[Orthodontic management of patients with cleft lip and palatebefore and after orthognathics]
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Journal Article↗
Biomedical subjects
B Fang
Publications and source records attributed to B Fang.
[Comparison of genotype and intellectual phenotype in untreated phenylketonuric children].
OBJECTIVE: The main feature of phenylketonuria(PKU) is mental retardation. Although classical PKU is defined as that the hepatic phenylalanine hydroxylase (PAH) activity ranges 0-1% of normal enzyme, the untreated PKU patients show a wide range of intellectual phenotype. This study sought to find the molecular basis of such variation of intellectual phenotype among PKU. METHODS: 45 classical PKU patients included in the research were screened for detecting six mutant alleles which were rather common among Chinese PKU patients, i.e. R243Q, R413P, Y204C, Y356X, W326X and R111X. PCR-ASO and PCR-SSCP techniques were used. The expression of those mutant PAH genes was analysed by methods of site-directed mutagencies. 27 PKU patients whose two mutant alleles were both defined were involved in this study. The IQ of these patients were tested by DDST system. RESULTS: Among 27 patients, 4/27 (15%) were mild retardation, 10/27(37%) were moderate, the severe mental retardation accounted for 12/27(44%). The relationship between genotype and intellectual phenotype in this group was examined. It was found that the intellectual phenotype of 8 patients were compatible with genotype but not well matched in 19 cases. The enzyme activity of Y204C expressed in vitro was 100%, but all 3 patients with Y204C/Y204C were severely mental retarded. Enzyme activities of R413P and Y356X were <3% and 0 respectively in expression analysis, but the patients in this group had mild or moderate mental retardation. CONCLUSION: Intellectual phenotype was not well matched with the genotype in classical PKU patients, so that genotype can not be used to predicte the intellectual phenotype in PKU patients.
Child↗
An evaluation of sialation of the nucleoporin p62.
Many nuclear and cytosolic proteins are modified by single residues of O-linked N-acetyl-D-glucosamine. These include many proteins found in nuclear pore complexes required for transport of macromolecules between the nucleus and the cytoplasm. The best characterized pore glycoprotein, p62, mediates its function as one component of a protein complex essential for nuclear transport. Although p62 sugar residues are not essential for nuclear transport, they appear to oppose protein phosphorylation occurring at sites predicted to destabilize protein-protein interactions of the p62 complex. Recently, a p62-like protein isolated from mouse neuroblastoma cells was reported to be modified by both GlcNAc and sialic acid. As there is little precedent for nucleoplasmic sialation, the finding that a characterized nuclear pore protein is sialated is significant because it may regulate pore function. To assess the biological importance of p62 sialation, GlcNAc and sialic acid-specific lectins were used to examine the state of p62 glycosylation in cells commonly used to study nuclear transport: frog eggs and normal rat kidney and HeLa fibroblasts. In addition, four mouse neuroblastoma cell lines derived from the same tumor were examined. The glycosylation of p62 in these cells appears to involve only single O-linked GlcNAc moieties; no significant sialation was detected.
Animals↗
Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human colon cancer.
Recent studies have indicated that angiogenesis may be regulated, in part, by p53 tumor suppressor gene function. We hypothesized that wild-type p53 replacement would down-regulate vascular endothelial growth factor (VEGF) expression and inhibit angiogenesis. KM12L4 and SW620, human colon cancer cell lines with p53 mutations, were transduced with a replication-defective adenoviral vector containing the wild-type p53 gene (Ad5/CMV/p53). Reverse transcription-PCR confirmed the presence of p53 in Ad5/CMV/p53-transduced cells. Transduction of colon cancer cells with wild-type p53 decreased VEGF RNA expression compared with that of controls. The decrease in VEGF expression in SW620 cells was dose dependent, with a 49% decrease observed at a multiplicity of infection of 50, and a 71% decrease observed at a multiplicity of infection of 100. Similar effects were seen in KM12L4 cells. VEGF supernatant protein levels were significantly reduced compared with those in nontransduced controls 48 h after the introduction of wild-type p53. Ad5/CMV/p53 inhibited tumor cell-induced angiogenesis in vivo. Restoration of wild-type p53 expression may decrease tumor growth by inhibiting the angiogenic response. These findings may explain, in part, the bystander effect seen with p53 tumor suppressor gene therapy.
Adenoviridae↗
Evaluation of GAL4/TATA in vivo. Induction of transgene expression by adenovirally mediated gene codelivery.
