Cytotoxic effects of differentiated PC12 cell infected by prion protein 106-126 peptide / 中国医师杂志

Objective To investigate the cytotoxic effects of differentiated PC12 cells afterinfected by prion protein 106-126 peptide.Methods The PC12 cells were infected by prion protein 106-126peptide after differentiated by nerve growthfactor(NGF).Cell viability andthe morphological changes were observed.The energy metabolize and apoptosis was detected.Results Afterinfected by this peptide,cell viability decreasedfrom(98.1±1.9)% to (69.2±4.7)%,and apoptosis peak Was observed byflow cytometry.Aboutthe process of the cytotoxic effects,afterthe cells affected by PrP106-126,oxidative stress presented and existed continually,and then the intracellular free calcium concentrate increased from (185.74±12.93)nmol/L to (493.00±58.71)nmol/L subsequently,the activity of Ca2+ ATPase decreased from 54.92±4.05 to 34.92±4.86,the mitochondrial membrane potential decreasedto 65%,and also the energy metabolize disorder,the cells presented apoptosisinthe end.The changed Bcl-2/Bax system involvedinthe apoptosis.Conclusions Prion protein106-126 peptide caninduce apoptosisin differentiated PC12 cells and presented cellulartoxicity definitely.It might be a perfect model to study the cellular toxicity of prion protein.Continual oxidative stress could causetheintracellularfree calcium concentrate and disturb the energy metabolize,and the apoptosis might be the end-result.The oxidative stress of might play a startup and important role.

A population-based study of the inducible nitric oxide synthase gene polymorphism for stroke with coronary artery disease in a Chinese population / 中华神经科杂志

Objective To investigate the genetic association between the inducible nitric oxide synthase (NOS) 2A gene and stroke with a history of coronary artery disease ( CAD). Methods 708 patients with stroke and 235 healthy controls were recruited in this study, and the stroke group was delaminated into 2 subgroups according to the history of CAD. SNP rs28944190, an A to C base change located in intron 22 of the gene, was used as a genetic marker. PCR-based restriction fragment length polymorphism analysis was applied to genotype rs28944190 (Hac Ⅲ site). Results The x2 test showed no association between patients with stroke and healthy controls. Of 708 patients, 94 had a history of CAD and the frequency of allele C of rs28944190 was significantly higher in patients with a history of CAD than those without (23.9% vs 16.6%, x2 =5.629, df= 1, P =0.018, OR = 1.580, 95% CI 1.083—2.306), especially in male patients (x2 = 8. 592, df= 1, P = 0. 003, OR = 1. 983, 95% CI 1. 255—3. 134). The frequency of genotype AA + AC of rs28944190 was significantly higher in patients with a history of CAD than those without such a history (47.9% vs 30. 8%, x2 = 10. 761, df= 1, P = 0. 001, OR = 2. 065, 95% CI 1.34—3.19), especially in male patients (x2 = 15. 762, df= 1, P =0. 000, OR =2. 985, 95% CI 1.74—5. 12). Conclusion The present study suggests that the NOS2A gene is unlikely to contribute to the etiology of stroke.

Investigation of prion protein gene in 10 sporadic Creutzfeldt-Jakob disease patients: a new novel mutation of prion protein gene / 中华神经科杂志

Objective To detect point mutations of the PRNP in 10 sporadic Creutzfeldt-Jakob disease (CJD) patients. Methods Priori protein gene open reading frame was amplified by PCR of genomic DNA extracted from peripheral blood leukocytes. Products were sequenced and digested with restriction endonuc lease Nsp I to check the phenotype at codon 129. Results Two CJD patients were confirmed at autopsy. One full sequencing of the PRNP open reading frame revealed normal, but the other revealed a single novel mutation consisting of a cytosine-to-guanine substitution at nucleotide 729, causing asparagine to replace glutamic acid at codon 211. Among 8 probable CJD patients, 2 full sequencing of the PRNP open reading frame revealed anadenine-to-guanine substitution at nucleotide 751, causing lysine to replace glutamic acid at codon 219. The patients were methionine homozygosity at codon 129. Conclusions The E211D mutation was identified in a confirmed CJD patient. The novel point mutation might be associated with familial CJD. However, E219K identified in 2 possible CJD patients was included in polymorphism of the PRNP as well as M129V. Analysis of PRNP plays an important role for diagnose of familial priori disease.

