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G Quinn

Publications and source records attributed to G Quinn.

At least 19 recordsLinked to original sources
PubMed2003

Structural and functional characteristics of a dominant-negative isoform of porcine MHC class II transactivator.

The MHC class II transactivator, CIITA, is critical for MHC class II gene expression in all species studied to date. We isolated an interferon (IFN)-gamma-inducible isoform of porcine CIITA (pCIITA') encoding a protein of 566 amino acids (aa) with significant homology to human CIITA (hCIITA). Analysis indicated that pCIITA' lacks the entire GTP-binding domain that is important for nuclear translocation and activation of target genes by hCIITA. In pCIITA' this region is replaced by a 14-aa motif with homology to several signalling peptide sequences. Expression of pCIITA' in porcine (ST-IOWA) and human (HeLa) cell lines resulted in suppression of IFN-gamma-stimulated MHC class II gene expression, at the protein and mRNA levels. We also identified two IFN-gamma-inducible variants of hCIITA, hCIITAlo and hCIITA' from Hela cells, both exhibiting dominant-negative suppression of MHC class II gene expression. Interestingly, hCIITA' encodes a predicted protein of 546 aa with a strikingly similar organization to pCIITA' including the 14-aa GTP-binding domain-replacement motif in which 10 out of 14 amino acids are identical to the pig sequence. Expression of hCIITA' and hCIITAlo sequences in Hela cells suppressed IFN-gamma-induced MHC class II gene expression. hCIITAlo, a predicted 303-aa protein with deleted GTP-binding and carboxy-terminal domain, displayed a more subtle suppression of IFN-gamma-induced MHC class II expression. These in vitro data indicate that there may be a role in vivo for isoforms of CIITA that can suppress full-length CIITA-mediated MHC class II gene expression. Both humans and now, potentially, pigs are candidate donors for organ and tissue allografts and xenografts, respectively. Regulation of MHC class II gene expression by manipulation of CIITA isoform expression in humans and pigs may provide a useful strategy for attenuation of T-cell-mediated cellular rejection.

Amino Acid Sequence↗
PubMed2001

The porcine endogenous retrovirus long terminal repeat contains a single nucleotide polymorphism that confers distinct differences in estrogen receptor binding affinity between PERV A and PERV B/C subtypes.

Porcine endogenous retroviruses (PERV) have been shown to have zoonotic potential, both in vitro and in vivo. Once integrated into the host cell genome activation of the proviral genes is ultimately dependent upon transactivation of the long terminal repeat (LTR). Currently there is no direct evidence of host cell transcription factors interacting with PERV LTRs. Using comparative genomics we discovered a potentially functional single nucleotide polymorphism (SNP) within the U5 region downstream of the TATA box in the PERV LTR that distinguishes PERV A from PERV B and PERV C subtypes. We demonstrated that the SNP occurs within a potential hormone-responsive region where it has a profound effect, not only upon estrogen receptor binding but also upon the binding of other transcription factors at this site. These results suggest that differences in transcriptional regulation between PERV subtypes are subtle and, as for other retroviruses, transcription can be mediated by steroid hormone receptors.

Animals↗
PubMed2001

Mapping full-length porcine endogenous retroviruses in a large white pig.

Xenotransplantation may bridge the widening gap between the shortage of donor organs and the increasing number of patients waiting for transplantation. However, a major safety issue is the potential cross-species transmission of porcine endogenous retroviruses (PERV). This problem could be resolved if it is possible to produce pigs that do not contain replication-competent copies of this virus. In order to determine the feasibility of this, we have determined the number of potentially replication-competent full-length PERV proviruses and obtained data on their integration sites within the porcine genome. We have screened genomic DNA libraries from a Large White pig for potentially intact proviruses. We identified six unique PERV B proviruses that were apparently intact in all three genes, while the majority of isolated proviruses were defective in one or more genes. No intact PERV A proviruses were found in this pig, despite the identification of multiple defective A proviruses. Genotyping of 30 unrelated pigs for these unique proviruses showed a heterogeneous distribution. Two proviruses were uncommon, present in 7 of 30 and 3 of 30 pigs, while three were each present in 24 of 30 pigs, and one was present in 30 of 30 animals examined. Our data indicate that few PERV proviruses in Large White pigs are capable of productive infection and suggest that many could be removed by selective breeding. Further studies are required to determine if all potentially functional proviruses could be removed by breeding or whether gene knockout techniques will be required to remove the residuum.

