BACKGROUND: Causes of Parkinson disease have not been mentioned clearly up to now yet. Theory of hereditary susceptibility is the main theory to explain Parkinson disease now. But there is no definite conclusion on which hereditary factors have relationship with it.OBJECTIVE: To study the relationship between gene polymorphism caused by point mutation C to T on cDNA609 basic group of reduced NAD(P) H:quinone oxidoreductase(NQO1) gene and hereditary susceptibility of Parkinson disease.DESIGN: A non-randomized synchronized control research based on patient and healthy people.SETTING: Neurology departments in two university hospitals and a senile disease research institute in a university hospital.PARTICIPANTS: Totally 126 patients(Parkinson disease group) diagnosed as Parkinson disease in Neurology Clinic of First Hospital Affiliated to Sun Yat-sen University from September 1994 to September 1997, aged 46 to 73 years, in which 74 were males and 52 were females. Totally 136 healthy adults (control group), in which 66 were males and 70 were females, who came to the clinic to do health examination at the same time, aged 40 to 72 years.METHODS: Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was used to analyze NQO1 gene polymorphism in Parkinson disease group and healthy adult control group.MAIN OUTCOME MEASURES: Mutation frequency and genotype of point mutation of basic group C to T on NQO1 gene cDNA609.RESULTS: T allele frequency in Parkinson disease group was 52% and that in control group was 43%. There was significant difference between two groups (P ＜ 0. 005) . There was significant difference on distribution of genotype in Parkinson disease group and control group( P ＜ 0.05). The risk incidence increased 3.8 times in individual with T allele.CONCLUSION: NQO1 gene cDNA609 mutation T allele may be a risk factor to Parkinson disease, which could be associated with the hereditary susceptibility of Parkinson disease.

[Objective] To explore the effects of rifampicin on cell morphology,intracellular reactive oxygen species (ROS),reduced glutathione (GSH),and cell apoptosis in rotenone-induced differentiated pheochromocytoma (PC12) cells.[Methods] Rotenone was added in rat PC12 cells to develop a model of Parkinson's disease in vitro.Cell morphology was observed by microscope.Intracellular GSH was determined by a microplate reader.The intracellular ROS and the apoptosis rate were measured by flow cytometry.[Results] Compared with control group and rifampicin control group,GSH significantly decreased but ROS and apoptosis rate significantly increased in rotenone group.Compared with rotenone group,GSH significantly increased but ROS and apoptosis rate significantly decreased in a dose-dependent manner in rifampicin control group (100,200,and 300 μmol/L).[Conclusion] Rifampicin may reduce the damage of rotenone-induced differentiated PC12 cells through inhibiting oxidative injury in a dose-dependent manner.

Objective To investigate the efficacy of breviscapine in the treatment of vascular cognitive impairment.Methods A self-controlled trial was carried out in 36 patients with vascular cognitive impairment.36 cases were treated with breviscapine injection 50mg intravenous infusion daily for 3 weeks.At the same time,all cases were also given citicoline 0.75g/d and enteric-coated aspirin 100mg/d as routine treatment.The means of the evaluation on therapeutic effect included MMSE and ADL,and the adverse reactions were also observed.Results After the treatment,the MMSE scales increased from(18.75 ± 3.25)to(21.62 ± 3.58)(t=2.52,P＜0.05),Meanwhile,ADL scales declined from(45.65 ±3.36)to(42.33 ±4.18)(t=3.71,P＜0.05).There was significant difference on the MMSE and ADL between the pre and post therapy.No obvious side effects were found.Conclusion The results indicated that the breviscapine injection is an effective medicine in the treatment of vascular cognitive impairment,while the adverse reactions were few.

AIM: To investigate the protective effect of rifampicin on rotenone-induced apoptosis of dopaminergic neurons and expression of ?-synuclein in rats.METHODS: Highly selective lesions and high expression of ?-synuclein in nigrostriatal dopaminergic neurons in rats were induced by chronic subcutaneous exposure to rotenone at dose of 1.5 mg?kg-1?d-1 for 3 weeks.At the same time,rifampicin was administered at dose of 30 mg?kg-1?d-1 by intragastric administration for 3 weeks.The changes of behavior,pathology and immunoreactivity of TH and ?-synuclein in SNc were observed.RESULTS: Obvious changes of behavior,pathology and TH immunoreactivity in SNc were observed in male SD rats injected subcutaneously with rotenone and rifampicin protected rats against these toxic effects induced by rotenone.CONCLUSION: Rifampicin has extensive protective effects against rotenone-induced neurotoxicity,which is related to inhibiting the expression and aggregation of ?-synuclein.

【Objective】To study the relationship between mutations on exon 1,2 of parkin gene and sporadic early-onset Parkinson's disease.【Methods】The deletion and single strand mobility shift on exon 1 and 2 of parkin gene in peripheral white blood cell DNA were detected by using PCR,agarose electrophoresis,and SSCP techniques in 52 patients with sporadic early-onset (onset age≤50) Parkinson's disease.The exons with mobility shift on SSCP were sequenced.【Results】One deletion（1.9%） of exon 2,2 cases with single strand mobility shift（3.8%）on exon 1 and exon 2 respectively,one heterozygous mutation (T103C) on exon 1 and one homozygous mutation (G237C) on exon 2 were found by sequencing.【Conclusion】Mutations on exon 1 and 2 of parkin gene are likely to be related to sporadic early-onset Parkinson's disease.

