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Y Chen

Publications and source records attributed to Y Chen.

At least 469 records · Page 26Linked to original sources
PubMed2001

Fas (CD95, Apo-1) ligand gene transfer.

Gene therapy represents a new form of medical intervention that relies on direct transfer of genetic materials into patients. Although initially envisioned as a treatment for genetic diseases, gene therapy is currently being explored for a wide range of acquired disorders including cancer, cardiovascular diseases, arthritis, and neurodegenerative disorders. Since most acquired diseases are not caused by single gene mutations, the choice of therapeutic genes is crucial for the success of the gene therapy. In this review, we discuss the progresses that have been made and problems that remain to be resolved in using Fas (CD95, Apo-1) ligand gene for the treatment of acquired disorders. Fas ligand is a member of the tumor necrosis factor family that can induce both apoptosis and activation of various cells. While Fas ligand gene transfer indeed eliminates cancer cells and inflammatory cells through apoptosis, it also kills normal cells and initiates inflammation in certain tissues. Thus, new strategies that can modify the apoptotic or proinflammatory activities of the FasL will help to fully realize the potential of the FasL gene therapy.

Apoptosis↗
PubMed2001

Identification of beta subunit of the rhesus monkey chorionic gonadotropin (rmCG).

Chorionic gonadotropin (CG) is a placental derived hormone that plays a crucial role in successful implantation and establishment of early pregnancy in the primates. The rhesus monkey was chosen as a model to understand the feasibility of developing human DNA immuno-contraceptive. The coding region of rhesus monkey CG beta-subunit (rmCGbeta) was isolated by the TDRT-PCR method. The nucleotide sequence including the leader peptide was 499 nucleotide long and encoded 166 amino acids. In comparing with the previous known primates CG beta-subunits, the rmCGbeta was the highest degree of homology with baboon CG beta-subunit at the deduced amino acid sequence (94%), 79.5% homology with human CG beta-subunit and 70.4% homology with marmoset monkey CG beta-subunit. The eukaryotic expression vector pCMV4-rmCGbeta inserted full-coding cDNA sequence of rmCGbeta was constructed, and the expression of rmCG beta-subunit in HeLa cells transient expressing system in vitro and BALB/c mice in vivo was determined. The results demonstrated that the recombinant PCMV4-rmCGbeta eukaryotic expression vector could express rmCG beta-subunit in vitro and in vivo.

Amino Acid Sequence↗
PubMed2001

Incidence of second primary breast cancer among women with a first primary in Manitoba, Canada.

Second primary breast cancer is of importance because of the increasing incidence of first primary breast cancer and improved survival. There is lack of information on the disease in Canada. We studied 14,220 women with a first primary breast cancer (invasive only) diagnosed during the period from 1970 to 1997, in Manitoba, Canada. A breast cancer was considered to be a second primary if it was an invasive lesion diagnosed at least six months after the diagnosis of an initial primary breast cancer. The incidence rate of second primary breast cancer was approximately six per 1,000 person-years, and the cumulative incidence during the 28-year study period was 14.3%. Average age at diagnosis of first primary breast cancer had increased significantly since 1970. The incidence was higher in 1975-1979, and there was no significant difference among other study periods after adjustment for the age at diagnosis of first primary breast cancer. Standardized incidence ratios showed no significant difference among six age groups after adjusting for calendar year. However, women with a first primary breast cancer had an increased risk of developing a second primary breast cancer compared with the risk of developing a first primary breast cancer among the general female population. The SIR was markedly greater among women who had a first primary breast cancer before the age of 40 years, and decreased significantly with increasing age at diagnosis of first primary breast cancer. The data provide epidemiological information on second primary breast cancer risk for the general female population in Manitoba, Canada.

Adult↗
PubMed2001

Modeling emotion and behavior in animated personas to facilitate human behavior change: the case of the HEART-SENSE game.

