56 research outputs found

    MafA and MafB Regulate Genes Critical to β-Cells in a Unique Temporal Manner

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    OBJECTIVE-Several transcription factors are essential to pancreatic islet beta-cell development, proliferation, and activity, including MafA and MafB. However, MafA and MafB are distinct from others in regard to temporal and islet cell expression pattern, with beta-cells affected by MafB only during development and exclusively by MafA in the adult. Our aim was to define the functional relationship between these closely related activators to the beta-cell. RESEARCH DESIGN AND METHODS-The distribution of MafA and MafB in the beta-cell population was determined immunohistochemically at various developmental and perinatal stages in mice. To identify genes regulated by MafB, microarray profiling was performed on wild-type and MafB(-/-) pancreata at embryonic day 18.5, with candidates evaluated by quantitative RT-PCR and in situ hybridization. The potential role of MafA in the expression of verified targets was next analyzed in adult islets of a pancreas-wide MafA mutant (termed MafA(Delta Panc)). RESULTS-MafB was produced in a larger fraction of beta-cells than MafA during development and found to regulate potential effectors of glucose sensing, hormone processing, vesicle formation, and insulin secretion. Notably, expression from many of these genes was compromised in MafA(Delta Panc) islets, suggesting that MafA is required to sustain expression in adults. CONCLUSIONS-Our results provide insight into the sequential manner by which MafA and MafB regulate islet beta-cell formation and maturation. Diabetes 59:2530-2539, 201

    Dynapenia and sarcopenia diabetes

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    Aims/Introduction: The present study aimed to clarify the prevalence and clinical characteristics of sarcopenia and dynapenia, which are muscle weakness with and without low muscle mass, respectively, in Japanese patients with type 1 diabetes mellitus and type 2 diabetes mellitus. Materials and Methods: This cross-sectional study enrolled 1,328 participants with type 1 diabetes (n = 177), type 2 diabetes (n = 645) and without diabetes (n = 506). Sarcopenia was defined as a low grip strength and slow gait speed with low skeletal muscle mass index, whereas dynapenia was defined as low strengths of grip and knee extension with a normal skeletal muscle mass index. Participants without sarcopenia and dynapenia were defined as robust. Results: Among participants aged ≥65 years, sarcopenia and dynapenia were observed in 12.2% and 0.5% of individuals without diabetes, 42.9% and 11.4% of type 1 diabetes patients, and 20.9% and 13.9% of type 2 diabetes patients. In both type 1 diabetes and type 2 diabetes patients, sarcopenic patients were significantly older and thinner, and showed a significantly higher rate of diabetic neuropathy than robust patients. In patients with type 1 diabetes and type 2 diabetes, dynapenic patients were older, and showed a higher rate of diabetic neuropathy and lower estimated glomerular filtration rate than robust patients. Patients complicated with sarcopenia and dynapenia showed a significantly lower physical quality of life and higher rate of incidental falls than robust patients. Conclusions: Sarcopenia and dynapenia were more frequent in patients with type 1 diabetes and type 2 diabetes than in individuals without diabetes, which might contribute to their impaired quality of life and incidental falls

    The MafA transcription factor becomes essential to islet β-cells soon after birth

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    The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial-temporal patterns in rodent islet cells. Analysis of Mafa(-/-) and pancreas-specific Mafa(∆panc) deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cells, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in Mafa(Δpanc) mice and compromised earlier in Mafa(Δpanc);Mafb(+/-) mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cells, but also why cell maturation involves coordinated actions with MafB

    Genome-wide SNP analysis reveals population structure and demographic history of the ryukyu islanders in the southern part of the Japanese archipelago.

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    The Ryukyu Islands are located to the southwest of the Japanese archipelago. Archaeological evidence has revealed the existence of prehistoric cultural differentiation between the northern Ryukyu islands of Amami and Okinawa, and the southern Ryukyu islands of Miyako and Yaeyama. To examine a genetic subdivision in the Ryukyu Islands, we conducted genome-wide single nucleotide polymorphism typing of inhabitants from the Okinawa Islands, the Miyako Islands, and the Yaeyama Islands. Principal component and cluster analyses revealed genetic differentiation among the island groups, especially between Okinawa and Miyako. No genetic affinity was observed between aboriginal Taiwanese and any of the Ryukyu populations. The genetic differentiation observed between the inhabitants of the Okinawa Islands and the Miyako Islands is likely to have arisen due to genetic drift rather than admixture with people from neighboring regions. Based on the observed genetic differences, the divergence time between the inhabitants of Okinawa and Miyako islands was dated to the Holocene. These findings suggest that the Pleistocene inhabitants, whose bones have been found on the southern Ryukyu Islands, did not make a major genetic contribution, if any, to the present-day inhabitants of the southern Ryukyu Islands

    New endoscopic ultrasonography criteria for malignant lymphadenopathy based on inter-rater agreement.

