脂肪肝与胰岛素抗性的关系

目的探讨脂肪肝与胰岛素抗性的关系。方法对30例诊断为脂肪肝患者作回顾性分析。结果多数患者合并胰岛素抗性综合征(高血压、肥胖症、糖尿病、高脂血症),18例接受口服葡萄糖耐量试验(OGTT)中,1例确诊为Ⅱ型糖尿病,17例患者中3例空腹血糖减损(IFG),1例糖耐量减退(IGT)及13例糖耐量正常(NGT)具有较正常人为高的血浆胰岛素(INS)浓度,胰岛素抗性脂数为8.91±1.52%。结论脂肪肝与胰岛素抗性所致的代谢紊乱关系紧密,呈正相关系。     

Polymorphism of human leukocyte antigen-DRB1, -DQB1, and -DPB1 genes of Shandong Han population in China

In the present study, polymerase chain reaction-sequence-based typing (PCR-SBT) was used to analyze human leukocyte antigen (HLA)-DRB1, -DQB1, and -DPB1 alleles of 98 unrelated healthy Shandong Han individuals. A total of 60 alleles, in which 28 in DRB1, 15 in DQB1 and 17 in DPB1 were found. Among the 28 detected DRB1 alleles, DRB1*150101, DRB1*070101, DRB1*090102, DRB1*120201, and DRB1*080302 were commonly observed, with frequencies of 16.3%, 11.2%, 10.2%, 8.2%, and 5.6%, respectively. The most predominant DQB1 allele was DQB1*030101/0309 with the frequency of 20.4%, followed by DQB1*0201/0202 (14.8%), DQB1*0602 (14.3%), DQB1*030302 (12.2%), and DQB1*060101/060103 (10.7%). Of the 17 detected DPB1 alleles, DPB1*0501 was the most frequent allele with the frequency of 37.2%. DPB1*020102 (18.4%), DPB1*040101 (11.2%), DPB1*0402 (7.1%), and DPB1*1701 (6.6%) were also very frequent alleles. A total of 53 estimated DRB1-DQB1 two-locus haplotypes were observed in Shandong Han population, of which DRB1*150101-DQB1*0602 was the most predominant, followed by DRB1*090102-DQB1*030302, DRB1*070101-DQB1*0201/0202 DRB1*120201-DQB1*030101/0309, and DRB1*080302- DQB1*060101/060103. The distribution of the HLA class II alleles and haplotypes frequencies as well as the dendrogram showed that the Shandong Han population belongs to the northern group of Chinese. The data have implications for anthropological studies and disease associations.     

Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RyR2 gene mutation: evidence of specific morphological substrates

We report on a family with a history of sudden death and effort-induced polymorphic ventricular arrhythmias. The index case was a 17-year-old boy who died suddenly and at postmortem had evidence of fibrofatty replacement in the right ventricular free wall, consistent with arrhythmogenic right ventricular cardiomyopathy, as well as calcium phosphate deposits within the myocytes. A molecular genetics investigation carried out in the paraffin-embedded myocardium of the subject and in blood samples of family members disclosed a missense mutation in exon 3 (230C-->T; A77V) of the cardiac ryanodine receptor type 2 gene. The carriers showed effort-induced polymorphic ventricular tachycardia in the setting of normal resting electrocardiogram and trivial echocardiographic abnormalities, consistent with catecholaminergic polymorphic ventricular tachycardia. The observation of both arrhythmogenic right ventricular cardiomyopathy type 2 and catecholaminergic polymorphic ventricular tachycardia in the same family suggests that the two entities might correspond to different degrees of phenotypic expression of the same disease. This experience underscores the importance of a precise autopsy diagnosis in the case of sudden cardiac death, including molecular genetics, and the mission of pathologists to guide further clinical investigation of family members.     

Novel Brugada syndrome‐causing mutation in ion‐conducting pore of cardiac Na+ channel does not affect ion selectivity properties

Aim: Brugada syndrome is an inherited cardiac disease with an increased risk of sudden cardiac death. Thus far Brugada syndrome has been linked only to mutations in SCN5A, the gene encoding the α‐subunit of cardiac Na⁺ channel. In this study, a novel SCN5A gene mutation (D1714G) is reported, which has been found in a 57‐year‐old male patient. Since the mutation is located in a segment of the ion‐conducting pore of the cardiac Na⁺ channel, which putatively determines ion selectivity, it may affect ion selectivity properties. Methods: HEK‐293 cells were transfected with wild‐type (WT) or D1714G α‐subunit and β‐subunit cDNA. Whole‐cell configuration of the patch‐clamp technique was used to study biophysical properties at room temperature (21 °C) and physiological temperature (36 °C). This study represents the first measurements of human Na⁺ channel kinetics at 36 °C. Ion selectivity, current density, and gating properties of WT and D1714G channel were studied. Results: D1714G channel yielded nearly 80% reduction of Na⁺ current density at 21 and 36 °C. At both temperatures, no significant changes were observed in V_1/2 values and slope factors for voltage‐dependent activation and inactivation. At 36 °C, but not at 21 °C, D1714G channel exhibited more slow inactivation compared with WT channel. Ion selectivity properties were not affected by the mutation at both temperatures, as assessed by either current or permeability ratio. Conclusion: This study shows no changes in ion selectivity properties of D1714G channel. However, the profoundly decreased current density associated with the D1714G mutation may explain the Brugada syndrome phenotype in our patient.     

