Hb Barika [α42(C7)Tyr→His (α2)] Leads to an α+-Thalassemia-like Syndrome

In human deoxyhemoglobin (deoxyHb), the hydrogen bond between Aspβ99(G1) and Tyrα42(C7), located in the α1β2 interface, is crucial for the stability of the T structure. All the variants that could arise from a single point mutation affecting codon β99 have already been observed, leading always to erythrocytosis. Conversely, up to now, Hb Barika is the only example found in a patient in whom the α42 is mutated. From a biochemical point of view, for theoretical reasons, this substitution has already been extensively studied on recombinant hemoglobin (rHb). In the patient, Hb Barika is expressed at a level lower than expected for an α2 gene variant and leads to an α⁺-thalassemic-like syndrome.     

α-Glukosidase-Hemmer und Thiazolidindione (Glitazone)

α-Glucosidase inhibitors

The cardiovascular effects of the α?glucosidase inhibitors acarbose and miglitol, which are licensed in Germany, cannot be safely judged because of insufficient data and a lack of appropriate outcome trials. A positive cardiovascular effect is as yet uncertain in this class of antidiabetic drugs; they do not appear to be associated with a cardiovascular risk.

Glitazones

The use of the licensed sensitizer pioglitazone is clearly associated with an increased risk for heart failure which, however, does not appear to cause an increase of cardiovascular or all-cause mortality.

     

胰岛素抵抗与脂蛋白(α)水平

本研究以酶联免疫法对照观察了糖尿病患者胰岛素抵抗和非抵抗组的脂蛋白(α)及其他代谢指标.结果显示两组的空腹血糖(FPG)、糖化血红蛋白(HbA1c)和高密度脂蛋白胆固醇(HDL-C)无显著差异(P>0.05),而组间脂蛋白(α)[Lp(α)](228±110;128±108;P<0.01)、总胆固醇(TC)(5.912±0.987;2.022±1.626;P<0.05)、低密度脂蛋白胆固醇(LDL-C)(4.329±1.223;3.482±1.116;P<0.05)有显著差异,特别是脂蛋白(α)值,胰岛素抵抗组较非抵抗组显著升高(P<0.01).结论在Ⅱ型糖尿病患者中,胰岛素抵抗可能是导致脂代谢紊乱,尤其是脂蛋白(α)升高的主要因素之一.     

MicroRNA-125b-1 accelerates a C-terminal mutant of C/EBPα (C/EBPα-Cm)-induced myeloid leukemia

MicroRNA-125b-1 (miR-125b-1) is a target of the chromosomal translocations t(11;14)(q24;q32) and t(2;11)(p21;q23), which are found in human B-lymphoid and myeloid malignancies, respectively. These translocations result in overexpression of mature miR-125b, consisting of 22 nucleotides. To analyze the role of miR-125b-1 in leukemogenesis, we created a bone marrow transplantation model using a retrovirus vector containing GFP expression elements. Sole transduction of miR-125b-1 into bone marrow cells resulted in expansion of hematopoietic cells expressing GFP. Compared with cells lacking GFP expression, we observed that GFP(+)/CD11b(+) or GFP(+)/Gr(-)1(+) cells were increased in the bone marrow and spleen. Although previous studies reported sole induction of miR-125b-induced leukemia, we did not find leukemic transformation in our model. Transduction of miR-125b-1 did accelerate myeloid tumors induced by a C-terminal mutant of CAAT-enhancer binding protein (C/EBPα-C(m)), a class II-like mutation. As miR-125b has been shown to hasten the development of leukemia in a BCR/ABL-transduced animal model, our present results support the conclusion that overexpression of miR-125b cooperates with other genetic alterations in the pathogenesis of myeloid malignancies.     

Differential Regulation by Glucocorticoids of Mouse Proα2(I) and Proα1(III) DNA-Binding Proteins

Multiple procollagen-specific DNA-binding proteins were identified for the α2(I) and the αl(III) procollagen promotor containing gene fragments. The proteins are genespecific, differing in their relative molecular weights and relative binding specificities. A major finding was the increased DNA-binding with specificity for the procollagen promoter containing DNAs by several nonhistone nuclear proteins in mouse embryo fibroblasts treated with dexamethasone. The previously reported coordinate decrease of type I and type III procollagens by glucocorticoids may involve differential regulation by glucocorticoids of procollagen gene specific DNA-binding proteins.     

