Search

A thin superconducting solenoid magnet has been developed for the WASA detector. The magnet consists of a pair of coils and it provides a central magnetic field of 1.3T at 900A in a cylindrical volume of 0.65m in diameter and 0.555m in length. The features of this solenoid magnet are the excellent transparency for particles, conducting cooling, thermo siphon method, applying aluminum strip for conduction cooling and corrugated outer wall. Recently, the performance test was successfully carried out. In this report, magnet design and fabrication of the WASA superconducting solenoid magnet will be presented and the test results will be described.

Aim/hypothesis. We analysed Japanese MODY patients for mutations in the HNF-1α gene. Methods. Fifty unrelated Japanese patients with early-onset diabetes (diagnosed at 25 years of age or younger) or with a strong family history of diabetes were screened for mutations in the HNF-1α gene. Functional studies of the mutant HNF-1α were carried out. Results. We identified three new mutations in the HNF-1α gene in the families with a strong family history for diabetes. One mutation (L518P519fsTCC→A) was identified in three unrelated families, while the other two mutations (T521I and V617I) were identified in one family. We also identified the A site of the promoter (+102G-to-C), which was reported previously. We examined the functional properties of the mutant HNF-1α. By increasing the amount of L518P519fsTCC→A-HNF-1α, increasing inhibition of the transcription of human transthyretin (TTR) was observed (up to 61% of the control). Increasing amounts of T521I-HNF-1α or V617I-HNF-1α mutant proteins increased TTR promoter transcription up to 4.3-fold and 2.4-fold, respectively, whereas both increased transcription up to 12.4-fold of the control. Conclusion/interpretation. The L518P519fsTCC→A was identified for the first time and this mutation might be a common cause of Japanese MODY3 in Okinawa area. In addition, both the T521I and V617I mutations were present in two patients in the same family. Since the prevalence of these mutations is relatively high (10%, 5/50), the HNF-1α gene needs to be screened for mutations in patients either with early-onset diabetes or with a strong family history for diabetes. [ABSTRACT FROM AUTHOR]

Pax4 is one of the transcription factors that play an important role in the differentiation of islet beta-cells. We scanned the Pax4 gene in 200 unrelated Japanese type 2 diabetic patients and found a missense mutation (R121W) in 6 heterozygous patients and 1 homozygous patient (mutant allele frequency 2.0%). The mutation was not found in 161 nondiabetic subjects. The R121W mutation was located in the paired domain and was thought to affect its transcription activity through lack of DNA binding. Six of seven patients had family history of diabetes or impaired glucose tolerance, and four of seven had transient insulin therapy at the onset. One of them, a homozygous carrier, had relatively early onset diabetes and slowly fell into an insulin-dependent state without an autoimmune-mediated process. This is the first report of a Pax4 gene mutation that exhibits loss of function and seems to be associated with type 2 diabetes. This work provides significant implications for the Pax4 gene as one of the predisposing genes for type 2 diabetes in the Japanese. [ABSTRACT FROM AUTHOR]

Highlights: [•] The NO reduction is predominant in the absence of O2 under EB processing. [•] The O2 presence in the gas stream increases the NO2 formation during EB operation. [•] The moisture content in the stimulated gas found to inhibit the NO2 formation. [•] The Na2SO3 scrubbing of the gas during EB operation increases the NO x removal. [•] The NO and NO x concentration is reduced to the extent of 95% using reactor type II. [ABSTRACT FROM AUTHOR]

Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, and LMYC, in human somatic cells improves the quality of reprogramming to both primed and naive pluripotency. H1FOO-DD expression was associated with altered chromatin accessibility around pluripotency genes and with suppression of the innate immune response. Notably, H1FOO-DD generates naive induced pluripotent stem cells with lower variation in transcriptome and methylome among clones and a more uniform and superior differentiation potency. Furthermore, we elucidated that upregulation of FKBP1A, driven by these five factors, plays a key role in H1FOO-DD-mediated reprogramming., Competing Interests: Declaration of interests A.K. and K.F. are co-inventors on a patent describing the method for producing human iPSCs from somatic cells using H1FOO-DD. K.F. is a co-founder and CEO of Heartseed Inc., and S.T., S. Yuasa, and K.F. own equity in Heartseed Inc. S.T. is an advisor of Heartseed Inc. J.K. and H.H. are employees and K.K. is a board member of ID Pharma Co., Ltd., without compensation relating to this study. S. Yamanaka is a scientific advisor to iPS Academia Japan without salary., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Human induced pluripotent stem cells (iPSCs) are expected to be useful for regenerative medicine for many diseases. Many researchers have focused on and enabled the generation of differentiated cells or tissue-like structures, including organoids, which help to ameliorate target diseases. To promote such cell therapies, we established a clinically applicable iPSC haplobank matching as many people as possible in Japan., Methods: Through cooperation with several organizations, we recruited donors whose human leukocyte antigens (HLAs) involved in immunorejection were homozygous. The peripheral or umbilical cord blood collected from the donors was used for iPSC production by electroporation of episomal vectors. These iPSC lines were then subjected to testing, including genome analyses and sterility, to maximize safety., Findings: We constructed a clinical-grade haplobank of 27 iPSC lines from 7 donors according to good manufacturing practice regulations. However, reasons to avoid using iPSC lines include the presence of residual episomal vectors or genetic mutations in cancer-related genes., Conclusions: This haplobank provides HLA-matched iPSC lines for approximately 40% of the Japanese population. Since the haplobank's release in 2015, these iPSC lines have been used in more than 10 clinical trials. The establishment of this haplobank is an important step toward the clinical application of iPSCs in cell therapies., Funding: This study was supported by a research center network for the realization of regenerative medicine of the Japan Agency for Medical Research and Development (AMED) under grant number JP20bm0104001h0108., Competing Interests: Declaration of interests S. Yamanaka is a member of the advisory board of MED., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Naive human induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with Sendai virus (SeV) vectors. However, only dermal fibroblasts have been successfully reprogrammed this way, and the process requires culture on feeder cells. Moreover, SeV vectors are highly persistent and inhibit subsequent differentiation of iPSCs. Here, we report a modified SeV vector system to generate transgene-free naive human iPSCs with superior differentiation potential. The modified method can be applied not only to fibroblasts but also to other somatic cell types. SeV vectors disappear quickly at early passages, and this approach enables the generation of naive iPSCs in a feeder-free culture. The naive iPSCs generated by this method show better differentiation to trilineage and extra-embryonic trophectoderm than those derived by conventional methods. This method can expand the application of iPSCs to research on early human development and regenerative medicine., Competing Interests: A.K. and J.K. are co-inventors on a patent describing the method for producing naive human iPSCs from somatic cells. J.K. and H.H. are employees and K.K. is a board member of ID Pharma Co., Ltd., without compensation relating to this study. K.T. is on the scientific advisory board of I Peace, Inc., without salary. S.Y. is a scientific advisor to iPS Academia Japan without salary., (© 2022 The Authors.)