Pathological alterative characteristics of the brain tissue in patients with dementia of frontal lobe: one case report / 中国组织工程研究

BACKGROUND: Pathological changes of the brain tissue in patients with dementia of frontal type(DFT) are still controversial. This paper brought forward the pathological alterative characteristics of brain tissue in DFT patients through one pathological case study of the brain tissue in one dead dementia patient.OBJECTIVE: To validate one uncommon neurodegenerative disease complicated with dementia, DFT.DESIGN: A case analysis.SETTING: Department of Neurology of the First Hospital of Jilin University METHODS: Brain anatomy, serials of histological staining and immunohistochemical staining for PrP, tau protein, etc. were performed after 3 hours since the death of one patient with progressive dementia.stainingfrontal lobes. EEG displayed a paroxysmal high-amplitude slow wave with and the brain atrophy was limited to frontal lobe and the temporal lobe loss of neurocyte companied with significant gliosis since the second layer; However, the pyramidal cell was relatively healthy. No abnormality was munohistochemical staining had negative reactions.CONCLUSION: This case was typical DFT. This type of dementia should be considered in future analysis of the neurodegenerative disease complicated with dementia.

Association of hyperhomocysteinemia and methylenetetrahydrofolate reductase gene polymorphisms with ischemic stroke in Northwest Chinese population / 中国组织工程研究

BACKGROUND: It is proposed that elevated serum homocysteine is an important independent risk factor for ischemic stroke (IS), and 5, 10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for homocysteine metabolism. The relationship between genetic mutation of MTHFR and IS remains controversial.OBJECTIVE: To examine the association of hyperhomocysteinemia and two MTHFR gene polymorphisms with IS in Northwest Chinese population.DESIGN: Case-control study.SETTING: Department of Neurology, First Hospital Affiliated to Jilin University, and Department of Neurology, Xijing Hospital, Fourth Military Medical University of Chinese PLA.PARTICIPANTS: Ninety-seven consecutive patients with ischemic stroke (71 males and 26 females) treated between November 2001 and May 2002were recruited, who were diagnosed by CT scan or MRI in the Department of Neurology, Xijing Hospital, Fourth Military Medical University of Chinese PLA. The control group consisted of 94 subjects (58 males and 36 females) without history of ischemic stroke. All the subjects were free of intracranial hemorrhage, cancer, renal dysfunction, and none used multivitamins or estrogen.METHODS: Serum homocysteine was measured by fluorescence polarization immunoassay. Polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method was employed to detect the genotype at the two sites of C677T and A1298C in MTHFR gene.MAIN OUTCOME MEASURES: Serum homocysteine levels and the genotypic frequency frequencies of the two mutations of MTHFR.RESULTS: The 677T allele frequency was 59.3% in IS patients and 44.7% in the controls, showing significant differences (P=0.006), but no difference in 1298C allele frequency was detected between the two groups (22.7% vs 19.7%, P ＞ 0.05). Homozygous 677TT genotype was closely associated with hyperhomocysteinemie (P ＜ 0.01). In multivariate logistic regression analysis,677T gene mutation and hyperhomocysteinemie were all associated with the IS, with an OR of 1.870 and 1.031 (P＜ 0.05), respectively.CONCLUSION: Hyperhomocysteinemie is a risk factor of IS, and C677T mutation significantly increases homocysteine levels, and serves also as an independent genetic risk factor of IS.