The goal of this research is to determine whether a computer based training game (HEART-SENSE) can improve recognition of heart attack symptoms and shift behavioral issues so as to reduce pre-hospitalization delay in seeking treatment. Since treatment delay correlates with adverse outcomes, this research could reduce myocardial infarction mortality and morbidity. In Phase I we created and evaluated a prototype virtual village in which users encounter and help convince synthetic personas to deal appropriately with a variety of heart attack scenarios and delay issues. Innovations made here are: (1) a design for a generic simulator package for promoting health behavior shifts, and (2) algorithms for animated pedagogical agents to reason about how their emotional state ties to patient condition and user progress. Initial results show that users of the game exhibit a significant shift in intention to call 9-1-1 and avoid delay, that multi-media versions of the game foster vividness and memory retention as well as a better understanding of both symptoms and of the need to manage time during a heart attack event. Also, results provide insight into areas where emotive pedagogical agents help and hinder user performance. Finally, we conclude with next steps that will help improve the game and the field of pedagogical agents and tools for simulated worlds for healthcare education and promotion.

Algorithms↗
PubMed2001

Uveal melanomas with optic nerve extension: report of two cases diagnosed by transvitreal biopsy, one of them with a multicentric tumour.

PURPOSE: To report two cases of invasive uveal melanomas, one of which showed multifocality. METHODS: Clinical examination, ultrasonography, colour Doppler analysis, cytological and histopathological evaluations. RESULTS: Transvitreal biopsy (case 1) or fine needle aspiration biopsy (FNAB) (case 2) revealed malignant melanomas in both patients. Light microscopy and immunohistochemical examinations substantiated the diagnosis of mixed cell type melanomas. In addition, one patient had a multifocal melanoma with papilloedema and colour Doppler findings suggestive of optic disc involvement. CONCLUSION: Transvitreal biopsy for histology or cytology is a reliable procedure to obtain an accurate diagnosis without delay of a lesion adjacent to the optic nerve head. In our two cases the biopsy findings led to enucleation.

Adult↗
PubMed2001

A candidate prostate cancer susceptibility gene at chromosome 17p.

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).

Amino Acid Sequence↗
PubMed2001

Imprinted X inactivation maintained by a mouse Polycomb group gene.

In mammals, dosage compensation of X-linked genes is achieved by the transcriptional silencing of one X chromosome in the female (reviewed in ref. 1). This process, called X inactivation, is usually random in the embryo proper. In marsupials and the extra-embryonic region of the mouse, however, X inactivation is imprinted: the paternal X chromosome is preferentially inactivated whereas the maternal X is always active. Having more than one active X chromosome is deleterious to extra-embryonic development in the mouse. Here we show that the gene eed (embryonic ectoderm development), a member of the mouse Polycomb group (Pc-G) of genes, is required for primary and secondary trophoblast giant cell development in female embryos. Results from mice carrying a paternally inherited X-linked green fluorescent protein (GFP) transgene implicate eed in the stable maintenance of imprinted X inactivation in extra-embryonic tissues. Based on the recent finding that the Eed protein interacts with histone deacetylases, we suggest that this maintenance activity involves hypoacetylation of the inactivated paternal X chromosome in the extra-embryonic tissues.

Acetylation↗
PubMed2001

Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease.

Little is known about the genetic regulation of medulloblastoma dissemination, but metastatic medulloblastoma is highly associated with poor outcome. We obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or non-metastatic (M0) and identified 85 genes whose expression differed significantly between classes. Using a class prediction algorithm based on these genes and a leave-one-out approach, we assigned sample class to these tumors (M+ or M0) with 72% accuracy and to four additional independent tumors with 100% accuracy. We also assigned the metastatic medulloblastoma cell line Daoy to the metastatic class. Notably, platelet-derived growth factor receptor alpha (PDGFRA) and members of the downstream RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway are upregulated in M+ tumors. Immunohistochemical validation on an independent set of tumors shows significant overexpression of PDGFRA in M+ tumors compared to M0 tumors. Using in vitro assays, we show that platelet-derived growth factor alpha (PDGFA) enhances medulloblastoma migration and increases downstream MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK1 (p42 MAPK) and MAPK3 (p44 MAPK) phosphorylation in a dose-dependent manner. Neutralizing antibodies to PDGFRA blocks MAP2K1, MAP2K2 and MAPK1/3 phosphorylation, whereas U0126, a highly specific inhibitor of MAP2K1 and MAP2K2, also blocks MAPK1/3. Both inhibit migration and prevent PDGFA-stimulated migration. These results provide the first insight into the genetic regulation of medulloblastoma metastasis and are the first to suggest a role for PDGFRA and the RAS/MAPK signaling pathway in medulloblastoma metastasis. Inhibitors of PDGFRA and RAS proteins should therefore be considered for investigation as possible novel therapeutic strategies against medulloblastoma.

