PubMed Health⌕ Search

Biomedical subjects

H Fukuhara

Publications and source records attributed to H Fukuhara.

At least 19 recordsLinked to original sources
PubMed2006

Mobilization of arsenic in groundwater of Bangladesh: evidence from an incubation study.

The extensive extraction of arsenic (As)-contaminated groundwaters for drinking, household and agricultural purposes represents a serious health concern in many districts of Bangladesh. This laboratory-based incubation study investigated the sources and mechanisms of As mobilization in these groundwaters. Several incubation studies were carried out using sediments collected from the Bangladesh aquifer that were supplemented, or not, with different nutrients, followed by an analysis of the sediment suspensions for pH, ORP (oxidation-reduction potential), EC (electrical conductivity) and As and Fe(II) concentrations. In the substrate-amended sediment suspensions incubated under anaerobic environment, there was a mobilization of As (maximum: 50-67 microg/l) and Fe(II) (maximum: 182 microg/l), while the ORP value decreased immediately and drastically (as much as -468 mV to -560 mV) within 5-6 days. In the sediment suspensions incubated under control and aerobic conditions, no significant As mobilization occurred. The simultaneous mobilization of As and Fe(II) from sediments is a strong indication that their mobilization resulted from the reduction of Fe oxyhydroxide by the enhanced activity of indigenous bacteria present in the sediments; this phenomenon also provides insights on the mobilization mechanism of As in groundwater. The concentrations of As in the sediments used in the incubation studies were strongly linked to the gradients of redox potential development that was stimulated by the quantity of organic nutrient (glucose) used. The penetration of surface-derived organic matter into the shallow aquifer may stimulate the activity of microbial communities, thereby leading to a reduction of iron oxyhydroxide and As release.

Arsenic↗
PubMed2006

Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine.

Reg I (regenerating gene product I) is a growth factor that plays a central role in the generation and regeneration of the gastric mucosal architecture. On the other hand, mouse Reg I mRNA is expressed at the highest levels in the small intestine among the gastrointestinal tissues. In the current study, with the aim to clarify the role of Reg I protein in the small intestine, the temporal and spatial pattern of Reg I expression and the phenotype of Reg I-knockout mice in the tissue were examined. In the wild-type mice, immunohistochemistry localized Reg I protein expression in absorptive cells located in the lower half of the intestinal villi. Reg I expression was undetectable until embryonic day 13 (E13), when the fetal intestine still lacks villous structure; however, it dramatically increased at E17 along with the formation and maturation of the fetal intestinal villi. In the small intestine of the adult Reg I-knockout mice, less densely packed, round-shaped aberrant morphology of the absorptive cells was observed light microscopically, and electron microscopical examination revealed a strikingly loose connection of these cells to the basement membrane. Antiproliferating cell nuclear antigen staining and anti-Ki67 staining demonstrated the marked decrease in the number of proliferating cells in the small intestinal mucosa of the knockout mice. The cell migration speed visualized by one shot labeling of 5-bromodeoxyuridine was significantly slower in the knockout mice. These phenotypes of Reg I-knockout mice emerged, in accordance with the temporal pattern of Reg I expression described above, from E17. Reg I was considered to be a regulator of cell growth that is required to generate and maintain the villous structure of the small intestine.

Animals↗
PubMed2006

Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett's dysplastic lesions.

BACKGROUND: Pit pattern diagnosis is important for endoscopic detection of dysplastic Barrett's lesions, though using magnification endoscopy can be difficult and laborious. We investigated the usefulness of a modified crystal violet chromoendoscopy procedure and utilised a new pit pattern classification for diagnosis of dysplastic Barrett's lesions. METHODS: A total of 1,030 patients suspected of having a columnar lined oesophagus were examined, of whom 816 demonstrated a crystal violet-stained columnar lined oesophagus. The early group of patients underwent 0.05% crystal violet chromoendoscopy, while the later group was examined using 0.03% crystal violet with 3.0% acetate. A targeted biopsy of the columnar lined oesophagus was performed using crystal violet staining after making a diagnosis of closed or open type pit pattern with a newly proposed system of classification. The relationship between type of pit pattern and histologically identified dysplastic Barrett's lesions was evaluated. RESULTS: Dysplastic Barrett's lesions were identified in biopsy samples with an open type pit pattern with a sensitivity of 96.0%. Further, Barrett's mucosa with the intestinal predominant mucin phenotype was closely associated with the open type pit pattern (sensitivity 81.9%, specificity 95.6%). CONCLUSIONS: The new pit pattern classification for diagnosis of Barrett's mucosa was found to be useful for identification of cases with dysplastic lesions and possible malignant potential using a crystal violet chromoendoscopic procedure.

