[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
D Zhang
Publications and source records attributed to D Zhang.
Advantages and challenges of using census and multiplier methods to estimate the number of female sex workers in a Chinese city.
Using census and multiplier methods to estimate the size of the population of female sex workers (FSWs) in a small city in western China, this study compared the advantages and challenges of the two methods. It was estimated that there were about 1,500 FSWs within the urban area using the census method, which was significantly lower than that estimated by the multiplier method (2,500). Each method has advantages and limitations, and could be applied to different situations. The census method is less time and resource consuming in smaller regions and has a tendency to underestimate, and therefore, the result can be viewed as a low limit. It is useful in a local setting, for example, when estimations are needed for planning HIV/AIDS prevention programmes in a single city. Using existing information or resources, multiplier method could be used to produce estimates for a large geographic area or at a national level.
Censuses↗
Bax and the mitochondrial permeability transition cooperate in the release of cytochrome c during endoplasmic reticulum-stress-induced apoptosis.
Endoplasmic reticulum (ER) stress induces apoptosis by mechanisms that are not fully clear. Here we show that ER stress induced by the Ca(2+)-ATPase inhibitor thapsigargin (THG) activates cytochrome c-dependent apoptosis through cooperation between Bax and the mitochondrial permeability transition (MPT) in human leukemic CEM cells. Pharmacological inhibition of the MPT as well as small interfering RNA (siRNA) knockdown of the MPT core component cyclophilin D blocked cytochrome c release and caspase-dependent apoptosis but did not prevent Bax activation, translocation or N-terminal exposure in mitochondria. siRNA knockdown of Bax also blocked THG-mediated cytochrome c release and apoptosis, but did not prevent MPT activation and resulted in caspase-independent cell death. Our results show that ER-stress-induced cell death involves a caspase and Bax-dependent pathway as well as a caspase-independent MPT-directed pathway.
Animals↗
Soluble triggering receptor expressed on myeloid cells-1 in acute respiratory infections.
Levels of the soluble form of the triggering receptor expressed on myeloid cells (sTREM)-1 are elevated in severe sepsis. However, it is not known whether sTREM-1 measurements can distinguish milder bacterial infections from noninfectious inflammation. The present authors studied whether serum sTREM-1 levels differ in community-acquired pneumonia, exacerbations of chronic obstructive pulmonary disease (COPD), asthma and controls, and whether sTREM-1 may be used as a surrogate marker for the need for antibiotics. Serum sTREM-1 levels in 150 patients with pneumonia, COPD and asthma exacerbations and 62 healthy controls were measured. Serum sTREM-1 levels were significantly elevated in pneumonia (median 295.2 ng x mL(-1)), COPD (280.3 ng x mL(-1)) and asthma exacerbations (184.0 ng x mL(-1)) compared with controls (83.1 ng x mL(-1)). Levels were higher in pneumonia and Anthonisen type 1 COPD exacerbations than in type 2 and 3 COPD and asthma exacerbations. The area under the receiver operating characteristics curve for sTREM-1 as a surrogate marker for the need for antibiotics was 0.77. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 were elevated predominantly in pneumonia and Anthonisen type 1 COPD exacerbations versus type 2 and 3 chronic obstructive pulmonary disease exacerbations, asthma and controls. Serum levels of the soluble form of the triggering receptor expressed on myeloid cells-1 has moderate but insufficient accuracy as a surrogate marker for the need for antibiotics in lower respiratory tract infections.
Adult↗
Are private school students more likely to smoke than public school students in China?
BACKGROUND: Tobacco use is prevalent among adolescents in China in general, however, little is known about tobacco use among students in private schools with an enrollment of 1.5 million. METHOD: In 2001, cross-sectional survey data from 2725 students in grades seven and eight (1307 sampled from private schools and 1418 sampled from public schools) were included. Smoking measures (risk of susceptibility to smoking, smoking onset, ever smoking, smoking in the past 7 days and past 30 days, established smoking) were compared between private and public school students using chi-square test, logistic regression, and survival analysis. RESULTS: Cigarette smoking was more prevalent among private school students than among public school students (private vs. public: 21.9% vs. 12.3% for susceptibility to smoking, 53.9% vs. 38.2% for ever smoking, 22% vs. 12.0% for 30-day smoking, 15.9% vs. 4.0% for 7-day smoking, 4.5% vs. 1.2% for established smoking). Students in private schools are 3.4 to 3.8 times more likely to smoke than students in public schools after the adjustment of important covariates (gender, grade, peer smoking, parental smoking, and parents' occupation). Risk of smoking onset by age was also greater for private school students than for public school students. CONCLUSIONS: Being in private schools was associated with three to four times increases in the likelihood of current cigarette smoking and heightened risk of smoking onset by age. Findings from this study suggest the urgent need to collect additional data on risk and protective factors as well as the willingness to participate in effective tobacco use intervention prevention among private school students.
