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Biomedical subjects

K Hayakawa

Publications and source records attributed to K Hayakawa.

At least 19 recordsLinked to original sources

Bisphenol A (BPA) and its source in foods in Japanese markets.

The determination of bisphenol A (BPA) and/or bisphenol A diglycidyl ether (BADGE) in foods sold in Japanese markets and in water leached from six epoxy resin cans with similar diameters was carried out using high-performance liquid chromatography (HPLC) with electrochemical detection (LC/ECD), LC-mass spectrometric detection (LC/MS) and LC-tandem mass spectrometric detection (LC/MS/MS). BPA concentrations were 0-842 ng g(-1) for 48 canned foods, 0-14 ng g(-1) for 23 foods in plastic containers, and 0-1 ng g(-1) for 16 foods in paper containers. No BADGE was detected in three canned foods. There was no difference in leaching concentrations of BPA into glycine buffers at pHs 8 and 11, and water. The amounts of BPA leached into water from six epoxy resin cans held at 121 degrees C for 20 min were almost the same as the cans' contents and were much higher than the amounts leached from cans held at or below 80 degrees C for 60 min. The amount leached depended on the type of can, but not on the amount of BADGE leached from the cans. Considerably more BPA than BADGE leached to water from six cans. Two cans whose contents had high concentrations of BPA showed no BADGE leaching even at 121 degrees C, suggesting the different kinds of epoxy resin can linings from others. The results imply that the main source of human exposure to BPA is food from cans with linings that contain high percentages of BPA as an additive or an unforeseen contaminant.

Benzhydryl Compounds↗

Screening and identification of substances that regulate nephrin gene expression using engineered reporter podocytes.

Downregulation of nephrin in podocytes leads to development of proteinuria in human and experimental kidney diseases. However, little is understood about pathophysiologic substances that regulate nephrin expression. In this report, we established conditionally immortalized reporter podocytes REPON for sensitive, continuous monitoring of nephrin gene expression. A murine podocyte cell line harboring a temperature-sensitive simian virus 40 large T antigen was stably transfected with a gene encoding secreted alkaline phosphatase (SEAP) under the control of the 5.4 or 8.3 kb nephrin gene promoter. The established reporter cells REPON5.4 and REPON8.3 were exposed to various pathophysiologic substances, and culture media were subjected to SEAP assay to identify regulators of nephrin gene expression. Among the bioactive substances tested, three physiological ligands of nuclear receptors including all-trans-retinoic acid, 1,25-dihydroxyvitamin D3, and dexamethasone significantly activated the nephrin gene promoter in a dose-dependent manner. These effects were observed in both REPON5.4 and REPON8.3 and were associated with upregulation of nephrin mRNA. The effects of these substances were synergistic, and the maximum effect was observed by combination of three agents. In contrast, inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha as well as phorbol ester significantly downregulated the activity of the nephrin promoter as well as nephrin gene expression. These results elucidated the bidirectional regulation of nephrin by distinct pathophysiologic substances and may provide molecular bases for explaining how proteinuria is induced under pathologic situations and why some ligands for nuclear receptors have the anti-proteinuric potential.

Alkaline Phosphatase↗

Solitary myofibroma of the lumbar vertebra: adult case.

We present the first known adult case of solitary myofibroma of bone, which affected a lumbar vertebra in a 33-year-old male. Radiography identified a purely lytic lesion with a sclerotic rim in the right pedicle of L1. CT showed an expansile lytic lesion with a sclerotic rim. MRI of the lesion revealed an isointense signal on T1-weighted images, an inhomogeneously hyperintense signal on T2-weighted images, and marked enhancement with gadolinium. Pathological study showed a mixed picture of nodular proliferation of spindle-shaped myoid cells and hemangiopericytomatous proliferation of short spindle/small round cells. The tumor cells were immunoreactive for smooth muscle actin and immunonegative for desmin. This case of solitary myofibroma of bone is exceptionally rare because of its occurrence in an adult older than 20 years of age and its location at an extra-craniofacial site.

Adult↗

Should we discard the renal allografts from cardiac death donors that have total ischemic time longer than 24 hours?

