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Biomedical subjects

Kiyoshi Maeda

Publications and source records attributed to Kiyoshi Maeda.

At least 19 recordsLinked to original sources
PubMed2005

Polymorphism of the regulatory region of the presenilin-2 gene in sporadic Alzheimer's disease: a case-control study.

OBJECTIVE: presenilin-2 is one of the causative genes for familial Alzheimer's disease, and the apolipoprotein E epsilon4 allele is a major genetic risk factor for late-onset and sporadic early-onset Alzheimer's disease. Polymorphism of the regulatory region of presenilin-2 has recently been reported to be associated with sporadic Alzheimer's disease in a Russian population. The purpose of this study was to determine whether Alzheimer's disease is associated with the presenilin-2 gene polymorphism and the apolipoprotein E genotype in an extended case-control study. METHODS: We examined 230 patients with Alzheimer's disease, along with an equal number of age- and sex-matched controls from the same community, in a Japanese population by using a Chi-square test for homogeneity and a logistic regression analysis. RESULTS: The presenilin-2 polymorphism frequencies were similar in early-onset Alzheimer's disease patients (0.17) and younger controls (0.15), and in late-onset Alzheimer's disease (0.20) and elderly controls (0.20). We found no evidence for an association between the presenilin-2 polymorphism and the apolipoprotein E epsilon4 allele. CONCLUSIONS: Our results fail to support an association of presenilin-2 gene polymorphism with Alzheimer's disease. The discrepancy between our results and the results of the Russian study appear to be due to racial differences.

Adult↗
PubMed2005

Association of 14-3-3 epsilon gene haplotype with completed suicide in Japanese.

Genetic factors have been suggested to be involved in suicide. Although some genetic factors, such as serotonergic transduction, have been associated with suicide, the results are inconsistent. There is a possibility that various signaling anomalies are involved in the biological vulnerability to suicide. We carried out a genome-wide gene-expression study in the brains of suicide victims using DNA microarrays;14-3-3 epsilon, which is related to neurogenesis, was one of the genes upregulated in the brains of suicide victims in the microarray analysis. This was confirmed by Western blot analysis. To examine the possibility of the involvement of 14-3-3 epsilon in the pathogenesis of suicide, we investigated the association of the 14-3-3 epsilon gene and completed suicide. We used three high-frequency SNPs (rs1532976, rs3752826, and rs9393) and found a significant association of two alleles (rs1532976 and rs3752826) with completed suicide (p < 0.05). Moreover, the distribution of haplotype revealed a more significant difference between completed suicide and controls (p=0.0005). This finding suggests that 14-3-3 epsilon is a potential suicide susceptibility gene and implies that dysregulation of neurogenesis may be involved in suicide.

14-3-3 Proteins↗
PubMed2005

A novel high-specificity approach for colorectal neoplasia: Detection of K-ras2 oncogene mutation in normal mucosa.

There is an important need for a high-specificity approach to colorectal cancer. Approximately 50% of colorectal tumors contain K-ras gene mutations, which occur as an early step in carcinogenesis. K-ras mutations were detectable not only in tumors but also in microscopically normal colorectal mucosa close to carcinomas in some patients with colorectal cancer. This is the first systematic analysis of K-ras mutations in normal colonic mucosa at multiple consistently-selected locations. A total of 480 normal colonic mucosal samples were obtained from 80 subjects, including 65 patients with sporadic colorectal cancer and 15 controls in whom a colorectal neoplasm was ruled out endoscopically. Normal mucosal samples were obtained at multiple consistently-selected locations using biopsy forceps during colonoscopy. Mutant allele-specific amplification (MASA)-PCR was performed; this could detect a K-ras mutation in normal colonic mucosa even though it was only sparsely present. The K-ras mutation was found in histologically normal mucosa from colorectal cancer patients (20 of 65 cases; 41 of 390 loci) by MASA-PCR, especially frequent (51%; 19 of 37 cases) when the tumor showed a K-ras mutation. In contrast, no mutation was found in normal mucosa from 15 controls (90 loci). K-ras mutation in normal mucosa showed a significant association with the presence of colorectal cancer (p = 0.008). The specificity of the MASA-PCR method for colorectal neoplasms was thus 100%. We conclude that detection of K-ras mutations in normal colonic mucosa might serve as a high-specificity approach to colorectal cancer.

Colon↗
PubMed2005

Phenotypic heterogeneity within a new family with the MAPT p301s mutation.