Acetates↗
PubMed2003

Engineered IGF-I expression induces glandular enlargement in the murine prostate.

IGF-I has been implicated as a factor that may predispose one to prostate cancer and to benign prostatic hypertrophy (BPH). We established murine IGF-I transgenic mice under the control of rat probasin promoter and analysed the histology of the murine IGF-I-overexpressing prostate. Immunohistochemically, IGF-I was expressed in prostatic epithelial cells or basement membranes of the ventral, dorsal and lateral lobes in a line of IGF-I transgenic mice, but not in their control littermates. The anterior lobe did not express IGF-I. IGF-binding protein-3 (IGFBP-3), inhibitory to the mitogenic action of IGF-I, was detected in epithelial cells of prostatic ventral lobes, but not in those of the dorsal, lateral or anterior lobes of IGF-I transgenic mice. In controls, IGFBP-3 was not detected in epithelial cells of any prostatic lobe. Macroscopic prostatic size and the appearance of IGF-I transgenic mice were comparable with those of their control littermates of the same age. With a computed morphometric analysis, epithelial glands and intraglandular lumens in the prostatic lobes except the ventral lobe were smaller at 17 Months of age than at 14 Months both in IGF-I transgenic mice and controls. Glands and intraglandular lumens in the ventral prostatic lobes of IGF-I transgenic mice expressing more IGF-I protein in the prostate than controls were dense and enlarged similar to cysts compared with those of non-transgenic littermates without showing epithelial growth. Glands and lumens in the dorsal and lateral lobes of the IGF-I transgenic mice were also larger than controls at 14 and/or 17 Months of age. Glands in the anterior prostatic lobe of the IGF-I transgenic mice were not morphologically or morphometrically different from those of non-transgenic littermates. In conclusion, IGF-I transgenic mice under the control of rat probasin promoter showed more dense and enlarged epithelial glands in their prostatic ventral, dorsal and lateral lobes.

Aging↗
PubMed2002

Relationship between perfectionism, personality disorders and agoraphobia in patients with panic disorder.

OBJECTIVE: In earlier reports, we found that perfectionism might be involved in the development and/or maintenance of agoraphobia in panic disorder. The present report extends this work by examining the relationship between perfectionism and comorbidity with personality disorders in panic disorder patients with agoraphobia (PDA) and those without agoraphobia (PD). METHOD: We examined comorbidity of personality disorders by Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and assessed perfectionism using multidimensional perfectionism scale in 56 PDA and 42 PD patients. RESULTS: The PDA group met criteria for at least one personality disorder significantly more often than the PD group. With stepwise regression analyses, avoidant and obsessive-compulsive personality disorders emerged as significant indicators of perfectionism in patients with panic disorder. CONCLUSION: These findings suggest that perfectionism in panic disorder patients may be more common in those with comorbid personality disorders, and may be an important target for preventive and therapeutic efforts.

Adult↗
PubMed2001

Isolation of the TSLL1 and TSLL2 genes, members of the tumor suppressor TSLC1 gene family encoding transmembrane proteins.