Neuropathological changes of central nervous system in Guillain-Barré syndrome / 中国神经精神疾病杂志

Objective 　To investigate the neuropathological changes of central nervous system in Guillain-Barré syndrom. Methods　Brain, spinal cord and sciatic nerve were obtained from 22 cases of Guillain-Barré syndrome. Eight cases were examined by general autopsy, 14 cases were examined by limited autopsy. HE, KB, Bielschowsky, Weil and Sudan Ⅲ　staining were carried out, the sections were observed by light microscopy. Results　1.Cerebral superficial veins congested, widening of the cortical sulci, narrowed gyri and mild cerebellar tonsillar hernia were present. 2. Majority of cerbral neurons presented an ischemic changes. Slightly loss of hippocampal pyramidal neurons were found. There was chromatolysis of motor neurons of brain stem. Lymphocytic infiltration around the small vessels occurred in the pons and medullary oblongata in 8 cases. Focal demyelination was noted in pons and frontal white matter in 2 cases. Loss of Purkinje cells and appearance of glial nodules were observed in molecular layer of cerebellum. 3. Swellin, central chromatolysis and eccentric nuclei of anterior horn cells appeared in 16 cases, which were pronounced in cervical and lumbal segment of spinal cord. Vaculated neuroplasma and lymphacytic infiltrition could be seen. 4. Segmental demyelination and lymphocytic infiltration were the main neuropathological changes observed in 20 cases. There were two other cases in which the axon were severely involved, which showed swelling and breakdown of axons and as well as axonal bulbs. Conclusions　1. Lymphocytic infiltration in brain stem and spinal cord were in continuousness of pathological changes of peripheral nerves. 2. Finding of glial nodules suggested that there was possibility of infection of neurotropic virus. 3. Occurence of focal demyelination in cerebrum and brain stem indicated that Guillain-Barré syndrome may have combined involvement of central and peripheral nervous system.

Studies on codon 129 genotype of PrP gene and phenotypic features of sporadic Creutzfeldt-Jakob disease in China / 中华神经科杂志

Objective To investigate the relationship between polymorphism at codon 129 of prion protein gene and the phenotypic features of sporadic Creutzfeldt Jakob disease(CJD)in China Methods The prion protein genotype of 14 cases with sporadic CJD were tested and clinical data were analysed Results (1) 8 cases with definite CJD and 6 cases with probable CJD were diagnosed depending on diagnostic criteria (2) Of the 8 definite CJD cases,6 were homozygous for methionine at codon 129, 2 cases were methionine/valine at codon 129,while all the probable CJD cases were methionine homozygotes (3) There were four group symptoms at onset in 12 cases with methionive homozygous at codon 129: cognitive and mental impairment as first symptom in 8 cases,ataxia in 1 case,blurred sight in 2 cases,myoclonus in 1 case;during illness there were epilepsy in 5 cases,myoclonus in 6 cases,blurred sight in 6 cases,PSD in 7 cases The longest illness duration was 20 months,and the shortest was two and a half months (4) Ataxia was the first symptoms in 2 cases with metionine/ valine at codon 129 The illness duration was 6 and 20 months,and there was no PSD (5) Spongyform degeneration in different degree and neuronal loss were seen in the 8 cases with definite CJD,synaptic deposition of abnormal PrP was shown in 5 cases Conclusions (1)Of the 14 cases with CJD, homozygosity for methionine at condon 129 of the prion protein gene was shown in 12 cases,but there was distinct phenotypic variant (2)The frequence of methionine and valine of 129 allilic distribution for sCJD was similar to that in Japan,and different from that in Western cases There was no sCJD case with valine homozygous genotype at codon 129 in our study

Clinical,imaging and pathological characteristics of twin brothers with adrenoleukodystrophy / 临床神经病学杂志

Objective To explore clinic,imageology and pathological characteristics of twin brothers with adrenoleukodystrophy(ADL).Methods Clinical data of twin brothers with ALD and pathological data of one case were analyzed retrospectively.Results Clinical manitestation of elder brother was cerebral ADL,T1-weighted of MRI with low intensity lesion and T2-weighted with high intensity lesion were shown widely in the parietooccipital and postero-corpus callosum white matter.The pathological changes were myelinopothy diffused in the parietooccipital white matter,but U fibber was maintained in the subcortex.Clinical manitestation of the young brother was shown spinal damage.His cerebral MRI was normal.Spinal MRI had shown spinal cord thinning,line-like equal signal was found in the periphery of the lesion.He might be juvenile adrenomyeloneuropathy.Conclusions Although the twin brothers are both suffer from adrenoleukodystrophy,their clinical manifestation,MRI and pathological changes are different.

