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Biomedical subjects

R Fukuda

Publications and source records attributed to R Fukuda.

At least 19 recordsLinked to original sources
PubMed2003

Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism.

MRI studies using the manual tracing method have shown a smaller-than-normal hippocampal volume in patients with posttraumatic stress disorder (PTSD). However, these studies have yielded inconsistent results, and brain structures other than the hippocampus have not been well investigated. A recently developed, fully automated method called voxel-based morphometry enables an exploration of structural changes throughout the brain by applying statistical parametric mapping to high-resolution MRI. Here we first used this technology in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based morphometry showed a significant gray-matter volume reduction in the left anterior cingulate cortex (ACC) in trauma survivors with PTSD compared with those without PTSD. The severity of the disorder was negatively correlated with the gray-matter volume of the left ACC in PTSD subjects. There were no significant differences in other gray-matter regions or any of the white-matter regions between two groups. The present study demonstrates evidence for structural abnormalities of ACC in patients with PTSD. Together with previous functional neuroimaging studies showing a dysfunction of this region, the present findings provide further support for the important role of ACC, which is pivotally involved in attention, emotional regulation, and conditioned fear, in the pathology of PTSD.

Adult↗
PubMed2003

Bonding efficacy of polyalkenoic acids to hydroxyapatite, enamel and dentin.

Previously, we introduced a methodology to determine the chemical bonding potential of polyalkenoic acids to mineralized tissues through quantification of the degree of ionic bond formation between the carboxyl groups of a polyalkenoic acid with calcium of hydroxyapatite. In a continuation of that study, we now investigated in how far the chemical bonding potential to synthetic hydroxyapatite is influenced by the molecular structure of the polyalkenoic acid and if this also may affect the self-adhesiveness to enamel and dentin. X-ray photoelectron spectroscopy and inductively coupled plasma atomic emission spectrometry were used to quantitatively analyze the chemical bonding efficacy of a polyalkenoic acid consisting of acrylic acid units (PAA) to synthetic hydroxyapatite (HAp) in comparison to the chemical bonding potential of the previously investigated synthesized polyalkenoic acid (s-PA) co-polymer consisting of 90w/w% acrylic and 10w/w% maleic acid units. In addition, the analysis was carried out for enamel and dentin samples. PAA revealed a significantly lower bonding effectiveness with only half of its carboxyl groups bonded to HAp versus about two-third of the carboxyl groups of s-PA. The difference in bonding potential was confirmed by the considerably lower adhesiveness of PAA to enamel and dentin as compared to that of s-PA The present findings indicate that the molecular structure of the polyalkenoic acid significantly influences the chemical bonding efficacy to Hap-based substrates.

Acrylic Resins↗
PubMed2002

1H-MR spectroscopy and gray matter volume of the anterior cingulate cortex in schizophrenia.

Schizophrenic and normal control subjects were examined using both H-magnetic resonance spectroscopy (MRS) and structural MR imaging, in order to accurately assess the partial volume within the spectroscopic volume of interest (VOI) in the anterior cingulate cortex. The gray matter volume within VOI correlated positively with the N-acetyl-aspartate (NAA) to choline (Cho) ratio in schizophrenics only, not in controls. Schizophrenic patients had a reduced NAA/Cho ratio and an elevated Cho/creatine ratio compared to controls after the partial volume effect was eliminated. There was a significant negative correlation between the NAA/Cho ratio and the severity of blunted affect symptom in schizophrenics. These results provide further support to the idea that the measures of H-MRS indicate not only neuronal loss but also neuronal dysfunction in schizophrenia.

Adult↗
PubMed2002

Association study of C825T polymorphism of the G-protein b3 subunit gene with schizophrenia and mood disorders.

Alterations of G proteins have been implicated in major psychiatric illnesses. A C825T polymorphism of a gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3) was reported to be associated with several pathological conditions, such as hypertension and depressive disorder. We examined whether this polymorphism is associated with functional psychoses in a Japanese sample of 370 schizophrenics, 164 bipolars, 68 depressive patients, and 198 controls. We obtained no evidence for an association of the polymorphism with any diagnostic group.

Adult↗
PubMed2002

Time-course changes of ECL cell markers in acetic acid-induced gastric ulcers in rats.