A synthetic GAL4-responsive promoter consisting of five GAL4-binding sites and a TATA box (GAL4/TATA) was evaluated for its transcriptional activity in an adenoviral backbone using luciferase as the reporter. Basal luciferase activities in vitro were the same for cells infected with either adenovirus-containing luciferase cDNA driven by GAL4/TATA (Ad/GT-Luc) or adenovirus-containing luciferase cDNA not driven by a promoter (Ad/PO-Luc). In vitro induction of GAL4/TATA by coinfection of cells with adenovirus expressing the GAL4/VP16 fusion protein (Ad/3-phosphoglycerate kinase (PGK)-GV16) was dose-dependent and reached as high as 4 x 10(4)- to 9 x 10(4)-fold above basal levels when GAL4/TATA and GAL4/VP16 were delivered at a ratio of 10:1. In vivo studies in Balb/c mice showed no detectable luciferase activities in liver or other tissues examined in mice infused with either Ad/GT-Luc or Ad/PO-Luc. High levels of luciferase activity were, however, elicited when animals were infused with Ad/GT-Luc and Ad/PGK-GV16. Together, these results suggest that combination of the GAL4 gene regulatory system with adenovirally mediated in vivo gene delivery may be applicable to the in vivo evaluation of promoter activities and in vivo targeting of gene expression.
Adenoviridae↗
Adenovirus-mediated wild-type p53 tumor suppressor gene therapy induces apoptosis and suppresses growth of human pancreatic cancer [seecomments].
BACKGROUND: The p53 tumor suppressor gene is mutated in up to 70% of pancreatic adenocarcinomas. We determined the effect of reintroduction of the wild-type p53 gene on proliferation and apoptosis in human pancreatic cancer cells using an adenoviral vector containing the wild-type p53 tumor suppressor gene. METHODS: Transduction efficiencies of six p53-mutant pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-1, CFPAC-1, MIA PaCa-2, and PANC-1) were determined using the reporter gene construct Ad5/CMV/beta-gal. Cell proliferation was monitored using a 3H-thymidine incorporation assay, Western blot analysis for p53 expression was performed, and DNA laddering and fluorescence-activated cell sorter analysis were used to assess apoptosis. p53 gene therapy was tested in vivo in a subcutaneous tumor model. RESULTS: The cell lines varied in transduction efficiency. The MIA PaCa-2 cells had the highest transduction efficiency, with 65% of pancreatic tumor cells staining positive for beta-galactosidase (beta-gal) at a multiplicity of infection (MOI) of 50. At the same MOI, only 15% of the CFPAC-1 cells expressed the beta-gal gene. Adenovirus-mediated p53 gene transfer suppressed growth of all human pancreatic cancer cell lines in a dose-dependent manner. Western blot analysis confirmed the presence of the p53 protein product at 48 hours after infection. DNA ladders demonstrated increased chromatin degradation, and fluorescence-activated cell sorter analysis demonstrated a four-fold increase in apoptotic cells at 48 and 72 hours following infection with Ad5/CMV/p53 in the MIA PaCa-2 and PANC-1 cells. Suppression of tumor growth mediated by induction of apoptosis was observed in vivo in an established nude mouse subcutaneous tumor model following intratumoral injections of Ad5/CMV/p53. CONCLUSIONS: Introduction of the wild-type p53 gene using an adenoviral vector in pancreatic cancer with p53 mutations induces apoptosis and inhibits cell growth. These data provide preliminary support for adenoviral mediated p53 tumor suppressor gene therapy of human pancreatic cancer.
Adenocarcinoma↗
Isradipine prevents global and regional cocaine-induced changes in brain blood flow: a preliminary study.
The L-type calcium channel antagonist, isradipine, reduces brain ischemia in animal models of ischemic stroke. These effects of isradipine appear more pronounced in dopamine (DA) rich brain regions. These same DA-rich brain regions have also been shown to be the areas most affected by cocaine-induced ischemic changes. Using a novel quantified approach to single photon emission computerized tomography, we demonstrated that isradipine pre-treatment prevented cocaine-induced ischemic changes, especially in these DA-rich brain regions. This is the first demonstration that any medication, including isradipine, can prevent the ischemic effects of cocaine on brain blood flow. Isradipine may, therefore, be a useful therapeutic agent for the prevention of brain ischemia in cocaine addicts.
Adult↗
Demonstration of dose-dependent global and regional cocaine-induced reductions in brain blood flow using a novel approach to quantitative single photon emission computerized tomography.