Amino Acid Sequence↗
PubMed2001

In vitro models to study cellular differentiation and function in human prostate cancers.

In Vitro Models to Study Cellular Differentiation and Function in Human Prostate Cancers. To augment the currently available models of human prostate cancer in vitro, we have established extended life-span epithelial cultures from biopsies of well-differentiated prostate cancers. The genetic identity of the target cells was assessed by allelotyping, using microsatellites located on chromosome 8p, and microdissection of tissues and primary cell cultures. Cells with an extended life span (PxE6) were derived by recombinant retrovirus infection to introduce the human papilloma virus E6 gene (epithelial cells). Immunophenotyping of the resultant cell strains confirmed retention of differentiated cell functions, and the genotype of the E6-expressing epithelial cells was stable, while SV40-immortalized cultures were more unstable, leading to tetraploidy. All PxE6 cells eventually senesced, but an immortalized epithelial culture, P4E6, was derived from one of the epithelial cultures. The properties of this cell line, which remains close to diploid, are similar to those of early prostate cancer cells, and it retains expression of many prostate-associated antigens, such as prostate-specific antigen (PSA).

Allelic Imbalance↗
PubMed2000

Mouse flt-1 promoter directs endothelial-specific expression in the embyroid body model of embryogenesis.

The endothelial-specific receptor tyrosine kinase flt-1 (VEGFR-1) is expressed early on during endothelial lineage commitment both in vivo and in vitro. However, the exact function of flt-1 in vascular development still remains unclear. Here we report that a 2.2-kb fragment 5' of the mouse flt-1 gene becomes transcriptionally active during endothelial cell differentiation in developing embryoid bodies derived from mouse ES cells. Reporter gene expression correlated well with PECAM-1 expression and mirrored the expression pattern of the endogenous flt-1 gene. The temporal and spatial activity of the 2.2-kb flt-1 promoter provides a means to (1) identify a living population of early committed endothelial/bipotential progenitors and (2) ectopically express biologically active genes during lineage commitment.

Alternative Splicing↗
PubMed2000

PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression.

Prostate cancer, the most frequent solid cancer in older men, is a leading cause of cancer deaths. Although proliferation and differentiation of normal prostate epithelia and the initial growth of prostate cancer cells are androgen-dependent, prostate cancers ultimately become androgen-independent and refractory to hormone therapy. The prostate-specific antigen (PSA) gene has been widely used as a diagnostic indicator for androgen-dependent and -independent prostate cancer. Androgen-induced and prostate epithelium-specific PSA expression is regulated by a proximal promoter and an upstream enhancer via several androgen receptor binding sites. However, little progress has been made in identifying androgen-independent regulatory elements involved in PSA gene regulation. We report the isolation of a novel, prostate epithelium-specific Ets transcription factor, PDEF (prostate-derived Ets factor), that among the Ets family uniquely prefers binding to a GGAT rather than a GGAA core. PDEF acts as an androgen-independent transcriptional activator of the PSA promoter. PDEF also directly interacts with the DNA binding domain of androgen receptor and enhances androgen-mediated activation of the PSA promoter. Our results, as well as the critical roles of other Ets factors in cellular differentiation and tumorigenesis, strongly suggest that PDEF is an important regulator of prostate gland and/or prostate cancer development.

Amino Acid Sequence↗
PubMed1999

Reply

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Journal Article↗
PubMed1999

Developing protein documentaries and other multimedia presentations for molecular biology.

