Hb F-Columbus-Ga or a2 Gγ2 94(FGJ)Asp→Asn

A new γ chain variant with an electrophoretic mobility at pH 8.1 between those of Hb S and Hb C was isolated and quantitated by DEAE-cellulose chromatography. It was readily identified with the use of various micro-chromatographic and sequencing procedures as α²Gγ² 94(FGl)Asp→Asn. The hemoglobin was named Hb F-Columbus-Ga. The quantity of this GY chain variant (as % total γ chain) was about 39% and the percentages of the normal Gγ and AγI chains were 37% and 24%, respectively.     

Hb Grand Junction (HBB: c.348_349delinsG; p.His117IlefsX42): A New Hyperunstable Hemoglobin Variant

Hyperunstable hemoglobinopathy (HUH) [dominantly inherited β-thalassemia (β-thal)] is a relatively rare form of congenital hemolytic anemia in which mutations occur in the genes encoding for α and β chains, or both chains of the hemoglobin (Hb) molecule. We describe two Hispanic adolescents with a new unstable Hb variant (HBB: c.348_349delinsG; p.His117IlefsX42), resulting from a frameshift mutation at codons 115/116 of the β-globin gene. Both patients also have a 3.7?kb deletion on one α gene, leading to a decreased imbalance between α and β chain formation, and subsequently a milder phenotype than that seen in other hyperunstable Hb variants.     

Long-term adherence of patients with relapsing-remitting multiple sclerosis to subcutaneous self-injections of interferon β-1a using an electronic device: the RIVER study

ABSTRACT

Objectives: The BRIDGE study has previously shown a high short-term (12 weeks) adherence rate (>85%) of patients with relapsing-remitting multiple sclerosis (RRMS) to subcutaneous self-injections of interferon β-1a using an electronic auto-injection device (RebiSmart®). The primary goal of the RIVER study was to investigate in a real-life setting the long-term adherence to the use of RebiSmart among patients enrolled in the parent BRIDGE study.

Methods: The RIVER study was designed as a real-life extension study of the BRIDGE trial. RRMS patients who completed BRIDGE and still had an indication for treatment were included. Data were collected prospectively through the RebiSmart device, and analyzed retrospectively. Long term adherence (administration of ≥ 80% of injections) to and safety of RebiSmart were assessed. The expected follow-up period ranged from 19 to 26 months.

Results: A total of 57 RRMS patients participated in the follow-up study. The mean observation period was 20.5 ± 5.7 months. The overall adherence to the use of RebiSmart in the entire study cohort was 79.8% (median = 85.2%, range = 16–100%). There were 36 patients (63.2%) who completed at least 80% of the scheduled injections. No statistically significant differences were found between adherent and non-adherent patients in terms of age, sex, duration of the observation period, and occurrence of relapses. No serious treatment-related adverse events occurred.

Conclusions: This study showed a high level of long-term adherence to the use of RebiSmart, with 63.2% of participants meeting the criterion for adherence to treatment.     

610株大肠埃希菌对抗菌药物的敏感性分析

目的 探讨大肠埃希菌(ECO)的耐药现状,为临床医师合理用药提供科学参考依据.方法 严格按照《全国临床检验操作规程》对610株ECO进行培养、鉴定；采用K-B法检测ECO对抗菌药物的敏感性,并根据CLSI2009年折点判断结果.结果 ECO检出率最高的科室是神经内科和ICU,分别占25.9％、21.3％;610株ECO中ESBLs阳性207株,阳性率33.9％,产与非产ESBLs菌株均对亚胺培南及美罗培南100.0％敏感.结论 临床医师应根据药敏结果合理选用抗菌药物,以提高临床治愈率.     

Partial regulation of serotonin transporter function by γ-synuclein

Human α-synuclein (α-Syn) is instrumental in maintaining homeostasis of monoamine neurotransmitters in brain, through its trafficking, and regulation of the cell surface expression and, thereby, activity of dopamine, serotonin and norepinephrine transporters. Here we have investigated whether other members of the synuclein family of proteins, γ-synuclein (γ-Syn) and β-synuclein (β-Syn) can similarly modulate the serotonin transporter (SERT). In Ltk⁻ cells co-transfected with SERT and γ-Syn, γ-Syn reduced [³H]5-HT uptake, in a manner dependent on its expression levels. The decrease in SERT activity was via decreased V_max of the transporter, without change in K_m, compared to cells expressing only SERT. By contrast, β-Syn co-expression failed to alter SERT uptake activity, and neither the V_max nor the K_m was changed in the presence of β-Syn. γ-Syn modulation of SERT was only partial, with a maximal ∼27% decrease in SERT activity seen even at high expression levels of γ-Syn. By contrast, α-Syn attenuated SERT activity by ∼65% at identical expression levels as γ-Syn. Co-immunoprecipitation studies showed the presence of heteromeric protein:protein complexes between γ-Syn or α-Syn and SERT, while β-Syn failed to physically interact with SERT. Both α-Syn and γ-Syn colocalized with SERT in rat primary raphae nuclei neurons. These studies document a novel physiological role for γ-Syn in regulating 5-HT synaptic availability and homeostasis, and may be of relevance in depression and mood disorders, where SERT function is dysregulated.     

