha protein. A total of 33 Japanese patients with schizophrenia were screened for mutations in the coding region of the RGS10 gene, and a novel missense polymorphism (Val38Met) in the RGS domain was detected. A case-control study did not reveal a significant association between this polymorphism and schizophrenia. The results do not provide evidence that the RGS10 gene is involved in biological vulnerability to schizophrenia.

Adult↗

[A case of corticobasal degeneration presenting with visual hallucination].

We report a case of corticobasal degeneration (CBD) presenting with visual hallucination. A 65-year-old woman showed clumsiness of the left hand. Clinical symptoms slowly progressed to include rigidity, which was left side dominant, limb-kinetic apraxia of the left hand, disorder of construction and dressing, unilateral spatial neglect, cortical sensory loss and alien limb phenomenon. Cranial MRI showed atrophy of the parietal and medial aspect of the frontal lobes, which was more severe on the right than on the left. SPECT images showed hypoperfusion in the parietal, frontal and temporal lobes, which were similarly more severe on the right than on the left. We diagnosed the patient as having CBD based on the clinical symptoms. Two years' later, she developed recurrent visual hallucinations that were typically well formed and detailed. Since patients with CBD generally do not experience visual hallucination, this case is considered the very rare and indicates the possibility that visual hallucination may be one of the clinical symptoms of CBD.

Aged↗

Cross-reactivity of yeast antigens in human colon and peripheral leukocytes.

Elevation of the serum anti-Saccharomyces cerevisiae antibody (ASCA) level has been reported in patients with Crohn's disease. This study investigated the antigenic distribution of S. cerevisiae in human colon and peripheral leukocytes. ASCA was isolated from sera from patients with Crohn's disease using immuno-affinity chromatography and then biotinylated and assayed immunohistologically and immunocytologically to determine the distribution of antigens recognized by ASCA in human colon and peripheral leukocytes. Immunoblot analysis of yeast extract and human peripheral leukocytes was performed. Immunohistological study using biotinylated ASCA revealed the presence of yeast-like particles in the granulation tissue of inflamed colonic mucosa. Biotinylated ASCA also stained lymphocytes and polymorphonuclear cells infiltrating inflamed intestine. Monocytes in epithelioid granulomas of colon with Crohn's disease were also stained. Polymorphonuclear leukocytes in peripheral blood were also stained with biotinylated ASCA. The antigens reactive to ASCA among heat-extracted, non-heat-extracted yeast antigens, and human leukocyte extract differed. The findings of cross-reactivity of polymorphonuclear leukocytes with S. cerevisiae antigen and the presence of S. cerevisiae antigen in Crohn's disease granulomas suggest the possibility of involvement of S. cerevisiae in the pathogenesis of Crohn's disease.

Adult↗

Correlation between vascular endothelial growth factor C expression and lymph node metastasis in T1 carcinoma of the colon and rectum.

PURPOSE: Vascular endothelial growth factor C (VEGF-C) is known to be associated with the development of the lymphatic vessel system. Recently, VEGF-C is thought to be correlated with lymph node metastasis in some malignant tumors. In this study, we investigated the correlation between VEGF-C expression and lymph node metastasis in early carcinoma of the colon and rectum. METHODS: Two hundred and twenty-one endoscopically biopsied specimens from patients with T1 colorectal carcinoma prior to operation were investigated by an immunohistochemical study. RESULTS: VEGF-C expression was more frequently observed in the tumors with nodal metastasis than in those without metastasis. Moreover, a multivariate analysis indicated that VEGF-C expression is an independent predictor of lymph node metastasis. CONCLUSION: VEGF-C staining using endoscopically biopsied specimens prior to operation could be of use in the prediction of lymph node metastasis and in preoperative selection of treatment in patients with T1 colorectal carcinoma.

Adult↗

Synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP) is expressed differentially in phencyclidine-treated rats and is increased in the nucleus accumbens of patients with schizophrenia.

Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Therefore, PCP-treated animals can provide a model for schizophrenia. Using differential display, we identified a gene regulated by the delayed action of PCP in rat nucleus accumbens (NAcs). Sequence analysis showed that the cDNA clone obtained was identical to rat synapse-associated protein 90/postsynaptic density-95-associated protein 1 (SAPAP1). Quantitative reverse transcriptase (RT)-PCR analysis showed that SAPAP1 mRNA had increased significantly in rat NAc (P<0.0001) and hippocampus (P<0.01) 24 h after a PCP (10 mg/kg) injection as compared to the controls. Immunoquantification using an anti-SAPAP1 antibody indicated that immunoreactivity for SAPAP1 increased significantly (P&<0.05) in the NAcs of unmedicated patients with schizophrenia, as compared to the control subjects and medicated patients with schizophrenia. Our findings support the hypothesis that there is abnormal glutamatergic neurotransmission in schizophrenia and show evidence of abnormalities in the intracellular signal transduction via N-methyl-D-aspartate (NMDA) receptors.

Adult↗

Mutation and association analysis of the DAP-1 gene with schizophrenia.

Glutamate dysfunction has been hypothesized to be involved in the pathophysiology of schizophrenia. The human homolog of Drosophila discs large protein (hDLG) and post-synaptic density-95-associated protein-1 (DAP-1) is one of the major proteins that are involved in intracellular signal transduction via N-methyl-d-aspartate receptors. In the present study 33 Japanese patients with schizophrenia were screened for mutations in the DAP-1 gene. A single nucleotide polymorphism was identified in the DAP-1 gene (1618A/G). A case-control study using a larger sample of unrelated patients and controls did not reveal a significant association between this polymorphism and schizophrenia. The results do not provide evidence that the DAP-1 gene is involved in vulnerability to schizophrenia.

Case-Control Studies↗

Analysis of intestinal HLA-DR bound peptides and dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.

Isolation of antigenic peptides from the MHC-groove has contributed to the understanding of T cell responses. However, these MHC-associated peptides have been isolated from various murine and human cell lines. The specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We examined antigenic peptides bound to the class II major histocompatibility complex (MHC) groove in human intestine by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. We detected 55 parent proteins from 4 controls, 9 patients with ulcerative colitis, and 9 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides ranged from 874.4 to 2727.4, representing 10-26 amino acid residues. Fifty-one of these 55 parent proteins were exogenous proteins. Escherichia coli-, Saccharomyces cerevisiae-, and Caenorhabditis elegans-derived peptides were found frequently in patients with inflammatory bowel disease. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine participate with exogenous antigen presentation. Increased immune responses against E. coli, S. cerevisiae and C. elegans found in patients with inflammatory bowel may participate as dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.

Adolescent↗

[Preservation of quality of life and its relation to lifestyle in centenarians in Japan: a visitation interview survey].

PURPOSE: To investigate quality of life (QOL) and associated factors in centenarians, we conducted a visitation interview survey for all male and one half of the female centenarians living in Japan, and studied QOL, lifestyle and health status. METHODS: All the male centenarians and a randomly-sampled half of the female centenarians living in Japan were included in the study based on the National Census. Finally, 556 male and 1341 female centenarians participated in the present visitation interview survey and were studied using a structured questionnaire. QOL was assessed from 3 aspects; activities of daily life (ADL), cognitive function (CF) and mental health (MH). RESULTS: Individuals having superior ADL accounted for 30.9% of the male and 13.6% of the female centenarians, those with superior CF were 58.1% and 35.6%, respectively, and those with superior MH were 39.2% and 26.8%, providing evidence that superior QOL was more dominant in males than in females. There were no effects of residential areas (north, east, middle, west, southwest and south of Japan) on the prevalence of ADL, CF and MH. Multiple logistic regression analyses conducted independently, for ADL, CF and MH as dependent valuables revealed that habitual exercise, less decline in visual ability and preservation of masticating ability were associated with better results for these 3 aspects of male centenarians' QOL, and that habitual exercise, less decline in visual ability, spontaneous awakening in the morning, good appetite and having cohabitating family members were associated with superior QOL in the females, suggesting that more factors are operating in the latter. CONCLUSIONS: Several lifestyle factors were found to be associated with preservation of QOL in centenarians in Japan. These results should facilitate establishing a public health and welfare policy for the most senior citizens, a group that has been increasing in Japan.