Molecular Diagnosis of a Case of Hb Phnom Penh [α117(GH5)Phe-I1e-α118(H1)Thr (α1)]

We report the first case of Hb Phnom Penh where a molecular study was done on the patient's sample. The result confirmed the predicted DNA sequence change involved in the mutation, which was delineated by another group in 1998 using amino acid analysis.     

胃镜检查对~(13)C和~(14)C尿素呼气试验结果影响的回顾性分析

目的分析胃镜检查前后对~(13)C和~(14)C尿素呼气试验结果的影响。方法回顾性分析广东省第二中医院2019年9月至2020年1月行~(13)C或~(14)C尿素呼气试验并行普通胃镜检查的受检者379例,比较胃镜检查前后行~(13)C或~(14)C尿素呼气试验阳性率的差异。结果 ~(13)C尿素呼气试验在胃镜检查前阳性率为31.08%,在胃镜检查后阳性率为31.51%,两者间比较,差异无统计学意义(P0.05);~(14)C尿素呼气试验在胃镜检查前阳性率为42.00%,在胃镜检查后阳性率为24.14%,两者间比较,差异有统计学意义(P0.05)。结论胃镜检查会影响~(14)C尿素呼气试验的检测结果,但不会影响~(13)C尿素呼气试验的检测结果。因此,在胃镜检查后若要行呼气试验,建议优先选择~(13)C尿素呼气试验;若要选择~(14)C尿素呼气试验,建议在胃镜检查前完成。     

螺内酯对大鼠肝纤维化α1(Ⅰ)、α1(Ⅲ)前胶原mRNA表达的影响

目的 探讨醛固酮受体拮抗剂螺内酯对大鼠α1(Ⅰ)、α1(Ⅲ)前胶原mRNA表达的影响,评价螺内酯的抗纤维化作用.方法 雄性SD大鼠50只,随机分为(1)肝硬化模型组(A、B组各10只)体积分数40%的四氯化碳(CCl4,用精制橄榄油配制),皮下注射,3 ml/kg,每周2次,其中A组注射10周,B组注射13周;(2)螺内酯组(C、D组各10只)CCl4注射的同时给予螺内酯20 mg/(kg·d)灌胃,其中C组灌胃10周,D组灌胃13周;正常对照组(10只)正常饮食、饮水.分别于第10周末处死A、C组大鼠,13周末处死B、D组及对照组大鼠.逆转录聚合酶链反应(RT-PCR)方法检测大鼠肝脏组织中α1(Ⅰ)、α1(Ⅲ)前胶原mRNA的表达.结果 第10周末时,螺内酯组d1(Ⅰ)、α1(Ⅲ)前胶原mRNA表达显著低于肝纤维化模型组(P＜0.05).第13周末时,螺内酯组与肝纤维化模型组相比差异无显著性意义.结论 螺内酯对肝纤维化有一定的抑制作用.     

冠心病患者血脂蛋白(α)水平及其临床意义

目的 观察血清脂蛋白(α)［LP(α)］水平与冠心病（CHD）类型、病变和预后的关系。方法 将CHD患者（95例）分为3组:急性心肌梗死（AMI）组30例,不稳定型心绞痛（UAP）组35例及稳定型心绞痛（SAP）组30例。取血测定LP(α)。对CHD患者在住院期间及出院1个月内进行观察,观察终点为主要急性心脏事件（MACE）。结果 ①当按CHD不同临床类型比较时,发现UAP与AMI组LP(α)水平与MACE发生率均显著高于SAP组(P<0.05或P<0.01),但UAP与AMI组差异未达到显著水平;②当按LP(α)水平分组比较时,≥300 mg/L组多支病变和MACE的发生率均显著高于LP(α)<300 mg/L组(均P<0.01)。结论 LP(α)水平与CHD的严重程度有关,并与CHD预后相关。     

冠心病与脂蛋白(α)及高血压的关系

脂蛋白(α)作为冠心病的独立危险因素已有报道,但从血管生理的角度来看,动脉在发生粥样硬化以前,内膜受损是前提,高血压是损伤动脉内膜的重要因素之一,本研究目的在于高血压与脂蛋白(α)对冠心病的发病有否协同作用.     

