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Koichi Suzuki

Publications and source records attributed to Koichi Suzuki.

At least 55 records · Page 3Linked to original sources
PubMed2005

TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF.

Toll-like receptors (TLR) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play an essential role in intracellular eradication of engulfed pathogens. Here, we demonstrate the physical and functional association between components of the cytosolic NADPH oxidase and TLR-mediated signaling molecules. Cytosolic components of NADPH oxidase suppressed TLR-mediated NF-kappaB activation as well as IFN-beta promoter activation. We demonstrate that TNF-associated factor (TRAF) 4 associates with p47(phox), a component of cytosolic NADPH oxidase, and physically interacts and functionally counteracts with TRAF6 and Toll-IL-1 receptor (TIR) domain-containing adaptor-inducing IFN-beta (TRIF) molecules that critically regulate TLR-mediated signaling. TRAF4 mRNA expression was elicited in RPMI 8226 cells following LPS or CpG DNA treatment. These results suggest that TRAF4 participates in the molecular mechanism underlying silencing of TLR-mediated signaling through the interaction with molecules harboring phagosome/endosome membrane.

Adaptor Proteins, Vesicular Transport↗
PubMed2005

Expression profiling of a diapause-specific peptide (DSP) of the leaf beetle Gastrophysa atrocyanea and silencing of DSP by double-strand RNA.

A diapause-specific peptide (DSP) composed of 41 amino acid residues including 6 cysteines, has been isolated from diapausing adults of the leaf beetle Gastrophysa atrocyanea. In this study, DSP was found to be expressed primarily in diapausing adults and to a minor extent in pupae, but not in eggs, larvae, or post-diapausing adults. DSP was not induced by bacterial or fungal challenge. DSP-less adults were generated by the injection of double-stranded RNA (dsRNA) corresponding to the dsp gene into pre-diapausing adults. Gene silencing induced by dsRNA was found to be a useful tool for the analysis of DSP in diapausing adults. DSP-less adults showed similar burrowing behavior and oxygen consumption as control insects suggesting that DSP is not essential for the normal onset and maintenance of diapause.

Animals↗
PubMed2005

ABO blood group alleles and genetic recombination.

The ABO blood group gene is known to code for a glycosyltransferase, which acts at the last step of sequential extension of oligosaccharide chains attached to glycoproteins or glycolipids. Since the first delineation of the molecular basis of ABO blood group, genotype-phenotype relationship of various ABO alleles has been extensively studied. Major differences between the coding sequences of them were found to reside in exons 6 and 7. Over 70 alleles have been analyzed for their sequences, more than half of which were found to exhibit hybrid nature in their sequence motifs. These alleles seem to result not from recurrent mutation but most likely from intragenic recombination due to crossing-over or genetic conversion. Occurrence of reciprocal products and de novo recombinant support the idea. The aim of this article is to outline the genetic mechanism underlying the ABO allelic diversity with a speculative model for genesis of an allele.

ABO Blood-Group System↗
PubMed2005

Latent IgA deposition from donor kidney is the major risk factor for recurrent IgA nephropathy in renal transplantation.

BACKGROUND: Previous studies have recognized risk factors for recurrent IgA nephropathy (r-IgAN) in renal transplantation. However the clinical significance of latent IgA deposition from the donor kidney remains to be determined. PATIENTS AND METHODS: Between 1992 and 1999, 0-hour allograft biopsies were performed in 510 renal transplantation recipients at the Kidney Center of Tokyo Women's Medical University. Among these 510 patients, there were 49 whose primary disease was identified as IgAN. Among these 49 patients, 13 patients (26.5%) were diagnosed as having r-IgAN based on renal biopsy. We compared risk factors of r-IgAN, including IgA deposition, between the r-IgAN and non-r-IgAN groups. RESULTS: We assessed factors previously reported to be risk factors for r-IgAN, such as follow-up period after transplantation, sex, ages of donors and recipients, donor type, ABO compatible or incompatible transplantation, number of HLA-A, B, and DR mismatches, number of donors with HLA-A2, B35, B46, and/or DR4, duration to end stage renal disease, duration of dialysis, and latent IgA deposition from donor kidneys. Latent IgA deposition was the only risk factor that differed significantly in frequency between patients with and without recurrence (38.5% in r-IgAN group vs. 9.1% in non-r-IgAN group, p = 0.037). Other factors did not differ significantly between the two groups. Clinical factors, such as urinary protein excretion, urinary red blood cell sediment and serum creatinine, were significantly worse and the number of patients who required hemodialysis 5 yr after transplantation was significantly higher in the r-IgAN group than in the non-r-IgAN group (38.5 vs. 5.6%, p = 0.001). Four of the five patients who required hemodialysis in the r-IgAN group had latent IgA deposition from the donor kidney. CONCLUSION: Our data suggest that 26.5% out of patients with primary IgAN will develop recurrence within 5 yr after transplantation. Latent IgA deposition from the donor kidney was one of the risk factors of r-IgAN and it would lead to the development of r-IgAN. Moreover, r-IgAN will compromise graft survival, especially in cases with latent IgA deposition from the donor kidney.