PURPOSE: The objective of this study was to investigate the outcome of transplantation using kidney grafts donated after cardiac death (DCD) with a total ischemic time (TIT) longer than 24 hours. PATIENTS AND METHODS: We followed 373 kidneys recovered from DCD donors and transplanted at 41 centers. All kidneys were procured from uncontrolled DCD donors. Grafts were classified into two groups according to TIT. We recorded renal function and duration of the survival period for each graft. RESULTS: Fifty-three grafts had a TIT longer than 24 hours (group 1). The other 320 grafts had a TIT less than 24 hours (group 2). The number of never functioning grafts were three in group 1 (5.7%) and 17 in group 2 (5.3%). Delayed graft function (DGF) occurred in 44 group 1 (83.0%) and 254 group 2 kidneys (79.4%) for intervals of 13.5 +/- 12.6 versus 10.9 +/- 12.6 days, respectively. Graft survival rates at 3, 5, and 10 years posttransplant were 84.9%, 73.0%, 64.1% for group 1, and 76.3%, 69.9%, 57.1% for group 2. In a Cox proportional hazards model, TIT longer than 24 hours was not a significant independent risk factor. CONCLUSION: Our results showed that even kidneys with TITs of over 24 hours yielded comparable results despite a higher incidence of DGF.

Death, Sudden, Cardiac↗

Is pulsatile perfusion necessary for renal transplantation engrafting kidneys from cardiac death donors?

BACKGROUND: There has been a considerable literature describing the use of pulsatile perfusion (PP) to evaluate the efficacy of organs from deceased donors. Since 1979, we recovered 469 kidneys from deceased donors after cardiac death (DCDs), using an in situ regional cooling technique and preservation by simple cold storage. In this study, the posttransplantation outcomes as well as long-term survivals of renal grafts from DCDs were compared with PP data in the recent literature. MATERIALS AND METHODS: We compared our recent data with 176 kidneys recovered between 1993-2002 using an in situ regional cooling technique. Patient and graft survivals were compared with those from the Scientific Registry of Transplant Recipients (SRTR) database. RESULTS: Following transplantation, 4.5% of the grafts never recovered; 10.3% of the grafts showed immediate renal function; 85.2% of the grafts had delayed graft function (DGF) with an average acute tubular necrosis (ATN) period of 13.1 days compared with 54.3% DGF from DCD using PP. Graft survival rates at 1, 3, 5, and 10 years were 90.8%, 86.5%, 77.8%, and 69.0%, respectively, compared with 89% at 1 year and 80% at 3 years reported for DCD by the SRTR in which almost 30% of the grafts underwent PP. CONCLUSIONS: Although PP seemed to have some advantage to decrease the DGF ratio, an in situ regional cooling technique with simple cold storage may provide excellent graft function and long-term graft survival as well as having benefits in cost and transportation.

Adult↗

Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock proteins in 1-hour biopsy from cardiac death donor kidneys.

AIMS: Since April 1979, 471 kidneys were retrieved from donors after cardiac death (DCD) using an in situ regional cooling technique, with excellent renal function and good long-term graft survival. However, the precise cascade of events following transplantation of DCD kidneys and the influence of ischemia-reperfusion injury remain unclear. In this study, we performed gene expression profiling using 1-hour biopsy samples from DCD kidneys versus those from living sources. METHODS: All kidney grafts were procured at our center using an in situ regional cooling technique from DCD. Living donor kidneys (LD) were harvested by open nephrectomy. All graft biopsies were performed 1 hour after reperfusion (DCD n = 8, LD n = 9). We analyzed the expression profile of 20,173 genes. RESULTS: One hundred seventy eight genes were up-regulated (>2-fold difference and DCD/LD > 1.5) and 120 down-regulated (<1/2-fold and LD/DCD > 1.5) in DCD kidneys. Expression of osteopontin (22.5 +/- 2.6-fold DCD vs 7.7 +/- 1.7 LD; P < .001), chemokines (CCL4 4.4 +/- 0.7 vs 2.5 +/- 0.3; P < .01), (CCL2 6.0 +/- 1.3 vs 2.8 +/- 0.5), CXCL1 (9.5 +/- 0.4 vs 2.0 +/- 0.2), and CXCL2 (16.7 +/- 5.3 vs 4.8 +/- 1.3; P < .05), adhesion molecule (ICAM-1 4.7 +/- 0.7 vs 2.5 +/- 0.4; P < .05), and heat shock proteins (HSPA1L 6.7 +/- 0.7 vs 1.6 +/- 0.3, HSPA1A 17.7 +/- 2.6 vs 2.4 +/- 0.5, HSPA1B 13.3 +/- 0.2 vs 3.0 +/- 0.7, HSPA5 6.7 +/- 0.8 vs 3.2 +/- 0.3, HSPB1 2.9 +/- 0.2 vs 1.0 +/- 0.1, and HSPH1 19.4 +/- 3.0 vs 5.9 +/- 1.1; P < .001) were up-regulated in the kidneys from DCD. CONCLUSION: This report analyzed global gene expression using 1-hour biopsy samples from DCD kidneys. These results may provide new insight into the identification of novel target genes for the development of therapeutic approaches and for determining graft viability of kidneys from DCD.

