Objective To explore the incidence ,clinical and neuroimaging features, possible risk factors and outcome of central nervous system (CNS) complications one year after hapilo-matched non-ablative hematopoietic stem cells transplantation. Methods The medical records of 36 consecutive patients who underwent hapilo-matched non-ablative hematopoietic stem cells transplantation for malignant and nonmalignant hematologic diseases between February 2004 and May 2009 were reviewed. Results CNS complications occurred in six (16.7 %) patients. Four of the six patients (66.7 %) died. Cerebral infarction occurred in three (8.3 %) patients. Cerebral softenness occurred in two (5.6 %) patients. Cerebral hemarrage occurred in 1 (2.8 %) patient. Epilepsy occurred in 1 (2.8 %) patient. The CNS complications occurred between 12 days and 286 days after stem cells transplantation. The age illness status and death rate were statistically different compared to patients without CNS complications (P ＜0.05). Conclusion The incidence and mortality of CNS complications are higher in those who underwent hapilo-matched non-ablative hematopoietic stem cells transplantation,which will make impacts on the patients' life quality and outcome.The illness status and eldly are probably the risk factors.

Objective To undertake an updated genetic spectrum analysis in patients with hereditary spinocerebellar ataxia (SCA) in mainland China. Methods SCA 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) nucleotide repeat mutations were detected in 430 families with autosomal dominant SCA (ADCA) and 237 patients with sporadic ataxias by PCR and DNA sequencing. Subsequently, point and Indel (Insertion/deletion) mutation analyses of SCA5, SCA11, SCA13, SCA14, SCA15/16/29, SCA27, SCA31 and SCA35 were detected in 91 families with ADCA and 196 patients with sporadic ataxias excluded from SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and DRPLA genotypes via PCR and Denaturing High Performance Liquid Chromatography (PCR-DHPLC), Multiplex ligation-dependent probe amplification and DNA direct sequencing analysis. Results Among the 430 ADCA families, there were 25 SCA1 (5.81%), 27 SCA2 (6.28%), 267 SCA3/MJD (62.09%), 8 SCA6 (1.86%), 8 SCA7 (1.86%), 1 SCA12 (0.23%), 1 SCA17 (0.23%) and 2 SCA35 (0.47%), and the remaining 91 families (21.16%) were genetically unidentified. Among the 237 sporadic SCA patients, there were 6 SCA1 (2.53%), 9 SCA2 (3.80%), 23 SCA3/MJD (9.70%) and 3 SCA6 (1.27%), and the remaining 196 (82.7%) were genetically unidentified. No pathogenic point mutation causing SCA5, SCA11, SCA13, SCA14, SCA27 or SCA31 subtypes was found. Conclusion SCA3/MJD is substantially the most common subtype in patients with ADCA and sporadic forms in mainland China, followed by SCA2, SCA1, SCA6 and SCA7. While SCA12, SCA17 and SCA35 are seldom found, SCA5, SCA8, SCA10, SCA11, SCA13, SCA27, SCA31 and DRPLA are very rare. The high proportion of genetically unidentified cases further verify that SCAs are of highly genetic heterogeneity, suggesting that other disease-causing genes might be involved in the negative ADCA pedigrees, and other etiological factors may involve in those sporadic cases other than genetics.

BACKGROUND:Theex-vivo expanded autologous adipose-derived stem cels have the capability of multipotential differentiation and have a broad application prospect in the field of tissue engineering and regenerative medicine. OBJECTIVE:To observe the nasal mucosal structural repair and functional reconstruction usingex-vivo expanded autologous adipose-derived stem cels. METHODS:Ten patients with mucosal damage due to the physical or chemical factors were enroled, including six cases of mucosal scar and four cases of mucosal ulceration. Autologous adipose tissue was extracted forin vitro isolation, culture and expansion of adipose-derived stem cels. Before transplantation, quality safety testing was done. Al the patients were injected adipose-derived stem cels (1×107/cm2 0.1 cm mucosal tissue sample at 30 days before and after transplantation for hematoxylin-eosin staining, Masson ) at an interval of 15 days, totaly for three times. Nasal volume, minimum cross-sectional area, and mucociliary clearance function were determined at 30, 90, 150 days after the final injection. Three of 10 patients were selected to take a 0.1 cm× trichrome staining, and AB-PAS staining. RESULTS AND CONCLUSION:Clinical symptoms were aleviated in al patients undergoing transplantation of adipose-derived stem cels. Compared with the baseline data, the nasal volume and minimum cross-sectional area were both decreased at 30, 90, 150 days after transplantation (P < 0.05), and the mucociliary clearance function was improved but not significantly (P > 0.05). Compared with the baseline data, the inflammation of the nasal mucosa was significantly reduced, colagen fibers arranged neatly, the deposition was decreased, and mucin secreted from goblet cels was increased in the selected three patients at 30 days after cel transplantation. These findings indicate thatex-vivo expanded autologous adipose-derived stem cels can be used to reconstruct the nasal mucosal structure and its function.