高浓度血浆肿瘤坏死因子-α(TNF-α)与百岁老人痴呆有关

衰老与机体免疫和血中单核细胞分裂失平衡有关,血浆白介素-6(IL-6)浓度的增高,白介素-1(IL-1)受体拮抗剂增加,可溶性肿瘤坏死因子受体-1(sTNFR-Ⅰ)增加与年龄之间的关系已有报道,血浆IL-6水平增加,TNFR-Ⅰ和TNFR-Ⅱ在淋巴细胞中的表达增强,单核细胞产生IL-6增加,血浆组胺增多均与痴呆有关,但血浆TNF-α浓度和与之有关的疾病尚无报道。本文作者研究的目的是评估一组百岁老人血浆中的TNF-α浓度并寻找其与动脉硬化、综合健康状况之间的关系。进而,研究血中TNF-α浓度是否与血中白细胞数、体重指数或血浆IL-6、sTNFR-Ⅰ、CPR浓度有关。     

Over-expression of protein kinase C isoforms (α, δ, θ and ζ) in squamous cervical cancer

Protein kinase C was found to be significantly over-expressed in cancer samples compared to adjacent normal cervical tissues by proteomics in our previous study. The aim of this study was to examine protein kinase C expression and to analyze the expression patterns of protein kinase C isoforms in squamous cervical cancer at the protein levels and their associations with clinical and pathologic factors of squamous cervical cancer. First, Western blotting was used to examine protein kinase C expression in the specimens of tumors and matched adjacent normal tissues which were collected from 12 patients with squamous cervical cancer. Protein kinase C isoforms (α, δ, θ and ζ) expression were then detected by immunohistochemistry in other 43 cases of squamous cervical cancer tissues, 32 cases of corresponding adjacent normal cervical squamous epithelial tissue and 31 cases of cervical intraepithelial neoplasia. Western blot analysis revealed that protein kinase C expression was positive in squamous cervical cancer while it was not expressed in normal cervical tissues. On the other hand, immunohistochemical analysis suggested that, protein kinase C isoforms (α, δ, θ and ζ) expression was significantly higher in squamous cervical cancer compared to cervical intraepithelial neoplasia, as well as in cervical intraepithelial neoplasia compared with normal tissues, respectively.High levels of protein kinase C α expression were associated with cellular differentiation(P<0.05). Protein kinase C δ was significantly associated with tumor stage (P<0.05) and protein kinase C ζ was associated with lymphatic metastasis (P < 0.05). These findings indicate that protein kinase C isoforms expression in cervical lesions was associated with carcinogenesis and might play important roles throughout the process of cervical cancer development.     

α78(EF7)Asn→Asp is a Posttranslational Modification in Hb J-Singapore [α78(EF7)Asn→Asp;α79(EF8)Ala→Gly]

In Hb J-Singapore, the α78(EF7)Asn→Asp and α79(EF8)Ala→Gly substitutions were initially thought to be genetic mutations. Subsequent studies on other similar hemoglobin variants suggested that the Asn→Asp change was a posttranslational modification. Nevertheless, lack of DNA evidence made it difficult to confirm the deamidation in Hb J-Singapore. We recently encountered a female patient with Hb J-Singapore trait. In this report, we present electrospray mass spectrometry and DNA data to confirm the α78(EF7)Asn→Asp is indeed a posttranslational modification.     

T_(1762)A_(1762)变异对乙型肝炎病毒C启动子活性影响

国的乙型肝炎病毒（ＨＢＶ）Ｃ基因调节序列存在较多变异,为探讨在诸多变异中,Ｔ１７６２Ａ１７６４变异对Ｃ区启动子（ＣＰ）活性究竟起何作用。方法用克隆及ＰＣＲ产物直接测序,检测Ｔ１７６２Ａ１７６４变异;并将含调节序列的ＰＣＲ产物插入到氯霉素乙酰转移酶（ＣＡＴ）表达质粒中,转染ＨｅｐＧ2细胞并瞬时表达。结果通过比较野生株及变异株在ＣＰ区序列及ＣＡＴ表达水平显示,Ｔ１７６２Ａ１７６４变异在使ＣＡＴ表达下调中起主要作用。结论Ｔ１７６２Ａ１７６４变异在使ＣＰ活性下调中起主要作用。