Mutation analysis of presenilin 1 gene in a Chinese family affected with early-onset familial Alzheimer's disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the clinical phenotype and genotype in a Chinese family affected with early-onset familial Alzheimer's disease (EOFAD).</p><p><b>METHODS</b>Potential mutation of beta-amyloid precursor protein (APP) gene, presenilin 1 (PSEN1) gene and apolipoprotein E (APOE) gene was detected with polymerase chain reaction (PCR) and direct sequencing.</p><p><b>RESULTS</b>Homozygous APOE ε 2 allele and no gene mutation of APP gene were detected in the proband (III1). A 488A>G mutation (His163Arg) of the PSEN1 gene was found in the proband and other 4 family members (IV1, IV12, IV21, V2).</p><p><b>CONCLUSION</b>A mutation (c.488A>G, p.His163Arg) of PSEN1 gene was found in a Chinese family affected with EOFAD.</p>

Clinical analysis of 19 AIDS patients coinfected with cryptococcus meningitis / 临床神经病学杂志

Objective To observe the clinical features of AIDS coinfected with cryptococcus meningitis. Methods The clinical data of 19 AIDS patients coinfected with cryptococcus meningitis were retrospectively analyzed.Results Among 19 patients, the main clinical manifestation including headache (100.0%), nausea/vomiting (94.7%), fever (78.9%) and neck stiffness (84.2%).Seven cases revealed increased CSF protein, 10 cases showed depressed CSF glucose levels and 11 patients revealed elevated CSF pressures.The mean CD4+cell count was (58.9 ±27.8)/mm3.Imaging examination showed the neurological complications were hydrocephalus, cerebral infarction, cerebral atrophy and cerebral hernia.The usage rate of amphotericin B, amphotericin B liposome, fluconazole and fluorine cytosine was 31.6%, 21.1%, 47.4% and 47.4%, respectively.Only 2 cases received antiretroviral therapy.The misdiagnosis rate was 31.6%, and mortality rate was 21.1%.Conclusions AIDS coinfected with cryptococcus meningitis onsets hidden, with the clinical manifestation is atypical, and the misdiagnosis rate is higher.Early diagnosis and early usage of appropriate antifungal therapy/antiretroviral therapy can help to prevent the development of it.

The effects of bone marrow mesenchymal stromal cells transplantation after mannitol pretreatment on behavioral performance and synaptophysin expression in the CA3 region in hippocampus of vascular dementia rats / 中华神经科杂志

Objective To investigate the effects of bone marrow mesenchymal stromal cells (BMSCs) transplantation after mannitol pretreatment on behavioral performance and synaptophysin expression in the CA3 region in hippocampus of vascular dementia (VD) rats.Methods The BMSCs of rats were isolated and purified by the whole bone marrow adherence method.The rats were subjected for permanent ligation of bilateral common carotid arteries at an interval of 3 days for each carotid artery.At the same time,Sham group was set in parallel.Four weeks after modeling,the VD rats were divided randomly into five groups:(1) VD control group; (2) culture media group; (3) mannitol group; (4) BMSCs group;(5) mannitol with BMSCs group.Morris water maze performance and synaptophysin expression in the CA3 region in hippocampus were observed at 4 weeks after transplantation.Results The morris water maze performance significantly improved in mannitol with BMSCs group when compared with BMSCs group,VD control group,culture media group,mannitol group.Moreover,the escape latency of fifth day decreased significantly ((9.3 ±2.9),(14.1 ±3.5),(23.5 ±4.4),(22.8 ±4.4),(23.2 ±2.8) s,F =43.900,P =0.000)),and the platform quadrant residence time increased significantly ((40.8 ± 6.3),(34.9 ±5.8),(26.4±4.8),(27.4 ±7.0),(28.5 ±6.2) s,F=13.000,P=0.000)).The synaptophysin expressions of the hippocampal CA3 region were significantly increased in the mannitol with BMSCs group (39 624 ± 7798) when compared with BMSCs group,VD control group,culture media group,mannitol group (27060 ±4668,18 294 ±6446,19 956 ±4244,18 946 ±4953,F =39.206,P =0.000).Conclusions Intravenous BMSCs transplantation after mannitol pretreatment improves the behavioral performance of VD rats and facilitates the synaptophysin expression of hippocampal CA3 region in VD rats than BMSCs transplantation alone.Mannitol pretreatment can amplify the therapeutic effect of intravenous BMSCs transplantation in VD rats.

