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In the field of continuous-variable quantum information processing, non-Gaussian states with negative values of the Wigner function are crucial for the development of a fault-tolerant universal quantum computer. While several non-Gaussian states have been generated experimentally, none have been created using ultrashort optical wave packets, which are necessary for high-speed quantum computation, in the telecommunication wavelength band where mature optical communication technology is available. In this paper, we present the generation of non-Gaussian states on wave packets with a short 8-ps duration in the 1545.32 nm telecommunication wavelength band using photon subtraction up to three photons. We used a low-loss, quasi-single spatial mode waveguide optical parametric amplifier, a superconducting transition edge sensor, and a phase-locked pulsed homodyne measurement system to observe negative values of the Wigner function without loss correction up to three-photon subtraction. These results can be extended to the generation of more complicated non-Gaussian states and are a key technology in the pursuit of high-speed optical quantum computation.
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Even though the toughness of hydrogels is usually adjusted by changing the cross-linking density and structure, or the polymer concentration, we have discovered a new strategy to control the toughness via modulating the side-chain length. In this study, this strategy was applied to biocompatible poly(oligo(ethylene glycol) methyl ether methacrylate) with long ethylene-oxide side chains.
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A 64-year-old man with gastric tumor in the antrum had been diagnosed with gastric neuroendocrine carcinoma(NEC) by biopsy and multiple lymph node metastases(#3 and #6)by abdominal computed tomography. After staging laparoscopy showed that there were no non-curative factors, neoadjuvant chemotherapy(S-1/cisplatin[CDDP]: 2 courses)and distal gastrectomy and D2 lymph node dissection were performed. The pathological diagnosis was shown as pathological complete response(pCR). After adjuvant chemotherapy(S-1/CDDP: 2 courses, S-1: 6 courses)was administered, the patient is alive at 8 years without recurrence.
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Carcinoma Neuroendócrino , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/cirurgia , Cisplatino , Combinação de Medicamentos , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Ácido Oxônico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , TegafurRESUMO
A 78-year-old man with advanced thoracic esophageal cancer underwent radical esophagectomy after neoadjuvant chemotherapy with cisplatin plus 5-FU. He had left adrenal metastasis 10 months after surgery and removed it, but 3 months later he had liver metastases. After 2 courses of chemotherapy with nedaplatin plus 5-FU, resection was performed. One course of nedaplatin plus 5-FU for adjuvant chemotherapy was added, but the patient was followed up without another chemotherapy after surgery because of intestinal obstruction due to infection and increase of the lymphatic cyst in the abdominal cavity. Six months after the liver resection, nodules appeared in the right lung, and 4 months later, multiple nodules extending to both lungs were observed. Therefore, it was judged that there were multiple lung metastases, and administration of nivolumab was started. He has been 3 years since the recurrence of esophageal cancer and 17 months after the start of nivolumab administration, but the recurrence lesion is only progressing to lung metastasis.
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Neoplasias Esofágicas , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Nivolumabe/uso terapêutico , Fluoruracila , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/secundário , EsofagectomiaRESUMO
Bifidobacterium animalis subsp. lactis GCL2505 in combination with inulin has been shown to have several health benefits, including an improvement in the intestinal microbiota and a reduction in human visceral fat. Previous studies have suggested that the visceral fat reduction of GCL2505 and inulin may be achieved by improving daily energy expenditure. This parallel, placebo-controlled, randomized, double-blind study was conducted to evaluate the effects of GCL2505 and inulin on resting energy expenditure (REE) in overweight or mildly obese Japanese adults (n = 44). Participants ingested 1 × 1010 colony forming units of GCL2505 and 5.0 g of inulin daily for 4 weeks. REE score at week 4 was set as the primary endpoint. At week 4, the REE score of the GCL2505 and inulin group was significantly higher than that of the placebo group, with a difference of 84.4 kcal/day. In addition, fecal bifidobacteria counts were significantly increased in the GCL2505 and inulin group. Our results indicated that the intake of GCL2505 and inulin improves energy balance, which is known to be a major factor of obesity, by modulating the microbiota in the gut. This is the first report to demonstrate the effects of probiotics and dietary fiber on REE in humans.
