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Biomedical subjects

Mitsuru Yanai

Publications and source records attributed to Mitsuru Yanai.

17 recordsLinked to original sources

Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats.

To date, no clinical trial has investigated the potential of CD34+ cells to treat diabetic nephropathy. This study examined the efficacy of human CD34+ cells against diabetic nephropathy in rats. Rats were administered streptozotocin (STZ) intraperitoneally and divided into three groups: normal control, STZ control, and STZ plus cell therapy. The STZ-plus-cell-therapy group was administered human umbilical cord blood-derived CD34+ cells weekly for three weeks. At eight weeks, the rats' renal function, pathology, and transcriptome profiles were assessed. Although blood glucose levels did not differ between the STZ-administered groups, urinary albumin excretion was significantly lower at 6 weeks in the STZ-plus-cell-therapy group than in the STZ control group (p < 0.001). Serum creatinine levels tended to be higher in the STZ control group and lower in the STZ-plus-cell-therapy group. Cell therapy significantly improved mesangial expansion, interstitial fibrosis, peritubular capillary rarefaction, and glomerular macrophage infiltration compared with the STZ control (p < 0.0001). Kidney transcriptomics revealed significant upregulation of genes related to M2 macrophage markers, cell homing, and angiogenesis in the STZ-plus-cell-therapy group. In rats with STZ-induced diabetic nephropathy, human CD34+ cells ameliorated renal injury through their anti-inflammatory and pro-angiogenic effects.

Animals↗

[The clinical usefulness of a newly rapid diagnosis kit, detection of respiratory syncytial virus].

ImmunoCard STAT! RSV (Meridian Bioscience, Inc, USA) is a rapid immunoassay method newly developed for detection of respiratory syncytial virus (RSV) by immunochromatography. We carried out an evaluation of the ImmunoCard STAT! RSV. One hundred fifty-nine nasal wash samples and nasopharyngeal aspirates from patients were used to evaluate three different kits, which are ImmunoCard STAT! RSV, RSV testpack (Abbott JAPAN) and Directigen EZ RSV (Nippon Becton, Dickinson and Company) . One hundred twenty-eight samples showed equivalent results. When nested reversed transcription-PCR (nested RT-PCR) results for 31 samples showing discrepancies among three kits, 10 samples were positive, and 21 samples were negative by nested RT-PCR. Compared to Nested RT-PCR results, ImmunoCard STAT! RSV showed a sensitivity of 90.5% (19/21) and a specificity of 80.0% (8/10), as well as RSV testpack showed a sensitivity of 10.0% (2/21) and a specificity of 100% (10/10), Directigen EZ RSV showed 95.2% (20/21) and 0.0% (0/ 10), respectively. Furthermore, the detection limits were also evaluated by using ACTT No. VR1540 for RSV A-2 strain, and ACTT No. VR1401 for Wash strain. The detection limit of ImmunoCard STAT! RSV was 5.15 x 10(6) TCID50/mL in subgroup A strain and was 7.58 x 10(5) TCID50/mL in subgroup B strain. This result was similar to RSV testpack, and was better than the detection limit of Directigen EZ RSV. It is concluded that ImmunoCard STAT! RSV is useful in detecting RSV in a clinical setting with equivalent performance to conventional other detecting kits.

Evaluation Studies as Topic↗

[Clinical analysis of allergic rhinitis (pollinosis) in Hokkaido].

We investigated the positive rate of specific IgE to various allergens in 548 patients with allergic rhinitis who visited 13 hospitals in Hokkaido in 2001. House dust and mite were most common allergen in our study. On the other hand, the positive rate for pollens were in the order of birch, timothy, orchard grass, and mugwort. In comparison with past study, the positive rate to birch had increased and the positive rate to timothy and orchard grass had decreased. The positive rate of specific IgE to birch was higher in Asahikawa, its neighborhood, and Sapporo, while Kushiro, Tomakomai, Wakkanai, and Nemuro lie on the coast were lower region. These findings suggested that the positive rate of specific IgE to birch varies in different region even in the same island, Hokkaido and might be influenced by climate.

Adolescent↗

Recognition of adult T-cell leukemia/lymphoma cells by CD4+ helper T lymphocytes specific for human T-cell leukemia virus type I envelope protein.

