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The aim of this study was to investigate the topographical distribution of dopamine transporter (DAT), dopamine D2 receptor, and glucose metabolism in Parkinson's disease (PD) using PET/computed tomography (CT) scanning and statistical parametric mapping (SPM) analysis.Seventy-four patients (58 PD patients and 16 normal controls) underwent DAT, D2 receptor, and glucose brain PET/CT scans using C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (C-β-CFT), C-raclopride (C-RAC), and fluorine-18-fluorodeoxyglucose (F-FDG) radiotracers for the respective scans. All three PET/CT procedures were performed in each participant. The uptake patterns were analyzed using SPM software.Striatal DAT binding was lower in PD patients than in controls, whereas D2 receptor binding did not differ between PD patients and controls. D2 receptor binding was increased in the putamen in only the 12 drug-naive patients. Glucose uptake was also slightly lower in the cingulate gyrus of PD patients than in the controls.Suite PET/CT scans using the ligands C-β-CFT, C-RAC, and F-FDG PET/CT are valuable for diagnosing PD. SPM-based analysis of static PET/CT scan data is potentially of great clinical use.

To design Keap1-tat peptide and explore its neuroprotective role on hipocampal CA1 neuron, as well as the effect on spacial learning and memory function following global cerebral ischemia.Adult male Sprague Dawley (SD) rats were subjected to global cerebral ischemia (GCI) by four-vessel occlusion for 15 min and randomly divided into five groups: sham, sham+Keap1-tat, ischemia/reperfusion (I/R), Keap1-tat peptide- and vehicle-administrated groups. For Keap1-tat or vehicle groups, the rats were treated with Keap1-tat (30, 50, 100 μg in 5 μL 0.9% saline) or the same volume vehicle by intracerebroventricular injection (icv) 30 min prior to ischemia. Cresyl violet staining was used to observe the surviving neurons and 4-hydroxy-2-noneal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunostaining were used to detect the change of markers response to oxidative stress in hippocampal CA1 region. The spatial learning and memory function of the rats was evaluated using Morris water maze.Compared with sham group, the number of surviving neurons in ischemia-reperfusion and vehicle groups significantly decreased in the hippocampal CA1 region (P0.05), while administration of Keap1-tat significantly decreased the damage following GCI (P0.05), and the dose of 50 μg existed the most effective neuroprotective role. Furthermore, immunostaining intensity of 4-HNE and 8-OHdG, markers of oxidative stress damage attenuated by Keap1-tat peptide as compared with vehicle group in CA1 region. Of significant interest, the time of finding underwater platform in Keap1-tat group animals was significantly short, and after removing the platform, the probe time of Keap1-tat group animals in the original quadrant where the platform was significantly increased compared with that of vehicle and I/R group animals (P0.05).Keap1-tat peptide can effectively attenuate neuronal damage in hippocampal CA1 region and improve learning and memory function, which might bedue to the attenuation of oxidative stress caused by GCI.

Objective We explored the clinical values of 11 C-choline ( 11 C-CHO) PET in optimization of target volume delineation and treatment regimens in postoperative radiotherapy for brain gliomas. Methods Sixteen patients with the pathological confirmation of the diagnosis of gliomas prior to receiving radiotherapy (postoperative) were included, and on whom both MRI and CHO PET scans were performed at the same position for comparison of residual tumors with the two techniques. 11 C-CHO was used as the tracer in the PET scan. A plain T1-weighted, T2-weighted and contrast-enhanced T1-weighted imaging scans were performed in the MRI scan sequence. The gliomas' residual tumor volume was defined as the area with CHO-PET high-affinity uptake and metabolism ( V CHO ) and one with MRI T1-weighted imaging high signal intensity ( V Gd ), and was determined by a group of experienced professionals and clinicians. Results (1) In CHO-PET images, the tumor target volume, i.e., the highly metabolic area with a high concentration of isotopes (SUV 1.016–4.21) and the corresponding contralateral normal brain tissues (SUV0.1–0.62), was well contrasted, and the boundary between lesions and surrounding normal brain tissues was better defined compared with MRI and 18 F-FDG PET images. (2) For patients with brain gliomas of WHO Grade II, the SUV was 1.016–2.5; for those with WHO Grades III and IV, SUVs were >26–4.2. (3) Both CHO PET and MRI were positive for 10 patients and negative for 2 patients. The residual tumor consistency between these two studies was 75%. Four of the 10 CHO-PET-positive patients were negative on MRI scans. The maximum distance between V Gd and V CHO margins was 1.8 cm. (4) The gross tumor volumes (GTVs) and the ensuing treatment regimens were changed for 31.3% (5/16) of patients based on the CHO-PET high-affinity uptake and metabolism, in which the change rate was 80% (4/5), 14.3 % (1/7) and 0% (0/4) for patients with WHO Grade II III, and IV gliomas, respectively. Conclusion Our data demonstrate that difference exists between CHO PET and MRI by which to judge and identify residual tumor for patients with brain gliomas. CHO PET is considered to be a supplementary diagnostic approach for MRI. Biological tumor target volume (BTV) displayed in the CHO PET images is useful in determining or delineating the radiotherapy target volume and making decisions in selecting treatment regimens. Tumor target volume may be defined more accurately and rationally when the CHO PET is combined with MRI.

