Erythropoietin induces association of the JAK2 protein tyrosine kinase with the erythropoietin receptor in vivo

Protein tyrosine phosphorylation has been hypothesized to play a key role in the growth signaling induced by erythropoietin (Epo), although the Epo receptor (EpoR), a member of the cytokine receptor superfamily, lacks a tyrosine kinase domain. Recently, the JAK2 tyrosine kinase was shown to be activated on Epo stimulation and to bind to the cytoplasmic domain of EpoR in vitro. To further explore the mechanisms of activation of JAK2 in EpoR-mediated signal transduction, we assessed the conditions for association of JAK2 with EpoR in vivo. Epo stimulation rapidly induced association of JAK2 with the EpoR in an interleukin 3 (IL-3)-dependent cell line transfected with the wild-type EpoR. On Epo stimulation JAK2 also associated with a truncated mutant EpoR (H-mutant), which is mitogenetically active but not tyrosine phosphorylated, indicating that association does not require receptor phosphorylation and occurs in the membrane proximal region. However, association was not detected with mutant receptors inactivated by an internal deletion or a point mutation, Trp282 to Arg, in a membrane- proximal cytoplasmic region (PB or PM4 mutant, respectively). Immune complex kinase assays of anti-EpoR immunoprecipitates also revealed that activated JAK2 associates with the EpoR in Epo-stimulated cells. By this approach, association also occurred with the mitogenically active H mutant but not with the mitogenically inactive PB or PM4 mutants. In the immune complex kinases assays, EpoR, JAK2, and a 150-kD protein were phosphorylated on tyrosine. Taken together, the results further support the hypothesis that, on Epo stimulation, JAK2 associates with the membrane-proximal cytoplasmic region of the EpoR to be activated and induces tyrosine phosphorylation of cellular substrates, including the EpoR, to transduce a growth signal.     

兔膝关节内注射透明质酸钠后胶原纤维及关节外相关韧带组织的变化

目的:在兔固定的膝关节内定期注入透明质酸钠,观察关节内外组织的变化。方法:实验于2003-10/2004-04在大连医科大学完成。实验分组:新西兰兔24只,随机分为透明质酸钠组、生理盐水组、单纯对照组,每组8只。实验干预:用树脂绷带将兔右膝关节固定于伸直位,膝关节注射部位开窗,左膝自由活动(自身对照侧)。透明质酸钠组膝关节腔内注入透明质酸钠0.1mL,生理盐水组注射同等剂量的生理盐水,单纯对照组不向关节内注射任何药物,每周1次,共5次。实验评估:5周后麻醉下处死动物,去除外固定,采用改良Clarke-Weeknesser关节伸屈范围检查标准测量右膝关节的活动范围;采用改良的Rydell-Balazes肉眼粘连评分标准评估膝关节内纤维粘连情况;光镜下观察股间肌、股直肌、髌内外侧支持带的纤维变性情况。结果:动物饲养过程中死亡4只,进入结果分析透明质酸钠组7只,生理盐水组6只,单纯对照组7只。①右膝关节的活动范围:透明质酸钠组大于生理盐水组和单纯对照组[(37.86±2.94)°,(15.67±2.23)°,(14.29±1.96)°,P<0.01]。②膝关节内纤维粘连评分:透明质酸钠组小于生理盐水组和单纯对照组(1.44±0.49,3.33±0.44,3.44±0.57,P<0.01)。③光镜下透明质酸钠组股间肌、股直肌的纤维变性较生理盐水组和单纯对照组减轻,髌内外侧支持带胶原纤维成分的变化也减轻。结论:在固定的兔膝关节内注射透明质酸钠不但可以明显抑制关节内的纤维性粘连;还可以抑制关节外股间肌、股直肌、髌内外侧支持带的组织变性。     

