Analysis of potato virus X replicase and TGBp3 subcellular locations

Potato virus X (PVX) infection leads to certain cytopathological modifications of the host endomembrane system. The subcellular location of the PVX replicase was previously unknown while the PVX TGBp3 protein was previously reported to reside in the ER. Using PVX infectious clones expressing the green fluorescent protein reporter, and antisera detecting the PVX replicase and host membrane markers, we examined the subcellular distribution of the PVX replicase in relation to the TGBp3. Confocal and electron microscopic observations revealed that the replicase localizes in membrane bound structures that derive from the ER. A subset of TGBp3 resides in the ER at the same location as the replicase. Sucrose gradient fractionation showed that the PVX replicase and TGBp3 proteins co-fractionate with ER marker proteins. This localization represents a region where both proteins may be synthesized and/or function. There is no evidence to indicate that either PVX protein moves into the Golgi apparatus. Cerulenin, a drug that inhibits de novo membrane synthesis, also inhibited PVX replication. These combined data indicate that PVX replication relies on ER-derived membrane recruitment and membrane proliferation.     

Increased Inflammation, Reduced Plasma Phospholipid Eicosapentaenoic Acid and Reduced Antioxidant Potential of Treated Hypertensive Patients with Metabolic Syndrome

Purpose

In the present study, we tested whether the presence of metabolic syndrome (MetS) would worsen the features of inflammation, plasma omega 3 fatty acid levels and antioxidant potential in treated hypertensive patients.

Materials and Methods

Two groups were classified by the components of MetS: a reference group of treated hypertensive subjects: hypertension (HTN) group (n = 39) and with more than two additional MetS components: HTN with Mets group (n = 40). We further compared the parameters between HTN group and HTN with MetS group.

Results

The results showed that age (p < 0.001) and body mass index (BMI) (p < 0.001) were significantly different between HTN group and HTN with MetS group. Age- and BMI-adjusted total radical trapping antioxidant potential (TRAP) (p < 0.01) was significantly lower, whereas age- and BMI-adjusted CD (p < 0.05) and interleukin (IL) 6 (p < 0.05) were significantly higher in HTN with MetS group than in HTN group. Moreover, HTN with MetS group had significantly lower levels of age- and BMI-adjusted plasma phospholipid eicosapentaenoic acid (EPA) than HTN group (p < 0.05). On the other hand, the levels of age- and BMI-adjusted intracellular cell adhesion molecule-1 (ICAM-1), adiponectin and high molecular weight (HMW)-adiponectin were not significantly different between the groups.

Conclusion

In conclusion, our results showed increased inflammatory marker, reduced antioxidant potential and EPA levels in treated hypertensive patients in the presence of MetS, suggesting the importance of changes of therapeutic lifestyle to modify the features of MetS.     

Association of early phase of colorectal carcinogenesis with STAT3 activation and its relevance in apoptosis regulation

Expression of STAT3/pSTAT3 in colorectal cancer (CRC) patients of Indian origin was studied to assess its significance in early detection and apoptosis regulation. Colorectal tissues with malignant lesions were STAT3/pSTAT3 positive in 66% of the cases and among these positive cases, well differentiated, moderately differentiated and poorly differentiated cancers were 86%, 60% and 0% respectively. All CRC specimens studied were immunoreactive with anti-carcinoembryonic antigen antibody. Cells purified from CRC tissues exhibited greater STAT3/pSTAT3 reactivity than peripheral blood mononuclear cells (PBMC) from healthy individuals, which served as control. apoptotic index (AI) was comparatively low in tissue specimens with STAT3/pSTAT3 expression. CRC cells with a comparatively less number of apoptotic cells, expressed a minimum number of Caspase-3 positive cells (4.73%), in comparison to healthy-PBMC (12.63%). CRC cells with high STAT3/pSTAT3 staining had cells with greater percentage of Bcl2 reactivity (23.05%), but less positivity with Caspase3 antibody (2.05%). Overall data suggests that CRC population was STAT3/pSTAT3 immunoreactive in a stage specific manner and STAT3 protects cancerous colorectal epithelial cells from apoptosis. Bcl-2, Cyclin D1 and Caspase-3 control the activity of apoptosis regulator, STAT3.     

A comparative neuropsychological test battery differentiates cognitive signatures of Fragile X and Down syndrome

Background Standardised neuropsychological and cognitive measures present some limitations in their applicability and generalisability to individuals with intellectual disability (ID). Alternative approaches to defining the cognitive signatures of various forms of ID are needed to advance our understanding of the profiles of strengths and weaknesses as well as the affected brain areas. Aim To evaluate the utility and feasibility of six non‐verbal comparative neuropsychological (CN) tasks administered in a modified version of the Wisconsin General Test Apparatus (WGTA) to confirm and extend our knowledge of unique cognitive signatures of Fragile X syndrome (FXS) and Down syndrome (DS). Method A test battery of CN tasks adapted from the animal literature was administered in a modified WGTA. Tasks were selected that have established or emerging brain–behaviour relationships in the domains of visual‐perceptual, visual‐spatial, working memory and inhibition. Results Despite the fact that these tasks revealed cognitive signatures for the two ID groups, only some hypotheses were supported. Results suggest that whereas individuals with DS were relatively impaired on visual‐perceptual and visual‐spatial reversal learning tasks they showed strengths in egocentric spatial learning and object discrimination tasks. Individuals with FXS were relatively impaired on object discrimination learning and reversal tasks, which was attributable to side preferences. In contrast, these same individuals exhibited strengths in egocentric spatial learning and reversal tasks as well as on an object recognition memory task. Both ID groups demonstrated relatively poor performance for a visual‐spatial working memory task. Conclusion Performance on the modified WGTA tasks differentiated cognitive signatures between two of the most common forms of ID. Results are discussed in the context of the literature on the cognitive and neurobiological features of FXS and DS.     