BACKGROUND AND AIM: Enterochromaffin-like (ECL) cells are the major source of histamine for the regulation of gastric acid secretion, and also contain histidine decarboxylase (HDC), vesicular monoamine transporter 2 (VMAT2), and chromogranin A (CgA). Although gastric acid secretion is suppressed during ulcer healing, the role of ECL cells in that process is not yet fully understood. In the present study, we investigated the changes in ECL cell number during healing of experimental ulcers in rats. MATERIALS AND METHODS: Seven-week-old male Wistar rats were used. Acetic acid-induced ulcers were caused by an application of 100% acetic acid to the serosal surface of the rat stomachs. At different time points following the induction (12 h-15 days), time-course changes of HDC, VMAT2, and CgA mRNA expression were investigated by Northern blot analysis. The expressions of HDC, VMAT2, and CgA were immunostained on gastric mucosal sections with ulcers. RESULTS: HDC, VMAT2, and CgA mRNA in gastric mucosa each showed an initial marked transient decrease, followed by an increase on day 10 back to the initial value. HDC, VMAT2, and CgA-immunoreactive cells at the ulcer margin were reduced in number on day 3, compared with those in distant areas. On day 10, however, they returned to levels similar to those in distant areas. CONCLUSION: The present study revealed a local down-regulation of HDC, VMAT2, and CgA in ECL cells at the ulcer margin. As a result, we concluded that a suppression of ECL cell activity during ulcer healing may be involved in suppressed gastric acid secretion.

Acetic Acid↗
PubMed2002

Activation of prostaglandin E2-receptor EP2 and EP4 pathways induces growth inhibition in human gastric carcinoma cell lines.

The effect of prostaglandin E2 (PGE2) on the proliferation of gastric cancer cells is still unclear. PGE2 receptors are divided into four subtypes - EP1, EP2, EP3, and EP4 - which are coupled to three different intracellular signal-transduction systems. Stimulation of EP2 and EP4 is linked with cyclic adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase A (PKA). In some human gastric cancer cells, PGE2 has been suggested to have an antiproliferative effect by way of increased cAMP production. Expression of EP2 and EP4 in human gastric carcinoma cells, however, has not been examined. We examined the expression of EP2 and EP4 and the antiproliferative effects of specific EP2 and EP4 agonists on four different human gastric cancer cell lines. Our data clarified that all the cell lines investigated in this study expressed EP2 and EP4 and that the specific agonists of these receptors induced growth inhibition with an accompanying increase in cAMP production. In summary, gastric cancer cells have EP2 and EP4 receptors, and their selective activation is linked with the decreased cell proliferation.

Cell Division↗
PubMed2001

Identification of tyrosine residues involved in ligand recognition by the phosphatidylinositol 3-kinase Src homology 3 domain: circular dichroism and UV resonance Raman studies.

Src homology 3 (SH3) domains are small noncatalytic protein modules capable of mediating protein-protein interactions. We previously demonstrated that the association of a ligand peptide RLP1 (RKLPPRPSK) causes environmental and structural changes of Trp55 and some of seven Tyr residues in the phosphatidylinositol 3-kinase (PI3K) SH3 domain by circular dichroism (CD) and 235-nm excited UV resonance Raman (UVRR) spectroscopies [Okishio, N., et al. (2000) Biopolymers 57, 208-217]. In this work, the affected Tyr residues were identified as Tyr12, Tyr14, and Tyr73 by the CD analysis of a series of mutants, in which every single Tyr residue was replaced by a Phe residue. Among these three residues, Tyr14 was found to be a main contributor to the UVRR spectral change upon the RLP1 binding. Interestingly, CD and UVRR analyses revealed that RLP1 associates with the Y14F and Y14H mutants in different ways. These results suggest that Tyr14 plays a crucial role in the ligand recognition, and the amino acid substitution at Tyr14 affects the mode of PI3K SH3-ligand interaction. Our findings give an insight into how SH3 domains can produce diversity and specificity to transduce signaling within cells.

Amino Acid Substitution↗
PubMed2001

Activation of the Ras-cAMP signal transduction pathway inhibits the proteasome-independent degradation of misfolded protein aggregates in the endoplasmic reticulum lumen.