Adolescent↗
PubMed2005

Managing patients with an overactive bladder and glaucoma: a questionnaire survey of Japanese urologists on the use of anticholinergics.

OBJECTIVES: To establish the views of urologists on the use of anticholinergic drugs for treating the overactive bladder (OAB) in patients with glaucoma. SUBJECTS AND METHODS: In February 2004 a self-description questionnaire was mailed to all 417 urologists who were members of the Tokai Society of Voiding Dysfunction, to determine current practice in Japan for patients with an OAB and glaucoma. Subgroups were analysed between the types of practice and the duration since the urologists had graduated from medical school. RESULTS: Of the 155 respondents, 76 (49%) routinely enquired about a history of glaucoma before prescribing anticholinergics, and 45 (29%) routinely referred patients with such a history to ophthalmologists. To treat patients with OAB and glaucoma, 102 (66%) would prescribe anticholinergics if permission were available from the ophthalmologist, 33 (21%) chose other treatments and 17 (11%) abandoned treatment. Forty-nine urologists (32%) were currently prescribing anticholinergics to patients with glaucoma. As to knowledge about glaucoma, 132 (85%) urologists knew that there were two types of glaucoma and 98 (63%) knew about laser iridotomy. The proportion of urologists who knew of the two types of glaucoma and asked patients for this information was significantly higher in university than in general hospitals (P < 0.05). CONCLUSIONS: Although anticholinergic drugs can precipitate angle-closure glaucoma by pupillary block, they are not contraindicated in open-angle glaucoma or in angle-closure glaucoma that has already been treated by laser iridotomy. Not all urologists are aware of this difference, at least in Japan. Some urologists avoid anticholinergics in all patients with glaucoma, while others pay little attention to glaucoma. Routine history taking and referral to ophthalmologists allows many patients with OAB and glaucoma to benefit safely from anticholinergics. Moreover, clinicians should be aware of patients with OAB who have not been evaluated by ophthalmologists but who are at risk of angle-closure glaucoma.

Attitude of Health Personnel↗
PubMed2005

Nephrin and podocin dissociate at the onset of proteinuria in experimental membranous nephropathy.

BACKGROUND: The slit diaphragm plays a critical role in maintaining the barrier function of the glomerular capillary wall. The pathogenic mechanism of proteinuria in membranous nephropathy remains uncertain. This study was undertaken to analyze the pathogenic role of slit diaphragm in proteinuria in experimental membranous nephropathy. METHODS: The expression and the localization of slit diaphragm-associated molecules (nephrin, podocin, and CD2AP) and other podocyte-associated molecules (podocalyxin and alpha(3) integrin) in passive and active Heymann nephritis were analyzed by immunofluorescence and Western blot analysis. The interaction of slit diaphragm-associated molecules was investigated by the dual-labeling immunofluorescence method. The mRNA expression of these molecules was also analyzed. RESULTS: Shifts in nephrin and podocin staining patterns, from linear to granular, were detected in the early stages of passive Heymann nephritis. These shifts were not parallel, and the dissociation of these molecules was detected by the dual-labeling immunofluorescence method in passive and active Heymann nephritis. Western blot analyses with sequentially solubilized materials indicated that the nephrin-rich fraction changed from being partly detergent-resistant to being predominantly detergent-soluble. This change did not occur with podocin. Nephrin excreted into urine was already detected in the early stages of passive Heymann nephritis. Decreased mRNA expression of nephrin and podocin was observed before the onset of proteinuria. By contrast, no extensive change in the expression of alpha(3) integrin was observed in this study. CONCLUSION: Nephrin is dissociated from podocin and excreted into urine in the early stages of Heymann nephritis. The reduced expression of nephrin and podocin, along with their dissociation, may contribute to the development of proteinuria in Heymann nephritis.