Ischemic stroke is a common cause of morbidity and mortality in cocaine addicts. Because the previous semiquantitative single photon emission computerized tomography (SPECT) method for measuring brain blood flow does not quantify blood flow, the magnitude and specificity of cocaine's effects during drug taking has not been well established. Here, using a novel quantitative approach to SPECT, we established that intravenous cocaine administration to nine recently abstinent cocaine-dependent subjects was associated with significant decreases in global and regional brain blood flow to dopamine-rich areas such as the prefrontal, frontal temporal, and subcortical gray matter. Establishing the utility of this relatively new quantitative SPECT technique provides an important tool for the management of vascular disorders of the brain. Additionally, identifying the site-specific effects of cocaine provides targets for the development of putative therapeutic medications to attenuate or minimize ischemic stroke in cocaine addicts.
Adolescent↗
Suppression of the immune response to an adenovirus vector and enhancement of intratumoral transgene expression by low-dose etoposide.
Adenoviral vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by cellular and humoral immune responses that result in temporary transgene expression and reduced efficacy of repeated vector administration. We hypothesized that certain oncolytic agents commonly used to treat cancer patients could suppress the immune response to adenoviral vectors, and enable repeated adenovirus-mediated cancer gene therapy. Etoposide and cyclophosphamide were tested for their ability to suppress the humoral and cellular immune responses to an adenoviral vector in immunocompetent C3H mice. Intratumoral transgene expression was monitored in adenovirus-immunized animals treated with etoposide or cyclophosphamide. Neutralizing antibodies to adenovirus and cytotoxic T lymphocyte (CTL) lysis of virally transduced cells were significantly suppressed in mice treated with etoposide at 2 or 10 mg/kg/day or cyclophosphamide at 10 mg/kg/day compared with untreated mice (P < 0.05). Significantly larger areas of gene transduction were observed in treated animals compared with untreated mice or the mice treated with cyclophosphamide at 2 mg/kg/day (P < 0.05). Our results suggest that repeated adenovirally mediated gene therapy is achievable in cancer patients who are concurrently undergoing treatment with chemotherapy.
Adenoviridae↗
Intercellular trafficking of VP22-GFP fusion proteins is not observed in cultured mammalian cells.
Herpes simplex virus type 1 (HSV-1) VP22 was recently reported to mediate intercellular trafficking of a protein fused to the C-terminus of VP22. To explore the application of such trafficking, we constructed plasmids expressing green fluorescent protein (GFP) fused to the C-terminus of either wild-type VP22 or a 160 amino acid peptide from VP22. In vitro studies showed that the majority of both fused proteins were localized to the nuclei of transfected cells. Quantitative analysis of GFP-positive cells, however, showed no significant increase in intercellular protein trafficking for cells transfected with either fusion protein compared with a lacZ-expressing plasmid. Our results suggest that the use of HSV-1 VP22 for mediating intercellular trafficking of transgene products is limited.
Animals↗
Roots and riches tempt Asians back to the fold.
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Asia↗
[The effects of diltiazem on pulmonary hemodynamics and oxygenation in copd induced pulmonary hypertension].
OBJECTIVE: To study hemodynamic the effects of intravenous diltiazem on COPD induced pulmonary hypertention. METHODS: 11 cases in exacerbation stage were chosen to study. Swan-Ganz catheterization were taken for hemodynamic monitoring. RESULTS: After the administration of diltiazem, pulmonary vascular resistance, pulmonary pressure, right artrial pressure and heart rate decreased significantly (the extents decreased were 14.0 kPa.s-1.L-1, 0.62-1.27 kPa, 0.27-0.40 kPa and 25-30 beats/min respectively, P < 0.05); Cardiac output and stroke volume increased identically (the extents increased were 0.3-0.6 L.min-1.m-2 and 5-9 ml.beat-1.m-2 respectively, P < 0.05); No significant changes found in Qs/Qt, PaO2 and systemic blood pressure. CONCLUSION: Our study showed that diltiazem produces beneficial pulmonary hemodynamic effects without oxygenation compromise in COPD cases and has a strong indication in those who complicated with superventricular tachycardia.
Aged↗
A packaging system for SV40 vectors without viral coding sequences.
SV40 vectors have been used as expression vectors for mammalian cells since the early 1980s. More recently, they have been used as gene transfer vectors in mice and in human peripheral blood cells. Here we described a system for packaging SV40 vectors without viral coding sequences. Recombinant adenovirus-expressing SV40 capsids can effectively package plasmids that contain the SV40 replication origin. The final yield of infectious SV40 vector is about 3 x 10(5), with a SV40 to adenoviral vector ratio of about 1000:1. Helper adenoviruses can be effectively heat-inactivated with no effect on the infectivity of SV40 vectors.
Adenoviridae↗
Diminishing adenovirus gene expression and viral replication by promoter replacement.