Aged↗

Differential expression of homing receptor CD103 on lamina propria lymphocytes and association of CD103 with epithelial adhesion molecules in inflammatory bowel disease.

Intraepithelial lymphocytes play an important role in mucosal immunology, and are involved in the pathogenesis of inflammatory bowel disease. We studied expression of CD103 on mucosal lymphocytes with epithelial adhesion molecules in patients with inflammatory bowel disease. Surgical specimens of human colon were obtained from 12 patients with ulcerative colitis, 12 patients with Crohn's disease, and 5 controls. Frozen sections were cut and expression of CD103 on lymphocytes, E-cadherin, CD44V3, and CD44v6 on intestinal epithelium was studied. Frequency of CD103-positive intraepithelial lymphocytes did not differ among controls, patients with ulcerative colitis, and patients with Crohn's disease. The frequency of CD103-positive lamina propria lymphocytes was significantly higher in patients with Crohn's disease than in controls and patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with that of lamina propria lymphocytes in patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with epithelial E-cadherin expression but that of lamina propria lymphocytes was not. Differential up-regulation of CD103 expression on lamina propria lymphocytes in Crohn's disease may indicate differential humoral or cellular regulation in inducing CD103 molecules on lymphocytes in patients with this disease.

Antigens, CD↗

[Self-expandable metallic stent for palliation of unresectable esophagogastric malignancies].

While self-expandable metallic stents (EMS) have been reported to be useful for palliation of unresectable esophagogastric malignancies, complications accompanying such stenting also have been pointed out. Both advantages and disadvantages of EMS stenting are discussed on the basis of 25 cases of esophageal cancer and 5 cases of gastric cancer treated in our institute. Although dysphagia improved in 26 of the 30 patients with stenosis, only 14 of the patients who had been able to ingest more than 1,200 kcal of food could be discharged to their homes. Complications were noted in 12 (48%) of the esophageal cancer patients and 4 (80%) of the gastric cancer patients, including incomplete sealing of esophagorespiratory fistula in 6, tumor ingrown in 3, mucosal hyperplasia in 2, stent migration in 2 and reflux of digestive juice in 1. The patients with complications took food for shorter periods than those who had no complications. Successful patient outcomes can be achieved by the prevention of complications accompanying stenting and mastering the techniques to overcome those complications described above.

Adult↗

Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine.

We investigated changes in signal transduction via calcineurin (CaN) in the striatum of rats behaviorally sensitized to methamphetamine (Meth). The rats were injected with Meth (4 mg/kg, s.c.) five times a week for 3 weeks and then were given a challenge dose of Meth (2 mg/kg, s.c.). Seven days after the challenge test, we determined the levels of CaN Aalpha and Abeta by Western blotting. We further immunoquantified DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, mw 32,000) and phosphothreonine-DARPP-32, which can be dephosphorylated at threonine sites by CaN. We found that both CaN Aalpha and Abeta were significantly decreased in the particulate fractions but were not changed in the soluble fractions from the striatum of Meth-sensitized rats as compared with control rats. The same findings were observed in the striatum of rats 6 h after the injection of PCP (10 mg/kg, s.c.). In the striatum of Meth-sensitized rats, phosphothreonine-DARPP-32 immunoreactivities significantly increased, but DARPP-32 immunoreactivities were not significantly different from those of the control rats. These results indicate that the activity of signal transduction via CaN is functionally decreased in the striatum of Meth-sensitized rats.

Animals↗