We have recently identified the TSLC1 gene as a novel tumor suppressor in human non-small cell lung cancers. TSLC1 encodes a membrane glycoprotein with an extracellular domain homologous to those of immunoglobulin superfamily proteins. Truncation of TSLC1 in the cytoplasmic domain in a primary human tumor suggests that this domain is important for tumor suppressor activity. Here, we report the isolation of two TSLC1-like genes, TSLL1 and TSLL2, based on their structural homology with the sequences corresponding to the cytoplasmic domain of TSLC1. Significant similarity was also observed in the extracellular domain as well as in the overall gene structure, indicating that these three genes form a unique subfamily (the TSLC1-gene family) in the immunoglobulin superfamily genes. In contrast to the ubiquitous expression of TSLC1, TSLL1 is expressed exclusively in adult and fetal human brain, while TSLL2 is expressed in several specific tissues including prostate, brain, kidney and some other organs. Expression of TSLL1 and TSLL2 was lost or markedly reduced in many human glioma cell lines or some prostate cancer cell lines, suggesting that loss of expression of these genes might be involved in some human cancers.

Adult↗
PubMed2001

Identification of tumor suppressor candidate genes by physical and sequence mapping of the TSLC1 region of human chromosome 11q23.

Loss of heterozygosity for a locus on human chromosome 11q22-23 is observed at high frequency in non-small cell lung carcinoma (NSCLC). Introduction of a 1.1 Mb fragmented yeast artificial chromosome (YAC) mapping to this region completely suppresses the tumorigenic properties of a human NSCLC cell line, A549. Smaller fragmented YACs give partial but not complete suppression. To further localize the gene(s) responsible for this partial suppression, a bacterial artificial chromosome (BAC) and P1-based artificial chromosome (PAC) contig was constructed, completely spanning the candidate region. End sequence generated in the construction of the BAC/PAC contig identified a previously unmapped EST and served to order genomic sequence contigs from the publicly available Celera Genomics (CG) and Human Genome Project (HGP) efforts. Comparison showed that CG provided larger contigs, while HGP provided more coverage. Neither CG nor HGP provided complete sequence coverage, alone or in combination. The sequence was used to map 110 ESTs and to predict new genes, including two GenScan gene predictions that overlapped ESTs and were shown to be differentially expressed in tumorigenic and suppressed A549 cell lines.

Cell Adhesion Molecule-1↗
PubMed2001

Secretion of human proteins from yeast: stimulation by duplication of polyubiquitin and protein disulfide isomerase genes in Kluyveromyces lactis.

The efficiency of secreted production of mammalian proteins from yeasts remains unpredictably variable, depending on each protein. On the hypothesis that the control of protein conformation during protein translocation is the bottleneck in many cases, we examined the effects of an increased dosage of the genes coding for protein disulfide isomerase and of polyubiquitin on the secretion of two human proteins, serumalbumin and interleukin 1 beta. The yeast Kluyveromyces lactis was used as a production host. Duplication of either one of these genes had a strong stimulating effect on the production of the highly disulfide-bonded serumalbumin, but not of interleukin 1 beta.

Biopolymers↗
PubMed2001

Functional evidence for the presence of tumor suppressor gene on chromosome 10p15 in human prostate cancers.

Loss of heterozygosity on chromosome 10p was observed frequently in human prostate cancers. Studies have demonstrated that the introduction of the short arm of human chromosome 10 into a human prostate cancer cell line, PPC-1, by microcell-mediated chromosome transfer (MMCT), suppressed the malignant phenotype, suggesting the presence of a prostate tumor suppressor gene(s) within a region of 17 cM at distal 10p. To narrow down the candidate region harboring the tumor suppressor gene, a series of 10p fragments were transferred into PPC-1 cells by MMCT using a panel of hamster-human hybrid cells containing various portions of 10p. Four of the six hybrid cells obtained showed decreased tumorigenicity when injected subcutaneously into athymic nude mice. Tumors developed only at six of 40 injection sites for these four hybrid cells. In contrast, the other two hybrid cells, as well as parental PPC-1 cells, were judged to be fully tumorigenic because tumors appeared at a total 26 of 32 sites for the two hybrid cells and 15 of 16 sites for PPC-1. Allelotyping of 10p combined with fluorescence in situ hybridization in these hybrid cells suggested that a prostate tumor suppressor gene was located within a fragment of approximately 1.2 Mb flanked by D10S1172 and D10S226 on 10p15.1.