PURPOSE: Human T-cell leukemia virus type I (HTLV-I) can cause an adult T-cell leukemia/lymphoma (ATLL). Because ATLL is a life-threatening lymphoproliferative disorder and is resistant to chemotherapy, the establishment and enhancement of T-cell immunity to HTLV-I through the development of therapeutic vaccines could be of value. Thus, the identification of HTLV-I epitopes for both CD8(+) and CD4(+) T cells should facilitate the development of effective vaccines. Although numerous HTLV-I epitopes for CTLs have been identified, few epitopes recognized by CD4(+) helper T cells against this virus have been described. EXPERIMENTAL DESIGN: Synthetic peptides prepared from several regions of the HTLV-I envelope (Env) sequence that were predicted to serve as helper T-cell epitopes were prepared with use of computer-based algorithms and tested for their capacity to trigger in vitro helper T-cell responses using lymphocytes from normal volunteers. RESULTS: The results show that the HTLV-I-Env(317-331), and HTLV-I-Env(384-398)-reactive helper T lymphocytes restricted by HLA-DQw6 and HLA-DR15, respectively, could recognize intact HTLV-I+ T-cell lymphoma cells and, as a consequence, secrete lymphokines. In addition, HTLV-I Env(196-210)-reactive helper T lymphocytes restricted by HLA-DR9 were able to directly kill HTLV-I+ lymphoma cells and recognize naturally processed antigen derived from killed HTLV-I+ lymphoma cells, which was presented to the helper T cells by autologous antigen-presenting cells. CONCLUSIONS: The present findings hold relevance for the design and optimization of T-cell epitope-based immunotherapy against HTLV-I-induced diseases such as ATLL.

Algorithms↗

Neuronal calcium sensor protein visinin-like protein-3 interacts with microsomal cytochrome b5 in a Ca2+-dependent manner.

Visinin-like protein-3, which is one of the neuronal calcium sensors, has been shown to be mainly expressed in cerebellar Purkinje cells, but cellular function of this protein has not yet been elucidated. We examined the tissue distribution of murine visinin-like protein-3 transcripts using real-time reverse transcription-PCR. Visinin-like protein-3 mRNA was found to be expressed in peripheral tissues. Particularly, the expression of the transcript in the thymus was significantly higher than in other peripheral tissues. In addition, B6RVTC1 thymoma cells robustly expressed visinin-like protein-3 mRNA. To identify a target protein of visinin-like protein-3, we performed a pull-down experiment using glutathione S-transferase-tagged visinin-like protein-3 and two-dimensional electrophoresis. We demonstrated that microsomal cytochrome b(5) was a Ca(2+)-dependent binding partner of visinin-like protein-3. In a co-immunoprecipitation experiment, it was observed that hippocalcin, as well as visinin-like protein-3, could interact with cytochrome b(5). Furthermore, we confirmed that the sequence Val(114)-Tyr(127) at the C-terminal tail of cytochrome b(5) is the minimal structural requirement for binding to visinin-like protein-3. In addition, the loop His(19)-His(25) at the N terminus of visinin-like protein-3 is essential for binding to cytochrome b(5). Microsomal cytochrome b(5) was also shown to be a potential activator of cytochrome P450. The present findings raise the possibility that visinin-like protein-3 may link Ca(2+) signaling to the machinery of microsomal monooxygenase complex composed of cytochrome b(5), cytochrome P450, and some reductases. This report provides the first evidence of an interaction between visinin-like protein-3 and microsomal cytochrome b(5).

Amino Acid Sequence↗

An overview of regular dialysis treatment in Japan (as of 31 December 2001).

Questionnaire forms for an annual survey conducted at the end of 2001 were sent out to 3520 institutions, and 3485 replies were received (response rate, 99.00%). According to the survey, the dialysis population of Japan at year end was 219 183 patients, up 6.3% (13 049) over the year before. This equals 1721.9 dialysis patients per million population. The gross mortality rate was 9.3% for the year extending from the end of 2000 to the end of 2001. The mean age of patients beginning dialysis was 64.2 years (+/- 13.7 SD). The mean age of the overall dialysis population in the study year was 61.6 years (+/- 13.1 SD), which was also a higher age than the year before. Among dialysis patients, the primary disease was diabetic nephropathy in 38.1% of patients, slightly down from 39.1% the previous year. Chronic glomerulonephritis was the primary disease in 32.4% of cases, a decrease from 34.7% the previous year. This survey included for the first time the items of the lowest blood pressure during hemodialysis session, vasopressor therapy before dialysis and vasopressor therapy during dialysis session. An analysis of the relationship between the type of vascular access used at the initiation of dialysis and the survival prognosis revealed a significantly higher risk of death in patients undergoing dialysis with synthetic arterio-venous (AV) fistula, AV shunt, or catheter implantation into a central vein than in those receiving dialysis treatments with a native fistula. There was a significantly lower risk of death in the patient group in whom the vascular access was created at 3-6 months before initiation of dialysis than in those in whom such access was created at the time of initiation or within 3 months before the initiation of dialysis. An analysis of the risk factors affecting survival prognosis in maintenance hemodialysis patients showed that risk factors for death are post-dialysis systolic blood pressure over 180 mm Hg and lower than 120 mm Hg, blood pressure elevating progressively from the start to the end of dialysis, serum high density lipoprotein cholesterol concentration of less than 30 mg/dL, and a higher ultrafiltration rate. In comparisons of the death risk between the patient group with a history of intervention for ischemic heart disease and the patient group with a history of myocardial infarction or heart failure but without such intervention, among diabetes patients, those who underwent percutaneous transluminal coronary angioplasty had a significantly lower risk of death than those in whom no intervention was made.