Butadienes↗
PubMed2001

Less attention is more in the preparation of antisaccades, but not prosaccades.

To make a saccadic eye movement to a target we must first attend to it. It is therefore not surprising that diverting attention increases saccade latency, but is latency increased in all cases? We show that attending to a peripheral discrimination task has a paradoxical effect. If the stimulus to be attended appears shortly (100 to 300 ms) before an eye movement is made in a direction opposite to that of a presented stimulus (an antisaccade), its latency is reduced to well below baseline performance. In contrast, latencies for saccades toward the stimulus (prosaccades) are increased under similar conditions. This paradoxical effect may arise from competition between the processes mediating prosaccades and antisaccades. When the discrimination task is presented at the critical moment, it interferes with a reflexive prosaccade, allowing faster antisaccades. The results suggest that the suppression of sensorimotor reflexes can facilitate volitional motor acts.

Attention↗
PubMed2001

Adenovirus-mediated transfer of type IV collagen alpha5 chain cDNA into swine kidney in vivo: deposition of the protein into the glomerular basement membrane.

Gene therapy of Alport syndrome (hereditary nephritis) aims at the transfer of a corrected type IV collagen alpha chain gene into renal glomerular cells responsible for production of the glomerular basement membrane (GBM). A GBM network composed of type IV collagen molecules is abnormal in Alport syndrome which leads progressively to kidney failure. The most common X-linked form of the disease is caused by mutations in the gene for the alpha5(IV) chain, the alpha5 chain of type IV collagen. Full-length human alpha5(IV) cDNA was expressed in HT1080 cells with an adenovirus vector, and the recombinant alpha5(IV) chain was shown to assemble into heterotrimers consisting of alpha3(IV) and alpha4(IV) chains, utilizing a FLAG epitope in the recombinant alpha5(IV) chain. The results indicate that correction of the molecular defect in Alport syndrome is possible. Previously, we had developed an organ perfusion method for effective in vivo gene transfer into glomerular cells. In vivo perfusion of pig kidneys with the recombinant adenovirus resulted in expression of the alpha5(IV) chain in kidney glomeruli as shown by in situ hybridization and its deposition into the GBM was shown by immunohistochemistry. The results strongly suggest future possibilities for gene therapy of Alport syndrome.

Adenoviridae↗
PubMed2001

Induction of ErbB-2/neu-specific protective and therapeutic antitumor immunity using genetically modified dendritic cells: enhanced efficacy by cotransduction of gene encoding IL-12.

Overexpression of ErbB-2/neu occurs in 20-30% of patients with breast cancer and indicates a poor prognosis. The presence of a detectable immune response to ErbB-2/neu in some patients suggests that this oncogene may be a useful target for vaccine therapy. We evaluated whether genetic immunization using dendritic cells (DC) transduced ex vivo with an adenovirus expressing the ErbB-2/neu gene (AdNeuTK) could induce protective and therapeutic immunity against a breast tumor cell line overexpressing ErbB-2/neu. Subcutaneous (s.c.) immunization with the DC vaccine elicited protective immunity in an average of 60% of animals. CTL analysis demonstrated specific cytotoxic activity against breast tumor cells, as well as syngeneic fibroblasts transduced with AdNeuTK. In vivo depletion studies demonstrated both CD4+ and CD8+ T cells were required. In a therapeutic setting, immunization with the DC vaccines could cure mice with pre-established tumors and efficacy was further enhanced by cotransducing DCs with a vector expressing murine IL-12 (AdmIL-12). These studies support DC vaccines as a therapeutic strategy for human breast cancer, while emphasizing the importance of optimizing an immune response by combining tumor antigen presentation with immunostimulatory cytokines.

Adenoviridae↗
PubMed2001

Identification of methylated CpG motifs as inhibitors of the immune stimulatory CpG motifs.

