Analysis of children with type 1 diabetes in Korea: high prevalence of specific anti-islet autoantibodies, immunogenetic similarities to Western populations with "unique" haplotypes, and lack of discrimination by aspartic acid at position 57 of DQB

This study analyzed the expression of anti-islet autoantibodies and HLA-DR and -DQ genotypes in Korean children with type 1 diabetes mellitus (T1DM). The positivity of the anti-ICA512, anti-GAD65, and anti-insulin autoantibodies in the newly onset T1DM patients (n = 15) was 66.7%, 86.7%, and 46.7%, respectively, and all of them had one or more of the autoantibodies. HLA analysis showed higher frequencies of HLA-DRB1*0301, *0405, *09012 and -DQB1*0201, *0401, *03032 alleles in T1DM patients compared to controls (P(c) < 0.05). Because HLA-DQB1*0401, *03032 alleles carry aspartic acid at position 57 of DQB, susceptibility to T1DM in Korean children was not related to the presence of aspartic acid at position 57 of DQB1 locus. We suggest this unique HLA-DR, -DQ allele distribution might be an important factor for the low incidence of T1DM in Korea, and the combined anti-islet autoantibody assays could be valuable screening markers for the early detection of T1DM in Korea.     

Mast cell–derived IL-13 downregulates IL-12 production by skin dendritic cells to inhibit the TH1 cell response to cutaneous antigen exposure

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The location and distribution of type A and type B atrial endings in cats

Summary In the attempt to explain the difference in discharge pattern of atrial endings, 131 endings were localized by punctate stimulation, 44 were type A, 77 type B and 10 of an intermediate type. All were located on the dorsal wall of the atria with none on the ventral wall or in the appendage. On the right side, 74% of type A were located in the atria and 63% of type B in or near the veins. On the left side, 67% of type A and 94% of type B were located in or near the veins. Thus, there appeared to be some difference in the location of type A and type B endings on the right side, but on the left side both types of endings were for the most part confined to the venous region. Further, on both right and left sides, these endings were present both in the central part of the atria and in or adjacent to veins. This leads to the suggestion that the difference in discharge patterns is not caused by the location but may be due to some other reasons, e. g. difference of arrangement in the atrial wall with respect to the contractile elements.     

Stimulation by hCRF of C-peptide release in type 2 diabetics during concomitant opioid receptor blockade

Summary Administration of synthetic human corticotropin-releasing factor (hCRF, 2 µg/kg body weight) during simultaneous application of the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) produced a significant increase in plasma C-peptide levels of six male Type 2 diabetic patients which even exceeded the postprandial values. This stimulatory effect of hCRF/naloxone on plasma C-peptide was less pronounced in six healthy men. hCRF alone did not provoke any reaction of plasma C-peptide in either group.The possibility of a paracrine, CRF-dependent mechanism in pancreatic islets which somehow involves inhibitory opioid receptors is preferentially discussed. Such a mechanism may underlie the stimulatory action of hCRF/naloxone on B cells and would explain the absent reaction of peripheral venous plasma C-peptide to hCRF alone as well as the amplifying effect of simultaneous opioid receptor blockade.Abbreviations ACTH adrenocorticotropic hormone - C-peptide connecting-peptide - CRF corticotropin-releasing factor - hCRF human CRF - oCRF ovine CRF - min minutes - S.D. standard deviation - S.E.M. standard error of the mean This study was supported by the Deutsche Forschungsgemeinschaft (Go 299/3-2)Dedicated to Professor Dr. N. Zöllner on the occasion of his 65th birthday     

GPR34-mediated sensing of lysophosphatidylserine released by apoptotic neutrophils activates type 3 innate lymphoid cells to mediate tissue repair

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1Alpha,25-dihydroxyvitamin D3 restores thymocyte apoptosis sensitivity in non-obese diabetic (NOD) mice through dendritic cells