Mutations in the gene encoding the microtubule-associated protein tau (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17. Clinical variability is seen not only among families with different mutations, but also among family members with the same mutation. We investigated a newly identified familial frontotemporal dementia and parkinsonism family. The disease was of early onset and was inherited as an autosomal dominant trait. Clinically, parkinsonism was the prominent and often early feature, and it preceded dementia. Three autopsied cases shared involvement predominantly in the frontal and temporal lobes and also in the subcortical nuclei, including substantia nigra, globus pallidus, and subthalamic nucleus, that microscopically consisted of neuronal loss, microvacuolation, and astrocytic fibrosis. Immunohistochemistry demonstrated neuropil threads, ballooned cells, and glial fibrillary tangles. Sequencing analysis of the MAPT gene showed an alteration in one allele, resulting in a P301S substitution. These findings suggest that the MAPT P301S mutation can cause pathologically subcortical-predominant, neuropil thread-rich, tau-containing lesions, which could result in consistent parkinsonism. Our study confirms the notion that the phenotype observed in affected individuals from P301S MAPT mutation families is heterogeneous and is broader than the phenotypes seen to date in affected family members carrying other MAPT mutations.

Adult↗
PubMed2005

Up regulation of ICAM-1 gene expression inhibits tumour growth and liver metastasis in colorectal carcinoma.

We have previously reported that decreased intercellular adhesion molecule-1 (ICAM-1) expression in cancer cells is associated with liver metastasis of colorectal cancer. In this study, we have investigated the effect of ICAM-1 gene transfection into the human colorectal cancer cell line LM-H3 on cell adhesiveness and cytotoxicity of peripheral blood mononuclear cells (PBMC) to cancer cells. Furthermore, we have investigated the effects of this gene transfer on subcutaneous tumour and liver metastases of LM-H3 in nude mice. More PBMC adhered to ICAM-1 transfected LM-H3 cells, LM-H3/ICAM-1, than to non-transfected LM-H3 cells and control LM-H3/Vector. Lysis of LM-H3/ICAM-1 cells by PBMC was significantly increased compared with LM-H3/Vector. Liver metastases with LM-H3/ICAM-1 cells were fewer in number and smaller than metastases with LM-H3/Vector. Intra-tumoural injection of ICAM-1 adenoviral vector significantly inhibited the growth of subcutaneous LM-H3 tumour. In conclusion ICAM-1 gene transfection using adenovirus vector might be an effective therapy for liver metastasis of colorectal carcinoma.

Adenoviridae↗
PubMed2005

Lack of an association between 5-HT receptor gene polymorphisms and suicide victims.

An association between serotonergic dysfunction in the brain and suicidal behavior has previously been suggested. The high affinity of some antipsychotic and antidepressant drugs to serotonin 6 (5-HT6) receptors, and the predominant localization of 5-HT6 receptors in some limbic regions, suggest that 5-HT6 receptors play a role in the pathogenesis of suicide. The objective of the present study was to examine the association between suicide victims and two polymorphisms of the 5-HT6 receptor gene: a biallelic polymorphism (267C/T) in exon 1 and a trinucleotide repeat polymorphism ([GCC](2/3)) in the 5'-upstream region of the gene. The two polymorphisms were genotyped in 163 suicide victims and 166 controls, and the distribution of genotype and allele frequencies between the two groups were compared. Haplotype frequencies of these two polymorphisms were estimated from genotypic data by the maximum-likelihood method. In both polymorphisms, there were no significant differences in genotype or allele frequencies between the suicide victims and the controls. Moreover, there were no significant differences in the haplotype distributions of these polymorphisms between the two groups. These findings suggest that it is unlikely that the 5-HT6 receptor gene is involved in the susceptibility to suicide.

Alleles↗
PubMed2005

Significance of increased proliferation of immature plasma cells in the appendix of patients with ulcerative colitis.

The etiology of ulcerative colitis (UC) is not known. Recent studies support a primary role of the appendix in the pathogenesis of UC, however phenotypical studies of proliferating cells in the appendix have not been reported. We report phenotypical studies of lymphocytes and of proliferating subpopulations in the appendix of patients with inflammatory bowel disease and of controls. Surgical samples of the appendix were obtained from 5 patients with colon cancer, 5 with acute appendicitis, 12 with UC and 7 with Crohn's disease (CD). Frozen sections were cut from fixed samples, and immunostained with lymphocyte markers and anti-Ki-67 antibodies. The number of Ki-67(+) proliferating cells, CD19, and CD138 cells was significantly higher in the appendix of patients with UC than in controls, patients with acute appendicitis, and patients with CD. Immunohistological double staining revealed significant proliferation of CD3, CD19, and CD138 cells in the appendix of patients with UC. The proportions of Ki-67(+) cells in CD3, CD19, and CD138 cells were significantly higher in both total UC patients and patients in remission-stage UC, than in controls, patients with acute appendicitis, and patients with CD. Lamina propria cells in the appendix of patients with UC showed augmented proliferation with increased numbers of CD19 and CD138 cells. The number of CD3 cells was not significantly increased, but the proportion of proliferating CD3 cells was increased. An increased proportion of Ki-67(+) cells in CD19 and CD138 cells represents proliferation of immature plasma cells in the appendix of patients with UC, and proliferation of such immature plasma cells was seen in both active- and remission-stage UC. Proliferation of immature plasma cells in the appendix of patients with UC suggests a primary role of humoral immune responses in the pathogenesis of UC.