Adolescent↗
Human periodontal ligament cells express osteoblastic phenotypes under intermittent force loading in vitro.
UNLABELLED: Mechanical strain applied to bone leads to bone remodeling. In the oral cavity, it is unclear how such mechanical force applied to move teeth orthodontically induces alveolar bone remodeling. It is known that osteoclasts are the only cells that are responsible for bone resorption, while the formation and activity of osteoclasts are regulated by osteoblasts. So it is believed that osteoblasts play an important role not only in bone formation but in bone remodeling as well. Therefore, the purpose of this study was to examine the effect of mechanical force on human periodontal ligament (PDL) cells and whether they express osteoblastic characters in vitro. METHODS: Human PDL cells cultured in vitro were loaded with intermittently stretching force for 24 hours. The expression of alkaline phosphatase (ALP), osteocalcin (OCN) and osteoprotegerin (OPG) were detected at mRNA and protein levels at 0, 2nd, 4th, 6th, 12th, 24th hours after intermittent force loading. RESULTS: Without any stimulation, ALP and OPG mRNA expressions were detected in human PDL cells by in-situ hybridization, but not that of OCN mRNA. ALP mRNA signal was up-regulated and that of OPG was down-regulated by mechanical force within 24 hours. OCN mRNA expression was induced by mechanical force in the late phase of the 24-hours loading cycle. The changes in secreted proteins showed similar results with those seen at the mRNA level. CONCLUSION: Human PDL cells express osteoblastic phenotypes under intermittent force loading and play a role in alveolar bone remodeling.
Alkaline Phosphatase↗
Central neurocytoma: clinical, pathological and neuroradiological findings.
AIM: To evaluate the clinical, pathological and neuroradiological features of intraventricular central neurocytoma in six patients. MATERIALS AND METHODS: Six patients were imaged using non-enhanced and contrast-enhanced magnetic resonance imaging (MRI); three of them were also examined using non-enhanced computed tomography (CT). Two radiologists read the images retrospectively. The imaging data were studied with regard to location, size, margin, signal intensity, enhancement characteristics and presence of calcifications. Clinical data (i.e. presenting signs and symptoms, physical findings and medical histories) were collected and histopathological and immunohistochemical studies were performed by two pathologists. RESULTS: All lesions were located in the lateral ventricles. Three tumors were confined to the left side, one to the right side and two cases involved both lateral ventricles. The growth of central neurocytoma was of close spatial relation to the septum pellucidum. On MRI, most of the cases showed a heterogeneous hypointensity on T1-weighted images and hyperintensity on T2-weighted images or FLAIR with a well-defined margin. The presence of cystic components, necroses and calcifications caused these internal heterogeneities. After intravenous administration of gadolinium (Gd-DTPA) all tumours showed a heterogeneous enhancement. CT provided additional information by distinguishing intratumoural calcifications in all three evaluated cases. Immunohistochemical analysis showed positive synaptophysin staining in all cases and positive neuron-specific enolase staining in four cases. In three cases a small proportion of the tumour cells could be labelled with antibodies to glial fibrillary acid protein (GFAP). CONCLUSION: Central neurocytoma should be considered when the following conditions occur: young patients with lesions in the lateral ventricle, which contain calcifications and show some enhancement. This is especially applicable for tumours involving both lateral ventricles with symmetrical growth around the centre of septum pellucidum or for unilateral ventricular tumors with a wide base attachment to the septum pellucidum.
Adolescent↗
HBV genes induce cytotoxic T-lymphocyte response upon adeno-associated virus (AAV) vector delivery into dendritic cells.