AIMS/HYPOTHESIS: Resistance of NOD thymocytes to apoptosis-inducing signals is restored by 1alpha,25-dihydroxyvitamin D3 (1alpha,25OH2D3), a therapy preventing diabetes in NOD mice. We studied whether modulation of thymocyte apoptosis is due to direct effects on thymic T lymphocytes or indirect effects via thymic dendritic cells, since both cell types constitute known targets for 1alpha,25OH2D3. METHODS AND RESULTS: Female NOD mice were treated with 1alpha,25OH2D3 (5microg/kg/2d) from 21 to 70 days. Vehicle-treated NOD and NOR mice served as controls. Analysis of thymic T lymphocytes from 1alpha,25OH2D3)-treated mice revealed a decrease in number of apoptosis-resistant CD4+CD8+ and CD4+CD8-HSA(high) T lymphocyte subsets, higher pro-apoptotic IL-2 and FasL, and lower anti-apoptotic Bclx-L mRNA expression levels. Thymic dendritic cells from 1alpha,25OH2D3-treated NOD mice had increased CD8alpha+FasL+ and CD80+/86+ expression compared to control NOD mice. In a syngeneic co-culture system of thymocytes and thymic dendritic cells, apoptosis levels were 20% higher only in co-cultures where both T cell- and dendritic cell-compartments originated from 1alpha,25OH2D3-treated mice. Activation-induced cell death-sensitivity in peripheral T lymphocytes was comparable to levels present in NOR mice, confirming better thymic selection in 1alpha,25OH2D3-treated mice. CONCLUSION/INTERPRETATION: We conclude that 1alpha,25OH2D3 needs both thymic T cell- and dendritic cell-compartments to exert its apoptosis-restorative effects in NOD thymocytes.     

血管内皮损伤标志物在2型糖尿病患者中的变化

目的:探讨2型糖尿病(DM)患者血管内皮损伤标志物的变化。方法:分别测定89例2型DM患者和76例正常对照者血浆可溶性血管内皮细胞蛋白C受体(sEPCR),血管性血友病因子(v WF)和可溶性血栓调节蛋白(sTM),并测定DM患者24h尿白蛋白排泄(UAE),根据尿UAE水平和病程分组进行比较分析。结果:2型DM患者血浆sEPCR、v WF及sTM水平高于正常对照组(P<0.05),并且与其尿UAE水平和病程呈显著正相关。结论:血浆sEPCR、v WF及sTM水平可作为观察2型DM并发血管病变以及严重程度的指标。     

A simple method for obtaining cultures enriched for Type II pneumonocytes from fetal rabbit

Summary A differential plating method permitted preparation of cultures significantly enriched for Type II pneumocytes. These cells were maintained in a differentiated state for at least 12 d, identifiable morphologically (by presence of osmiophilic lamellar inclusion bodies) and bio-chemically (by demonstration of synthesis of phosphatidyl choline and production of disaturated lecithin).     

2型糖尿病肾病患者血清胱抑素C的检测及意义

目的:检测糖尿病患者血清胱抑素C浓度变化,分析其在糖尿病患者早期肾损伤中的作用。方法:根据24h尿白蛋白排泄率(UAER)的测定结果,将104例糖尿病患者分为3组:单纯糖尿病组(SDM组)、早期糖尿病肾病组(EDN组)和临床糖尿病肾病组(CDN组);46名健康者作对照组;采用颗粒增强散射免疫比浊法测定血清胱抑素C水平,常规测定内生肌酐清除率、血肌酐和UAER,并对全部患者胱抑素C血清浓度与尿UAER进行直线相关分析。结果:SDM组,EDN组及CDN组间血清胱抑素C水平均有非常显著性统计学意义(P<0.01),血清胱抑素C与UAER、内生肌酐清除率及血肌酐值有良好相关性(r值分别为0.772,-0.754,0.785,P均<0.01)。结论:血清胱抑素C水平测定有助于2型糖尿病肾病的早期诊断,优于血肌酐和内生肌酐清除率,具有临床应用价值。     

The Effects of Menstrual Cycle Phase on Cardiovascular and Pulmonary Responses to Behavioral and Exercise Stress

The present study was designed to compare the differential cardiopulmonary and hemodynamic responses of Type A and B women to an exercise and a psychological stressor. In addition, the effects of menstrual cycle phase on the resting and response levels of a wide range of physiological variables were explored. Thirty-two women participated in a progressive exercise stress test and a threat of shock video game during both the luteal and follicular phases of the menstrual cycle. Half of these subjects expressed the coronary-prone behavior pattern referred to as Type A, as assessed by the Jenkins Activity Survey. The remaining women were relatively free of these behaviors (Type B). Heart rate, oxygen consumption, carbon dioxide production, minute ventilation, and end-tidal carbon dioxide were monitored and recorded on a breath-by-breath basis. Systolic and diastolic blood pressure measures were taken at 2-min intervals. Results indicated similar baseline, exercise, and behavioral stress responses among Type A and B women. The stress responses were also the same between the follicular and luteal phases for all measured physiological variables. However, resting levels of heart rate, metabolism, and ventilation were all elevated at rest during the luteal phase. A regression analysis based on the exercise heart rate and oxygen consumption data demonstrated that a majority of subjects exhibited heart rate responses in excess of that expected during the psychological stressor. These data are discussed with special reference to possible mechanisms of the pathophysiology of cardiovascular disease.