Adenocarcinoma↗
PubMed2001

Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector.

The purpose of this study was to test the possibility of gene transfer as a new therapy for oral cancer. Adeno-associated virus (AAV) has already been used in the fields of cystic fibrosis and Parkinson's disease as a potential vector for gene therapy because of its wide host range, high transduction efficiency, and lack of cytopathogenicity. Four human oral squamous cell carcinoma cell lines were transduced with an AAV vector containing the beta-galactosidase gene (AAVlacZ) in vitro. Gene transduction efficiency was from 20 to 50% at a multiplicity of infection (MOI; for the purposes of this study the number of vector genomes per target cell) of 1x10(3), and nearly 100% of each cell line were transduced at an MOI of 1x10(4). Next, four cell lines were transduced with an AAV vector containing the herpes simplex virus thymidine kinase (HSVtk) gene, which sensitizes transduced cells to ganciclovir (GCV). Subsequent administration of GCV resulted in nearly 100% tumor cell killing at an MOI of 1x10(4) and from 70 to 80% tumor cell killing at an MOI of 1x10(3). These results suggest that AAV-mediated gene transfer of HSVtk and administration of GCV has potential as a new therapy for oral squamous cell carcinoma.

Antiviral Agents↗
PubMed2001

TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer.

The existence of tumor-suppressor genes was originally demonstrated by functional complementation through whole-cell and microcell fusion. Transfer of chromosome 11 into a human non-small-cell lung cancer (NSCLC) cell line, A549, suppresses tumorigenicity. Loss of heterozygosity (LOH) on the long arm of chromosome 11 has been reported in NSCLC and other cancers. Several independent studies indicate that multiple tumor-suppressor genes are found in this region, including the gene PPP2R1B at 11q23-24 (ref. 7). Linkage studies of NSCLC are precluded because no hereditary forms are known. We previously identified a region of 700 kb on 11q23.2 that completely suppresses tumorigenicity of A549 human NSCLC cells. Most of this tumor-suppressor activity localizes to a 100-kb segment by functional complementation. Here we report that this region contains a single confirmed gene, TSLC1, whose expression is reduced or absent in A549 and several other NSCLC, hepatocellular carcinoma (HCC) and pancreatic cancer (PaC) cell lines. TSLC1 expression or suppression is correlated with promoter methylation state in these cell lines. Restoration of TSLC1 expression to normal or higher levels suppresses tumor formation by A549 cells in nude mice. Only 2 inactivating mutations of TSLC1 were discovered in 161 tumors and tumor cell lines, both among the 20 primary tumors with LOH for 11q23.2. Promoter methylation was observed in 15 of the other 18 primary NSCLC, HCC and PaC tumors with LOH for 11q23.2. Thus, attenuation of TSLC1 expression occurred in 85% of primary tumors with LOH. Hypermethylation of the TSLC1 promoter would seem to represent the 'second hit' in NSCLC with LOH.

Animals↗
PubMed2001

Atrial pacing during radiofrequency ablation of junctional ectopic tachycardia--a useful technique for avoiding atrioventricular bloc.

Radiofrequency catheter ablation (RFCA) was performed on a 5-year-old boy with congenital junctional ectopic tachycardia (JET) that was refractory to medical management. Because of the lack of retrograde atrial depolarization during tachycardia, radiofrequency energy was delivered during atrial overdrive pacing to confirm the presence of preserved atrioventricular (AV) conduction. Although the procedure was complicated by complete right bundle branch block after ablation of the para-Hissian region, the patient regained sinus rhythm accompanied by normal AV conduction. Rapid atrial pacing during RFCA of JET may be safely used to avoid AV block.

Cardiac Pacing, Artificial↗
PubMed2001

Traumatic rupture of the bronchus.

We experienced a case of incomplete traumatic rupture of the bronchus which was operated on two months after a traffic accident. Traumatic rupture of the bronchus is rare after blunt chest injury but it can have serious consequences. Early surgical repair is recommended without repeated attempts to remove granulation tissue if the initial attempt at non-surgical repair results in failure, even in the case of incomplete rupture.