Biopsy↗

Components of diesel exhaust particles differentially affect Th1/Th2 response in a murine model of allergic airway inflammation.

BACKGROUND: Diesel exhaust particles (DEP) can enhance various respiratory diseases. However, it is unclear as to which components in DEP are associated with the enhancement. We investigated the effects of DEP components on antigen-related airway inflammation, using residual carbonaceous nuclei of DEP after extraction (washed DEP), extracted organic chemicals (OC) in DEP (DEP-OC), and DEP-OC plus washed DEP (whole DEP) in the presence or absence of ovalbumin (OVA). METHODS: Male ICR mice were intratracheally administrated with OVA and/or DEP components. We examined the cellular profile of bronchoalveolar lavage (BAL) fluid, histological changes, lung expression of inflammatory molecules, and antigen-specific production of IgG1 in the serum. RESULTS: DEP-OC, rather than washed DEP, enhanced infiltration of inflammatory cells into BAL fluid, magnitude of airway inflammation, and proliferation of goblet cells in the airway epithelium in the presence of OVA, which was paralleled by the enhanced lung expression of eotaxin and IL-5 as well as the elevated concentration of OVA-specific IgG1. In contrast, washed DEP with OVA showed less change and increased the lung expression of IFN-gamma. The combination of whole DEP and OVA caused the most remarkable changes in the entire enhancement, which was also accompanied by the enhanced expression of IL-13 and macrophage inflammatory protein-1 alpha. CONCLUSION: DEP-OC, rather than washed DEP, exaggerated allergic airway inflammation through the enhancement of T-helper type 2 responses. The coexistence of OC with carbonaceous nuclei caused the most remarkable aggravation. DEP components might diversely affect various types of respiratory diseases, while whole DEP might mostly aggravate respiratory diseases.

Adjuvants, Immunologic↗

Imaging of cauda equina edema in lumbar canal stenosis by using gadolinium-enhanced MR imaging: experimental constriction injury.

BACKGROUND AND PURPOSE: It has been reported that disturbance of blood flow arising from circumferential compression of the cauda equina by surrounding tissue plays a major role in the appearance of neurogenic intermittent claudication (NIC) associated with lumbar spinal canal stenosis (LSCS). We created a model of LSCS to clarify the mechanism of enhancement within the cauda equina on gadolinium-enhanced MR images from patients with LSCS. METHODS: In 20 dogs, a lumbar laminectomy was performed by applying circumferential constriction to the cauda equina by using a silicon tube, to produce 30% stenosis of the circumferential diameter of the dural tube. After 1 and 3 weeks, gadolinium and Evans blue albumin were injected intravenously at the same time. The sections were used to investigate the status of the blood-nerve barrier function under a fluorescence microscope and we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve. The other sections were used for light and transmission electron microscopic study. RESULTS: In this model, histologic examination showed congestion and dilation in many of the intraradicular veins, as well as inflammatory cell infiltration. The intraradicular edema caused by venous congestion and Wallerian degeneration can also occur at sites that are not subject to mechanical compression. Enhanced MR imaging showed enhancement of the cauda equina at the stenosed region, demonstrating the presence of edema. CONCLUSION: Gadolinium-enhanced MR imaging may be a useful tool for the diagnosis of microcirculatory disorders of the cauda equina associated with LSCS.

Animals↗

Optimal dose for stage IIIB adenocarcinoma of the uterine cervix on the basis of biological effective dose.