Beta-catenin is temporally regulated during normal liver development

BACKGROUND & AIMS: beta-Catenin, a key component of the Wnt pathway, plays an important role in unregulated liver growth in liver tumors, in regulated growth during liver regeneration, and in ex vivo embryonic liver cultures. METHODS: We used developing livers from several stages of gestational development to examine beta-catenin expression, protein-protein interactions, localization, and regulation in prenatal and postnatal livers. RESULTS: Microarray, Northern, and protein analyses showed peak expression of beta-catenin during early liver development at Embryonic day 10 (E10)-E12, followed by a decrease and a complete loss of normal beta-catenin (97-kilodalton species) after E16 through the remaining prenatal period. At the early stages, beta-catenin localized to the cytoplasm and nuclei of resident cells in addition to its normal membranous localization, which was seen at all later stages and in adult liver. Decreases in beta-catenin levels at E14 onward coincided with its decreased gene expression and increased degradation, as seen by an increase in serine 45/threonine 41-phosphorylated beta-catenin and its other negative regulators, such as axin, adenomatous polyposis coli gene product (APC), and glycogen synthase kinase-3 beta. Finally, we showed an intact association of E-cadherin and beta-catenin despite the loss of beta-catenin at E16-E18, owing to the presence of membrane-associated smaller-molecular-weight beta-catenin species. CONCLUSIONS: We also identified a stage-specific expression and regulation of beta-catenin during liver development that might be crucial for physiological liver development. Nuclear and cytoplasmic beta-catenin corresponded to cell proliferation in liver development. Finally, a smaller-molecular-weight species of beta-catenin might be maintaining normal interactions at the membrane.     

奥美沙坦通过减低整合素β5的表达促进心肌肥大的消退

目的研究整合素β5和心肌肥大的关系,比较新型血管紧张素Ⅱ-Ⅰ型受体拮抗剂(ARB)奥美沙坦和血管紧张素转换酶抑制剂(ACEI)替莫普利对心肌肥大的作用.方法雄性脑卒中易感型自发性高血压大鼠(SHRSP)33只,5周龄雄性京都种Wistar(WKY)大鼠11只,随机分为SHRSP空白组,SHRSP的奥美沙坦给药组(10 mg·kg-1·d-1),SHRSP的替莫普利给药组(10 mg·kg-1·d-1),WKY作为对照组.给药6周后,取出心脏称重,制作标本进行病理学检查,检测血管紧张素Ⅱ-1型受体(AT1)以及整合素β5的表达量.结果奥美沙坦和替莫普利的使用使SHRSP的收缩压降低,但奥美沙坦比替莫普利的促心肌肥大消退作用更显著.半定量RT-PCR测定表明,SHRSP的AT1和整合素β5的表达量明显高于WKY,奥美沙坦和替莫普利的使用降低了两者的表达量,奥美沙坦的作用更显著.AT1和整合素β5的表达成正相关关系.结论奥美沙坦在抑制心肌细胞肥大和降低AT1、整合素β5的表达量方面比替莫普利有更多获益.整合素β5的表达受抑参与了心肌肥大的消退.整合素β5在心肌细胞的表达可能受到血管紧张素Ⅱ(AngⅡ)通过AT1受体的调节.     

ICU产ESBLs大肠埃希菌和肺炎克雷伯菌耐药性分析

目的探讨医院重症监护病房产超广谱β-内酰胺酶(ESBLs)大肠埃希菌和肺炎克雷伯菌的耐药性。方法采用BD Phoenix100全自动微生物分析仪对莒县中医医院重症监护病房产超广谱β-内酰胺酶(ESBLs)大肠埃希菌和肺炎克雷伯菌进行细菌鉴定和药物敏感试验。结果产ESBLs大肠埃希菌和肺炎克雷伯菌均呈现多重耐药,大肠埃希菌对亚胺培南、哌拉西林/他唑巴坦和阿米卡星的耐药率分别为1.8%、5.5%和20.0%,其余14种抗生素的耐药率在54.6%~100.0%;肺炎克雷伯菌对亚胺培南无耐药现象,其余16种抗生素的耐药率在56.0%~100.0%。结论重症监护病房分离的产ESBLs大肠埃希菌和肺炎克雷伯菌多重耐药严重;同样是产ESBLs菌株,大肠埃希菌和肺炎克雷伯菌对相同抗生素的敏感率明显不同。