Adaptor Proteins, Signal Transducing↗
PubMed2005

[Current advances in leprosy research activities].

Due to the advent of multi-drug therapy (MDT) recommended by the WHO, for the treatment of leprosy, presently, leprosy is regarded as a "curable disease". The number of new cases in Japan is relatively very low, due to which the disease is likely to be neglected, but on scientific grounds, there is a necessity to perform in depth studies. Leprosy caused by M. leprae is still unclear on various aspects including transmission, immunology, nerve damage etc. Here we introduce the recent advances in the field of basic leprosy research.

Animals↗
PubMed2005

[Bladder stone caused by olive oil following TVT operation].

Tension-free vaginal tape (TVT), a less-invasive variation of the suburethral sling, has been rapidly gaining popularity worldwide in the treatment of female stress urinary incontinence. We report on two cases of bladder stones composed of fatty acid calcium following TVT operations. Case 1: A 76-year-old woman with a history of hysterectomy due to cervical cancer was suffering from vault prolapse. The insertion of a ring pessary lead to the development of stress urinary incontinence, and she was referred to our hospital. As she was frail, sexually inactive, and elderly, she underwent partial colpocleisis (Le Fort operation) combined with a TVT operation. One-month postoperative videourodynamics and chain cystourethrography (CUG) using olive oil as the lubricant showed cure of incontinence and mild support of the urethra. Her maximum flow rate was 18.8 ml/s and no residual urine was observed. Six months postoperatively she developed postmiction pain and pyuria that were not improved by antibiotics. Cystoscopy showed a small bladder stone, whose removal cured cystitis. Case 2: A 49-year-old woman, with a history of abdominal hysterectomy due to myoma uteri, visited our hospital complaining of stress urinary incontinence. A periurethral collagen injection was only temporarily effective, and she underwent a TVT operation. A 1-month postoperative evaluation including chain CUG using olive oil as the lubricant showed cure of incontinence, mild support of the urethra, a maximum flow rate of 28.8 ml/s, and no residual urine. Two months postoperatively she developed miction pain and pyuria that were solved by removing a small bladder stone. Anti-incontinence surgery increases the risk of developing bladder stones due to either foreign bodies (bladder erosion) or obstruction. However, neither of our cases had these conditions; instead, both bladder stones were composed of fatty acid calcium that appeared to be related to the olive oil used as the lubricant in chain CUG. Only four cases (including ours) of bladder stones composed of fatty acid calcium have been documented, but they may indicate that care is necessary when using olive oil as a contrast medium or lubricant in the urinary tract. When a woman with a history of anti-incontinence surgery has persisting or recurrent cystitis, cystoscopy should be performed to exclude bladder erosion and stones.

Aged↗
PubMed2004

Expression of class II major histocompatibility complex molecules on thyrocytes does not cause spontaneous thyroiditis but mildly increases its severity after immunization.

Class II major histocompatibility complex (MHC) molecules are classically expressed on antigen-presenting cells of the hematopoietic lineage but have also been described on epithelial cells in association with autoimmunity. In this context, however, it remains debatable whether class II MHC molecules are the initiating event or rather the consequence of the autoimmune attack. In addition, the role of epithelial class II expression once the autoimmune attack has begun is unknown. We generated transgenic mice expressing in the thyroid follicular cells the class II transactivator, the master regulator of all the genes in the class II MHC pathway. The study used a cohort of 245 CBA/J mice (127 wild-type and 118 transgenic), both in basal conditions (n = 63) and at different time points after immunization with mouse thyroglobulin (n = 182). In basal conditions, transgenic mice were similar to wild-type controls and did not develop spontaneous autoimmune thyroiditis, despite the aberrant expression of class II MHC molecules on thyrocytes. After immunization, thyroiditis was 8% more severe in transgenics than controls (95% confidence interval from 1.8-13.4%; P = 0.033), especially during the florid stages of disease. These findings suggest that expression of class II MHC molecules on epithelial cells is not sufficient to initiate autoimmunity but mildly modulates an already established autoimmune attack against the target organ.