In order to expand the promise of regenerative medicine using allogeneic induced pluripotent stem cells (iPSCs), precise and efficient genome editing of human leukocyte antigen (HLA) genes would be advantageous to minimize the immune rejection caused by mismatches of HLA type. However, clinical-grade genome editing of multiple HLA genes in human iPSC lines remains unexplored. Here, we optimized the protocol for good manufacturing practice (GMP)-compatible CRISPR-Cas9 genome editing to deplete the three gene locus (HLA-A, HLA-B, and CIITA genes) simultaneously in HLA homozygous iPSCs. The use of HLA homozygous iPSCs has one main advantage over heterozygous iPSCs for inducing biallelic knockout by a single gRNA. RNA-seq and flow cytometry analyses confirmed the successful depletion of HLAs, and lineage-specific differentiation into cardiomyocytes was verified. We also confirmed that the pluripotency of genome-edited iPSCs was successfully maintained by the three germ layers of differentiation. Moreover, whole-genome sequencing, karyotyping, and optical genome mapping analyses revealed no evident genomic abnormalities detected in some clones, whereas unexpected copy number losses, chromosomal translocations, and complex genomic rearrangements were observed in other clones. Our results indicate the importance of multidimensional analyses to ensure the safety and quality of the genome-edited cells. The manufacturing and assessment pipelines presented here will be the basis for clinical-grade genome editing of iPSCs., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Cell therapy using induced pluripotent stem cell (iPSC) derivatives may result in abnormal tissue generation because the cells undergo numerous cycles of mitosis before clinical application, potentially increasing the accumulation of genetic abnormalities. Therefore, genetic tests may predict abnormal tissue formation after transplantation. Here, we administered iPSC derivatives with or without single-nucleotide variants (SNVs) and deletions in cancer-related genes with various genomic copy number variant (CNV) profiles into immunodeficient mice and examined the relationships between mutations and abnormal tissue formation after transplantation. No positive correlations were found between the presence of SNVs/deletions and the formation of abnormal tissues; the overall predictivity was 29%. However, a copy number higher than 3 was correlated, with an overall predictivity of 86%. Furthermore, we found CNV hotspots at 14q32.33 and 17q12 loci. Thus, CNV analysis may predict abnormal tissue formation after transplantation of iPSC derivatives and reduce the number of tumorigenicity tests., (© The Author(s) 2022. Published by Oxford University Press.)

Mesenchymal stem cells (MSCs) can show trisomy 7; however, the safety of these cells has not been fully investigated. The purposes of this study were to determine the ratio of patients whose synovial MSCs were transplanted clinically, to intensively investigate MSCs with trisomy 7 from a safety perspective, and to follow up the patients for 5 years after transplantation. Synovial MSCs at passage 0 were transplanted into a knee for degenerative meniscus tears in 10 patients, and the patients were checked at 5 years. The synovial MSCs were evaluated at passages 0 to 15 by G-bands and digital karyotyping, and trisomy 7 was found in 3 of 10 patients. In those three patients, 5% to 10% of the synovial MSCs showed trisomy 7. The mRNA expressions of representative oncogenes and genes on chromosome 7 did not differ between MSCs with and without trisomy 7. Whole-genome sequencing and DNA methylation analysis showed similar results for MSCs with and without trisomy 7. Transplantation of human synovial MSCs with trisomy 7 into eight mouse knees did not result in tumor formation under the skin or in the knees after 8 weeks in any mouse, whereas transplanted HT1080 cells formed tumors. In vitro chondrogenic potentials were similar between MSCs with and without trisomy 7. Five-year follow-ups revealed no serious adverse events in all 10 human patients, including 3 who had received MSCs with trisomy 7. Overall, our findings indicated that synovial MSCs with trisomy 7 were comparable with MSCs without trisomy 7 from a safety perspective., (© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

In Japan, induced pluripotent stem cell (iPSC) Stock Project has started from 2013. The goal of the Project is to manufacture and release clinical-grade HLA homozygous iPSC lines that can cover almost the entire of Japanese population. We show the summary of the cell lines distributed, test results for quality control and future plans., (Copyright © 2020. Published by Elsevier B.V.)