Objective To determine the neuronal damage or loss and gliosis at the cellular level in spinocerebellar ataxia type 3/Machado-Joseph disease(SCA3/MJD), and evaluate the potential use of neuron-specific enolase (NSE) and protein S 100 B(S100B) serum concentrations as biochemical markers. Methods Serum concentrations of NSE and S100B were measured in 102 SCA3/MJD patients and 100 healthy subjects matched by sex and age. The correlations between both markers and age, age of onset, disease duration, CAG repeat size, scores of international cooperative ataxia rating scale(ICARS), and scale for the assessment and rating of ataxia(SARA) were analyzed. Results Compared with the healthy controls, patients with SCA3/MJD had higher NSE serum concentrations [(6.95±2.83)ng/mL vs (4.83±1.70) ng/mL, P<0.05] and higher S100B serum concentrations [(0.07±0.06) ng/mL vs (0.05±0.02) ng/mL, P<0.05]. In the SCA3/MJD patients group, NSE levels presented a positive correlation with age, disease duration, ICARS scores and SARA scores, whereas S100B levels did not correlate with age, age of onset, disease duration, ICARS scores and SARA scores. CAG repeat size did not correlate with the NSE levels and S100B levels in different age groups of SCA3/MJD patients. Conclusion Serum NSE might be a useful marker to monitor disease progression and represent the degree of severity of a certain disease. Elevated S100B serum concentrations in patients compared to healthy controls may suggest an application of this protein as a peripheral marker of brain impairment in SCA3/MJD.

Objective To investigate the related factors of international cooperative ataxia rating scale (ICARS) and scale for the assessment and rating of ataxia scores (SARA) in patients with spinocerebellar ataxia type 3/Machado-Joseph disease. Methods A total of 126 SCA3/MJD patients were assessed by ICARS and SARA. The relation between ICARS or SARA scores and age of onset, disease duration and CAG repeat size was analyzed. Results Either the total ICARS or the total SARA score was positively related with the disease duration(r=0.586,P＜0.05；r=0.643,P＜0.05). Simple linear regression equations were: Y1(total ICARS score)=13.072+2.388 X2(disease duration)(F=68.874,P＜0.05); Y2(total SARA score)=4.403+ 0.961 X2(disease duration)(F=87.254, P＜0.05). Either age adjusted the total ICARS score or age adjusted the total SARA score was positively related with CAG repeat size(r=0.328, P＜0.05; r=0.335, P＜0.05). Both the ICARS subscores and the SARA subscores were positively related with the disease duration(r=0.257-0.589, P＜0.05; r=0.432-0.623, P＜0.05). Both age adjusted ICARS subscores and age adjusted SARA subscores were positively related with CAG repeat size(r=0.263-0.403, P＜0.05; r=0.189-0.366, P＜0.05). Analysis of variance showed that the total ICARS score and the total SARA score increased with the disease stage. Conclusion ICARS and SARA are both reliable and effective scales in assessing the severity of ataxia in patients with SCA3/MJD, and researchers can choose the most suitable scale according to specific requirement.