We investigated the expression and subcellular localization of the multidomain protein POSH (plenty of SH3s) by immunohistochemistry and western blot analysis, as well as its role in the selective activation of mixed-lineage kinases (MLKs) 3, MAP kinase kinase (MKK) 4, c-Jun N-terminal kinases (JNKs) and the c-Jun signalling cascade in the rat hippocampal CA1 region following cerebral ischaemia. Our results indicated that the cytosol immunoreactivity of POSH was strong in the CA1-CA3 pyramidal cell but weak in the DG granule cell of the rat hippocampus both in sham control and after reperfusion. Co-immunoprecipitation experiments showed that the interactions of MLK3, MKK4 and phospho-JNKs with POSH were persistently enhanced during the early (30 min) and the later reperfusion period (from 1 to 3 days) compared with sham controls. Consistently, MLK3-MKK4-JNK activation was rapidly increased with peaks both at 30 min and 3 days of reperfusion. Intracerebroventricular infusion of POSH antisense oligodeoxynucleotides (AS-ODNs) not only significantly reduced the protein level of POSH, markedly decreased its interactions with MLK3, MKK4 and phospho-JNKs, but also attenuated the activation of the JNK signalling pathway. In addition, infusion of POSH AS-ODNs significantly increased the neuronal density in the CA1 region at 5 days of reperfusion. Our results suggest that POSH might serve as a scaffold mediating JNK signalling activation in the hippocampal CA1 region following cerebral ischaemia, and POSH AS-ODNs exerts its protective effects on ischaemic injury through a mechanism of inhibition of the MLK3-MKK4-JNK signalling pathway, involving c-Jun and caspase 3 activation.

Activation (phosphorylation) and the possible mechanism of extracellular signal-regulated kinase 5 (ERK5) were evaluated after cerebral ischemia-reperfusion (I/R) in the hippocampus in a four-vessel occlusion model of Sprague-Dawley rats. Western blotting showed that ERK5 was strongly activated from 10 min to 1 day and peaked at 30 min of reperfusion after 15 min ischemia. Pretreatment with N-acetylcysteine, a free radical scavenger, effectively inhibited ERK5 activation in a dose-dependent manner. Consistently, ERK5 activation was significantly suppressed by genistein (protein-tyrosine kinase inhibitor), PP2 (specific inhibitor of Src family kinases), nifedipine (L-VGCC blocker) and dextromethorphan (NMDA receptor antagonist), but not 6,7-dinitroquinoxaline-2, 3(1H, 4H)-dione (AMPA receptor antagonist). These results suggested that ERK5 could be significantly activated by I/R, which might be mediated by NMDA receptor and L-VGCC through Src kinase pathway involving oxidative stress in rat hippocampus.

Solid pseudopapillary tumors (SPT) are rare, unique pancreatic tumors with benign entity and low malignant potential. Limited information is available in the literature reporting their accumulation of fluorine-18 fluoro deoxyglucose ((18)F-FDG) using positron emission tomography/computed tomography (PET/CT). The aim of this retrospective study was to define t he uptake-accumulation of (18)F-FDG PET/CT in a comparatively large cohort of SPT, and to compare their uptake with the uptake of (18)F-FDG in pancreatic ductal adenocarcinomas (PAC) and neuroendocrine tumors (PNET). Between June 2007 and January 2013, 18 pathologically proven SPT were identified from the total of patients studied by PET/CT in our Center, including 13 women and 5 men, aging from 23 to 56 years old (mean age, 38.5 years). Malignant SPT was histologically classified using the WHO criteria. Eighty-six PAC patients and 28 PNET patients were also identified and included in this study for comparison. Positron emission tomography results were considered as positive if focal accumulation of (18)F-FDG exceeded the surrounding normal pancreatic tissue. Regions of interest were drawn on the pancreatic lesions, and the maximal standardized uptake values (SUVmax values) were calculated. The mean values of SUVmax were compared with independent-samples t test or with the nonparametric Mann-Whitney U method. Correlation of SUVmax values and tumor size were analyzed in cases of SPT. Receiver operating characteristics (ROC curve) were used to study the efficiency of SUV values for the differential diagnosis between SPT versus (vs) PAC and SPT vs PNET. A value of P0.05 was considered statistically significant. All SPT cases were (18)F-FDG-PET positive, with SUVmax values ranging from 3.5-18.3. The SUVmax values of SPT had poor correlation with tumor size, and no significant difference by gender and age. Areas under the curve ROC were 0.619 and 0.526, respectively for the differentiation of SPT from PNET and PAC tumors. Five SPT tumors were malignant, and exhibited relatively low (18)F-FDG uptake (SUVmax range, 3.0-4.5) except a tumor after recurrence (SUVmax 17.7). Images of CT were of low dose and thus were not evaluated. In conclusion, our results suggest that SPT benign or malignant are consistently hyperaccumulating (18)F-FDG above SUVmax 3. Differentiation from PAC and PNET if only based on the higher SUVmax values was not possible but if based on lower SUVmax, of ≤2.6 (in 14%) and ≤2.5 (in 21,4%) of PAC and PNET, respectively, these pancreatic tumors could be differentiated from SPT.