Animals↗
PubMed2004

Transcriptional regulation of the human TLR9 gene.

To clarify the molecular basis of human TLR9 (hTLR9) gene expression, the activity of the hTLR9 gene promoter was characterized using the human myeloma cell line RPMI 8226. Reporter gene analysis and EMSA demonstrated that hTLR9 gene transcription was regulated via four cis-acting elements, cAMP response element, 5'-PU box, 3'-PU box, and a C/EBP site, that interacted with the CREB1, Ets2, Elf1, Elk1, and C/EBPalpha transcription factors. Other members of the C/EBP family, such as C/EBPbeta, C/EBPdelta, and C/EBPepsilon, were also important for TLR9 gene transcription. CpG DNA-mediated suppression of TLR9 gene transcription led to decreased binding of the trans-acting factors to their corresponding cis-acting elements. It appeared that suppression was mediated via c-Jun and NF-kappaB p65 and that cooperation among CREB1, Ets2, Elf1, Elk1, and C/EBPalpha culminated in maximal transcription of the TLR9 gene. These findings will help to elucidate the mechanism of TLR9 gene regulation and to provide insight into the process by which TLR9 evolved in the mammalian immune system.

Animals↗
PubMed2004

The 90K protein increases major histocompatibility complex class I expression and is regulated by hormones, gamma-interferon, and double-strand polynucleotides.

Here we report the cloning of the rat 90K, a homolog of the mouse cyclophilin C-associated protein/mouse adherent macrophage and human 90K. The protein is constitutively expressed by FRTL-5 thyrocytes, and its levels are modulated by TSH, insulin/IGF-I, and gamma-interferon. Transfection of the cells with 90K cDNA or exposure to purified 90K resulted in a significant increase of the expression of major histocompatibility complex class I but not class II antigens. An increased expression of 90K was obtained after viral infection or introduction into the cells of fragments of viral, bacterial, or mammalian double-strand polynucleotides. The increase was sequence independent, not CpG mediated, and associated with the expression of molecules characterizing antigen-presenting-cell phenotype. The present data along with results from previous studies suggest that 90K plays an important role in the maintenance of an appropriate level of immune response.

Amino Acid Sequence↗
PubMed2004

Mechanism of iodide/chloride exchange by pendrin.

We performed an electrophysiological study to investigate ion transport of pendrin and thereby understand the pathogenesis of Pendred syndrome. Using pendrin-transfected COS-7 cells, we could show that pendrin transports both iodide and chloride measured as voltage-dependent inward and outward membrane currents. Chloride in the culture medium, [Cl-]o, was efficiently exchanged with cytoplasmic iodide, [I-]i, under physiological concentrations, indicating that pendrin is important for chloride uptake and iodide efflux. Although exchange of iodide in the medium, [I-]o, with cytoplasmic chloride, [Cl-]i, was observed, a significantly high concentration of iodide (10 mm) was required. In addition, either iodide or chloride was required on both sides of the cell membrane for the anion exchange activity of pendrin, indicating that iodide and chloride activate the exchange activity of pendrin while they are transported. The present study further supports that pendrin is responsible for the iodide efflux in thyroid cells where intracellular iodide concentration is high and that the general function of pendrin in other tissues is to transport chloride through exchange with other anions.

Animals↗
PubMed2004

Mammalian D-aspartyl endopeptidase: a scavenger for noxious racemized proteins in aging.