Objective To evaluate the metabolite pattern and the severity in patients with spinocerebellar ataxia type 3/ Machado-Joseph disease (SCA3/MJD) by 1H magnetic resonance spectroscopy (1H-MRS) on different cerebellar regions, including cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum. Methods Thirty-six SCA3/MJD patients, and 27 sex, age-matched healthy controls were scanned with 1H-MRS for N-acetylaspartate (NAA), choline (Cho) and creatine (Cr). We made cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum as the region of interests (ROI), and finally got access to NAA/Cr, Cho/Cr, and NAA/Cho ratios. We also examined the CAG repeat numbers of MJD1 gene, scored the 36 patients by the scale for the assessment and rating of ataxia (SARA), analyzed the differences in ratios between SCA3/MJD patients and the control group, and explored whether relevance existed between these ratios and duration of the disease, age of onset, CAG repeat times, and SARA scores respectively. Results The ratio of NAA/Cr in SCA3/MJD patients showed a significant reduction in the cerebellar cortex, dentatum, cerebellar vermis and medipeduncle (P<0.01) compared with the controls. The ratio of NAA/Cho also showed significant reduction in the dentatum and cerebellar vermis (P<0.01). A number of correlations were found between the metabolite ratios of 1H-MRS and duration of the disease, age of onset, expanded CAG and SARA score in SCA3/MJD patients. Conclusion 1H-MRS, which shows the neural metabolic changes in the cerebella of SCA3/MJD patients, provides useful information about the severity of SCA3/MJD.

Objective To assess the frequency of different subtype of spinocerebellar ataxias (SCAs) in Chinese Han population. Methods The nueleotide repeat mutations of SCA1, SCA2, SCA3/ MJD, SCA6, SCAT, SCA8, SCA10, SCA12, SCA17 and dentatorubral-pallidoluysian atrophy (DRPLA) were detected by the polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis (PAGE), Southern blot, recombinant DNA technology by T-vector cloning and direct sequencing technique in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 families with autosomal dominant SCA (AD-SCA) and 196 sporadic cases. Results Among the 363 AD-SCA families, 15 families (4. 13%) were positive for SCA1, 26 (7. 16%) for SCA2, 187 (51.52%) for SCA3/MJD, 6 (1.65%) for SCA6, 7 (1.93%) for SCA7, 1 (0. 28%) for SCA12 and 1 (0. 28%) positive for SCA17; 120(33. 06%) were negative for all the tested SCAs. There were 2 (1.02%) SCAI, 3 (1.53%) SCA2, 15 (7. 65%) SCA3/MJD, 3 (1.53%) SCA6 and 173 (88.27%) not identified in the 196 sporadic SCA patients. None of the SCA8, SCA10 and DRPLA mutation was found. Conclusions SCA3/MJD is a substantially common subtype of AD-SCAs and sporadic SCA in Chinese Han patients with SCAs, subsequently followed by SCA2, SCA1, SCAT and SCA6; SCA12 and SCA17 are uncommon subtypes, while SCA8, SCA10, and DRPLA are rare, if not absent. SCA17 subtype was initially identified in mailand China. Some other genes might be causative in those unidentified AD-SCA pedigrees, and other etiological factors besides genetic cause might contribute for those sporadic cases.

OBJECTIVETo study the single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene in spinocerebellar ataxia (SCA) patients in China.

METHODSThe single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene was detected by PCR, digested with EcoN I, separated on 8% polyacrylamide gel in 68 probands of autosomal dominant SCA families and 119 sporadic SCA patients, who had been excluded CAG/CAA repeat expansion at the SCA1, 2, 3, 6, 7, 17 and dentatorubral-pallidolluysian atrophy (DRPLA) loci. The results were confirmed in four patients by direct sequencing.

RESULTSThe single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene was not identified in authors' cohort.

CONCLUSIONThe mutation of c.-16C to T of the PURATROPHIN-1 gene might be rare in SCA patients in China.

Asian Continental Ancestry Group ; genetics ; Cohort Studies ; Guanine Nucleotide Exchange Factors ; genetics ; Humans ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Spectrin ; genetics ; Spinocerebellar Ataxias ; genetics

OBJECTIVETo investigate the CAG trinucleotide repeat expansion in spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, 12, and 17 from Chinese Han.

METHODSThe pathological CAG triplet repeat expansions of the SCA1, SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA12 and SCA17 genes were analyzed in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 probands from families with autosomal dominant SCA and 196 sporadic cases. Polymerase chain reaction, agarose gel electrophoresis, recombinant DNA technology by T-vector cloning and direct sequencing were performed to detect the CAG-repeat number of abnormal allele.