Many kinds of misfolded secretory proteins are known to be degraded in the endoplasmic reticulum (ER). Dislocation of misfolded proteins from the ER to the cytosol and subsequent degradation by the proteasome have been demonstrated. Using the yeast Saccharomyces cerevisiae, we have been studying the secretion of a heterologous protein, Rhizopus niveus aspartic proteinase-I (RNAP-I). Previously, we found that the pro sequence of RNAP-I is important for the folding and secretion, and that Deltapro, a mutated derivative of RNAP-I in which the entire region of the pro sequence is deleted, forms gross aggregates in the yeast ER. In this study, we show that the degradation of Deltapro occurs independently of the proteasome. Its degradation was not inhibited either by a potent proteasome inhibitor or in a proteasome mutant. We also show that neither the export from the ER nor the vacuolar proteinase is required for the degradation of Deltapro. These results raise the possibility that the Deltapro aggregates are degraded in the ER lumen. We have isolated a yeast mutant in which the degradation of Deltapro is delayed. We show that the mutated gene is IRA2, which encodes a GTPase-activating protein for Ras. Because Ira2 protein is a negative regulator of the Ras-cAMP pathway, this result suggests that hyperactivation of the Ras-cAMP pathway inhibits the degradation of Deltapro. Consistently, down-regulation of the Ras-cAMP pathway in the ira2 mutant suppressed the defect of the degradation of Deltapro. Thus, the Ras-cAMP signal transduction pathway seems to control the proteasome-independent degradation of the ER misfolded protein aggregates.

Aspartic Acid Endopeptidases↗
PubMed2001

Peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition of human hepatocellular carcinoma.

Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been implicated in the growth inhibition and differentiation of certain human cancers with diverse tissue origin. In this study, expression of PPARgamma in human hepatocellular carcinoma (HCC) and the effect of PPARgamma ligands on HCC cells were investigated in vitro using Hep G2, HuH-7, KYN-1 and KYN-2 cell lines. All cell lines were found to express functionally active PPARgamma and a marked growth inhibition was induced by thiazolidinedione ligands troglitazone, and pioglitazone as well as with its natural ligand 15-deoxy-Delta(12,14)-prostaglandin J(2). The growth inhibitory effect was associated with a dose-dependent inhibition of DNA synthesis, cell cycle progression and alpha fetoprotein expression.

Carcinoma, Hepatocellular↗
PubMed2001

Corpus callosum area and functioning in schizophrenic patients with auditory--verbal hallucinations.

Auditory--verbal hallucinations (AVH) are a characteristic feature of schizophrenia. Patients with AVHs have been found to differ from non-hallucinating patients in volumes of certain asymmetrical brain structures on MRI, and on certain neuropsychological measures. There is also evidence of corpus callosum (CC) abnormalities in schizophrenia, and it has been proposed that abnormalities of inter-hemispheric transmission may underlie hallucinations and other symptoms. The aim of this study was to examine whether patients with AVHs have smaller corpora callosa than those without AVH, and whether CC size is related to performance on neuropsychological tests of functional cerebral asymmetry. Seventy-one DSM-IV male schizophrenics were recruited on the basis of their hallucination history plus 33 matched normal controls. Twenty-nine patients had no history of AVH, and 42 had a strong history of AVH. The mid-sagittal surface area and longitudinal length of the CC were measured from T(1)-weighted spin echo images. Callosal area was divided into four sections. There were no significant differences in any of the measurements between the two patient groups, or between patients with schizophrenia and controls. There was no association between CC measures and handedness, or performance on dichotic listening or finger tapping tasks. The results of this study do not lend support for there being a major morphological abnormality of the corpus callosum in schizophrenic patients, or for a specific relationship to AVH. However, a significant association between CC area and overall grey and white matter volumes was noted in the hallucinating patients and, to a lesser extent, in the non-hallucinators, which may point to differing influences on brain development or degeneration in such patients compared with normal controls.

Adolescent↗
PubMed2001

Analysis of gastrin receptor gene expression in proliferating cells in the neck zone of gastric fundic glands using laser capture microdissection.

Gastrin stimulates proliferation of progenitor cells in the neck zone of gastric fundic mucosa. However, whether it directly enhances this proliferation through its receptors remains unclear. We investigated the expression of gastrin receptors in neck zone proliferating cells in rat gastric fundic glands using a reverse transcription polymerase chain reaction (RT-PCR) coupled with laser capture microdissection and in situ RT-PCR. Gastrin receptor expression was identified in c-fos-expressing cells located in the neck zone, and results of the RT-PCR analysis argued against contamination by other cells, such as enterochromaffin-like, parietal or D cells. Supporting this finding, gastrin receptor gene expression was identified in the neck zone as well as base glands by in situ RT-PCR. Therefore, it is suggested that proliferating cells in the neck zone are stimulated directly by gastrin via their gastrin receptors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Correlation between microsatellite instability and metachronous disease recurrence after endoscopic mucosal resection in patients with early stage gastric carcinoma.