The unmethylated CpG motifs within E. coli DNA (EC) cause immune stimulation. In contrast, mammalian DNA such as calf thymus (CT) DNA had been thought to be immunologically inert. In this article, we demonstrate that CT DNA unexpectedly specifically inhibits the immune activation by EC but not that by endotoxin. This inhibitory effect was mediated in the signaling pathway activated by EC since CT DNA markedly inhibited the CpG-induced nuclear translocation of the transcription factors, NF-kappaB and AP-1. In addition, CT DNA significantly inhibited the synergistic immune activation by EC and endotoxin. The mechanism of the inhibition by CT DNA probably did not involve the inhibition of the cellular uptake of EC. Using a CpG-depleted plasmid, we demonstrated that CpG methylation played an important role in the inhibition by CT DNA. Compared with unmethylated plasmid DNA, CpG-methylated DNA inhibited the immune activation by EC to the same extent as did CT DNA. Importantly, the inhibitory effect of CT DNA was also observed in vivo. Our results suggest that methylated DNA may be applied to alleviate the unwanted immune stimulation and inflammation in systemic inflammatory response syndrome and in gene therapy with plasmid DNA.

Animals↗
PubMed2001

Urine specific gravity and water hardness in relation to urolithiasis in persons with spinal cord injury.

STUDY DESIGN: A matched case-control study. OBJECTIVES: To clarify the influence of urine specific gravity and drinking water quality on the formation of urinary stones in persons with spinal cord injury (SCI). SETTING: A rehabilitation center within a university hospital. METHODS: Between 1992 and 1998, 63 stone cases (31 kidney, 27 bladder, and five both) and 289 age-duration-matched controls were recruited from a cohort of SCI patients enrolled in an on-going longitudinal study. Data on urine specific gravity and other characteristics of study participants were retrieved from the database and medical charts. Community water supply information was provided by the Alabama Department of Environmental Management. Multivariable conditional logistic regression analysis was performed to evaluate the association with stone formation. RESULTS: SCI individuals who had urinary stones were more likely than control subjects to use indwelling catheters and have decreased renal function. The occurrence of stones was not significantly related to gender, race, severity of injury, urinary tract infection, nor urine pH. After controlling for the potential confounding from other factors, a continuously increasing stone occurrence with increasing specific gravity was observed (P=0.05); this association was stronger for kidney (odds Ratio [OR]=1.8 per 0.010 g/cm(3)) versus bladder stones (OR=1.2) and for recurrent (OR=2.0) versus first stones (OR=1.5). Increased water hardness was not significantly associated with a decreased stone occurrence. CONCLUSIONS: Study results suggest that maintaining urine specific gravity below a certain level might reduce the occurrence of urinary stones. This could be easily achieved by using a dipstick for self-feedback along with appropriate fluid intake. For persons with SCI who are at an increased risk of a devastating stone disease, this prophylactic approach could be very cost-effective; however, this requires further confirmation.

Adult↗
PubMed2001

Epidemiology of extraspinal fractures associated with acute spinal cord injury.

STUDY DESIGN: A descriptive study of concurrent extraspinal fractures collected prospectively during initial hospital care. OBJECTIVES: To examine the frequency and related characteristics of concurrent extraspinal fractures among patients with a new onset of spinal cord injury (SCI). SETTING: Model SCI care systems throughout the United States. METHODS: A consecutive sample of 5711 subjects admitted to the National SCI Database between 1986-1995 was recruited to estimate the incidence of extraspinal fractures associated with acute SCI, stratified by anatomic sites, demographics, and injury related characteristics. RESULTS: Of 5711 subjects, 1585 (28%) patients had extraspinal fractures; 580 (37%) patients had more than one fracture site. The most common region of fractures was chest, followed by lower extremity, upper extremity, head, others, and pelvis. The overall incidence rate was higher for women than men, for whites than non-whites, for paraplegics than tetraplegics, and for those injured in motor vehicle crashes than others. Compared with patients having single fracture, those who had multiple fractures were likely to be white, paraplegic, and injured in motor vehicle crashes. There was no age difference in the incidence of concurrent fractures, single or multiple. CONCLUSIONS: Extraspinal fractures are not uncommon at the same time as SCI. The fracture occurrence varies by gender, race, injury level, and etiology of injury. The knowledge of these associated factors will aid in early recognition of fractures, preventing complications, and facilitating rapid mobilization and rehabilitation outcomes among persons with SCI.