The use of allogeneic, pluripotent stem-cell-derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator-initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cell (iPSC)-derived anti-glypican-3 (GPC3) chimeric antigen receptor (CAR)-expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder-free production of CAR-expressing NK/ILC cells from CAR-transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8-3.6 × 10 6 iPSC within 7 weeks was 1.8-4.0 × 10 9 . These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN-γ) production against GPC3-expressing tumor cells. When the CAR-NK/ILC cells were injected into a GPC3-positive, ovarian-tumor-bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non-clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR-NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell-based immune cell cancer therapies., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Induced pluripotent stem cells (iPSCs) can be produced from various somatic cells and have the ability to differentiate into various cells and tissues of the body. Regenerative medicine using iPSCs is expected to manage diseases lacking effective treatments at present. We are establishing a safe and effective iPSC stock that can be used for regenerative medicine. Our iPSC stock is recruited from healthy, consenting HLA-type homozygous donors and is made with peripheral blood-derived mononuclear cells or umbilical cord blood. We hope to minimize the influence of immune rejection by preparing HLA homozygous iPSCs. Our stock is made at the Cell Processing Center (CPC), Center for iPS Cell Research and Application (CiRA). We are preparing iPS cells that maximize matching of the Japanese population at the major HLA loci. This iPSC stock is intended to be offered not only to Japanese centers but also overseas medical institutions and companies. In August 2015, we began offering the iPSC stock for regenerative medicine and now offer 21 clones made from 5 donors., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: Reactive oxygen species (ROS) have been implicated in cisplatin-induced nephrotoxicity. The aim of this study was to investigate the potential of using [(3)H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([(3)H]hydromethidine) for ex vivo imaging of regional ROS overproduction in mouse kidney induced by cisplatin., Methods: Male C57BL/6 J mice were intraperitoneally administered with a single dose of cisplatin (30 mg/kg). Renal function was assessed by measuring serum creatinine and blood urea nitrogen (BUN) levels and morphology by histological examination. Renal malondialdehyde levels were measured as a lipid peroxidation marker. Autoradiographic studies were performed with kidney sections from mice at 60 min after [(3)H]hydromethidine injection., Results: Radioactivity accumulation after [(3)H]hydromethidine injection was observed in the renal corticomedullary area of cisplatin-treated mice and was attenuated by pretreatment with dimethylthiourea (DMTU), a hydroxyl radical scavenger. Cisplatin administration significantly elevated serum creatinine and BUN levels, caused renal tissue damage, and promoted renal lipid peroxidation. These changes were significantly suppressed by DMTU pretreatment., Conclusions: The present study showed that [(3)H]hydromethidine was rapidly distributed to the kidney after its injection and trapped there in the presence of ROS such as hydroxyl radicals, suggesting that [(3)H]hydromethidine is useful for assessment of the renal ROS amount in cisplatin-induced nephrotoxicity.

Goniodysgenesis, malformation of the filtration angle, was observed in a New Zealand white rabbit supplied with 100 g/day rabbit chow containing 0.2% cholesterol for 10 months. Histopathology revealed cupping of the optic disc, atrophy of the retina and hyalinization of the ciliary body in the bilateral eyeballs. These findings corresponded with histopathological features caused by glaucoma. On the basis of these findings, we diagnosed this lesion as glaucoma, and classified it as primary glaucoma because of the presence of developmental defects of the filtration angle. In this case, hypercholesterolemia-induced changes, such as aggregation of lipid-laden macrophages and cholesterin clefts in the sclera or choroid, might cause deterioration of the lesions in glaucoma.

TWO TRABS: TSBAb and TSAb. TSBAb causes hypothyroidism. TSAb causes Graves' hyperthyroidism. TSBAb and TSAb block TSH-binding to cells as TRAb, measured as TSH-binding inhibitory immunoglobulin (TBII). We reevaluate TSBAb and TSAb. We studied TSBAb, TSAb, and TBII over 10 years in 34 TSBAb-positives with hypothyroidism and in 98 TSAb-positives with hyperthyroidism. Half of the 34 TSBAb-positives with hypothyroidism continued to have persistently positive TSBAb, continued to have hypothyroidism, and did not recover from hypothyroidism. Ten of the 98 TSAb-positives with hyperthyroidism continued to have positive TSAb and continued to have hyperthyroidism. TSBAb had disappeared in 15 of the 34 TSBAb-positives with hypothyroidism. With the disappearance of TSBAb, recovery from hypothyroidism was noted in 13 (87%) of the 15 patients. TSAb had disappeared in 73 of the 98 TSAb-positives with hyperthyroidism. With the disappearance of TSAb, remissions of hyperthyroidism were noted in 60 (82%) of the 73. Two of the 34 TSBAb-positives with hypothyroidism developed TSAb-positive Graves' hyperthyroidism. Two of the 98 TSAb-positive Graves' patients with hyperthyroidism developed TSBAb-positive hypothyroidism. TSBAb and TSAb are TRAbs. TSBAb-hypothyroidism and TSAb-hyperthyroidism may be two aspects of one disease (TRAb disease). Two forms of autoimmune thyroiditis: atrophic and goitrous. We followed 34 TSBAb-positive patients with hypothyroidism (24 atrophic and 10 goitrous) over 10 years. All of the 10 TSBAb-positive goitrous patients recovered from hypothyroidism and 19 (79%) of the 24 TSBAb-positive atrophic patients continued to have hypothyroidism.