苏皖地区汉族人群不稳定型心绞痛患者与血小板反应素4基因A387P多态性的关系

目的:观察血小板反应素4基因G29926C(A387P)多态性与中国苏皖地区汉族人群不稳定型心绞痛的可能关系。方法:选择2004-11/2006-05在南京医科大学第一附属医院和江苏大学附属武进医院住院不稳定型心绞痛患者110例,病例均符合2002年AHA/ACC关于不稳定型心绞痛诊断指南的诊断标准,同期选择337例非冠心病者为对照。酚-氯仿法提取白细胞DNA,应用聚合酶链反应-限制性片段长度多态性方法分析血小板反应素4A387P多态性,取部分PCR扩增产物进一步测序鉴定,比较两组间多态性频率分布差异,探讨血小板反应素4基因多态性与不稳定型心绞痛发病的可能关系。结果:447例均进入结果分析。GC基因型在不稳定型心绞痛组和对照组的分布无统计学差异(5.5%,7.1%,P=0.54),未检测到CC纯合子。C等位基因频率在不稳定型心绞痛组和对照组分别为2.7%,3.6%(P=0.55)。GC基因型与不稳定型心绞痛无显著性关联(OR=0.75,95%CI:0.30￣1.89,P=0.54)。结论:血小板反应素4基因387A→P不是中国苏皖地区汉族人群常见的多态位点,且与不稳定型心绞痛的发病无显著相关性。     

Peritoneal cystic mesothelioma presenting as a cystic mass in the pelvis: a challenging differential diagnosis

Peritoneal cystic mesothelioma is a relatively rare neoplasm, characterized by cystic lesions of various sizes on both visceral and parietal peritoneal surfaces. When located in the pelvis, a wide spectrum of cystic or multicystic lesions should be included in the differential diagnosis. From an imaging point of view, no definite differential diagnostic suggestions can be made, because reports of peritoneal cystic mesothelioma are few and consist mostly of case reports. The rarity of this disease, as well as its malignant potential, include it among the challenging differential diagnoses of pelvic/peritoneal cystic masses, especially in the case of a paraovarian cyst with identification of ovaries with non-suspect morphology. In this case, repetition of transvaginal ultrasound examination after a few weeks seems to be appropriate. When the findings persist, cystic peritoneal mesothelioma must be included in the differential diagnosis. Nevertheless, it seems that the definitive diagnosis of peritoneal cystic mesothelioma can be made only after surgery. Imaging with ultrasonography and magnetic resonance could play an important role in disease follow-up.     

Haemoptysis in patients with a normal chest radiograph: Bronchoscopy–CT correlation

The exact role of fibre-optic bronchoscopy (FOB) and CT of the chest in the diagnosis of patients presenting with haemoptysis and a normal or non-localizing chest radiograph has not been clearly defined. A study was designed to evaluate 50 patients presenting with haemoptysis and a normal or non-localizing chest radiograph using FOB and high-resolution computed tomography (HRCT). A definitive diagnosis was established in 17 (34%) patients. The aetiologies included bronchiectasis (24%), bronchial adenoma (6%), tuberculosis (2%) and bronchitis (2%). The diagnosis was made by HRCT in 15 (30%) patients, while FOB was diagnostic in five (10%) patients. The diagnosis was made by HRCT and FOB in all patients with focal airway abnormalities. Therefore, HRCT effectively delineated abnormalities of both the central and peripheral airways. It is concluded that CT should be obtained prior to FOB in all patients presenting with haemoptysis and a normal or non-localizing chest radiograph.     

Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype

Whole exome sequencing and chromosomal microarrays are two powerful technologies that have transformed the ability of researchers to search for potentially causal variants in human disease. This study combines these tools to search for causal variants in a patient found to have maternal uniparental isodisomy of chromosome 2. This subject has a complex phenotype including skeletal and renal dysplasia, immune deficiencies, growth failure, retinal degeneration and ovarian insufficiency. Eighteen non‐synonymous, rare homozygous variants were identified on chromosome 2. Additionally, five genes with compound heterozygous mutations were detected on other chromosomes that could lead to a disease phenotype independent of the uniparental disomy found in this case. Several candidate genes with potential connection to the phenotype are described but none are definitively proven to be causal. This study highlights the potential for detection of a large number of candidate genes using whole exome sequencing complicating interpretation in both the research and clinical settings. Forums must be created for publication and sharing of detailed phenotypic and genotypic reports to facilitate further biological discoveries and clinical counseling.