Summary Background and purpose To assess the clinical effect of transplantation of human retinal pigment epithelial (hRPE) cells into the unilateral postcommissural putamen for treatment for Parkinson disease (PD). Methods and results Cells from postmortem human eye tissue (10–20 weeks of gestation) were cultured in vitro. Cells from -generation passage were implanted in PD postcommissural putamen with stereotactic operation in 12 patients with PD. All patients tolerated surgery well, and no major adverse events occurred. Eleven patients showed improvement in the primary outcome measure at 3 months post-treatment, particularly the Unified Parkinson's Disease Rating Scale-M score in the off state. Response reached a peak at 12 months and declined during the next 24 months. At the 36-month endpoint, there were eight patients who felt better than at baseline. Positron emission tomography (PET) showed a trend with increased dopamine (DA) release during the first 6 months. Conclusion Human retinal pigment epithelial cells have the characteristics of neural progenitor cells and can be induced to differentiate into DA neurons. The results of this clinical trial suggest that the treatment of transplanted hRPE cells could improve symptoms of PD. These cells might serve as a useful source of DA neurons for neural graft in the treatment for PD.

The aim of this study was to evaluate the role of (18)F-FLT positron emission tomography/computed tomography (PET/CT) in diagnosis and staging of diffuse large B-cell lymphoma (DLBCL) patients and compare with CT. Thirty-six patients with DLBCL in our hospital from September 2008 to December 2009 were prospectively evaluated. All 36 patients underwent whole body and head (18)F-FLT PET/CT and CT (chest, abdomen cavity and pelvis) were studied before therapy. The maximal standardized uptake value (SUV(max)) of every single focus and the SUV(max) of aortic arch blood pool were measured and used to calculate the median T/MB value (tumor SUV(max)/mediastinal SUV(max)) of every patient. The results showed that the consistency of (18)F-FLT PET/CT and CT examinations in focus of DLBCL was 79.10%, the sensitivity, specificity, positive predictive value, negative predictive value and accurate rate of (18)F-FLT PET/CT were 96.65%, 100%, 100%, 61.11% and 96.82%, respectively, which were much higher than that of CT (85.44%, 57.14%, 96.70%, 21.05% and 83.64%). It is concluded that the (18)F-FLT PET/CT is a good means for DLBCL diagnosis and staging, which is more sensitive and specific than CT.

The percutaneous transcatheter closure of secundum atrial septal defect (ASD) is increasingly a widespread alternative to surgical closure. The aim of this study was to assess long-term results of percutaneous closure of secundum-type atrial septal defect (ASDII).Between January 2001 and December 2005, 61 patients underwent a successful percutaneous closure of ASDII; including 25 male and 36 female. All were included in the patient study and were followed up to monitor by electrocardiogram and echocardiography, at intervals of 3 days, 3 months, 6 months, 1 year, 2 years, and 5 years after operation.Three days after percutaneous transcatheter septal closure (PTSC), the right atrium diameter, right ventricular end-diastolic left-right diameter and right ventricular end-diastolic volume (RVEDV) decreased significantly (P0.05). Right ventricular end-diastolic anteroposterior diameter (RVEDD), right ventricular end-systolic volume (RVESV) and right ventricular ejection fraction (RVEF) also decreased (P0.01). During the period from 3 to 6 months, the size of the right atrium and right ventricle returned to normal range. Three days after PTSC, the left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular-systolic volume (LVSV) and left ventricular ejection fraction (LVEF) were significantly increased (P0.05). At 1 year, the size of the left atrium, left ventricle and left cardiac function returned to normal range (P0.01). There were no deaths or significant complications during the study. At five year follow-up, all defects were completely closed and remained closed thereafter.Transcatheter closure of ASDII effectively eliminated the abnormal shunt and, subsequently improved the dimensions of each chamber and cardiac function.