Adolescent↗
PubMed2000

Protein disulphide isomerase genes of Kluyveromyces lactis.

Two genes of Kluyveromyces lactis, KlPDI1 and KlMPD1, were studied. They code for a protein disulphide isomerase and its structural and functional homologue, respectively. The KlPDI1 product was 52.6% identical to Pdi1p and the KlMPD1 product 47% identical to Mpd1p of S. cerevisiae. Both genes contained the thioredoxin-active site-related signature. Their C-termini showed a new variant of the endoplasmic reticulum-retention signal, QDEL. A single copy of KlPDI1 was able to complement the growth defect of a pdi1 mutation. KlMPD1 on a multicopy vector partially suppressed the klpdi1 and pdi1 mutations. The Klpdi1 null mutation was lethal. The klmpd1 disruptant was viable, but showed an increased sensitivity to high temperature. Several stress response motifs were present in the upstream sequence of KlMPD1, but not of KlPDI1, whilst the opposite is known for the S. cerevisiae homologues. The viability of the klmpd1 mutant under starvation for nitrogen or carbon source was not different from that of the wild-type. The syntenic relationship is discussed for the KlPDI1 gene regions with respect to the duplicated segments PDI1/EUG1 in S. cerevisiae.

Amino Acid Sequence↗
PubMed2000

The ubiquitin-encoding genes of Kluyveromyces lactis.

The ubiquitin encoding genes of Kluyveromyces lactis were cloned. Three genes, KlUBI1, KlUBI3 and KlUBI4, were found in this yeast, while in Saccharomyces cerevisiae there are four genes, UBI1, -2, -3 and -4. The UBI1/UBI2 duplication is thus absent from the K. lactis genome. General structural features of ubiquitin genes were very similar in these two species (presence of an intron in KlUBI1, fusion to ribosomal protein genes in KlUBI1 and KlUBI3, spacer-less polyubiquitin repeats in KlUBI4). Disruption or deletion of K. lactis ubiquitin genes showed that: (a) disruption of KlUBI1 was lethal (in S. cerevisiae, ubi1/ubi2 double deletion is lethal); (b) KlUBI3 is also an essential gene for cell growth; (c) deletion of KlUBI4 led to an increased sensitivity to high temperature, similar to the ubi4 mutation in S. cerevisiae, but, in contrast to the latter, the klubi4 mutant was not sensitive to carbon or nitrogen source starvation. The syntenic relationship of ubiquitin loci between K. lactis and S. cerevisiae genomes is also described.

Base Sequence↗
PubMed2000

Differentially expressed mRNAs in androgen-independent but not androgen-dependent Shionogi carcinoma.

UNLABELLED: Recently, a new and highly effective method termed suppressive subtractive hybridization (SSH) has been introduced to clone differentially expressed mRNAs. Genes expressed in androgen-independent but not in androgen-dependent tumors, and vice versa, are obviously significant to delineate the mechanisms of androgen dependency/independency of these tumors. Mouse mammary cancer (Shionogi carcinoma-115) has been extensively used to analyze the mechanism of androgen-dependent cancer growth. METHODS: We cloned androgen-independent and androgen-dependent Shionogi carcinoma-115 specific mRNAs by the SSH method. Cloned sequences were compared with known sequences using NCBI BLAST across the Internet. Two clones were positive for cDNA insert when androgen-independent cDNA was used as tester cDNA, while no clones were positive using the androgen-dependent tester cDNA. One of the former was mouse protein kinase C beta-II while the other was a new DNA sequence. Mouse protein kinase C beta-II mRNA and the new mRNA were shown to be differentially expressed by RT-PCR analysis in androgen-independent but not androgen-dependent Shionogi carcinoma. Two mRNA species differentially expressed in androgen-independent but not androgen-dependent Shionogi carcinoma were cloned by the SSH method. The significance of these mRNAs for androgen-dependency/independency of Shionogi carcinoma should be explained in future studies.

Androgens↗