PURPOSE: Prognosis of uterine cervical adenocarcinoma in locally advanced stage treated with radiation therapy has been considered to be much worse than that of squamous cell carcinoma because the optimal dose for the former one has not been determined. Thus, the current study was performed to investigate the optimal dose for Stage IIIB, locally advanced stage, adenocarcinoma of the uterine cervix on the basis of the biological effective dose (BED). METHODS: One-hundred and seventy-nine patients with Stage IIIB carcinoma of the uterine cervix were treated with curative intended therapy at Kitasato University Hospital between 1976 and 2000. Out of them, 13 patients had an adenocarcinoma component in pathological findings. Nine patients were diagnosed with adenocarcinoma and four patients were diagnosed with adenosquamous cell carcinoma. All patients were treated with external radiation therapy combined with intracavitary radiation therapy. The total BED10 (T-BED10) was caluculated from the BED of the external beam radiation therapy (E-BED10) plus the BED of the intra-cavitary radiation therapy (A-BED). RESULTS: Overall survival rate was 51%. Stratified by T-BED10 overall survival rate of the T-BED10 > or = 100 Gy group was 57% and that of the T-BED10 < 100 Gy group was 30%. There was a trend toward a better survival rate of the T-BED10 > or = 100 Gy group than the T-BED10 < 100 Gy group. CONCLUSION: The current study suggested that the optimal dose for Stage IIIB adenocarcinoma of the uterine cervix might be T-BED10 > or = 100 Gy.

Adenocarcinoma↗

Weil's disease with elevated plasma D-dimer.

We report a case of Weil's disease manifesting elevation of plasma D-dimer in the acute phase. Later, in the convalescent phase after treatment, the plasma levels of D-dimer returned to normal. Plasma D-dimer can be used as a marker of fibrin formation and degradation. Based on our observations, we conjecture that fibrin formation and fibrinolysis may occur in the acute phase of Weil's disease.

Acute Disease↗

Novel method of inactivation of human immunodeficiency virus type 1 by the freeze pressure generation method.

It has been reported that high-pressure (over 600 MPa) treatment at room temperature inactivates human immunodeficiency virus type 1 (HIV-1), and it has recently been shown that the high pressure generated by the expansion of water due to freezing (freeze pressure generation method, or FPGM) has an inactivating effect on bacteria and fungi. In this study, we examined the effects of treatment by FPGM on HIV-1. A sturdy vessel filled with water and securely closed with a lid was kept at 0 degrees C to -30 degrees C. High pressures of 200 MPa and 250 MPa were generated at -20 degrees C and -30 degrees C, respectively. When T-cell-tropic and macrophage-tropic laboratory strains of HIV-1 were kept at -10 degrees C, the virus infectivity decreased to approximately 1/100, and was completely lost at -20 degrees C and -30 degrees C. Four T-cell-tropic and four macrophage-tropic laboratory strains and clinical isolates of HIV-1 became completely inactivated at -30 degrees C. Treatment by FPGM at -20 degrees C to -30 degrees C reduced HIV-1 reverse transcriptase activity to approximately one tenth. In addition, treatment by FPGM at -20 degrees C was found to destroy the ability of HIV-1 to bind to CD4+ cells. In conclusion, this study showed that treatment by FPGM at -20 degrees C to -30 degrees C destroyed the infectivity of a wide range of HIV-1 strains, and suggested that the mechanisms of HIV-1 inactivation were the reduction in viral enzyme activity and the loss of the cell-binding ability of a viral envelope protein.

Cell Line, Tumor↗

Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells.

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.

Alkaline Phosphatase↗

Blood-pressure-lowering effect of a novel fermented milk containing gamma-aminobutyric acid (GABA) in mild hypertensives.

OBJECTIVE: To study the effect of a new fermented milk product containing GABA (FMG) on the blood pressure (BP) of patients with mild hypertension. DESIGN: A randomized, placebo-controlled, single-blind trial. SETTING: The study was carried out at the outpatient clinic of the Cardiovascular Disease Center, Tokyo Metropolitan Police Hospital, Japan. SUBJECTS: The study population comprised 39 mildly hypertensive patients (16 women and 23 men) aged 28-81 y (mean, 54.2 y). INTERVENTIONS: The study consisted of a 12-week period of daily intake of FMG or placebo (weeks 1-12) followed by 2 weeks of no intake (weeks 13 and 14). We measured the peripheral BP and heart rate of seated patients at weeks 0, 2, 4, 8, 12 and 14. Routine blood study and urinalysis were performed before and after the intake. RESULTS: There was a significant decrease of BP within 2 or 4 weeks, and it remained decreased throughout the 12-week intake period. For the FMG recipients, the mean decrease after 12 weeks was 17.4+/-4.3 mmHg in the systolic BP (SBP) and 7.2+/-5.7 mmHg in the diastolic BP (DBP). Both of these values differed statistically from baseline levels (P<0.01), and the SBP of the FMG group differed from the placebo group (P<0.05). Heart rate, body weight, hematological and blood chemistry variables, and urinalysis results (glucosuria and proteinuria) did not vary both groups throughout the study. CONCLUSION: FMG may contribute to lowering BP in mildly hypertensive people.

