Angiopoietin-Related/Angiopoietin-Like Proteins Regulate Angiogenesis

A general understanding of the molecular mechanisms underlying angiogenesis is emerging from the analysis of targeted mutations in vasculature-related genes. These analyses reveal that angiopoietin signaling through the TIE2 receptor is involved in regulating angiogenesis. Recently, we and several other groups have independently identified several molecules containing a coiled-coil domain and a fibrinogen-like domain, both of which are structurally conserved in angiopoietins. Because these molecules do not bind to the angiopoietin-specific receptor,TIE2, they have been named angiopoietin-related proteins (ARPs) or angiopoietin-like proteins (Angptls). ARPs/Angptls, which are all currently orphan ligands, also have potent activity for regulating angiogenesis as proangiogenic or antiangiogenic factors, suggesting that their receptors may be expressed on endothelial cells. In addition, ARPs/Angptls show pleiotropic effects not only on vascular cells but also on cells of other lineages, such as skin and chondrocyte cells. More recent studies have proposed that ARPs/Angptls are involved in various pathologies, such as tumor angiogenesis and metabolic diseases. To summarize the current findings relating to these proteins, we focus in this review on the functions of ARPs/Angptls as new angiogenic modulating factors in the vascular system and discuss the pleiotropic functions of ARPs/Angptls in nonvascular cell lineages.     

首发精神分裂症患者调节性T细胞及相关细胞因子变化

目的 探讨首发精神分裂症患者调节性T细胞及细胞因子变化及与精神症状的关系。方法 采用流式细胞仪技术检测27例首发精神分裂症患者和27例健康体检者外周血CD4+CD25+Foxp3+调节性T细胞（Treg）占CD4+T细胞的百分率,酶联免疫吸附试验检测血清IL-10及TGF-β1水平,采用阳性与阴性症状量表（PANSS）评定精神分裂症患者精神症状。Treg细胞、TGF-β1与年龄、病程、教育年限和精神症状以及细胞因子的相关性采用Spearman相关分析。结果首发精神分裂症患者Treg细胞百分率为（0.03±0.01）%,明显低于对照组（0.04±0.02）%（t=-3.681,P=0.001）;首发精神分裂症患者血清TGF-β1[（1.40±1.16）pg/ml]水平明显高于对照组[（0.75±0.81）pg/ml]（t=2.376,P=0.021）,但IL-10水平在精神分裂症组[（0.12±0.25）pg/ml]和对照组[（0.12±0.26）pg/ml]间比较差异无统计学意义（t=0.432,P=0.668）。首发精神分裂症患者的Treg百分率与教育年限呈正相关（r=0.452,P=0.018）,与年龄、病程和精神症状无相关性;TGF-β1与年龄、病程、教育年限和精神症状之间均无相关性。首发精神分裂症患者的Treg细胞百分率与IL-10、TGF-β1间均无相关性。结论首发精神分裂症存在免疫抑制机制受损,Treg及TGF-β1可能在首发精神分裂症患者免疫失衡的病理生理机制发挥着重要的作用。     

Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open‐label,phase 3 trial

Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV – peginterferon and ribavirin for 24 weeks – is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open‐label study to assess the efficacy and safety of an all‐oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment‐naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight‐based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment‐naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment‐naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.     

Heterogeneous Immunoreactivity of Emerin,a Nuclear Envelope LEM-domain Protein,in Normal Thyroid Follicles

Emerin is a LEM domain-containing integral membrane protein of the vertebrate nuclear envelope. Recently it has been reported that emerin regulates tissue-specific gene/protein expression. We studied the relationship between emerin expression and follicle function in normal and hyperplastic human thyroid tissues using immunohistochemistry and statistical methods. Emerin immunoreactivity was heterogeneous among follicular cells and follicles in normal thyroid tissue. It tended to be strong in the nuclei of tall follicular cells of small follicles and weak or negative in the nuclei of flat follicular cells of large follicles. Follicles with strong expression of emerin were also strongly positive for thyroglobulin (Tg) and thyroxine (T4) in follicular cells and colloid substance, suggesting active functioning follicles. In contrast, large follicles with weak expression of emerin were also weak or negative for Tg and T4. Emerin immunoreactivity was strong in almost all nuclei of hyperplastic follicular cells in Graves’ disease tissues. These findings suggest that emerin expression may be related with follicular function and may contribute to the understanding of hormonogenesis in normal thyroid follicles.     

Endoscopic submucosal dissection with sheath-assisted counter traction using a novel sheath for early gastric cancers

Background/Aims: Endoscopic submucosal dissection (ESD) is technically demanding and requires considerable skill. We previously described sheath-assisted counter traction ESD that uses simple materials and methods to improve cutting line visualization. We recently improved counter-traction of the submucosal layer using a novel chemically treated sheath that reduces slippage and maintains traction, and investigated the utility of the novel sheath for ESD. Methodology: Forty-three and 25 consecutive patients with early gastric carcinomas were treated by standard ESD and traction ESD assisted with novel sheaths, respectively. The mean duration of procedures relative to tumor size and location, as well as complications after ESD between the two groups were compared. Results: The mean duration of ESD procedures for lesions =20mm in diameter was significantly reduced using the novel sheath. The mean duration of procedures for all locations of resected tumors in the stomach was significantly reduced using the novel sheath. However, no perforation and delayed bleeding developed after treatment with the novel sheath. Conclusions: Sheath-assisted counter traction ESD by the novel sheath was technically simpler and thus less time-consuming regardless of the location of lesions, especially when =20mm in diameter. The traction ESD with the novel sheath is safe and not invasive, and it can be universally applied to standard ESD.     

Evolutionary Anatomy and Phyletic Implication of the Extrinsic Cardiac Nervous System in the Philippine Tarsier (Tarsius syrichta,Primates) in Comparisons With Strepsirrhines and New World Monkeys

To provide information on evolutionary morphological differences and similarities between Tarsiformes (tarsiers) and other primates (Strepsirrhini and Platyrrhini), we examined the previously undescribed extrinsic cardiac nervous system (ECNS) and surrounding structures in three Philippine tarsiers (Tarsius syrichta). We found that the complicated ECNS morphology shows little variation in contrast to significant anatomical diversity of the surrounding somatic structures in tarsiers as reported in our previous primate studies. Further, our comparative morphological data on the ECNS show the following aspects of evolutionary anatomical significance; (1) the traits of the general relationship between the superior cervical ganglion and the spinal nerves are common to the Tarsii and Strepsirrhini, (2) the traits of the general composition of the cervicothoracic ganglion, its communicating branches to spinal nerves, and its cardiac nerve are common to the Tarsii and Platyrrhini, and (3) the traits of the general relationship between the middle cervical ganglion and the spinal nerves and its cardiac nerve are common among Strepsirrhini, Tarsii, and Platyrrhini. Therefore, the general anatomical characteristics of the ECNS in tarsiers retain a primitive state for some traits and exhibit a derived state for others. These characteristics of the ECNS also reflect an evolutionary history without the modification and specialization as seen in the surrounding somatic structures. It may play a key role in unifying future studies on molecular phylogeny and updating evolutionary anatomical information. Anat Rec, 296:798–806, 2013. © 2013 Wiley Periodicals, Inc.