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Fibras na Dieta , Fezes , Microbioma Gastrointestinal , Inulina , Obesidade , Probióticos , Humanos , Método Duplo-Cego , Masculino , Feminino , Probióticos/administração & dosagem , Fibras na Dieta/administração & dosagem , Fibras na Dieta/farmacologia , Pessoa de Meia-Idade , Adulto , Inulina/administração & dosagem , Inulina/farmacologia , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/microbiologia , Obesidade/dietoterapia , Metabolismo Energético , Bifidobacterium , Sobrepeso/microbiologia , Sobrepeso/dietoterapia , Bifidobacterium animalis , Japão , Metabolismo Basal/efeitos dos fármacosRESUMO
[This corrects the article DOI: 10.1007/s13340-023-00679-1.].
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The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for "a definitive diagnosis of SPIDDM": (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement of insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity < 0.6 ng/mL) at the last observed point in time. When a patient fulfills the only (1) and (2), but not (3), he/she is diagnosed with "SPIDDM (probable)" because the diabetes is non-insulin-dependent state.
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The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for 'a definitive diagnosis of SPIDDM': (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement for insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and the presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity <0.6 ng/mL) at the last observed point in time. When a patient fulfills only (1) and (2), but not (3), he/she is diagnosed with 'SPIDDM (probable)' because the diabetes is non-insulin-dependent type.
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Diabetes Mellitus Tipo 1 , Hiperglicemia , Diabetes Autoimune Latente em Adultos , Feminino , Humanos , Japão , Insulina/uso terapêutico , AutoanticorposRESUMO
AIMS/INTRODUCTION: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state. MATERIALS AND METHODS: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: Compared with the non-progressor group (fasting C-peptide [F-CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F-CPR levels and a higher prevalence of insulinoma-associated antigen-2 autoantibodies (IA-2A). The PPV of RIA-GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2, F-CPR <1.41 ng/mL and IA-2A positivity, respectively. In contrast, the PPV of ELISA-GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F-CPR level, respectively. CONCLUSIONS: Our findings show that, unlike RIA-GADA, ELISA-GADA shows no association between GADA titers and the risk of progression to an insulin-dependent state. The PPV improves when age at diagnosis, BMI and F-CPR levels are considered in combination.
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Autoanticorpos , Diabetes Mellitus Tipo 1 , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Glutamato Descarboxilase , Humanos , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/sangue , Autoanticorpos/sangue , Glutamato Descarboxilase/imunologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Insulina , Valor Preditivo dos Testes , Adulto Jovem , Adolescente , Peptídeo C/sangue , Fatores de Risco , PrognósticoRESUMO
The role of low-frequency variants in type 1 diabetes (T1D) susceptibility still remains to be clarified. In the present study, we analyzed low-frequency variants of the T1D candidate genes in Japanese. We first screened for protein-changing variants of 24 T1D candidate genes in 96 T1D patients and 96 control subjects, and then the association with T1D was tested in 706 T1D patients and 863 control subjects recruited from the collaborating institutions in Japan. In total, 56 protein-changing variants were discovered; among them, 34 were low-frequency variants (allele frequency < 5%). The association analysis of the low-frequency variants revealed that only the A908V variant of GLIS3 was strongly associated with resistance to T1D (Haldane's odds ratio = 0.046, p = 8.21 × 10(-4), and pc=2.22 × 10(-2)). GLIS3 is a zinc finger transcription factor that is highly expressed in pancreatic beta cells, and regulates beta cell development and insulin gene expression. GLIS3 mRNA is also moderately expressed in the human thymus. The precise mechanism responsible for the association is unclear at present, but the A908V variant may affect autoimmunity to the GLIS3 protein itself; the 908V containing epitope may induce central or peripheral tolerance more efficiently than that of 908A.