The adenovirus E4 promoter was replaced by a synthetic promoter composed of a minimal TATA box and five consensus 17-mer yeast GAL4-binding-site elements. The viral vectors, which also contained human factor IX (hFIX) cDNA driven by Rous sarcoma virus long terminal repeat in the E1 region, were then constructed and expanded in 293 cells permanently expressing GAL4/VP16 fusion protein. Viral replication and expression of adenovirus E4 genes and late genes (hexon and fiber) were evaluated in vitro in the human lung carcinoma cell line H1299. Viral replication and viral gene expression were dramatically reduced in the cells transduced by vectors with a replaced E4 promoter compared to the levels in the cells transduced by vectors with the wild-type E4 promoter. The levels of transgene (hFIX) expression remained similar between vectors with or without E4 promoter replacement. These results indicate that diminution of viral gene expression and viral replication is achievable by promoter replacement.
Adenoviridae↗
[Craniofacial growth changes following premature closure of the bilateral coronal sutures in rabbits].
The study was designed to examine the amount and the direction of craniofacial growth changes following bilateral coronal sutures (BCS) closure in young rabbits. At 2 weeks of age, the BCS were fused by the application of enamel adhesive. These animals and a control group also received amalgam implants on the frontonasal, coronal, and lambdoid sutures to monitor suture growth. At 4 or 8 weeks after suture fusion, separate groups of animals underwent release of fused sutures. Immobilization of BCS resulted in growth cessation of the coronal suture. The normal sutures underwent very rapid growth from 2 to 8 weeks of age. BCS release at 8 weeks after fusion resulted in growth restriction. Significant compensatory growth was also noted in the frontal and the lambdoid sutures from 2 to 8 weeks. Nasal bone length was increased significantly. Vault length and craniofacial length were reduced. The results of the present study give experimental documentation to emphasize that surgical correction of craniosynostosis should be performed at a young age to achieve better functional and cosmetic results.
Animals↗
Lack of persistence of E1- recombinant adenoviral vectors containing a temperature-sensitive E2A mutation in immunocompetent mice and hemophilia B dogs.
Two recombinant adenoviruses expressing either human alpha 1-antitrypsin (hAAT) or canine factor IX (cFIX) were modified so that they also contained a temperature-sensitive mutation (ts125) in the DNA binding protein encoded within the viral E2A region. The effects of the inclusion of the ts125 mutation on transgene expression in vivo were evaluated in Balb/c mice and hemophilia B dogs by comparison with adenoviral vectors containing the same transgene but lacking the ts125 mutation. No significant differences in the duration of transgene expression were observed in either animal model. Insufficiency of the ts125 mutation in the prolongation of transgene expression in these two animal models suggests that further modification of the vector backbone may be required to achieve long-term gene expression in a wide variety of applications. Additionally, humoral immune response to transgene products has been demonstrated in immunocompetent animal models, which will also need to be surmounted for long-term efficacy in disease treatment by gene therapy.
Adenoviridae↗
[Analysis of the A/C polymorphic site within the phenylalanine hydroxylase gene].
An A/C polymorphism was identified at nucleotide-11 from the acceptor site of IVS3 of the phenylalanine hydroxylase gene. This polymorphism can be detected easily by means of single strand conformation polymorphism analysis. The frequency for the majior allele (A) was 0.656 and 0.344 for the minor allele (C) with the PIC being 0.351 in Chinese population. There was no linkage disequilibrium between this site and the STR polymorphic site located upstream within the same intron of the gene. The ejjicincy of prenatal gene diagnosis fro PKU was estimated to be 78.1% by haplotype linkage analysis using these two polymorphic sits.
Humans↗
[The relationship between peripheral edema and right heart function in COPD induced cor pulmonale].
OBJECTIVE: To estimate the role of right heart function in the development of edema in COPD induced cor pulmonale. METHOD: 44 cases in exacerbation stage with hypoxia and hypercapnia were studied. Pulmonary hemodynamic parameters were measured by Swan-Ganz catheter and compared with the presence and extent of peripheral edema. RESULTS: Peripheral edema was noted in 40 cases and right arterial pressure < or = 1.33 kPa in 23 cases (23/40 = 57.5%), 17 cases showed edema, with right artrial pressure > 1.33 kPa. There was no significant difference in peripheral edema between that two groups. CONCLUSION: A high proportion of COPD patients with edema do not show right heart failure. The development of edema in COPD may be related to a complex mechanism, including hypoxia and hypercapnia induced natrium and water retention, Right heart failure is not a prerequisite for edema. The significance of edema in COPD induced cor pulmonale should be interpreted correctly in clinical practice.
Aged↗