To discuss the value of 11C-PIB PET and 18F-FDG micro PET imaging in Alzheimer's disease (AD) rat model.The AD rat model was established by injection of Abeta1-40 into rat's hippocampus. Learning and memory function were estimated by the Morris water maze. Amyloid deposit and neuron loss were observed by Congo red staining and HE staining respectively. 11C-PIB PET and 18F-FDG micro PET scan were performed. Meanwhile the findings of PET imaging were compared with the results of behavior test and histology.The uptake of 18F-FDG in hippocampus of AD rat model group was lower than that of control group (P0.01). The Morris water maze showed that the escape latent period of rat model group was longer than that of control group (P0.01). Neuron loss was found in rat model brain. Thus the result of micro-PET imaging was matched with those of the Morris water maze and HE staining. 11C-PIB was specifically bound to beta-amyloid in rat model brain, the uptake of 11C-PIB in AD rat model was higher than that of control (P0.05). Abeta deposit was observed in Congo red staining so that the result of 11C-PIB Micro-PET imaging was matched with that of beta-amyloid deposition.11C-PIB Micro-PET imaging shows the plaque deposition while 18F-FDG PET imaging reflects the change of glucose metabolism in hippocampus in AD rat model. And PET scan can be used to verify the successful establishment of AD model rat model.

To investigate the potential association of the C-reactive protein (CRP) gene +1444C/T polymorphism with symptomatic carotid artery stenosis.Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of CRP +1444C/T genotypes in 192 patients with symptomatic carotid artery stenosis and 197 healthy controls. Serum high sensitivity-CRP (hs-CRP) levels were measured by routine method.No TT genotype was detected in this study. Patients with70% stenosis had higher CC genotype compared with those with70% stenosis after adjusting for major cerebrovascular risk factors (OR: 2.958; 95% CI: 1.198 - 7.305; P=0.019). CRP levels were significantly higher in patients than in controls. Subgroup analysis according to clinical characteristics (single or double stenosis;70% or70% stenosis) did not show difference in CRP levels. There was no significant difference in the prevalence of CT genotype between patients and controls, or between single and double stenosis (P0.05).The CRP +1444 CC genotype is a risk factor for70% carotid artery stenosis. The serum CRP level is associated with the presence of carotid stenosis. However, it is not associated with the number and severity of stenosis.

Accumulating evidence implicates activation (phosphorylation) of mitogen-activated protein kinases (MAPK) during nonlethal ischemic preconditioning in the protection of hippocampal CA1 neuron against subsequent ischemic events. In this paper, we undertook to identify the role of extracellular signal regulated kinase (ERK) 5 in cerebral ischemic preconditioning (CIP). Three minutes of ischemia was induced as preconditioning stimulus. Three days later, 6 min of ischemia was induced. The levels of ERK5 protein expression and its activation were detected with or without the CIP in hippocampal CA1 and the dentate gyrus (DG) regions. Our results showed that ERK5 was activated selectively in hippocampal CA1 region with, but not without, the ischemic preconditioning. Notably, during the later phase of reperfusion, the rise in ERK5 activation was strong and persistent with a peak occurring at the third day. The activation peak was effectively prevented and ERK5 protein expression was significantly decreased by intracerebroventricular infusion of ERK5 antisense oligonucleotide (every 24 h for 3 days before the preconditioning), but not by sense oligonucleotide or vehicle. Subsequently, the CA1 neuronal loss was largely elevated. Moreover, both MK801 (10 microM), an antagonist of NMDA receptor, and EGTA (100 mM, but neither 50 nor 150 mM), an extracellular Ca2+ chelator, not only effectively inhibited the ERK5 activation but also markedly abolished CIP-induced survival of the CA1 neurons. These results suggested that activation of the ERK5 pathway by CIP was at least partly dependent on moderate Ca2+ influx via NMDA receptor, which might contribute to ischemic tolerance in hippocampal CA1 region of rats.