Adolescent↗

[An attempt for standardization of serum CA19-9 levels, in order to dissolve the gap between three different methods].

It is well known that serious method-related differences exist in results of serum CA19-9, and the necessity of standardization has been pointed out. In this study, differences of serum tumor marker CA19-9 levels obtained by various immunoassay kits (CLEIA, FEIA, LPIA and RIA) were evaluated in sixty-seven clinical samples and five calibrators and the possibility to improve the inter-methodological differences were observed not only for clinical samples but also for calibrators. We supposed an assumed standard material using by a calibrator. We calculated the serum levels of CA19-9 when using the assumed standard material for three different measurement methods. We approximate the CA19-9 values using by this method. It is suggested that the obtained CA19-9 values could be approximated by recalculation with the assumed standard material would be able to correct between-method and between-laboratory discrepancies in particular systematic errors.

Biomarkers, Tumor↗

[Evaluation of renal damage using urinary ATP analysis].

It is reported that urinary ATP concentration analysis is useful for determining urinary tract infection and renal damage caused by drugs. By means of the firefly luciferin-luciferase method, we determined the reference value of urinary free ATP and evaluated the effects of urine sediments and conditions of storage. The reference value was established as 1.77 x 10(-10) to approximately 7.70 x 10(-9)M using urine samples obtained from 63 outpatients who seemed to have no renal disease. There was no significant difference in ATP concentration between 33 males and 30 females. No significant changes were observed in 11 healthy volunteers during a 1-year period. Within-run reproducibility of ATP was satisfying (8.28% and 11.4% of coefficient value in low and high concentration samples, respectively). ATP concentration was significantly decreased after centrifugation (p < 0.05) and after filtration (p < 0.01). The amounts of the red blood cells (RBC) and white blood cells (WBC) in samples whose ATP concentration was decreased after centrifugation or filtration were significantly higher than those in samples whose concentration did not decrease (p < 0.05). Urine containing many RBCs and/or WBCs might show an artificially higher ATP concentration if no preparations has been performed. There were significant positive correlations between the ATP concentrations before and after refrigeration, but no correlations before and after freezing. It is concluded that the reference value of urinary free ATP concentration was 1.77 x 10(-10) to approximately 7.70 x 10(-9) M and that care is required in the estimation of urinary ATP concentrations in samples containing many sediments, especially with WBC and RBC.

Adenosine Triphosphate↗

[Urinary ATP].

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Adenosine Triphosphate↗

Identification of naturally processed helper T-cell epitopes from prostate-specific membrane antigen using peptide-based in vitro stimulation.

PURPOSE: There is growing evidence that CD4(+) helper T lymphocytes (HTLs) play an essential role in the induction and long-term maintenance of antitumor CTL responses. Thus, approaches to develop effective T-cell-based immunotherapy should focus in the stimulation of both CTLs and HTLs reactive against tumor-associated antigens. The present studies were performed with the purpose of identifying HTL epitopes for prostate-specific membrane antigen (PSMA) for the optimization of vaccines for prostate cancer. EXPERIMENTAL DESIGN: Synthetic peptides from regions of the PSMA sequence that were predicted to serve as HTL epitopes were prepared with use of computer-based algorithms and tested for their capacity to trigger in vitro HTL responses in lymphocytes from normal volunteers. RESULTS: Our results show that 4 peptides from PSMA were effective in eliciting HTL responses. Moreover, HTL reactive to 3 of the 4 peptides were capable of reacting with naturally processed antigen in the form of freeze/thaw lysates or apoptotic cells produced from PSMA-positive LNCaP tumor cell lines. CONCLUSIONS: Human HTLs are capable of effectively recognizing epitopes derived from PSMA. The information presented here should facilitate the design of improved vaccination strategies for prostate cancer.

Animals↗

Modulation of hepatic granulomatous responses by transgene expression of DAP12 or TREM-1-Ig molecules.