The efficiency of expressing human neprilysin by using lentiviral vector transduction in neural stem cells / 中华神经科杂志

Objective To study the transduction efficiency of expressing human neprilysin by using a lentiviral vector (Lenti-NEP) in mouse embryonic neural stem cells (NSC) in vitro.Methods Primary NSC were harvested from C57BL/6J pregnant mouse at embryonic day 11.5 and transducted with LentiNEP.Immunofluorescent stainingand Western blot were performed to detect NEP protein expression in NSC.Degradation of amyloid beta 1-40 (Aβ1-40) by NEP protein transduced with Lenti-NEP in NSC was analyzed using ELISA and HPLC.Results Over 90％ NSC were successfully transduced with Lenti-NEP via observation of fused protein green fluorescent protein under the microscopy.Expressions of NEP transduced with Lenti-NEP in NSC and of the markers of NSC (nestin) and neuron (MAP2).The enzyme activity of 2.5 μg (21.00 ± 2.51) and 1.0 μg (15.00 ± 0.54) NEP on degrading Aβ1-40 was shown to improve significantly compared to 0.5 μg NEP(8.00 ±0.81,t =40.4 and 12.7,respectively,both P ＜0.01).The activity of NEP was inhibited in the presence of 50 μmol/L phosphoramidon (0.5 pg:0.08 ±0.01 ;1.0 μg:0.04 ±0.01 ;2.5 μg:0.05 ±0.01,t =17.2,51.3 and 14.1,respectively,all P ＜0.01).The hydrolytic cleavage on degrading Aβ1-40 by NEP was 11.4％,28.4％ and 93.7％ with incubation for 1 h,4 h and 12 h,respectively.Conclusions Lentiviral vector successfully delivers NEP gene to NSC in vitro.Targeting on NEP and NSC may provide potential therapeutic tool for Alzheimer' s disease.

Diffusion changes in substantia nigra following striatum infarction with diffusion tensor imaging / 中华神经科杂志

Objective To investigate the diffusion changes in ipsilateral substantia nigra after a chronic striatum infarction with diffusion tensor imaging ( DTI ) and its connotation for clinical lecture.Methods Participators underwent a DTI scan and were divided into three groups. The striatum infarction (SI) group consisted of twenty patients with chronic basal ganglia infarction with striatum involved, while the non striatum infarction (NSI) group consisted of another twenty patients with chronic basal ganglia infarctions without striatum involved. The control group consisted of twenty healthy volunteers. Before the DTI scan all patients underwent a clinical evaluation with Modified Rankin Scale (mRS) and Barthol Index,and the four patients of SI group with symptoms like Parkinson disease underwent an additional evaluation with the third subscale of Unified Parkinson' s Disease Rating Scale ( UPDRS Ⅲ ). Results Compared with NSI and control groups, the infarct side substantia nigra MD of SI group increased by 30. 86 percent (t =40.07,P=0.000) and 31.42 percent (t =42. 64,P =0.000). The FA values from the three groups were not different. There were four patients with some symptoms like Parkinson disease in SI group. Compared with those patients without symptom like Parkinson disease in SI group, the infarct side substantia nigra MD of these four patients increased by 22 percent(t = 18.03, P =0. 01 ). Moreover, the infarct side substantia nigra MD of these four patients was correlated with their UPDRS Ⅲ positively ( r = 0. 97, P = 0. 03 ).Conclusions The secondary degeneration in the ipsilateral side substantia nigra after striatum infarction could be detested quantitatively with diffusion tensor imaging. The secondary degeneration in substantia nigra may be responsible for the symptoms like Parkinson disease in striatum infarction patients.