The MRI findings of sporadic Creutzfeldt-Jakob disease / 中华神经科杂志

Objective To study the MRI findings of sporadic Creutzfeldt-Jakob disease and its clinical relations. Methods MRI of 10 cases CJD patients were examined 2-12 months after the onset. 6 cases were diagnosed using cerebral biopsy, 8 cases received CSF analysis for 14-3-3 protein, 8 cases showed special changes of electroencephalogram, PrP gene of 9 cases were analyzed. Results Symmetric bilateral high signals were observed in caudate nucleus and Putamen in T 2-weighted imaging and Flair imaging in 5 cases, but the pallidum and thalamus were normal. No changes were found in T1-weighted imaging. 2 cases showed brain atrophy, 1 case showed mild lacunar infarction,and the other 2 were normal. Conclusions Abnormal signals in basal ganglia of 4 patients of 129Met/Met homozygote occurred after 2.5 months averagely, they survived for 10.5 months at average. 1 patient of 129 Met/Val heterozygote showed abnormal signals in basal ganglia after 12 months, and survived for 16 months. The mean duration of patient with abnormal signals in basal ganglia (12.2 months) is longer than those without changes in basal ganglia (5.5 months). Symmetric high signal in bilateral caudate nucleus and Putamen is an important imaging feature of sCJD. It might be served as a diagnostic index in some circumstances.

Clinical and pathologpcal studies on Frontal lobe dementia / 中华神经科杂志

Objective To verify a uncommon neurodegenerative disease accompanying with dementia--frontal lobe dementia, or dementia of frontal lobe type (DFT). Methods A brain sample was obtained from a patient of 46-year-old male with progressive dementia. Conventional neurohistopathological examination and immunostaining for prion protein (PrP) and tau protein were performed, and clinical data were analysed. Results (1) It was shown having progressive neurological and psychical symptoms and a three month illness duration. (2) Atrophy was found in bilateral frontal gray matter in CT scan. Slow waves of high amplitude with long intermission of two second in whole course of electroencephalography examination were seen. (3) Brain weight was 1 050 g. The cerebral cortex was atrophied and restricted to frontal lobes. The temporal lobes were unaffected. (4) A severe loss of nerve cells from second frontal cortical layer with glioses was revealed, but pyramidal cells in this region remained intact. There were no positive findings on staining of Beilschowky and Gallyas methods. (5) No inclusions were seen in remaining nerve cells and gliocyte. (6) Immunohistochemistry revealed no significant changes on PrP and tau protein.Conclusion This is more typical a case of DFT , and now increasingly recognized. It suggests that a dementia of frontal lobe type should be considered when differential diagnosis of neurodegenerative disease with dementia have been made.

Protective effects of adeno-associated viral gene transfer of BDNF on the hippocampal neurons / 中国免疫学杂志

Objective:To investigate the effective mechanism for transfection of rat brain derived neurotrophic factor(BDNF) gene by recombinant adeno-associated virus in the cultured hippocampal neurons.Methods:rAAV-BDNF was injected into the serum free-induced neurons.DAPI,PI and Actin stain was performed to measure the apoptosis cells and morphogenesis of the cells.Results:After the gene transfer,the survival rate of the serum free-induced neurons was increased by 65%.Conclusion:The recombinant adeno-associated virus vector can protect the serum free-induced neurons from Apoptosis.

Studies on the diagnostic values of the neuron-specific enolase and S-100 protein to Creutzfeldt-Jakob disease / 临床神经病学杂志

Objective To find an easy to do testing method to diagnose CJD in the early stage.Methods The values of NSE and S 100 protein in the serum and CSF of 10 cases of CJD, 10 cases of non CJD dementia and 10 cases of healthy control were measured by ELISA and sandwich ELISA.while the expression of PrP gene of CJD patients being detected.Results The values of NSE and S 100 protein in the serum and CSF of CJD patients were higher than those of non CJD dementia(all P