Hepatitis B virus (HBV) has been an increasing problem throughout the world and remains difficult to treat. But immunotherapeutic approaches offer new, effective treatments. Three recombinant adeno-associated virus (AAV) type 2 vectors, carrying one of the HBV S, C or X gene, were used to load (transduce) professional antigen-presenting dendritic cells (DC) for the purpose of stimulating cytotoxic T lymphocytes (CTL) in vitro. It was found that all three recombinant AAV/HBV antigen virus loaded DC at approximately 90% transduction efficiency. Most importantly, all three AAV-loaded DC stimulated rapid, antigen-specific and major histocompatibility complex (MHC)-restricted CTL. In vitro, these CTL killed (30-50%) synthetic antigen-positive autologous targets as well as HepG2 liver cell targets. In comparing the three antigens, it was found that AAV/HBV-C-derived CTL consistently had the highest killing efficiency. CTL derived from AAV/HBV-C-loaded DC also showed significantly higher killing of targets than that from bacterially generated C-protein-loaded DC. Further studies showed that AAV/HBV-C-derived CTL had higher interferon (IFN)-gamma. These data suggest that AAV/HBV antigen gene-loading of DC may be useful for immunotherapeutic protocols against HBV infection and that the HBV C antigen may be the most useful for this purpose.
Antigens, CD↗
Islet autoimmunity and genetic mutations in Chinese subjects initially thought to have Type 1B diabetes.
AIMS: To explore the contribution of islet autoimmunity and genetic mutations in Chinese patients initially thought to have Type 1B diabetes. METHODS: A group of 33 Chinese patients with newly diagnosed Type 1B diabetes, were identified by the absence of autoantibodies to glutamic acid decarboxylase (GAD), IA-2, insulin, thyroid globulin or thyroid peroxidase, or high-risk HLA-DQ haplotypes. The cohort was further characterized by measurement of autoantibodies to carboxypeptidase H (CPH) and SOX13 using radioligand assays, and testing for genetic mutations associated with MODY3/MODY6 and mitochondrial diabetes. Mutations of HNF-1alpha (MODY3) and neuroD1/beta2 (MODY6) genes were screened using the single-strand conformation polymorphism (SSCP) technique and sequencing. Mitochondrial DNA mutations were analysed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Within the cohort, we found one patient with a novel mutation, R321H (CGC-->CAC) in exon 5 of the HNF-1alpha gene, one with ND1 mt3316 G-->A mutation in mitochondrial DNA, five with Ala45Thr polymorphisms in the neuroD1/beta2 gene, and two patients with autoantibodies to SOX13. CONCLUSIONS: Some of the Chinese patients originally thought to have Type 1B diabetes do have other evidence of islet autoimmunity and genetic mutations involved in the underlying aetiology. This suggests that more rigorous screening for these conditions is needed before classifying subjects as having Type 1B diabetes.
Adolescent↗
Mutations responsible for Larsen syndrome cluster in the FLNB protein.
BACKGROUND: A gene for Larsen syndrome was recently described, and mutations were reported in five cases. OBJECTIVE: To test whether mutations in this gene, FLNB, could explain the disease in our independent collection of sporadic and dominant Larsen syndrome cases; and to test whether mutations occurred in a non-random pattern. RESULTS: Missense mutations were found in each of five cases. Four of the five were new; one was reported in a sporadic case in the original Larsen syndrome study of five cases. All mutations from the two studies were compiled. Clustered mutations were observed within three filamin B protein domains: the calponin homology 2 domain, repeat 14, and repeat 15. This suggested that as few as five (of the total of 46) coding exons of FLNB could be screened to detect Larsen syndrome mutations. Four of these exons were screened in a sixth (sporadic) case and a previously reported G1691S substitution mutation detected. CONCLUSIONS: Mutations in FLNB may be responsible for all cases of Larsen syndrome. They appear to occur in specific functional domains of the filamin B protein. This should simplify diagnostic screening of the FLNB gene. Analyses in larger patient series are warranted to quantify this. The study confirmed the extreme variability in clinical presentation and the presence of unaffected carriers. A molecular screen would be valuable for diagnosis and genetic counselling.
Abnormalities, Multiple↗
High diversity of the chicken growth hormone gene and effects on growth and carcass traits.
The chicken growth hormone (cGH) gene plays a crucial role in controlling growth and metabolism, leading to potential correlations between cGH polymorphisms and economic traits. In this study, DNA from four divergent chicken breeds were screened for single nucleotide polymorphisms (SNPs) in the cGH gene using denaturing high-performance liquid chromatography and sequencing. A total of 46 SNPs were identified, of which 4 were in the 5' untranslated region, 1 in the 3' untranslated region, 5 in exons (two of which are nonsynonymous), with the remaining 36 in introns. The nucleotide diversity in the cGH gene ( theta = 2.7 x 10(-3)) was higher than that reported for other chicken genes, even within the same breeds. The associations of five of these SNPs and their haplotypes with chicken growth and carcass traits were determined using polymerase chain reaction-restriction fragment length polymorphism analysis in a F2 resource population cross of two of the four chicken breeds (White Recessive Rock and Xinghua). This analysis shows that, among other correlations, G+1705A was significantly associated with body weight at all ages measured, shank length at three of four ages measured, and average daily gain within weeks 0 to 4. Thus, this cGH polymorphism, or another polymorphism that is in linkage disequilibrium with G+1705A, appears to correspond to a significant growth-related quantitative trait locus difference between the two breeds used to construct the resource population.