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    Background and aimsVarious studies have been previously conducted on the diagnosis of lymphadenopathy as benign or malignant, but the results vary. These studies did not describe the inter-rater agreement on the EUS features of lymphadenopathy. In this study, we evaluate the inter-rater agreement on EUS features and propose EUS diagnostic norms for lymphadenopathy based on inter-rater agreement.MethodA total of 68 lymph nodes subjected to EUS-fine needle aspiration (FNA) were reviewed by five endoscopic experts. The EUS features evaluated lymph node size, shape, border, margin, echogenicity, homogeneity, and the hilum of the lymph node. Inter-rater agreement (multi-rater kappa statics) was performed. We established new criteria using results with a high degree of inter-rater agreement from EUS features and compared them with the former criteria.ResultThere was a moderate agreement on shape, kappa (K) = 0.44 (95% confidence interval [CI]: 0.34-0.54), and fair agreement on echogenicity, homogeneity, border, and hilum of the lymph node, K (95% CI) = 0.33 (0.17-0.38), 0.34 (0.26-0.35), 0.22 (0.21-0.31), and 0.22 (0.11-0.26), respectively. This resulted in the establishment of new EUS diagnostic criteria using shape, long axis > 20 mm and short axis > 10 mm. New criteria were superior to old criteria (area under the curve 0.82 vs 0.52, P ConclusionEUS diagnostic criteria for lymphadenopathy based on inter-rater agreement were more accurate than old criteria. This result will be useful for the diagnosis of lymphadenopathy

    The Feasibility and Histological Diagnostic Accuracy of Novel Menghini Needle (EUS Sonopsy CY™) for Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy of Solid Pancreatic Masses: A Prospective Crossover Study Comparing Standard Biopsy Needles

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    Background and Objectives. Recently, a 21G Menghini-type needle for EUS-guided fine-needle aspiration biopsy (EUS-FNAB) has been developed. The stylet of the EUS Sonopsy CY™ remains inside the needle during aspiration. Therefore, it is expected to obtain higher-quality histological core specimens without crushing the material or blood contamination. The aim of this study is to evaluate the feasibility and diagnostic accuracy of EUS-FNAB of solid pancreatic masses with this new biopsy needle. Methods. A total of 30 patients with solid pancreatic masses who underwent EUS-FNAB with two different types of needles, EUS Sonopsy™ and ProCore™, were included in a prospective, randomized, controlled, crossover study. All the pancreatic masses were punctured with the two needles and were randomized regarding the order of the needle to be used. The primary outcome was to compare the diagnostic accuracy and the rates of tissue acquisition of the two needles. Results. The tissue acquisition rate was not significantly different between the EUS Sonopsy CY™ needle and the ProCore™ needle (78.6% vs. 82.1%, P=1.00). The histological diagnostic accuracy was also similar between the two needles (73% vs. 80%, P=.63). There was also no difference regarding the accuracy of cytology alone and the combination of both histological and cytological assessments between the EUS Sonopsy CY™ needle and the ProCore™ needle (90% vs. 87%, P=1.00 and 90% vs. 90%, P=1.00, respectively). Conclusions. EUS Sonopsy CY™ is a reliable device for EUS-FNAB of solid pancreatic masses

    Simultaneous Gastric Metastasis From Renal Cell Carcinoma: A Case Report and Literature Review

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    While some reports are available regarding metachronous gastric metastasis from renal cell carcinoma after treatment, there are few reports of primary lesion detection based on the diagnosis of a gastric metastatic lesion. The patient in this case was an 80-year-old woman who underwent upper gastrointestinal endoscopy after having developed anorexia 2 months earlier. A submucosal tumor with central umbilication was found in the gastric greater curvature. Endoscopic ultrasonography revealed a solid and hypoechoic mass with hypervascularity on color Doppler imaging that proliferated mainly within the submucosal layer. There was partial exposure of the tumor on the superficial layer. Biopsy was performed, as a neuroendocrine tumor was suspected; however, histopathological findings with immunostaining revealed gastric metastasis from clear renal cell carcinoma. Subsequently, contrast enhanced computed tomography showed right renal cell carcinoma and liver metastasis. Thus, molecularly targeted drug treatment was initiated by the Department of Urology. Our findings indicate that a primary lesion can be identified and prognosis can be assumed based on biopsy of the gastric metastatic lesion. Immunostaining of biopsy samples collected endoscopically could help achieve definite diagnosis
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