Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

DREAM (downstream regulatory element antagonist modulator), Calsenilin and KChIP3 (potassium channel interacting protein 3) belong to the neuronal calcium sensor (NCS) superfamily, which transduces the intracellular calcium signaling into a variety of activities. They are encoded by the same gene locus, but have distinct subcellular locations. DREAM was first found to interact with DRE (downstream regulatory element) site in the vicinity of the promoter of prodynorphin gene to suppress gene transcription. Calcium can disassemble this interaction by binding reversibly to DREAM protein on its four EF-hand motifs. Apart from having calcium dependent DRE site binding, DREAM can also interact with other transcription factors, such as cAMP responsive element binding protein (CREB), CREB-binding protein (CBP) and cAMP responsive element modulator (CREM), by this concerted actions, DREAM extends the gene pool under its control. DREAM is predominantly expressed in central nervous system with its highest level in cerebellum, and accumulating evidence demonstrated that DREAM might play important roles in pain sensitivity. Novel findings have shown that DREAM is also involved in learning and memory processes, Alzheimer's disease and stroke. This mini-review provides a brief introduction of its discovery history and protein structure properties, focusing on the mechanism of DREAM nuclear translocation and gene transcription regulation functions.

Objective To evaluate a microarray-based mutation screening method for genetic deafness and its application in prenatal diagnosis.Methods Mutation screening of common deafness genes was performed in pregnant women and volunteers spouses.Nine common mutations in four major deafness genes,GJB2,GJB3,SLC26A4 and mitochondrial 12S rRNA,were detected simultaneously by a microarray-based method.Genetic counseling was given based on their testing results.Results 5.11％ of pregnant women carried at least one mutation.Among them,seven carried mutation in the mitochondria 12S rRNA gene and were offered aminoglycoside-induced ototoxicity warning.For other mutation carriers of GJB2 or SLC26A4 genes,additional mutation screening was performed in their husbands by direct sequencing.A total of 20 couples were at risk of giving birth to children with genetic deafness.Of five couples who selected to undergo prenatal diagnostic testing of the fetus,four were diagnosed as wild type or heterozygous for the tested genes and one as p.V37I/c.235delC compound heterozygous for GJB2.Conclusions DNA microarray is a quick,easy and reliable method to screen mutations in genetic deafness genes.Application of this method in prenatal screening and diagnosis might effectively reduce the occurrence of genetic deafness.

OBJECTIVETo examine vibrio cholera (V.C) in aquatic products of littoral area, Zhejiang Province and to provide scientific evidence for administration of aquatic products and cholera epidemic control.

METHODSAll 990 samples of aquatic products collected from local markets, eateries and aquafarms in three chosen areas. Samples were proliferated in alkaline liquid medium, and purified in NO: 4 medium, the isolations were identified biochemically, and phenotype of strains were defined by phagocyte and coagulation with V.C. diagnostic serum. Three virulence genes (ctx, ace, zct) of the isolated strains were detected by polymerase chain reaction (PCR).

RESULTSThere were 1.41% samples caught by V.C., having a carrying rate highest in turtles of 8.9%. 14 strains were defined as three serogroups, and the numbers of Inaba, Ogawa, and Hikojima types were 2, 2, 10 respectively. Virulence genes had detected in 9 of 12 stains. All genes were detected in 5 strains, only ZOT genes in 3 strains, and both CTX and ACE genes in 1 strain.

CONCLUSIONSAquatic products from inshore in Zhejiang Province caught with V.C. strains might be divided into three serogroups. Most of them should be virulence genes. Cholera epidemic outbreak might be caused by those contaminated products.

China ; Food Microbiology ; Genes, Bacterial ; Seafood ; microbiology ; Vibrio cholerae ; genetics ; isolation & purification ; Virulence Factors ; genetics

OBJECTIVETo study apoptosis and gene FasL expression induced by carbon disulfide in sertoli cells of male rats.

METHODSSertoli cells were exposed to different concentrations of CS(2) (0, 0.36, 0.72, 1.44 micromol/ml) for 24 hours. Survival rate, apoptosis rate, expression level of gene FasL were measured using MTT, FCM, and RT-PCR methods respectively.

RESULTSSertoli cell survival rate decreased as the concentration of CS(2) increased. The survival rate (73.34% +/- 1.39%) was significantly lower than the control group (99.98% +/- 5.48%) when the concentration of CS(2) > or = 1.44 micromol/ml (P < 0.05). Apoptosis rate increased as the CS(2) concentration increased. Apoptosis rate (7.93% +/- 0.43%) was significantly higher when the concentration of CS(2) > or = 1.44 micromol/ml (P < 0.05). Expression level of the FasL significantly increased as the concentrations of CS(2) (P < 0.05).

CONCLUSIONCS(2) is cytotoxic to sertoli cells. It could cause apoptosis of sertoli cells.

Animals ; Apoptosis ; drug effects ; Carbon Disulfide ; toxicity ; Cell Line ; Cell Survival ; Fas Ligand Protein ; metabolism ; Male ; Rats ; Sertoli Cells ; drug effects ; metabolism ; Testis ; cytology

OBJECTIVETo describe the epidemiological characteristics and related factors of SARS in Shanxi in order to provide scientific basis for prevention and control of severe acute respiratory syndrome (SARS).

METHODSData on clinically-diagnosed SARS cases reported to Shanxi Center for Disease Control and Prevention through SARS reporting system of Shanxi province and epidemiological reports were collected from early March to 20 May, 2003. The characteristics of SARS distribution in time, place and population in Shanxi were described. The epidemiological characteristics and related influential factors were analyzed with EPI info 6.0 software.

RESULTSSince the first imported SARS case was diagnosed clinically on 7 March and till 20 May in Shanxi province, the number of cumulative clinically-diagnosed SARS cases were 445 with an attack rate of 1.34/10,000. 20 deaths occurred in that period with the mortality rate 4.49%. The number of cases increased from 28 March and formed the first peak. However, the number continued to increase until 18 April to have formed the second peak. Since then, the number of cases has gradually decreased gradually. Since 19 May, there has been no clinically-diagnosed cases being reported. SARS cases were mostly seen in urban areas of the city (83.82% of the total SARS cases) with sporadic cases found in rural areas. Students and medical staff and people from 20 - 59 years of age occupied the large part of the cases. Age specific mortality rate increased with age and the male/female ratio was 1:0.87.

CONCLUSIONIn Shanxi province, the SARS epidemic seemed to have had the following stages: importation of the first case, gradual increase of the number of cases to reach the peak and decreasing. Case identification at early stage as well as taking measures to decrease the chance of transmission were strategically crucial for controlling the spread of SARS virus in the community.

China ; epidemiology ; Female ; Humans ; Male ; Occupations ; Severe Acute Respiratory Syndrome ; diagnosis ; epidemiology ; mortality