BACKGROUND: Since endoscopic treatment was first evaluated and established as a treatment for patients with early stage gastric carcinoma, metachronous disease recurrence at other sites in the stomach after endoscopic treatment has become a major problem. METHODS: A retrospective case-control study was conducted on 10 patients with metachronous recurrence of gastric carcinoma after undergoing successful endoscopic mucosal resection (EMR) therapy for early stage gastric carcinoma and on 14 patients without recurrence. Gastric mucosal tissues obtained during the initial EMR were dissected, and DNA samples from the tumor tissue and surrounding nonneoplastic mucosa were extracted separately. Microsatellite instability (MSI) was tested in five microsatellite markers (D2S137, D3S1067, TP53, TGFbetaRII, and BAX). The authors also looked for K-ras codon 12 point mutations in the tumor tissues. In addition, immunohistochemical staining was done to test for the presence of proliferating cell nuclear antigen (PCNA), p53, hMSH2, and hMLH1 in the mucosal tissues. Finally, the correlation between the presence or absence of metachronous recurrence and the characteristics of the primary tumor (MSI, K-ras, p53, etc.) were investigated. RESULTS: Three of 10 patients with recurrent disease showed MSI in more than two microsatellite markers among 3-5 investigated site (MSI-H), whereas none of the patients with nonrecurrent disease did so. There was no significant correlation between metachronous recurrence after EMR and immunohistochemical staining reactions, including those for PCNA, p53, hMSH2, and hMLH1. None of the patients showed K-ras mutations. CONCLUSIONS: Thirty percent of patients with recurrent disease showed MSI-H, whereas none of the patients with nonrecurrent disease did so.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Role of the conserved acidic residue Asp21 in the structure of phosphatidylinositol 3-kinase Src homology 3 domain: circular dichroism and nuclear magnetic resonance studies.

To elucidate a role of the Src homology 3 (SH3)-conserved acidic residue Asp21 of the phosphatidylinositol 3-kinase (PI3K) SH3 domain, structural changes induced by the D21N mutation (Asp21 --> Asn) were examined by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies. In the previous study, we demonstrated that environmental alterations occurred at the side chains of Trp55 and some Tyr residues from the comparison of the near-UV CD spectra of the PI3K SH3 domain with or without a D21N mutation [Okishio, N., et al. (2000) Biopolymers 57, 208-217]. In this work, the affected Tyr residues were identified as Tyr14 and Tyr73 by the CD analysis of a series of mutants, in which every single Tyr residue was replaced by a Phe residue with or without a D21N mutation. The (1)H and (15)N resonance assignments of the PI3K SH3 domain and its D21N mutant revealed that significant chemical shift changes occurred to the aromatic side-chain protons of Trp55 and Tyr14 upon the D21N mutation. All these aromatic residues are implicated in ligand recognition. In addition, the NMR analysis showed that the backbone conformations of Lys15-Asp23, Gly54-Trp55, Asn57-Gly58, and Gly67-Pro70 were affected by the D21N mutation. Furthermore, the (15)N[(1)H] nuclear Overhauser effect values of Tyr14, Glu19, and Glu20 were remarkably changed by the mutation. These results show that the D21N mutation causes structural deformation of more than half of the ligand binding cleft of the domain and provide evidence that Asp21 plays an important role in forming a well-ordered ligand binding cleft in cooperation with the RT loop (Lys15-Glu20).

Amino Acid Substitution↗
PubMed2001

Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver.

Intrahepatic mRNA levels of type-I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co-infection by serologically-silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co-infection of serologically-silent HBV and type-I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the two subunits of the type-I IFN receptor, were quantified and compared with both the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative for hepatitis B surface antigen. Co-infection, as evaluated by a nested polymerase chain reaction, was present in 22 patients (48.9%), with dominance of the HCV genotype 1b (65.2%) over genotype 2a (31.8%). Co-infection was associated with lower IFNAR2 mRNA levels, higher levels of serum HCV RNA, and a poor IFN response, regardless of the HCV genotype. The findings suggest the possibility that co-infection by serologically-silent HBV is one of the factors that can lead to an unfavorable IFN response in chronic hepatitis C by down-regulation of IFN receptor gene expression in the liver.