Peripheral nervous system pathology in fragile X tremor/ataxia syndrome (FXTAS)

Fragile X tremor/ataxia syndrome (FXTAS) occurs in individuals with moderate CGG expansion of the fragile X mental retardation 1 (FMR1) gene and is associated with intranuclear inclusions in neurons and astrocytes. Although the neuropathologic findings in the brain and spinal cord were described, pathological features in the peripheral nervous system were not reported. Here, we report on novel neuropathological findings in the peripheral nervous system and especially in autonomic ganglia at autopsy in a man with FXTAS. In addition to the characteristic brain and spinal cord findings, typical intranuclear inclusions were identified in the ganglion cells of adrenal medulla, dorsal root ganglia, paraspinal sympathetic ganglia, myenteric ganglia of the stomach and subepicardial autonomic ganglion of the heart. Our findings indicate that FXTAS diffusely involves the central and peripheral nervous systems, which explains the protean neurological symptoms ranging from dementia to dysautonomia.     

Treatment of imbalance with varenicline Chantix(R): report of a patient with fragile X tremor/ataxia syndrome

We describe the case of a man with Fragile X tremor/ataxia syndrome, whose ataxia and imbalance improved with the use of varenicline (Chantix) and reverted to baseline 10 days after varenicline was discontinued. Varenicline was started as part of a smoking cessation program.     

多层螺旋CT血管成像评价肝移植受者移植前后血管结构

背景：多层螺旋CT具有先进的扫描技术和强大的图像后处理功能,其亚秒级的扫描速度及各向同性的成像功能,在血管成像上有很多优势。 目的：探讨多层螺旋CT血管成像技术对肝移植受者移植前后血管结构评价的应用价值。 设计、时间及地点：回顾性分析,以肝移植受者肝脏血管为观察对象,自身对照观察,于2003-10/2006-12在中山大学附属第五医院放射科完成。 对象：选择拟行原位肝移植患者27例,年龄31~67岁,男17例,女10例。 方法：轴位螺旋扫描范围为膈顶上方2 cm至双肾下极以下。电压120 kV,动脉期准直0.75 mm,平扫、门脉期、肝静脉期准直1.5 cm;使用非离子型对比剂优维显,注射速度为3 mL/s,三期增强扫描延迟时间分别为20~25 s,50~55 s,75~80 s。重建增强的薄层图像序列,动脉期层厚1 mm,间隔0.7 mm;门脉期、肝静脉期层厚2 mm,间隔1 mm。将图像序列传入后处理工作站,以MIP、VR等方式显示腹腔干系、门脉系、肝静脉及下腔静脉血管的三维结构。 主要观察指标：肝移植前后患者血管三维结构。 结果：移植前所有患者腹腔干系均得到良好显示,21例肝动脉走形正常,6例患者肝动脉变异,其中门静脉海绵样变2例,门脉多发血栓1例,因不适宜手术此3例未进行肝移植。24例患者第二肝门及下腔静脉肝内段血管结构显示清楚,肝右静脉单独汇入下腔静脉、肝左静脉和肝中静脉先汇合后再注入下腔静脉18例,肝右静脉、肝中静脉及肝左静脉分别单独汇入下腔静脉6例,下腔静脉肝后段狭窄2例。17例肝移植后CT血管成像发现肝动脉吻合口部狭窄2例,门脉高压侧支迂曲缓解10例,另7例患者因检查费用问题选择B超检查。 结论：多层螺旋CT血管成像能够清晰显示肝移植患者移植前后血管结构,对适宜手术的病例筛选、指导手术方案及移植后血管结构的评价具有重要意义。     

Inhibition of P2X receptor-mediated inward current by protein kinase C in small-diameter dorsal root ganglion neurons of adult rats

Objective

The aim of the present study is to verify the ATP-induced varied responses in isolated dorsal root ganglion (DRG) neurons of the adult rat, and investigate the modulatory effects of specific P2X receptor agonist β, γ-me-ATP and protein kinase C (PKC) on P2X receptor-mediated inward current in DRG neurons.

Methods

Whole cell patch-clamp was employed to record the currents on acutely isolated DRG neurons in the adult rats.

Results

β, γ-me-ATP, similar as ATP, evoked 2 distinct subtypes of P2X receptor-mediated inward currents in a dose-dependent manner in DRG neurons. Activation of PKC by phorbol 12,13-dibutyrate (PDBu) significantly inhibited both subtypes of inward currents mediated by P2X receptors in a dose-dependent manner.

Conclusion

Activation of PKC negatively modulated the P2X receptor-mediated currents in rat DRG neurons, which may be of benefit to preventing the over-excitation of nociceptor under inflammatory or neuropathic conditions.