Computer-based multimedia technology for distance learning and research has come of age--the price point is acceptable, domain experts using off-the-shelf software can prepare compelling materials, and the material can be efficiently delivered via the Internet to a large audience. While not presenting any new scientific results, this paper outlines experiences with a variety of commercial and free software tools and the associated protocols we have used to prepare protein documentaries and other multimedia presentations relevant to molecular biology. A protein documentary is defined here as a description of the relationship between structure and function in a single protein or in a related family of proteins. A description using text and images which is further enhanced by the use of sound and interactive graphics. Examples of documentaries prepared to describe cAMP dependent protein kinase, the founding structural member of the protein kinase family for which there is now over 40 structures can be found at http://franklin.burnham-inst.org/rcsb. A variety of other prototype multimedia presentations for molecular biology described in this paper can be found at http://fraklin.burnham-inst.org.

Computer-Assisted Instruction↗
PubMed1999

Control of fine particulate (PM2.5) emissions from restaurant operations.

This paper describes efforts to reduce particulate matter (PM) emissions from restaurant operations, including application of an existing control method to a new equipment type. Commercial charbroiling in the South Coast Air Basin results in emissions of approximately 10 tons/day of fine particulate matter (PM2.5) and 1.3 tons/day of volatile organic compounds (VOCs). Over a seven-year period, the South Coast Air Quality Management District worked with industry to develop test methods for measuring emissions from various cooking operations, evaluate control technologies, and develop a rule to reduce these emissions. Of the two basic types of charbroilers--chain-driven and underfired--underfired produce four times the emissions when equivalent amounts of product are cooked. Cost-effective control technology is currently available only for chain-driven charbroilers. The application of flameless catalytic oxidizers to chain-driven charbroilers was found to effectively reduce emissions by at least 83% and is cost-effective. The catalysts have been used worldwide at restaurants for several years. Research efforts are underway to identify control options for underfired charbroilers. Implementation of Rule 1138, Control of Emissions from Restaurant Operations, adopted November 14, 1997, will result in reductions of 0.5 tons/day of PM2.5 and 0.2 tons/day of VOCs. Future rules will result in reductions from underfired charbroilers and possibly other restaurant equipment when cost-effective solutions are available.

Air Pollution↗
PubMed1997

Benazepril, an angiotensin converting enzyme inhibitor: drug interaction with salbutamol and bronchial response to histamine in normal subjects.

AIMS: To investigate the effect of the angiotensin converting enzyme inhibitor, benazepril, on pulmonary function. METHODS: We investigated the influence of benazepril, on lung function and the interaction with inhaled salbutamol (0.1 to 6.6 mg) and histamine (0.03 to 30.69 g l-1) in normal subjects. Benazepril 20 mg, salbutamol 8 mg, propranolol 160 mg, and placebo were given orally once daily over 10 days. RESULTS: On day 8, there was no difference in the area under the salbutamol dose-response curves between benazepril, placebo and oral salbutamol (P > 0.05), propranolol shifted the curves to the right (P < 0.05). On day 10, histamine challenge resulted in following PD35sGaw values (geometric mean and 95% CI): with placebo 1.02 (0.95-1.09) g l-1, benazepril 1.04 (0.99-1.08), salbutamol 1.19 (1.13-1.25), propranolol 0.57 (0.50-0.65). CONCLUSIONS: Benazepril had no influence on baseline lung function, caused no interaction with inhaled salbutamol and the bronchial response to histamine was similar to placebo. However, our findings in normal subjects cannot be extrapolated automatically to asthmatics.

Adult↗
PubMed1996

The human placenta expresses transcription enhancer factor-1 but there is no correlation with the expression of placental lactogen.

A transcriptional enhancer which has a consensus binding sequence for transcription enhancer factor-1 (TEF-1) has been found 3' of the hPL(3) gene. We examined whether TEF-1 is expressed by the human placenta and whether such expression is co-ordinated with that of human placental lactogen (hPL). Probing Northern blots of total RNA from first trimester and term placenta, the choriocarcinoma-derived cell line JAr and primary cultured cytotrophoblast cells with a cDNA for TEF-1 revealed transcripts of 12-13 kb and 3-4 kb. The level of TEF-1 expression was the same in first trimester as compared with term placenta and in undifferentiated JAr as compared with differentiated cytotrophoblast cells. hPL expression was tenfold higher in term compared with first trimester placenta and, whilst detectable in cytotrophoblast cells, was undetectable in JAr cells. These data show that TEF-1 is expressed by the placenta but is not co-ordinated with hPL expression.