Animals↗
Determination of acidic and basic species by headspace gas chromatography.
This paper reported a novel headspace gas chromatographic (GC) technique on quantification of acidic and basic species. It is based on an acid-base reaction between the measured species and bicarbonate in an aqueous solution, which generates carbon dioxide in a closed headspace sample vial. By operating at 60 degrees C, carbon dioxide is completely released to the headspace and thus can be measured by GC with a thermal conductivity detector. Bicarbonate concentrations of 0.030 and 0.0025 mol/L are recommended for general applications and very small species content, respectively. This method is able to accurately measure small sample sizes (down to few milligrams or microliters). The present method is simple, accurate, and automatic.
Acids↗
Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis.
T-lymphocytes play an important role in rheumatoid arthritis (RA). In this study, we evaluated the hypothesis that common T-cell receptor (TCR) structural features may exist among infiltrating T cells of different RA patients, if the TCR repertoire is shaped by interaction with common self or microbial antigens in the context of susceptible HLA genes in RA. Synovial lesion tissue (ST), synovial fluid (SF) and blood specimens from RA patients and controls were analyzed for TCR V gene repertoire by real-time PCR. There was highly skewed BV14 and BV16 usage in synovial T cells of RA as opposed to those of controls, which was accompanied with a trend for correlation between skewed BV16 and DRB1(*)0405. Immunoscope analysis of the V-D-J region of ST-derived T cells demonstrated oligoclonal and polyclonal expansion of BV14(+) and BV16(+) T cells. Detailed characterization using specific BV and BJ primers further revealed common clonotypes combining the same BV14/BV16, BJ and CDR3 length. DNA cloning and sequence analysis of the clonotypes confirmed identical CDR3 sequences and common CDR3 sequence motifs among different RA patients. The findings are important in the understanding of BV gene skewing and CDR3 structural characteristics among synovial infiltrating T cells of RA.
Arthritis, Rheumatoid↗
Association between arterial stiffness and platelet activation.
Increased arterial stiffness is strongly associated with atherosclerosis, while platelet activation is an important trigger of thrombotic events in patients with atherosclerosis. However, little is known about the effect of arterial stiffness on platelet activation. We therefore investigated the association between arterial stiffness and platelet activation in 38 normal volunteers (20 men and 18 women) aged 23-77 years (mean = 49 +/- 15 years). Arterial stiffness was assessed by measuring brachial-ankle pulse wave velocity (ba-PWV) and heart-brachial PWV (hb-PWV). Flow cytometric analyses were performed to evaluate platelet activation by measuring surface expression of P-selectin and platelet-neutrophil complexes (PNC) before and after activation by ADP. We also calculated the difference between basal and stimulated states of P-selectin and PNC to assess platelet activation reserve. PWVs were significantly correlated with age and BP (r = 0.60-0.81). For platelet activation and activation reserve, correlations with age were less strong but remained significant (r = 0.36-0.61), with the exception of P-selectin (not significant, NS), and correlations with SBP were similar (r = 0.35-0.53). A significant correlation was found between PWVs and platelet activation (r = 0.43-0.74). Multiple regression analysis demonstrated significant correlations between platelet activation and reserve and PWVs (coefficient = 2.17-6.59), when both age and BP were adjusted for simultaneously. In conclusion, platelet activation was associated with arterial stiffness, suggesting that arterial stiffness may play an important role in thrombotic events.
Adult↗
Population pharmacokinetics of mycophenolic acid in kidney transplant pediatric and adolescent patients.