Adolescent↗
PubMed2001

Feasibility and clinical significance of real-time quantitative RT-PCR assay of PML-RARalpha fusion transcript in patients with acute promyelocytic leukemia.

INTRODUCTION: To study the relationship between the expression level of the PML-RARalpha fusion transcripts and the clinical status and efficiency of the therapy in acute promyelocytic leukemia (APL) patients, we applied a very sensitive and specific real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) system to quantify the dose of PML-RARalpha fusion transcripts in a series of APL patients at distinct disease stages. MATERIALS AND METHODS: A total of 31 APL patients (19 males and 12 females; aged from 8 to 74 years) from eight hospitals in Shanghai were analysed. Real-time Quantitative RT-PCR was used to measure the normalized dose (DoseN) of PML-RARalpha fusion transcripts. RESULTS: A wide range of PML-RARalpha DoseN above 1 x 10(3) was noted in 25 newly diagnosed patients. PML-RARalpha DoseN was significantly decreased after remission induction with ATRA, ATRA/chemotherapy or As2O3 and further reduced after consolidation. The fact that all patients with long disease free survival had a constantly low PML-RARalpha DoseN below 2 x 10(2) and a higher level predicted impending relapse suggests that this value could serve as a 'threshold' for molecular remission. PML-RARalpha DoseN was also of prognostic value in a group of relapsed patients, since good response to As2O3 reinduction was accompanied by a remarkable reduction of fusion transcript level, whereas patients with high PML-RARalpha Dose(N) after the second CR tended to relapse again rapidly. CONCLUSION: These results confirm that real-time RT-PCR assay for PML-RARalpha transcripts in APL patients is useful in reflecting leukemic burden, assessing response to treatment and indicating the ultimate clinical outcome or curability of disease.

Adolescent↗
PubMed2001

Alzheimer's disease: dysfunction of a signalling pathway mediated by the amyloid precursor protein?

All individuals with Alzheimer's disease (AD) experience a progressive loss of cognitive function, resulting from a neurodegenerative process characterized by the deposition of beta-amyloid (A beta) in plaques and in the cerebrovasculature, and by the formation of neurofibrillary tangles in neurons. The cause of the neuronal death is unknown but it is thought to be linked in some way to the beta-amyloid precursor protein (APP), which is the source of the A beta that accumulates in the AD brain. There are two pieces of supporting data for this: first, APP is overexpressed in Down's syndrome, which leads to AD-like neuropathology by the age of 40 in virtually all affected individuals; secondly, specific point mutations in APP cause some forms of familial AD. Our laboratory has focused on a specific aspect of APP and its connection with the neuronal destruction seen in AD. We have hypothesized that AD results from a progressive dysfunction of APP. In addition, on the basis of recent data generated by our laboratory and others, we propose that in the normal brain a percentage of APP is present as an integral protein of the plasma membrane that mediates the transduction of extracellular signals into the cell via its A beta-containing C-terminal tail. In AD, accumulation of abnormal levels of the C-terminus in the neuron disturbs this signal-transduction function of APP, causing disorders in the cell-cycle machinery and consequent apoptosis. Here, we discuss the key findings that support this hypothesis, and discuss its therapeutic implications for AD.

Alzheimer Disease↗
PubMed2001

Acoustic comparison of vowel articulation in normal and reverse phonation.

Acoustic characteristics of the vowels /i,u,a/ produced by adult females and males during normal phonation were compared with the same vowels produced on deliberate ingressive airflow (i.e., "reverse" phonation). Results of the analysis revealed the average fundamental frequency (F0) of reverse phonation to be significantly higher than the corresponding normal phonations. There were no significant differences noted in the vocal tract resonance (F1 and F2 frequency) values for /i/ during normal and reverse phonation. However, the F1 values for /a/ were significantly lower, and the F2 values for /u/ significantly higher, during reverse phonation. The results are discussed with regard to differences in the articulatory control of the speech mechanism during reverse phonation as compared to normal expiratory phonation. Also discussed are the implications of using reverse phonation as a voice management technique.

Adult↗