RESULTSAmong the 559 SCA patients, twenty-three were positive for SCA1, the ranges of expanded CAG repeats were from 39 to 60 (mean:51.09+/-4.88); thirty-two were positive for SCA2, the ranges of expanded CAG repeats were from 36 to 51 (mean:40.34+/-4.40); three hundred and five were positive for SCA3/MJD, the ranges of expanded CAG repeats were from 49 to 86 (mean:73.84+/-5.07); nine were positive for SCA6, the ranges of expanded CAG repeats were from 23 to 29 (mean:25.56+/-1.94); twenty-seven were positive for SCA7, the ranges of expanded CAG repeats were from 38 to 71(mean:58.22+/-10.90); three were positive for SCA12, the ranges of expanded CAG repeats were from 51 to 52 (mean:51.33+/-0.58); and finally, two were positive for SCA17, the range of expanded CAG repeats were from 53 to 55 (mean:54.00+/-1.41).

CONCLUSIONThe 39 CAG repeats of SCA1, 49 CAG repeats of SCA3 and 51 CAG repeats of SCA12 are all the shortest known causative expanded alleles, while the 86 CAG repeats of SCA3/MJD is the largest full expanded allele that has never been reported. Furthermore, it is the first report of SCA17 subtype in Mainland Chinese and first research that established the abnormal reference standard of CAG repeat number of different subtypes of SCA in Chinese Han.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Ataxin-7 ; Ataxins ; Base Sequence ; Child ; Child, Preschool ; Cohort Studies ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Nerve Tissue Proteins ; genetics ; Protein Phosphatase 2 ; genetics ; Spinocerebellar Ataxias ; ethnology ; genetics ; Trinucleotide Repeat Expansion ; Young Adult

Objective: Spinocerebellar ataxia type 2 (SCA2) is one of the most common autosomal dominant ataxias in the world. Several reports revealed that CAG repeats in some polyQ-containing genes may affect the age at onset (AAO) of patients with SCA2, however, little studies were conducted among Chinese patients with SCA2. Thus, the aim of this study is to evaluate the effect of CAG repeats on the AAO of patients with SCA2 in China.Methods:A total of 119 patients with SCA2 were enrolled and were divided into 2 groups according to their major phenotype:17 patients from 9 families with Parkinson ' s syndrome were grouped as the Parkinson ' s disease-SCA2 (PD-SAC2); 91 patients from 66 SCA2 families and 11 sporadic SCA2 patients were grouped as the ataxia-SCA2 (A-SCA2). Blood samples were obtained from the subjects, and the CAG repeat length in ATXN2 and other (CAG)n-containing genes was screened using fluorescent PCR. The Spearman ' s rank correlation between the CAG repeat length in (CAG)n-containing genes and AAO was analyzed. Regression analysis was performed to investigate whether the CAG repeat length could explain the variant of AAO. A t-test was used to compare the difference of CAG repeat length in (CAG)n-containing genes between the PD-SAC2 and A-SCA2 groups. Results:The CAG repeat length in the longer allele of ATXN2 was negatively correlated with AAO of SCA2 (R=?0.251, P<0.05), and the CAG repeat length could explain 41.7％of the variation of AAO. AAO negatively correlated with the CAG repeat length in the shorter allele of ATXN7 (R=?0.251, P=0.006) or in the longer allele of TBP gene (R=?0.197, P=0.034). A tendency of delay in the AAO was also observed in patients with SCA2 carrying the CAG repeat within the ATXN3, CACNA1A, ATXN7, TBP, and RAI1. In addition, we found that the CAG repeat length in ATXN7 and ATXN2 between the A-SCA2 and the PD-SCA2 groups was significantly different (both P<0.05).Conclusion:The CAG repeat in ATXN2 is a major genetic factor for the AAO of patients with SCA2 in China. The CAG repeat length in ATXN3, CACNA1A, ATXN7, TBP, and RAI1 genes might be a potential factor associated with the AAO of SCA2. The CAG repeat in ATXN7 might be a potential factor affecting the Parkinson??s syndrome in SCA2.