Current data on mycophenolate mofetil (MMF) suggest that there is a pharmacokinetic/pharmacodynamic relationship between the mycophenolic acid (MPA) area under the curve (AUC) during treatment and both the risk of acute rejection and the occurrence of side effects. The aim of this study was to characterize the population pharmacokinetics of MPA in kidney transplant patients between the ages of 2 and 21 years and to propose a limited sampling strategy to estimate individual MPA AUCs. Forty-one patients received long-term oral MMF continuous therapy as part of a triple immunosuppressive regimen, which also included cyclosporine or tacrolimus (n=3) and corticosteroids. Therapy was initiated at a dose of 600 mg/m twice daily. The population parameters were calculated from an initial group of 32 patients. The data were analyzed by nonlinear mixed-effect modeling using a 2-compartment structural model with first-order absorption and a lag time. The interindividual variability in the initial volume of distribution was partially explained by the fact that this parameter was weight-dependent. Fifteen concentration-time profiles from 13 patients were used to evaluate the predictive performance of the Bayesian approach and to devise a limited sampling strategy. The protocol, involving two sampling times, 1 and 4 hours after oral administration, allows the precise and accurate determination of MPA AUCs (bias -0.9 microg.h/mL; precision 6.02 microg.h/mL). The results of this study combine the relationships between the pharmacokinetic parameters of MPA and patient covariates, which may be useful for dose adjustment, with a convenient sampling procedure that may aid in optimizing pediatric patient care.
Adolescent↗
Identification of a novel HLA-DRB1 allele (HLA-DRB1*111902*).
In this paper, we report a new HLA-DRB1 allele identified in a male acute myeloid leukaemia Chinese patient. This sample was initially typed as DRB1*11XX using commercial polymerase chain reaction-sequence-specific primers kit. When it was typed using a chip-based sequence-specific oligonucleotide technique, a novel hybridization pattern that does not match any known alleles was observed. Through sequencing, we have identified this allele as a new HLA-DRB1 allele, which was later named HLA-DRB1*111902 by the WHO Nomenclature Committee. The sequence of this new allele differs from DRB1*111901 by one nucleotide (from G to C) at 203nt of exon 2 but does not cause any amino acid substitution.
Alleles↗
[Experimental study on simultaneous selective reinnervation of the adductors and the abductor muscle for the treatment of the laryngeal paralysis].
OBJECTIVE: The aim of this study is to estimate the value of a new surgical procedure in the treatment of the chronic unilateral laryngeal paralysis. METHODS: The recurrent laryngeal nerve of the left side of the dog was totally cut and served as a model of unilateral laryngeal paralysis at the first step of the research. The adductor and abductor branches of the recurrent laryngeal nerve were then, selected and cut. Afterwards, they were micro-sutured respectively with one branch of ansa cervicalis and phrenic nerve immediately (group 1) and 4 months later (group 2). Six months after this reinnervation, the laryngeal physiologic function of the lateral crico-arytenoid muscle (LCA) and the posterior crico-arytenoid muscle (PCA) have been checked by the methods of electromyography (EMG) and direct laryngoscopy. All the data have been analysed by the statistic methods. RESULTS: Among all the data of EMG, only the wave amplitude of action potential of the LCA muscle of the group 2 was diminished (p < 0.05). Under the direct laryngoscopy, the adductor movement of the left vocal cord of the group 2 was also lightly reduced. But the adductor and abductor movements of the left vocal cord were synchronous with the mouvements of the right vocal cord. CONCLUSION: Though the result of nervous reinnervation of a four month's laryngeal paralysis was not so good by comparison with that of an immediate reinnervation, this surgical procedure can however on the clinical point of view, reach a satisfactory level. The duration maximum of the reinnervation operation after laryngeal paralysis, is, at the present, not clear. It is necessary for us to make further studies.
Animals↗
MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by (213)Bi-C595 radioimmunoconjugate.
Control of micrometastatic pancreatic cancer remains a major objective in pancreatic cancer treatment. The overexpression of MUC1 mucin plays an important role in cancer metastasis. The aim of this study was to detect the expression of MUC1 in human primary tumour tissues and three pancreatic cancer cell lines (CAPAN-1, CFPAC-1 and PANC-1), and target MUC1-positive cancer cells in vitro using (213)Bi-C595 alpha-immunoconjugate (AIC). The expression of MUC1 on pancreatic tumour tissues and cancer cell lines was performed by immunohistochemistry and further confirmed by confocal microscope and flow cytometry analysis on the cell surface. Cytotoxicity of (213)Bi-C595 was tested by MTS assay. Apoptosis was documented using TUNEL assay. Overexpression of MUC1 was found in approximately 90% of tested tumour samples and the three pancreatic cancer cell lines. (213)Bi-C595 is specifically cytotoxic to pancreatic cancer cells in a concentration-dependent fashion. These results suggest that overexpression of MUC1 in pancreatic cancer is a useful target, and that the novel (213)Bi-C595 AIC selectively targets pancreatic cancer cells in vitro. (213)Bi-C595 may be a useful agent for the treatment of micrometastases or minimal residual disease (MRD) in pancreatic cancer patients with overexpression of MUC1 antigen.
Antibodies, Monoclonal↗