DAP12 (also known as KARAP) is a novel ITAM-bearing transmembrane adapter molecule that is expressed on the cell surface of natural killer cells, monocytes, dendritic cells, and macrophages. Several myeloid cell-specific DAP12-associating receptors, such as TREM receptor family, SIRP-beta1, and MDL-1 have been identified. The in vivo function of DAP12 and its associating molecules in inflammation has remained primarily unknown. To investigate DAP12 signaling during chronic inflammation, we constructed two adenoviral gene transfer vectors to express FLAG/DAP12 (Ad-FDAP12) and the extracellular domain of mouse TREM-1 and the Fc portion of human IgG1 (Ad-TREM-1 Ig), respectively, and observed their modulatory activities in a mouse model of hepatic granulomatous inflammation elicited by zymosan A. Mice were injected with zymosan A intravenously and 24 hours after zymosan A, they were injected with Ad-FDAP12 or Ad-TREM-1 Ig. Zymosan A-induced hepatic granuloma formation peaked at day 7 and markedly declined by day 10. Although adenoviral-mediated DAP12 gene transfer did not enhance granuloma formation by day 7, it sustained and enhanced granuloma formation beyond day 7. However, an anti-FLAG monoclonal antibody used to potentiate the signaling of adenoviral-derived DAP12, enhanced granuloma formation at day 7. In sharp contrast to the effect by Ad-FDAP12, transgene expression in the liver of soluble form of extracellular domain of TREM-1 as an antagonist of DAP12 signaling, remarkably inhibited zymosan A-induced granuloma formation at all time points examined. Our findings thus suggest that both DAP12 and TREM-1 are involved in the development of granulomatous responses in the liver.

Adaptor Proteins, Signal Transducing↗

Dialysis-membrane-dependent reduction and adsorption of circulating hepatitis C virus during hemodialysis.

BACKGROUND/AIMS: Patients on chronic hemodialysis (HD) are often infected with hepatitis C virus (HCV), a common cause of chronic liver disease. In some cases, however, decreases in the serum HCV load after HD have been documented. To better understand this phenomenon, we investigated the effects of various types of dialysis membrane on virus load in the circulation in vivo and in vitro. METHODS: HCV RNA levels in patients' serum, filtrate and dialyzer membranes were analyzed semiquantitatively by reverse transcription-polymerase chain reaction (RT-PCR) before and after HD treatment with two to four different types of dialysis membrane. HCV RNA was also determined from each fraction in in vitro dialysis and ultrafiltration. RESULTS: In HD patients treated with a polysulfone (PS) membrane and a hemophan membrane, the HCV RNA titer reproducibly decreased by a factor of 10(-1)-10(-2). In contrast, a cuprophan (CU) membrane had no detectable effect on HCV viremia, and HD with the AN69 membrane reduced HCV RNA levels in only a subset of the patients. In addition, a PS membrane, but not a CU membrane, reduced the level of circulating HCV in an in vitro assay. In both in vivo and in vitro experiments, HCV RNA was recovered from the PS membrane itself, but not from the ultrafiltrate. CONCLUSIONS: Membrane-dependent adsorption of HCV occurs during HD, causing a transient reduction in HCV in the circulation of patients.

Adsorption↗

[Novel renal function marker, ATP--establishing the normal range, cases of anti-tumor drags administration for urinary-track tumor, diabetic diseases and a newborn baby].

Urinary free ATP assay by the firefly luciferin-luciferase method is a rapid and simple method for determining renal function, especially uriniferous tubule function. Normal range of urinary free ATP concentration, daily ATP excretion in urine, urinary ATP/creatinine value and ATP decomposition activity in urine is 1.1 x 10(-9)-3.4 x 10(-8) M, 4.0 x 10(-9)-4.1 x 10(-8) mole, 5.0 x 10(-13)-5.9 x 10(-11) mol/mgCr and 100-77% express for the remaining rate of additional ATP, respectively. A significant correlation was found between free ATP concentration and daily ATP excretion in urine with a correlation coefficient of 0.84. In cases of anti-tumor drug(cisplatin = cis-diamminedichloroplatinum II) administration for urinary-track tumor, abnormal urinary free ATP concentration and ATP decomposition activity in urine were clearly demonstrated after a few days of cisplatin administration. The appearance of a tendency toward abnormal relative ATP values were similar to changes in beta 2-MG and NAG values. Diabetic patients often demonstrate unusually high values of urinary free ATP concentration. In asphyxia of the newborn, urinary ATP/creatinine value were significantly higher than those in healthy newborn, but urinary NAG values did not differ.

Adenosine Triphosphate↗

[Costs and benefits in hospital infection control].

Economic concerns have taken on increasing importance in infection control since the mid 1970s in the US. The US studies on the economics of infection control have been mainly of the following types: 1) Cost estimates, 2) Effectiveness estimates, 3) Cost-effectiveness analysis, 4) Cost-benefit analysis, 5) Cost-utility analysis, 6) Cost-containment studies, 7) Cost minimization analysis and 8) Meta-analysis. The Japanese Society of Environmental Microbiology was established in 1986. There are, however, few papers on the economics of infection control in Japan. The main problems are shortage in human resources and the health care system. It is high time that a new research system of hospital infections will be established in Japan.

Cost-Benefit Analysis↗