Adolescent↗
PubMed2005

[Thermal imaging properties of toes after walking stress test in diabetic patients].

In consecutive 50 diabetic patients hospitalized for medical education, without subjective symptoms of autonomic neuropathy (DM group), performed treadmill walking stress test and thermography, for clarify the feature of the pattern typical of diabetic autonomic neuropathy. Thermal images were collected, before, immediately after, 3, 6, 12 minutes after walking. The mean temperature of toes fell more than 1 degree C than that of baseline level and returned within 0.5 degrees C of baseline level within 6 minutes (N type) in 66% of 30 normal subjects (C group) and 24% of DM group. In 10% of C and 24% of DM, the temperature fell but not returned within 0.5 degrees C of baseline level in 6 minutes (D type). In 17% of C and 38% of DM, the temperature changed within 0.5 degrees C (F type), or rose more than 0.5 degrees C after exercise (U type) in 7% in C and 14% in DM groups. Pts D, F group, have more complications (HbA1c, nephropathy, retinopathy or somatic neuropathy), but not so in C, U type. We concluded D, F types were the typical thermographic features of the toes of pts with diabetic autonomic neuropathy.

Aged↗
PubMed2004

Inflammatory glial activation in the brain of a patient with hereditary sensory neuropathy type 1 with deafness and dementia.

The brain of a patient with hereditary sensory neuropathy type 1 (HSN-1) associated with sensorineural deafness and early-onset dementia was neuropathologically investigated. Widespread neuronal degeneration in cerebral neocortex, hippocampus and basal ganglia was revealed, accounting for the clinical features. Loss of neurons with ballooning of residual neurons was remarkable in the hippocampus and frontal, parietal, and occipital lobes. Neuronal degeneration in these regions was accompanied by axonal dystrophy and glial reactions such as microgliosis and astrocytosis, however, only glial responses were prominent in the basal ganglia, brain-stem and cerebellum with mild neuronal loss. These results indicate that the widespread neuronal degeneration may be accelerated by inflammatory processes including glial activation in the brain of a patient with HSN-1 associated with deafness and dementia.

Deafness↗
PubMed2004

Intraductal papillary-mucinous adenoma developed in the ventral pancreas in a patient with pancreas divisum.

A 34-year-old man was admitted to our hospital with the chief complaints of back pain and epigastralgia. The physical examinations on admission disclosed no abdominal tumor. The serum concentration of total bilirubin was 1.4 mg/dl. The serum elastase-1 level was elevated to 526 ng/dl. Computed tomography showed a cystic lesion, 1 cm in diameter, in the head of the pancreas, without dilatation of the main pancreatic duct. Endoscopic retrograde cholangiopancreatography via the papilla of Vater and the accessory papilla revealed an enlarged ventral pancreatic duct and pancreas divisum. The preoperative diagnosis was mucin-producing pancreatic tumor in the ventral pancreas of a patient with pancreas divisum. A pylorus-preserving pancreatoduodenectomy was performed. The gross findings of the cut surface of the resected specimen disclosed mural nodules in the dilated duct of the ventral pancreas. A histological examination of the mural nodules in the ventral pancreas revealed mucin and intraductal papillary adenoma. Benign tumors associated with pancreas divisum are rare; to the best of our knowledge, only three cases have been reported. Although in these three patients the tumor developed in the dorsal pancreas, the tumor developed in the ventral pancreas in our patient.

Adenoma↗
PubMed2004

Differences in dihydropyrimidine dehydrogenase activities between gastric and colorectal cancer.

We studied the relation between clinicopathological factors and dihydropyrimidine dehydrogenase (DPD) activity in gastric and colorectal carcinomas. Specimens obtained by surgery from 27 gastric and 17 colorectal carcinomas and their normal mucosa were examined. The levels of DPD activity in the gastric carcinomas and their normal mucosa were significantly higher than those in colorectal carcinomas and their normal counterparts, respectively (both P's < 0.0001). The gastric carcinomas had significantly higher DPD activities than their normal mucosa (P = 0.028), but the colorectal carcinomas did not. Among the clinicopathological factors, which included invasion/metastatic status and staging, the only effect was that of the histological differences of gastric cancer on DPD activity. That is, the level of DPD activity of the histologically undifferentiated gastric carcinoma was significantly higher than that of the differentiated type. No prognostic predictive values of DPD were recognized in either gastric and colorectal cancer. In conclusion, the higher DPD activity in gastric cancer than colorectal cancer may be due to the higher DPD activity in the background mucosa of origin, and the higher population of undifferentiated type of histological classification, compared to the colorectal counterparts.

Biomarkers, Tumor↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

[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↗