Cell Differentiation↗
PubMed1994

Dental health. 2. Working together in dental health education.

Dental caries affects three quarters of five-year old children in Northern Ireland. It should be seen as a priority target for health education and health promotion initiatives, argue Grainne Quinn and Ruth Freeman. A study to investigate co-operation between health visitors and community dental officers demonstrates the importance of the frequent sharing of knowledge and expertise between the two professionals in the promotion of dental health.

Community Dentistry↗
PubMed1990

Systemic complications associated with retinal cryoablation for retinopathy of prematurity.

Eighty infants with proliferative retinopathy of prematurity (ROP) were treated with peripheral retinal cryoablation. Among the serious systemic complications encountered were three instances of respiratory arrest and one of cardiorespiratory arrest. Recommendations that may help prevent these adverse systemic effects in premature infants include: (1) avoidance of excess subconjunctival anesthetic doses, (2) preoperative administration of systemic atropine to minimize the oculocardiac reflex, (3) consideration of an analgesic agent to decrease the pain and exhaustion, and (4) cardiorespiratory monitoring in a hospital setting, with an intravenous line in place, at the time of treatment.

Anesthetics↗
PubMed1990

Medico-legal aspects of cross infection: dental scenario.

The epidemiology of Hepatitis B infection is used to show that dental health care workers are at greater risk of acquiring serious infective diseases than is the population at large. The significance of this greater risk is that dental employers must take the proper steps to protect their employees' health. A five fold strategy is put forward to achieve this end. The law governing a (dental) employer's duty in this regard is examined. Failure to take appropriate action leaves the dental employer open to legal action in the event that an employee acquires a serious infection in the course of his work. The similarity is stressed between Irish and British law in protecting the needs of authority and established bodies such as for instance the dental profession. However, the developments in Irish law are mentioned which show that following established practice in a profession does not guarantee protection from legal suit.

Cross Infection↗
PubMed1990

Early results of combined electrohydraulic shock-wave lithotripsy and oral litholytic therapy of gallbladder stones at the University of Iowa.

One hundred thirty-three patients were entered into a randomized, double-blind, placebo-controlled trial of extracorporeal shock-wave lithotripsy for symptomatic gallstones versus extracorporeal shock-wave lithotripsy plus adjuvant litholytic therapy with ursodeoxycholic acid (UDCA). Six months after lithotripsy, patients receiving placebo were crossed over to UDCA therapy without unblinding the study. One hundred sixteen patients have completed 6 months of follow-up. Five patients were dropped from the study. Nine percent have required cholecystectomy (11 patients with biliary colic and 1 with acute cholecystitis). Ninety-one patients had a solitary stone (64 patients had stones less than or equal to 20 mm and 27 patients had stones greater than 20 mm in diameter), and 25 patients had two to three stones. Fifty percent were retreated. Cumulative stone-free rates at 6, 12, and 18 months were 26%, 39%, and 41%, respectively. At 6 months there was a significant advantage for patients treated with UDCA versus placebo (36% vs 17% were stone free) that had disappeared by 12 months (placebo-treated patients had received 6 months of UDCA). Patients with solitary stones equal to or less than 20 mm in diameter treated with UDCA had stone-free rates at 6, 12, and 18 months of 58%, 58%, and 62%, respectively, versus 27%, 56%, and 50%. The difference was significant only at the 6- month follow-up. Stone-free rates for patients with large solitary stones and multiple stones were very low. Extracorporeal shock-wave lithotripsy is both safe and effective therapy for treatment of symptomatic gallstones in patients with a solitary stone equal to or less than 20 mm in diameter. UDCA markedly improves the efficiency of the procedure and results in a stone-free gallbladder sooner.

Administration, Oral↗