Localized pretibial myxedema (PTM) is a sign of Graves' disease. A 53-year-old man with Graves' disease was admitted with the development of PTM following radioisotope (131)I treatment for Graves' hyperthyroidism. TSH receptor antibody (TRAb) titer was also increased after (131)I treatment. TRAb was measured as thyroid stimulating antibody (TSAb) or TSH-binding inhibitory immunoglobulin (TBII). PTM was noted several months after (131)I treatment. The PTM-development seems to be associated with the increased TRAb-activities. The localized pretibial myxedema was effectively treated with topical steroid (triamcinolone acetonide) ointment application with sealing cover (steroid occlusive dressing technique: steroid ODT). We also report our experience of PTM-treatment with steroid ODT in 5 other PTM patients with positive TRAb. PTM was successfully treated with steroid ODT in two patients. In these two patients, the treatment was started within several months of the appearance of PTM. In the other 4 patients, the treatment was started 5-10 years after the appearance of PTM without any beneficial effects. Early detection and early treatment are necessary for the remission of PTM.

A 75-year-old woman was found to be unconscious in hospital. She was febrile with a temperature of 38.4 degrees C. She had hypotension (blood pressure 80/40 mmHg) with serum Na 132 mEq/L and K 5.7 mEq/L (serum Na/K = 23.2), and serum cortisol 0.91 microg/dL, indicative of adrenal failure. She was admitted for the treatment of Graves' hyperthyroidism, and was found to be unconscious in hospital. We encountered a patient with unrecognized adrenocortical disease, in whom development of Graves' hyperthyroidism caused an adrenal crisis. The ACTH stimulation test indicated that she had 21-hydroxylase deficiency (21OHD); after ACTH stimulation, 17-OH-progesterone increased from 0.6 to 10.4 ng/mL (17.3 times), and 17-OH-progesterone/cortisol from 0.0049 to 0.045 (9.2 times). She did not have clinical signs of classical 21OHD. She had non-classical 21OHD (NC21OHD). Development of Graves' hyperthyroidism caused an adrenal crisis in a patient with previously unrecognized NC21OHD. A patient with unrecognized adrenocortical disease developed Graves' hyperthyroidism, which induced an adrenal crisis. She had NC21OHD.

We report a rare case of primary cutaneous diffuse large B-cell lymphoma (DLBCL) with Burkitt-like morphology. A 54-year-old man presented with multiple subcutaneous tumors. Pathological examination showed morphological features resembling Burkitt or Burkitt-like lymphoma (BL/BLL) with high MIB-1 positivity. Cytogenetic studies revealed no 8q24/c-myc translocation. After the diagnosis of Burkitt-like DLBCL, the patient was treated with CODOX-M chemotherapy (cyclophosphamide, doxorubicin, vincristine, cytarabine and methotrexate), which led to durable remission. The present case suggests that short-term, high-intensity chemotherapy used for BL/BLL may be appropriate for primary cutaneous Burkitt-like DLBCL, as well as systemic lymphoma with Burkitt-like morphology.

