The gamma-secretase complex mediates the final cleavage of APP to generate the principal component of amyloid plaques in the brains of Alzheimer's disease patients.Four integral membrane proteins (PS,NCT,PEN-2 and APH-1) are essential and sufficient for gamma-secretase activity.To identify the promoter of human nicastrin gene (NCT),its 5' -flanking region has been characterized and a 270 bp fragment containing the TSS (transcription start site) for the promoter activity has been identified.EMSA assays confirmed that all four AP-1 binding sites and two NFAT sites in the NCT promoter region were able to bind relative transcription factors in vitro.Mutations,as well as treatment with PDTC,which adjust the regulatory effect of AP-1 and NFAT,altered NCT promoter activity in both HeLa cells and rat cortical neurons.The results demonstrated that AP-1 and NFAT are involved in the regulation of hNCT transcription and suggest that balanced activation of AP-1 and NFAT ensures a strict temporal and tissue-specific control of NCT transcription.

OBJECTIVETo develop dataset for basic medical information system.

METHODSAll items of basic medical information system dataset were drafted by literature review, brain storm and group discussion. A Delphi study was conducted to evaluate and adjust the candidate items; then items were finalized based on comprehensive scores.

RESULTSThe final dataset developed through two-round Delphi study contained 20 first-level items, 102 second-level items, 40 third-level items and 88 fourth-level items. The response rates were 71.79% and 92.86% in round 1 and 2, respectively. The authority coefficient was both 0.77 and the coordination coefficient of the specialists' opinion was 0.239 and 0.516, respectively.

CONCLUSIONThe dataset for basic medical information system determined from Delphi study is credible and can be used for development of related software.

Delphi Technique ; Information Systems ; Software Design

G mutation of SLC26A4, the parents and the second child were carriers of the same mutation, while the fetus had a wild-type form. Conclusion It is feasible to identify deafness related genes by screening for GJB2 and SLC26A4 mutation, thus providing correct prenatal diagnosis and avoiding deaf delivery of baby.

OBJECTIVETo evaluate and compare mail and meeting forms in evaluation of Delphi study.

METHODSDelphi study by mail and meeting approaches was used to determine the health information dataset. Experts were required to grade the listed items through three indexes: importance, necessity and availability. Study duration, coefficient of variation of items, authority coefficient and coordination coefficient of the experts' opinion of two forms of study were calculated and compared.

RESULTThe study duration was four months through mail form and 2 days through meeting. Compared with the first round, the coefficient of variation decreased (P<0.001, all of the three indexes by two forms), and the cooperation index increased (P<0.005) in the second round. The experts' opinions were easier to be consistent through meeting than through mail(P<0.033). And the authority coefficient by meeting consultation (0.83 ± 0.05) was higher than that by mail (0.77 ± 0.03) (P=0.001).

CONCLUSIONBoth mail and meeting forms of Delphi study can determine the health information dataset,but meeting consultation is better and requires shorter study duration.

Communications Media ; Delphi Technique ; Postal Service ; Records as Topic

OBJECTIVETo observe the therapeutic efficacy of dietary boron supplement on retinoic acid-induced osteoporosis in rats, so as to provide experimental evidence for clinical management of osteoporosis with boron.

METHODSThirty-two SD rats were randomized into normal control group (8 rats) and osteoporotic group (24 rats), and osteoporosis was induced in rats of the latter group by intragastric retinoic acid administration at the daily dose of 80 mg/kg for 15 consecutive days. The osteoporotic rats were subdivided into control group (8 rats) without treatment, boron treatment group (8 rats) and estradiol treatment group (8 rats). After 30 days of treatment, the serum contents of Ca, P, boron and the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) in the rats were assayed, the bone mineral density (BMD) of the whole body, lumbar vertebrae and tibia were determined, and the morphological changes of the femurs were observed.

RESULTSThe serum contents of Ca and P in the rats of the 4 groups differed scarcely, but the content of boron in boron treatment group was markedly higher than that in the other three groups. In the osteoporotic control group, the activities of serum AKP and TRAP, the masses of spongy bone and cortical bone of the femurs, and the quantity of the osteoclasts were increased, with the BMD of the lumbar vertebrae and tibia decreased, suggesting osteoporotic conditions. The mean trabecular plate density and thickness, trabecular bone volume and cortical bone volume of the femurs in the osteoporotic rats treated with boron or estradiol were significantly increased, but the active osteoclast quantity in the spongy bone and serum TRAP activities were obviously decreased, and the bone quality was comparable with that of the normal group. In addition, the serum AKP activity and the active osteoblast quantity in the spongy bone were obviously increased in boron treatment group.