Adult↗

TCR beta chain influences but does not solely control autoreactivity of V alpha 14J281T cells.

CD1d-dependent accumulation of alphabeta T cells bearing a canonical Valpha14Jalpha281 alpha-chain (Valpha14+ T cells) is thought to model positive selection of lipid-specific T cells, based on their ability to recognize CD1d-presented self glycolipid(s). However, it has been difficult to demonstrate self ligand specificity in this system, as most Valpha14+ T cells do not exhibit significant autoreactivity despite high reactivity to alpha-galactosylceramide presented by CD1d (alpha-GalCer/CD1d). To assess the role of TCRbeta chain in determining the alpha-GalCer/CD1d vs autoreactive specificity of Valpha14+ T cells, we conducted TCRalpha or TCRbeta chain transduction experiments. In this study we demonstrate, by combining different TCRbeta chains with the Valpha14 alpha-chain in retrovirally transduced T cell lines, that the Valpha14 alpha-chain plays a primary role, necessary but not sufficient for imparting alpha-GalCer/CD1d recognition. beta-Chain usage alone is not the sole factor that controls the extent of autoreactivity in Valpha14+ T cells, since transduction of TCRalphabeta chains from a high CD1d autoreactive Valpha14+ T cell line conferred the alpha-GalCer/CD1d specificity without induction of autoreactivity. Thus, heterogeneity of Valpha14+ T cell reactivity is due to both beta-chain diversity and control mechanism(s) beyond primary TCR structure.

Amino Acid Sequence↗

Direct chiral resolution of tartaric acid in food products by ligand exchange capillary electrophoresis using copper(II)-D-quinic acid as a chiral selector.

Chiral resolution of native DL-tartaric acid was performed by ligand-exchange capillary electrophoresis using copper(II)-D-quinic acid as a chiral selector. Factors affecting chiral resolution, migration time, and peak area of tartaric acid were studied. The running conditions for optimum separation of tartaric acid were found to be 1 mM copper(II) sulfate-10 mM D-quinic acid (pH 5.0) with an effective voltage of -15 kV at 30 degrees C, using direct detection at 250 nm, and resolution of racemic tartaric acid was approximately 1.3. With this system, chiral resolution of DL-tartaric acid in food products was conducted successfully.

Copper↗

Dioxin-like PCBs released from waste incineration and their deposition flux.

To investigate the formation and decomposition behaviors of dioxin-like PCBs during incineration of municipal solid wastes in a recently constructed facility, the concentrations of dioxin-like PCBs were measured in municipal solid waste before incineration and in the incinerator emission gas and residues. Using these values, release/inflow ratios of dioxin-like PCB congeners (ratio of the amount released from the incinerator to the amount flowing into the incinerator through waste) were calculated. For PCB congeners 126, 169, and 189, these ratios were greater than 1. In contrast, ratios of the other dioxin-like congeners were much less than 1. To take into account atmospheric sources, the amounts of dioxin-like PCBs released via emissions from municipal solid waste incineration were compared with atmospheric depositions in the Kyoto City area. Most of the PCDD/F congeners and homologue groups were deposited in amounts similar to those found in emissions from the waste incinerator. Deposition of dioxin-like PCB congeners 81, 126, 169, and 189 were also found in amounts similar to those released via the waste incinerator emissions. However, depositions of congeners 105, 114, and 118 greatly exceeded the amounts released via waste incinerator emissions. In reviewing the congener profiles of industrial PCB products and emission gas, the following general trends were observed: (i) For congeners whose contents are high in industrial PCB products (e.g., 105 and 118), the amounts deposited were much higher than the amounts released with waste incineration emission gas. (ii) For congeners whose percentages were high in the waste incineration emission gas (e.g., 126 and 189), the amounts deposited were similar to the amounts released in the waste emission gas.

Air Pollutants↗