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Diabetes Mellitus Tipo 1/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Fatores de Transcrição/genética , Adolescente , Adulto , Alelos , Povo Asiático , Estudos de Casos e Controles , Proteínas de Ligação a DNA , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Variação Genética , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Japão , Masculino , Pessoa de Meia-Idade , Proteínas Repressoras , Timo/metabolismo , Transativadores , Adulto Jovem , Dedos de ZincoRESUMO
Background: To date, there is no effective long-lasting treatment for cartilage tissue repair. Primary chondrocytes and mesenchymal stem/stromal cells are the most commonly used cell sources in regenerative medicine. However, both cell types have limitations, such as dedifferentiation, donor morbidity, and limited expansion. Here, we report a stepwise differentiation method to generate matrix-rich cartilage spheroids from induced pluripotent stem cell-derived mesenchymal stem/stromal cells (iMSCs) via the induction of neural crest cells under xeno-free conditions. Methods: The genes and signaling pathways regulating the chondrogenic susceptibility of iMSCs generated under different conditions were studied. Enhanced chondrogenic differentiation was achieved using a combination of growth factors and small-molecule inducers. Results: We demonstrated that the use of a thienoindazole derivative, TD-198946, synergistically improves chondrogenesis in iMSCs. The proposed strategy produced controlled-size spheroids and increased cartilage extracellular matrix production with no signs of dedifferentiation, fibrotic cartilage formation, or hypertrophy in vivo. Conclusion: These findings provide a novel cell source for stem cell-based cartilage repair. Furthermore, since chondrogenic spheroids have the potential to fuse within a few days, they can be used as building blocks for biofabrication of larger cartilage tissues using technologies such as the Kenzan Bioprinting method.
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AIM/INTRODUCTION: To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA-GADA) and ELISA (ELISA-GADA) in patients with type 1 diabetes. METHODS: A total of 415 patients with type 1 diabetes were enrolled, including 199 acute-onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C-peptide (F-CPR) were examined. RESULTS: While the ELISA-GADA displayed a higher sensitivity than the RIA method in diagnosing type 1 diabetes in acute-onset patients, about 40% of SPIDDM patients with low-titer RIA-GADA were determined as negative by the ELISA method. Patients with type 1 diabetes with RIA-GADA alone had an older age of onset, less diabetic ketoacidosis, a higher BMI, and a higher F-CPR compared with patients positive for both RIA-GADA and ELISA-GADA. Additionally, 36% of RIA-GADA-positive patients had low-affinity GADA (<1010 L/mol), which was significantly higher than in the ELISA-GADA-positive patients (4%, P < 0.0001). Furthermore, over a 3 year monitoring period, F-CPR levels decreased in ELISA-GADA-positive SPIDDM, whereas it was maintained in patients with RIA-GADA alone, regardless of GADA affinity. CONCLUSIONS: These results suggest that bivalent ELISA for GADA is superior to the RIA method in diagnosing type 1 diabetes. Moreover, the diagnostic superiority of the ELISA-GADA made possible the concurrent identification of SPIDDM patients at high-risk of early progression, and allowed for more accurate clinical diagnosis and management.
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Diabetes Mellitus Tipo 1 , Humanos , Adulto , Diabetes Mellitus Tipo 1/diagnóstico , Autoanticorpos , Glutamato Descarboxilase , Ensaio de Imunoadsorção Enzimática , JejumRESUMO
AIMS/INTRODUCTION: This study aimed to investigate the clinical significance and antigen specificity of autoantibodies to insulinoma-associated antigen-2 (IA-2A) by radioimmunoassay (RIA; IA-2A-RIA) and enzyme-linked immunosorbent assay (ELISA; IA-2A-ELISA) in Japanese patients with type 1 diabetes. MATERIALS AND METHODS: A total of 338 type 1 diabetic patients were enrolled, including 38 fulminant type 1 diabetes, 168 acute-onset type 1 diabetes and 137 slowly-progressive type 1 diabetes (SPIDDM). The concordance, correlation of autoantibody titer, and the relationship between IA-2A and progression to the insulin-deficient state were examined. Also, competitive assay was used to examine the antigen specificity. RESULTS: The prevalence of IA-2A-ELISA was 4-5% lower than that of IA-2A-RIA in both the acute-onset type 1 diabetes and SPIDDM, but the diagnostic sensitivities of both subtypes, when measured in combination with glutamic acid decarboxylase autoantibody, were comparable. The diagnosis of type 1 diabetes using either the RIA or ELISA methods showed substantial agreement with the exponential correlation of autoantibody titers detected by RIA and ELISA. Among the SPIDDM patients, the fasting C-peptide for IA-2A-positive cases by ELISA, but not the RIA method, was significantly lower than in the negative cases (P < 0.05). Furthermore, IA-2A-ELISA proved superior to the RIA method in predicting the progression to insulin deficiency in SPIDDM. Competitive analysis showed that even sera with discrepant results by RIA and ELISA have IA-2-specific autoantibodies. CONCLUSION: These results suggest that IA-2A-ELISA is a reliable marker not only for the diagnosis of type 1 diabetes, but also for the prediction of future insulin dependency; that is, detection of IA-2A-ELISA helps identify a subtype of SPIDDM patients who would likely progress onto insulin-deficient state.