Adult↗
PubMed2001

Nonrotation of the midgut with appendiceal mucocele in an adult.

Nonrotation of the midgut in adults and appendiceal mucocele are both rare pathological conditions. We report here the first case of nonrotation of the midgut associated with appendiceal mucocele. The patient was a 51-year-old man admitted to hospital with ileus. An upper gastrointestinal series and a barium enema revealed nonrotation of the midgut without midgut volvulus and with a mass in the ileocecal area. Laparotomy revealed an appendiceal mucocele adhering to the urinary bladder and the rectum. The mucocele had partly ruptured; yellowish mucinous material had entered the abdominal cavity, resulting in pseudomyxoma peritonei. Histological examination revealed a mucinous tumor of the appendix with borderline malignancy. In this patient, the ileus was caused by the appendiceal mucocele rather than being caused by nonrotation of the midgut.

Appendix↗
PubMed2001

Intragastric distribution of Helicobacter pylori during short-term omeprazole therapy: study using Carnoy's fixation and immunohistochemistry for detection of bacteria.

BACKGROUND: There is controversy about the effect of acid-suppressive therapy on Helicobacter pylori density and the severity of histological gastritis in the corpus. AIM: To evaluate the precise distribution of H. pylori, both on the surface mucus cells and in the surface mucus gel layer, by using Carnoy's fixation and immunostaining for the detection of bacteria. METHODS: A total of 19 peptic ulcer patients with H. pylori infection were studied. All patients received a 6-week course of treatment with omeprazole (20 mg/day). Before and after the therapy, H. pylori density in Carnoy-fixed tissue sections was examined immunohistochemically. The effect of omeprazole therapy on the severity of gastritis was also evaluated. RESULTS: H. pylori density and the grade of gastritis significantly decreased in the antrum after omeprazole therapy. In the corpus, however, there were no significant changes in H. pylori density or the severity of gastritis after omeprazole therapy. CONCLUSION: Carnoy's fixation and immunostaining was found to be useful for the detection of H. pylori in the surface mucus gel layer as well as on the surface mucus cells in biopsy tissue sections. By using this method, H. pylori density decreased in the antrum, but remained unchanged in the corpus after a 6-week course of omeprazole therapy.

Acetic Acid↗
PubMed2001

T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter pylori-infected gastric corpus.

BACKGROUND: Helicobacter pylori infection induces T helper-1 immune responses in inflamed mucosa. However, the role of T cell-mediated cytotoxicity in the induction of epithelial apoptosis is still unclear. The aim of this study was to investigate the involvement of the Fas/Fas ligand (Fas/Fas-L) system in the H. pylori-infected gastric corpus. MATERIALS AND METHODS: Gastric fundic biopsy specimens were taken from patients with and without H. pylori infection. The expression of Fas and Fas-L was examined by immunohistochemistry and RT-PCR. Subsets of gastric infiltrating T cells in the biopsy specimens were studied by immunohistochemistry and flow cytometry. In histological sections, apoptosis was detected by the TUNEL method. We studied the in vitro expression of Fas-L in peripheral T cells after stimulation with H. pylori antigen and interferon-gamma (IFN-gamma). The Fas-mediated in vitro cytotoxicity of activated T cells was assessed by flow cytometry. RESULTS: The numbers of CD4+ and CD8+ T cells were greater in H. pylori-infected subjects. Fas expression was abundantly increased on fundic gland epithelium, and Fas-L was detected on lamina propria mononuclear cells in H. pylori-infected mucosa. TUNEL-positive epithelial cells were also increased in H. pylori-infected subjects. H. pylori antigen and IFN-gamma induced Fas-L mRNA expression in both CD4+ and CD8+ T cells. In cytotoxic assay, activated T cells induced apoptosis in AGS cells, which could be significantly inhibited by neutralizing Fas-L antibody. CONCLUSIONS: T cell-mediated cytotoxicity via Fas/Fas-L signaling may contribute to the induction of apoptosis in gastric epithelial cells during H. pylori infection.

Adult↗