Objective　 To investigate whether Parkinson's disease(PD) is associated with genetic polymorphism of intron 13 of monoamine oxidase B(MAO-B) and NAD(P)H: quinone oxidoreductase(NQO1) gene cDNA 609C to T. Methods　 Association study was performed in 126 PD patients and 136 healthy control subjects matched for age, sex and origin. The NQO1 gene polymorphism was analyzed with the polymerase chain reaction-restriction fragment length polymorphism, the polymorphism of intron 13 of MAO-B was analyzed by allele-specific PCR. Results　 The allelic frequency of the mutant T allele of NQO1 gene was significantly higher in the PD patients as compared to the controls(P<0.05). The relative risk of suffering from PD increased (OR=3.8) in the individuals with T allelic genotype of NQO1 gene, and the odds ratio was as high as 5.7 when the individuals with A or AA genotype of MAO-B gene coexisted with the T allele genotype of NQO1 gene. Conclusion　 The cDNA 609T allele of NQO1 gene might be a risk factor of PD, which could be associated with the genetic susceptibility of PD. The high activity A or AA genotype of MAO-B and the low activity genotype of NQO1 gene might have synergistic effect. When both genotypes coexist, the risk of suffering PD will be increased greatly.

Objective To analyze the clinical and electrophysiological features of one geneology with limbgirdle muscular dystrophy(LGMD). Methods Twenty-seven members of one family with limb-girdle muscular dystrophy(LGMD)were investigated.Fourteen of them were examined with electromyography(EMG)and their motor conduction velocities(MCV)and sensory conduction velocities(SCV)were measured.Among them,10 had no clinical manifestations,while 4 demonstrated symptoms and signs of LGMD. Results Three of the 4 patients had suffered from LGMD when young.They demonstrated the typical clinical features,including the progressive muscle weakness in the upper and lower extremities,positive Gower signs,duck gait,muscle atrophy distributed tO the proximal extremity,and no gastrocnemius hypertrophy.One subject presented atypical characteristics.The MCVs and SCVs of the 4 patients were normal,but neuropathic manifestations were found in the EMGS of 3 of them.and mixed neuropathic and myopathic manifestations were found in the EMG of the other.Conclusion LGMD patients in the same family can vary in their clinical characteristics.The longer the duration,the more severe the clinical features.Electrophysiological examination can reveal normal MCV and SCV but abnormal elctromyography.

OBJECTIVETo detect the relationship between point mutations on exon 2 of parkin gene and sporadic early-onset Parkinson's disease.

METHODSThe point mutations on exon 2 of parkin gene were detected using polymerase chain reaction(PCR), agarose electrophoresis, single strand conformation polymorphism(SSCP), DNA sequencing and analysis of restrict enzyme in DNA of 60 Parkinson's disease patients with an onset age under 50 and 120 normal controls.

RESULTSOne homozygous mutation (G(237)-->C) on exon 2 was found by sequencing and verified by analysis of restrict enzyme, whereas no mutation was found in normal controls.

CONCLUSIONPoint mutations on exon 2 of parkin gene are likely to be related to sporadic early-onset Parkinson's disease.

Adult ; Aged ; Aged, 80 and over ; Exons ; Female ; Humans ; Ligases ; genetics ; Male ; Middle Aged ; Parkinson Disease ; genetics ; Point Mutation ; Polymorphism, Single-Stranded Conformational ; Sequence Analysis, DNA ; Ubiquitin-Protein Ligases

OBJECTIVETo ascertain whether a coding mutation (Ile93Met) in ubiquitin carboxy-terminal hydrolase (UCH-L1) gene plays a role in idiopathic Parkinson's disease (IPD).

METHODSPolymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) was used to distinguish the wild-type (two DNA fragments of 34 and 126 bp) from the variant allele (three fragments of 34, 60 and 66 bp) because the mutation created a new site for restriction endonuclease BsmF1. DNA was isolated from various blood samples using a phenolchloroform extraction.

RESULTSIle93Met substitution was found neither in PD patients nor in controls.

CONCLUSIONSOur study suggested that Ile93Met of UCH-L1 gene did not influence risk of IPD.

Aged ; Amino Acid Substitution ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Parkinson Disease ; genetics ; Thiolester Hydrolases ; genetics ; physiology ; Ubiquitin Thiolesterase

Objective To explore the clinical features of a family with myotonic dystrophy type 1 (DM1) in order to improve the knowledge of this disease.Methods Clinical data of members from the family were collected.Electrocardiogram (ECG),electromyogram (EMG) and blood biochemistry were performed in some members of the family.Characteristics of pathology and gene of the propositi were detected.Results Anticipation was found in the family which was verified as DM1.In the all 19 patients,17 had myasthenia gravis,14 had muscle atrophy,16 had myotonia,5 had complicated with cataract,and 7 had complicated with hypophrenia.The 5 patients accepted ECG all had abnormal results,3 of them had myotonic discharge and metabolic abnormalities.Pathological analysis showed the main fibers atrophy was type Ⅰ,and the protein dystrophin expression was completely in the propositi.Conclusions The clinical manifestations of patients are various.DM1 affects eye (the lens),heart (mainly the conduction system),reproductive system besides skeletal muscle.Necessary auxiliary examinations and regular follow-up should be performed to evaluate and deal with multisystemic involvement in DM1 patients.EMG and pathological results are helpful in the diagnosis.Gene analysis can verify the disease and identify subclinical patients.