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Diabetes Mellitus Tipo 1 , Insulinoma , Neoplasias Pancreáticas , Humanos , Radioimunoensaio/métodos , Relevância Clínica , População do Leste Asiático , Autoanticorpos , Ensaio de Imunoadsorção Enzimática/métodos , Insulina , Glutamato DescarboxilaseRESUMO
The C-857T promoter polymorphism of TNF-α gene is associated with obese type 2 diabetes, while the adiponectin G+276T gene polymorphism in intron 2 may influence the fat accumulation in the liver. In this study, we examined effects of these polymorphisms on clinical markers of insulin resistance and fatty liver (a liver/spleen CT ratio < 0.9). These polymorphisms were determined in 342 Japanese subjects with type 2 diabetes. The liver/spleen CT ratio was lower in the subjects with the adiponectin +276G/G genotype than that in the subjects with the +276T allele (P < 0.05), indicating that fat accumulation in the liver is associated with the +276G/G genotype. Multiple comparisons among the 4 combinations of each polymorphism of the TNF-α and adiponectin genes revealed a significant difference in the liver/spleen CT ratio (P < 0.05) among the 4 groups, indicating that the gene combinations influence the degree of fat accumulation in the liver. The subjects carrying the TNF-α -857T allele (C/T or T/T genotype) and the adiponectin +276G/G genotype had greater risks for fatty liver and insulin resistance that was evaluated by higher levels of fasting insulin and homeostasis model assessment of insulin resistance, as compared with the other groups. Therefore, Japanese subjects with the TNF-α -857T allele and the adiponectin +276G/G genotype may be more susceptible to insulin resistance and fatty liver. The present study provides the evidence for the interaction between TNF-α and adiponectin genes in the insulin resistance and fatty liver in Japanese subjects with type 2 diabetes.
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Adiponectina/genética , Diabetes Mellitus Tipo 2/genética , Fígado Gorduroso/genética , Predisposição Genética para Doença/genética , Resistência à Insulina/genética , Polimorfismo de Nucleotídeo Único/genética , Fator de Necrose Tumoral alfa/genética , Análise de Variância , Antropometria , Análise Química do Sangue , Primers do DNA/genética , Diabetes Mellitus Tipo 2/complicações , Fígado Gorduroso/complicações , Frequência do Gene , Genótipo , Humanos , Japão , Fígado/patologia , Regiões Promotoras Genéticas/genética , Baço/anatomia & histologia , Estatísticas não ParamétricasRESUMO
Cryogenic electron microscopy is one of the fastest and most robust methods for capturing high-resolution images of proteins, but stringent sample preparation, imaging conditions, and in situ radiation damage inflicted during data acquisition directly affect the resolution and ability to capture dynamic details, thereby limiting its broader utilization and adoption for protein studies. We addressed these drawbacks by introducing synthesized giant carbon nano-test tubes (GCNTTs) as radiation-insulating materials that lessen the irradiation impact on the protein during data acquisition, physical molecular concentrators that localize the proteins within a nanoscale field of view, and vessels that create a microenvironment for solution-phase imaging. High-resolution electron microscopy images of single and aggregated hemoglobin molecules within GCNTTs in both solid and solution states were acquired. Subsequent scanning transmission electron microscopy, small-angle neutron scattering, and fluorescence studies demonstrated that the GCNTT vessel protected the hemoglobin molecules from electron irradiation-, light-, or heat-induced denaturation. To demonstrate the robustness of GCNTT as an imaging platform that could potentially augment the study of proteins, we demonstrated the robustness of the GCNTT technique to image an alternative protein, d-fructose dehydrogenase, after cyclic voltammetry experiments to review encapsulation and binding insights. Given the simplicity of the material synthesis, sample preparation, and imaging technique, GCNTT is a promising imaging companion for high-resolution, single, and dynamic protein studies under electron microscopy.