氧化型低密度脂蛋白对人脐静脉内皮细胞ICAM-1及NO表达的影响

目的研究氧化型低密度脂蛋白(oxidized low density liprotein,ox-LDL)对脐静脉内皮细胞细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)及一氧化氮(nitric oxide,NO)表达的影响.方法采用细胞ELISA法测定细胞表面ICAM-l的含量,硝酸还原酶法测定细胞培养上清液中NO,免疫组化法结合图象分析测定细胞一氧化氮合酶(nitric oxide synthase,NOS)含量.结果 ox-LDL可明显增加脐静脉内皮细胞ICAM-l的表达,并减少NO及NOS的表达,且有浓度依赖性,但无明显的时间依赖性.结论 ox-LDL可损害内皮细胞的功能,减少内皮细胞NO、NOS的表达并增加内皮细胞ICAM-1的表达.这可能为ox-LDL促进动脉粥样硬化的机制之一.     

In vivo requirements for rDNA chromosome condensation reveal two cell-cycle-regulated pathways for mitotic chromosome folding

Chromosome condensation plays an essential role in the maintenance of genetic integrity. Using genetic, cell biological, and biochemical approaches, we distinguish two cell-cycle-regulated pathways for chromosome condensation in budding yeast. From G(2) to metaphase, we show that the condensation of the approximately 1-Mb rDNA array is a multistep process, and describe condensin-dependent clustering, alignment, and resolution steps in chromosome folding. We functionally define a further postmetaphase chromosome assembly maturation step that is required for the maintenance of chromosome structural integrity during segregation. This late step in condensation requires the conserved mitotic kinase Ipl1/aurora in addition to condensin, but is independent of cohesin. Consistent with this, the late condensation pathway is initiated during the metaphase-to-anaphase transition, supports de novo condensation in cohesin mutants, and correlates with the Ipl1/aurora-dependent phosphorylation of condensin. These data provide insight into the molecular mechanisms of higher-order chromosome folding and suggest that two distinct condensation pathways, one involving cohesins and the other Ipl1/aurora, are required to modulate chromosome structure during mitosis.     

The developmentally regulated neural crest-associated glycotope HNK-1 predicts metastasis in cutaneous malignant melanoma

Aberrant glycosylation is a common feature of metastatic sub-clones of malignant tumours and in uveal melanoma in particular, the HNK-1 glycotope has been positively correlated with poor prognosis. So far, no such correlation has been investigated in cutaneous melanoma. In order to do so, HNK-1 expression was evaluated immunohistochemically in 100 primary cutaneous melanomas and correlated with metastasis after up to 10-years' follow-up. Furthermore, HNK-1 expression was analysed in metastatic deposits (19 distant cutaneous metastases and six sentinel lymph node metastases), as well as in benign nevi. Kaplan-Meier analysis revealed a positive association between HNK-1 expression and metastasis (p < 0.005) and multivariate Cox regression analysis adjusted for the standard prognostic markers ulceration and vertical tumour thickness confirmed HNK-1 expression as an independent prognostic marker. HNK-1 expression was preserved in 42% of the distant cutaneous metastases, but metastatic cells in lymph nodes were devoid of HNK-1 immunoreactivity. None of the benign pigmented lesions exhibited HNK-1 immunoreactivity. Expression of the HNK-1 glycotope in cutaneous malignant melanoma is an independent prognostic marker of metastasis. Differential HNK-1 expression at the metastatic sites implies that its expression is modulated by the surrounding environment. As HNK-1 is also transiently expressed during migration of melanocyte precursor cells derived from the neural crest, recapitulation of this transient expression might occur during metastatic spread of cutaneous malignant melanoma.     

Characterization of a novel HLA-DQB1 allele, DQB1*020102

A novel human leukocyte antigen (HLA)-DQB1 allele, DQB1*020102, was detected in a 28-year-old woman of Han ethnic in Guangzhou, China. Compared with HLA-DQB1*020101 and HLA-DQB1*0202, they differed in only one nucleotide at the position 167 (C to T) of exon 2, which was a highly conserved position. This is a synonymous mutation, which does not cause any change in the amino acid sequence of mature protein.     

Changes in Hemodynamics and Respiration in Rats with Different Resistance to Acute Hypoxia

Effects of acute hypoxia on hemodynamics and respiration were studied in acute experiments on narcotized rats. The animals were divided into groups characterized by high, low-, and medium- resistance to hypoxia by the time of respiration arrest during inhalation of gas mixture containing 3% O2. Hemodynamic parameters of highly resistant animals were higher than in low-resistant rats throughout the entire hypoxic period. The development of a rare (with prolonged inspiratory phase) respiratory rhythm in highly resistant rats is an adaptive reaction, which allows them longer tolerate hypoxia compared to low-resistant animals.