Multiple lymphomatous polyposis (MLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL is reviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

Clinical trials for treatment of adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) using all-trans-retinoic acid (ATRA) have shown satisfactory therapeutic responses, although efficacies were limited. Recently, many synthetic retinoids have been developed and among them, a novel synthetic retinoid, Am80 (Tamibarotene) is an RARalpha- and RARbeta-specific retinoid expected to overcome ATRA resistance. The present study examined the inhibitory effects of Am80 on HTLV-I-infected T-cell lines and ATL cells. Am80 had negligible growth inhibition of peripheral blood mononuclear cells but marked growth inhibition of both HTLV-I-infected T-cell lines and ATL cells. Am80 arrested cells in the G1 phase of the cell cycle and induced apoptosis in HTLV-I-infected T-cell lines. It inhibited also the phosphorylation of IkappaBalpha and NF-kappaB-DNA binding, in conjunction with reduction of expression of proteins involved in the G1/S cell cycle transition and apoptosis. Am80 also inhibited the expression of JunD, resulting in suppression of AP-1-DNA binding. Furthermore, severe combined immunodeficient mice with tumors induced by subcutaneous inoculation of HTLV-I-infected T cells, responded to Am80 treatment with partial regression of tumors and no side-effects. These findings demonstrate that Am80 is a potential inhibitor of NF-kappaB and AP-1, and is a potentially useful therapeutic agent against ATL.

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, has been widely studied because of its aberrant expression in human cancer. Survivin has multiple functions, including cell-cycle regulation at mitosis, inhibition of apoptosis and caspase-independent cytoprotection. Clinical studies have shown that survivin is associated with resistance to treatment and its expression is linked to poor prognosis. Recent studies indicated that Ras pathways up-regulate survivin expression in hematopoietic cells. Here we analyzed downstream pathways of Ras in interleukin-3 (IL-3)-dependent Baf-3 murine-derived pro-B lymphocytic cells that express constitutively active Ras mutants, using signaling pathway-specific inhibitors. Both mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways are involved in the induction of survivin. Downstream of PI3-K, the signaling pathway is composed of two kinases, Akt and mammalian target of rapamycin (mTOR) pathways. In the downstream targets of PI3-K, mTOR but not Akt is responsible for survivin expression. Using a counterflow centrifugal elutriator, we observed G2/M phase-dominant survivin expression in Baf-3 cells. Interestingly, constitutively active Ras mutants also induced survivin in a cell cycle-dependent manner. Reporter assays of the survivin gene promoter revealed a transcriptional regulatory cis-acting region that is responsible for Ras signaling, indicating that Ras increases the transcription of the survivin gene through specific enhancer elements. These data illustrate the pathways regulating survivin expression by Ras. Ras activates the MAPK, PI3-K and mTOR pathways, and these signals enhance survivin transcription. Our data will provide the new information about mechanisms of survivin expression by Ras-signalling pathways.

Background: Abnormalities during the postprandial state contribute to the development of atherosclerosis. Reportedly, postprandial hyperglycemia, hypertriglyceridemia, and hyperlipacidemia independently cause postprandial cytokine activation. However, it is not clear which dietary composition preferentially affects postprandial endothelial function in healthy subjects., Objective: We aimed to examine the associations of dietary composition and postprandial endothelial function in healthy subjects., Design: The effects of a single ingestion of a high-carbohydrate meal (300 kcal, 100% carbohydrate), a high-fat meal (30 g fat/m(2), 35% fat), or a standard test meal (478 kcal; 16.4% protein, 32.7% fat, 50.4% carbohydrate) on postprandial plasma concentrations of adiponectin and forearm blood flow (FBF) during reactive hyperemia were studied in healthy subjects., Results: The peak FBF response and the total reactive hyperemic flow (flow debt repayment; FDR), indexes of resistance artery endothelial function, were unchanged after ingestion of a high-carbohydrate and standard test meal but decreased 120 and 240 min after a high-fat meal. After a high-fat meal, decreases in peak FBF and FDR were well correlated with an increase in plasma free fatty acid (FFA) concentrations but not with the other biochemical variables, including triacylglycerol, insulin, glucose, total cholesterol, HDL cholesterol, and adiponectin., Conclusions: Postprandial endothelial function was impaired only after the high-fat diet and not after the high-carbohydrate or standard test meal in healthy subjects. Because such endothelial dysfunction after a high-fat meal was closely correlated with FFA concentrations, postprandial state could be hazardous, mostly through acute hyperlipacidemia in healthy subjects.