The accumulation of D-isomers of aspartic acid (D-Asp) in proteins during aging has been implicated in the pathogenesis of Alzheimer's disease, cataracts, and arteriosclerosis. Here, we identified a specific lactacystin-sensitive endopeptidase that cleaves the D-Asp-containing protein and named it D-aspartyl endopeptidase (DAEP). DAEP has a multi-complex structure (MW: 600kDa) and is localized in the inner mitochondrial membrane of mouse and rabbit, but DAEP activity was not detected in Escherichia coli, Saccharomyces cerevisiae, and Caenorhabditis elegans. A specific inhibitor for DAEP was newly synthesized, and inhibited DAEP activity (IC(50), 3microM), a factor of 10 greater than lactacystin on DAEP. On the other hand, the inhibitor did not inhibit either the 20S or 26S proteasome.

Aging↗
PubMed2004

Effects of the length and modification of the separation channel on microchip electrophoresis-mass spectrometry for analysis of bioactive compounds.

Analyses of amino acids and peptides were performed using a quartz microchip and an interface for microchip electrophoresis-electrospray ionization mass spectrometry (MCE-ESI-MS). In MCE-ESI-MS, negative pressure caused by ESI increased band broadening and deteriorated separation. We tried to suppress the negative pressure and improve separation using a microchip with a long separation channel. Separations of peptide standards were compared using two microchips with long separation channel (58.9 mm) and short one (22.9 mm). Theoretical plate numbers and resolution were improved significantly using the former. The theoretical plate numbers of [Val4]angiotensin was 8600 using the former and 1700 using the latter. When background electrolytes of low pH were used in an uncoated quartz microchip, electrokinetic injection was difficult because of weak electroosmotic flow. The use of successive multiple ionic polymer layers coating of the microchip channel stabilized electrokinetic injection and permitted analysis of amino acids and peptides even under low pH conditions. Separation of amino acids was successfully performed using formic acid solution (pH 2.5) as background electrolyte.

Electrophoresis↗
PubMed2004

Serum tryptase levels in sudden infant death syndrome in forensic autopsy cases.

An elevated serum tryptase concentration is considered to be a specific marker for systemic mast-cell activation, a central feature of anaphylaxis, which has been observed in some cases of sudden infant death syndrome (SIDS). However, it is still unclear whether anaphylaxis is involved in the etiology for SIDS. In the present study, we measured serum tryptase levels in 21 infants with SIDS, and 14 control infants from forensic autopsy cases by Uni-CAP TRYPTASE Fluoroenzyme immunoassay system, which detects both alpha- and beta-tryptase. The assay did not show any significant elevation of tryptase levels in the SIDS group compared with controls. Additionally, increased concentrations of tryptase were not observed in any SIDS case. Our results indicated that anaphylaxis does not seem to be involved in the etiology of SIDS.

Autopsy↗
PubMed2004

Interferon-alpha and antisense K-ras RNA combination gene therapy against pancreatic cancer.

Interferon alpha (IFN-alpha) is used worldwide for the treatment of a variety of cancers. For pancreatic cancer, recent clinical trials using IFN-alpha in combination with standard chemotherapeutic drugs showed some antitumor activity of the cytokine, but the effect was not significant enough to enlist pancreatic cancer as a clinically effective target of IFN-alpha. In general, an improved therapeutic effect and safety are expected for cytokine therapy when given in a gene therapy context, because the technology would allow increased local concentrations of this cytokine in the target sites. In this study, we first examined the antiproliferative effect of IFN-alpha gene transduction into pancreatic cancer cells. The expression of IFN-alpha effectively induced growth suppression and cell death in pancreatic cancer cells, an effect which appeared to be more prominent when compared with other types of cancers and normal cells. Another strategy we have been developing for pancreatic cancer targets its characteristic genetic aberration, K-ras point mutation, and we reported that the expression of antisense K-ras RNA significantly suppressed the growth of pancreatic cancer cells. When these two gene therapy strategies are combined, the expression of antisense K-ras RNA significantly enhanced IFN-alpha-induced cell death (1.3- to 3.5-fold), and suppressed subcutaneous growth of pancreatic cancer cells in mice. Because the 2',5'-oligoadenylate synthetase/RNase L pathway, which is regulated by IFN and induces apoptosis of cells, is activated by double-strand RNA, it is plausible that the double-strand RNA formed by antisense and endogenous K-ras RNA enhanced the antitumor activity of IFN-alpha. This study suggested that the combination of IFN-alpha and antisense K-ras RNA is a promising gene therapy strategy against pancreatic cancer.

Adenoviridae↗