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Type 1 diabetes (T1D) is classified into three subtypes: acute-onset, slowly progressive, and fulminant T1D, according to the heterogeneity of clinical course in Japan. Although several cross-sectional databases of T1D have been reported, prospective longitudinal databases to investigate clinical outcomes are lacking in our country. Therefore, we herein construct multi-center prospective longitudinal database of the three subtypes of T1D, accompanied with genetic information and biobanking, which is named Japanese Type 1 Diabetes Database Study (TIDE-J). Inclusion criteria of this study are as follows: (1) the duration of T1D was less than 5 years, (2) the patients had one or more islet-related autoantibodies and/or fasting serum C-peptide levels were less than 1.0 ng/mL, (3) the patients could clearly understand the study consent in writing. In the TIDE-J, clinical data, including glycemic control, endogenous insulin secretion, islet-related autoantibodies, diabetic complications, and treatment, are collected annually using electric data collection system, which is named REDCap. Furthermore, HLA genotypes of each participant were analyzed at entry and the blood samples were stored for assessing exploratory markers and further genetic analysis annually. The TIDE-J certainly helps in revealing distinct clinical course of each T1D subtype. Moreover, this database may help in identifying novel markers for diagnosing each subtype of T1D and predicting clinical outcomes (including pancreatic beta cell function and disease severity) in patients.
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BACKGROUND: Identification of unique inflammatory markers may facilitate prediction of type 1 diabetes mellitus (T1DM). We previously compared transcript profiles of bone marrow-derived dendritic cells from non-obese diabetic mice with those from non-obese non-diabetic mice and found that bone marrow-derived dendritic cells' expressions of inflammatory mediators, including chemokine (C-X-C motif) ligand 1 (CXCL1), were three to five times higher in 4-week-old female non-obese diabetic mice than in non-obese non-diabetic mice. In humans, microarray analysis results have suggested this chemokine be a biomarker representing active anti-islet autoimmunity. We investigated whether serum CXCL1 levels, reflecting active autoimmune processes, might serve as biomarkers for T1DM. METHODS: The study groups consisted of 26 subjects with acute-onset T1DM, 20 with slowly progressive T1DM, and 20 with type 2 diabetes mellitus as disease controls. All subjects were Japanese. CXCL1 in sera were quantified by solid phase enzyme-linked immunosorbent assays. RESULTS: Serum CXCL1 levels were significantly higher in subjects with acute-onset [median 113.2 ng/mL (41.75-457.2)] or slowly progressive [median 100.8 ng/mL (32.87-225.0)] T1DM than in those with type 2 diabetes mellitus [median 71.58 ng/mL (32.45-152.6), p=0.01 and 0.03, respectively, Mann-Whitney U-test]. Decreases in fasting C-peptide levels per year correlated significantly with CXCL1 levels (n=11, r2=0.524, p=0.012) in a subpopulation of slowly progressive T1DM subjects displaying preserved beta-cell function. CONCLUSIONS: To our knowledge, this is the first study to show elevated serum CXCL1 in T1DM subjects, regardless of diabetes subtype, as compared to control type 2 diabetes mellitus subjects. We propose serum CXCL1 elevation to be a good T1DM marker, possibly indicating a predisposition to autoimmune disease development.