CONCLUSIONThe dietary boron supplement can increase the serum content of boron of osteoporotic rats to stimulate bone formation and inhibit bone resorption, producing therefore obvious therapeutical effect against osteoporosis.

Acid Phosphatase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Bone Density ; drug effects ; Boron ; administration & dosage ; therapeutic use ; Dietary Supplements ; Female ; Femur ; drug effects ; growth & development ; metabolism ; Isoenzymes ; blood ; Osteoporosis ; blood ; chemically induced ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tartrate-Resistant Acid Phosphatase ; Time Factors ; Tretinoin

Biopsy ; methods ; standards ; Chronic Disease ; Humans ; Liver ; pathology ; Liver Diseases ; diagnosis ; pathology ; Quality Control

OBJECTIVETo identify the pathogenic gene for a non-syndromic hearing loss family.

METHODSMutation analysis was carried out by polymerase chain reaction and direct sequencing of all exons of SLC26A4 (solute carrier family 26, member 4) gene.

RESULTSCompound heterozygous mutations N392Y and S448X were detected in the proband of the family, heterozygous mutation S448X was detected in the father, heterozygous mutation N392Y was detected in the mother.

CONCLUSIONThe proband's hearing loss resulted from the compound heterozygous mutations N392Y and S448X for SLC26A4 gene.

Adult ; Base Sequence ; DNA Mutational Analysis ; Deafness ; diagnostic imaging ; genetics ; pathology ; Family Health ; Female ; Humans ; Male ; Membrane Transport Proteins ; genetics ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; Tomography, X-Ray Computed

OBJECTIVE: To localize the gene of autosomal dominant familial dilated cardiomyopathy with conduction defect. METHODS: A Chinese family which was diagnosed as dilated cardiomyopathy with conduction defect was studied. Venous blood (3 - 5 mL) from some family members was collected, and genomic DNA was extracted from the blood. Then whole genome wide scan was performed after excluding the known markers on the candidate loci (CMD1A, CMD1 E, CMD1F, and CMD1H) by two-point linkage analysis. RESULTS: No significant evidence for linkage was found in the two point linkage analyses to the known markers in the analyzed family. And the whole genome wide scan showed the maximum LOD score reached 2.68 at marker D3S1614 ( at recombination fraction theta = 0). CONCLUSION The related gene in this kindred is located on 3q26 other than on CMD1A, CMD1H, CMD1E, and CMD1F.
Adult ; Arrhythmias, Cardiac ; etiology ; genetics ; Cardiomyopathy, Dilated ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Female ; Genetic Linkage ; Humans ; Male ; Microsatellite Repeats ; Middle Aged ; Pedigree

OBJECTIVE: To identify the origin of the marker chromosome in a patient with chromosome aberration, and to provide the precise genetic diagnosis. METHODS: Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) were performed to detect the known small marker chromosome in this patient. RESULTS: The small marker chromosome originated from chromosome 13 pter->q12. CONCLUSION CGH and FISH can be used to detect the small marker chromosome, which is convenient and quick in detecting the origin of small marker chromosome.
Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 13 ; genetics ; Female ; Genome, Human ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Nucleic Acid Hybridization ; methods

OBJECTIVETo investigate the gene mutations and the clinical features of Chinese patients with autosomal recessive juvenile parkinsonism(AR-JP).

METHODSthe polymerase chain reaction (PCR), DNA sequence analysis, and restriction enzyme digestion analysis were applied to check parkin gene mutations of 15 index patients from 15 families with AR-JP.

RESULTSThree families were detected to have parkin mutations. Two of them had heterozygous deletion mutations (202-203 del AG in exon 2, 1069-1074 del GTGTCC in exon 9) and another of them carried a heterozygous missense mutation [1422(T-->C) in exon 12]. Two of the mutations [1069-1074delGTGTCC and 1422(T-->C)] were not reported previously. There were six patients in the three families. Mean age at onset was 25.2+/-5.7 years, ranging from 18 to 31 years. The symptoms were under slow progression, diurnal fluctuation with sleep benefit, and hyperreflexia were relatively prominent. Response to levodopa was satisfactory.

CONCLUSIONThere are parkin mutations happened in Chinese patients with AR-JP. Patients with parkin mutations have distinct clinical features besides the common clinical features of Parkinson's disease.

Adult ; Family Health ; Female ; Gene Deletion ; Genotype ; Humans ; Male ; Mutation ; Parkinsonian Disorders ; genetics ; Phenotype ; Ubiquitin-Protein Ligases ; genetics