Multicenter controlled randomized clinical trial of akatinol memantine for treatment of Aizheimer's disease / 中华神经科杂志

Objective To evaluate the clinical efficacy and safety of akatinol memantine in the treatment of Alzheimer's disease (AD).Methods Two hundred and forty-one patients with AD were randomly assigned to receive 10 mg of donepezil daily or 20 mg of memantine daily for 24 weeks.The primary efficacy variables were the Clinician' s Interview-Based Impression of Change Plus (CIBIC-Plus),the Alzheimer Disease Assessment Scale-cognition (ADAS-cog) and the Activities of Daily Living (ADL).The secondary efficacy variables were the Neuropsychiatric Inventory (NPI) and the Mini-Mental Status Examination (MMSE).Results Two hundred and seven patients completed the study and were evaluated at week 24.Both memantine and donepezil had significant efficacies at the end point, according to the ADAS-cog, the ADL, the NPI and the MMSE.Patients receiving memantine had a similar outcome as those receiving donepezil, according to the results of all the variables changes (CIBIC-Plus: memantine 3.4±0.8vs donepezil 3.5±0.8; ADAS-cog: memantine-4.7±5.8 vs donepezil-4.6±6.5; ADL: memantine -2.4±6.7 vs donepezil-2.2±5.3 ; NP1: memantine-5.8±9.0 vs donepezil-3.1±8.5 ; MMSE:memantine 1.7±3.1 vs donepezil 1.8±2.8, all P >0.05).The adverse events were as following: donepezil group 41.88% and memanintine group 30.58%.Conclusion The memantine as a new drug for AD, has the similar efficacy as donepezil, and it is safe.

The correlation between interleukin-4,15 as well as 18 and telomerase activity in myasthenia gravis / 中国免疫学杂志

Objective:To detect the serum levels of IL-4,IL-15 and IL-18 in myasthenia gravis( MG) and investigate the correlations between telomerase activity of CD4~+ T lymphocytes and these interleukins.Methods:The serum levels of IL-4,IL-15 and IL-18 were detected with ELISA and telomerase activity was detected by polymerase chain reaction enzyme-linked immonosorbent assay(PCR-ELISA) in 30 MG patients and 30 negative controls.Results:The levels of IL-4,IL-15,IL-18 and telomerase of CD4~+ T lymphocytes in MG were significantly higher than those in negative controls (P<0.01).There were positive correlations between the serum levels of IL-4,IL-15,IL-18 and telomerase activity of CD4~+ T cell in MG patients (P<0.01).Conclusion:IL-4,IL-15,IL-18 and telomerase activity of CD4~+ T lymphocytes are involved in the pathogenesis of MG;IL-4,IL-15 and IL-18 may upregulate the telomerase activity of CD4~+ T cells.

Elementary study of mobilization and harvesting after autologous peripheral blood stem cell transplantation on myasthenia gravis / 临床神经病学杂志

Objective To explore the clinical effect of mobilization and harvesting by autologous peripheral blood stem cell transplantation (APBSCT) on treating myasthenia gravis (MG).Methods One patient with MG was enrolled in the study. Autologous peripheral blood stem cells(APBSCs) were mobilized with cyclophosphamide(CTX) and granulocyte colony-stimulating factor(G-CSF). PBSCs harvesting was performed by continuous flow leukapheresis using a CS-3000 plus blood separator.CD +_ 34 cells were analyzed by flow cytometer and granulocyte-macrophage progenitors (GM-CFU) was detected by semisolid methlcelluose after mobilization. The clinical effect was evaluated by a relative score system.Results The numbers of mononuclear cells (MNC),GM-CFU and CD +_ 34 cells were 8.08?10 8/kg,7?10 5/kg or 81/10 5/MNC and 1.09?10 6/kg after mobilization in graft respectively. The clinic relative score of the patient was 7/8.Conclusion CTX and G-CSF can mobilize effectively and provide enough peripheral blood stem cells for transplantation in treating MG.