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Quimiocina CXCL1/sangue , Diabetes Mellitus Tipo 1/sangue , Adolescente , Adulto , Idoso , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: We previously reported the associations of human leukocyte antigen (HLA) (DRB1 and DQB1), INS, CTLA4, IL2RA, ERBB3 and CLEC16A with Japanese type 1 diabetes (T1D). In this study, we jointly analysed these loci in addition to IFIH1 and IL7R. METHODS: A maximum of 790 T1D patients and 953 control subjects were analysed. HLA was determined by sequencing-based typing. Seven non-HLA single nucleotide polymorphisms were genotyped using TaqMan assay. RESULTS: HLA DRB1*0405, DRB1*0901 and DRB1*0802-DQB1*0302 haplotypes were positively associated with T1D, while the DRB1*15 haplotypes were negatively associated. Non-HLA single nucleotide polymorphisms, INS, IL2RA, ERBB3, CLEC16A and IL7R were associated with T1D. By a prediction model using the HLA loci alone (HLA model) or the non-HLA loci alone (non-HLA model), it was revealed that the cumulative effect of the non-HLA model was much weaker than that of the HLA model (average increase in odds ratio: 1.17 versus 3.14). Furthermore, the area under the receiver operating characteristic curve of the non-HLA model was also much smaller than that of the HLA model (0.65 versus 0.81, p<10(-11)). Finally, a patient-only analysis revealed the susceptible HLA haplotypes and the risk allele of INS to be negatively associated with slower onset of the disease. In addition, the DRB1*0901 haplotype and the risk alleles of ERBB3, CLEC16A and CTLA4 were positively associated with the co-occurrence of thyroid autoimmunity. CONCLUSIONS: Although several non-HLA susceptibility genes in Japanese were confirmed trans-racially and appear to contribute to the heterogeneity of the clinical phenotypes, the cumulative effect on the ability to predict the development of T1D was weak.
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Diabetes Mellitus Tipo 1/genética , Antígenos de Histocompatibilidade Classe II/genética , Idade de Início , Povo Asiático/genética , Autoanticorpos/análise , Feminino , Predisposição Genética para Doença/genética , Antígenos HLA-DR/genética , Cadeias HLA-DRB1/genética , Haplótipos , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Insulina/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Lectinas Tipo C/genética , Masculino , Proteínas de Transporte de Monossacarídeos/genética , Polimorfismo de Nucleotídeo Único , Glândula Tireoide/imunologiaRESUMO
Associations of thyroid hormones with visceral obesity and insulin resistance in obese subjects with euthyroidism have been reported. However, there are no such reports in subjects with type 2 diabetes. The purpose of our study is to observe a relationship between thyroid hormones and components of metabolic syndrome (MetS) in type 2 diabetic subjects with euthyroidism defined by normal thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels. Subjects were 301 Japanese patients with type 2 diabetes. Serum TSH, FT4, free triiodothyronine (FT3), and variables related to MetS were measured. MetS was defined by the Japanese criteria and the criteria of the National Cholesterol Education Program modified for Asians. We found that serum FT3 levels were significantly and positively associated with BMI, visceral fat area, systolic and diastolic blood pressure, estimated glomerular filtration rate, serum triglyceride, and urine C peptide as a marker of insulin production, whereas negatively with age and HbA1c. In contrast, fewer numbers of variables were associated with serum TSH and FT4 levels. By a multiple regression analysis, FT3 level was independently associated with components of MetS such as visceral fat area, systolic blood pressure, and fasting blood glucose levels. On the other hand, the presence of these MetS components was independently associated with FT3 levels and urine C peptide. In conclusion, these results suggest a significant relationship between serum FT3 levels and components of MetS in type 2 diabetic subjects with euthyroidism, and imply a role of FT3 in MetS in type 2 diabetes.
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Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/complicações , Tri-Iodotironina/sangue , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Force-responsive ordered carbonaceous frameworks (OCFs) are synthesized for the first time. Carbonization of Ni porphyrin monomers having eight polymerizable ethynyl groups yields OCFs with atomically dispersed divalent Ni species and developed micropores. The highest specific surface area (673 m2 g-1) among the OCFs has been achieved. The OCFs thus synthesized comprise non-stacked graphene sheets, affording a unique mechanical flexibility that enables force-driven reversible phase transition.