Mitogen-activated protein kinase kinase (MKK) 7, a specific upstream activator of Jun N-terminal kinases (JNKs) in the stress-activated protein kinase (SAPK)/JNK signaling pathway, plays an important role in response to global cerebral ischemia. We investigated the subcellular localization of activated (phosphorylated) MKK (p-MKK) 7 using western blotting, immunoprecipitation and immunohistochemistry analysis in rat hippocampus. Transient forebrain ischemia was induced by the four-vessel occlusion method on Sprague-Dawley rats. Our results showed that both protein expression and activation of MKK7 were increased rapidly with peaks at 10 min of reperfusion in the nucleus of the hippocampal CA1 region. Simultaneously, in the cytosol activated MKK7 enhanced gradually and peaked at 30 min of reperfusion. In addition, we also detected JNK-interacting protein (JIP) 1, which accumulated in the perinuclear region of neurons at 30 min of reperfusion. Interestingly, at the same time-point the binding of JIP-1 to p-MKK7 reached a maximum. Consequently, we concluded that MKK7 was rapidly activated and then translocated from the nucleus to the cytosol depending on its activation in the hippocampal CA1 region. To further elucidate the possible mechanism of MKK7 activation and translocation, the antioxidant N-acetylcysteine was injected into the rats 20 min before ischemia. The result showed that the levels of MKK7 activation, translocation and binding of p-MKK7 to JIP-1 were obviously limited by N-acetylcysteine in the cytosol at 30 min after reperfusion. The findings suggested that MKK7 activation, translocation and binding to JIP-1 were closely associated with reactive oxygen species and might play a pivotal role in the activation of the JNK signaling pathway in brain ischemic injury.

Extracellular signal-regulated kinase 5 (ERK5), the newest member of the mitogen-activated protein (MAP) kinase family of proteins, is widely expressed in many tissues, including the brain. Here we investigated the activation and subcellular localization of ERK5 by immunoblotting and immunohistochemistry as well as its potential role following cerebral ischemia in rat hippocampus. Transient cerebral ischemia was induced by the four-vessel occlusion method in Sprague-Dawley rats. Our results first indicated that the strongly activated ERK5 immunoreactivity was seen in the CA3/DG region but not in the CA1 pyramidal cell of rat hippocampus following reperfusion. In cytosol extracts, ERK5 activation was rapidly increased, with a peak at 30 min, and then gradually decreased to basal level at 3 days of reperfusion. In nucleus extracts, both phospho-ERK5 and its protein expression were persistently enhanced during the later reperfusion period (from 6 hr to 3 days). To elucidate further the possible role of ERK5 activation and subcellular localization in ischemic insult, rats were intraperitoneally administrated with nifedipine (ND) and dextromethorphan (DM), inhibitors of two types of calcium channels, 20 min prior to ischemia. Our findings showed that ND or DM significantly reduced activated ERK5 immunoreactivity in the nucleus and that most of the CA3/DG neurons were lost 3 days later. Most importantly, intracerebroventricular infusion of ERK5 antisense oligonucleotides (AS; every 24 hr for 3 days before ischemia), but not sense oligonucleotides or vehicle, not only markedly decreased the level of ERK5 and p-ERK5 but also largely caused neuronal loss in the CA3/DG region at 3 days of reperfusion. Taken together, the results strongly suggest that ERK5 was selectively activated in the hippocampal CA3/DG region and subsequently translocated from the cytosol to the nucleus through activation of N-methyl-D-aspartate receptor and L-type voltage-gated calcium channel, which might act as an important survival signal in ischemia-induced neuronal cell damage of the CA3/DG region. © 2005 Wiley-Liss, Inc.

Background Bone marrow-derived endothelial stem cells participate in vascular repairs. Numbers of circulating endothelial progenitor cells (cEPCs) are associated with atherosclerosis. Fibrinogen plays a key role in atherosclerosis. Objective was to assess if cEPC counts were associated with atherosclerotic intracranial artery stenosis (IAS). Methods Three hundred subjects (108 patients with stroke and IAS (IAS), 120 control patients with stroke without IAS (CP), and 72 healthy controls (HC)) were retrospectively analyzed. cEPCs were identified and counted by flow cytometry using CD34, CD133 and KDR. Plasma fibrinogen was measured by immunoturbidimetry. cEPC counts were compared between the three groups. Results cEPC numbers were significantly higher in IAS (0.059 ± 0.031%) than in CP (0.026 ± 0.012%) (P P P = 0.401). Multiple logistic regression analysis showed that cEPC levels (OR 3.31, 95%CI 1.26-8.87, P = 0.025; IAS vs. CP) were independent markers of IAS after adjustment for hypertension, diabetes and smoking. No significant correlation between cEPC counts and plasma fibrinogen levels was observed (P > 0.05). Conclusion cEPC numbers were associated with degrees of IAS. This measurement may be useful for non-invasive evaluation of atherosclerotic IAS.