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G Stewart

Publications and source records attributed to G Stewart.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphisms within the CTLA4 gene are associated with infant atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is one of the most common childhood disorders. It can have a significant impact on the physical and psychological well-being of affected individuals. Although environmental triggers are important, AD also has a strong genetic component. Identifying genes associated with AD may help to understand better the basis of this disorder and its relationship with other allergic disorders such as asthma. OBJECTIVES: Polymorphisms in the gene encoding the inhibitory CTLA4 receptor, an important regulator of T cells, are associated with asthma as well as autoimmune disorders. We have now tested whether polymorphisms in the CTLA4 gene are also associated with early childhood AD. METHODS: A family-based cohort of 112 children and their parents was recruited from Western Sydney, Australia. All children were seen by a paediatric dermatologist and presented with AD within the first 3 years of life. Using the transmission disequilibrium test, individual and haplotypic associations with the +49 and CT60 polymorphisms in exon 1 and the 3' nontranslated DNA of the CTLA4 gene were tested. RESULTS: Single tests of association revealed significant association of the +49(A) [P = 0.037, odds ratio (OR) 1.59, 95% confidence interval (CI) 1-2.55] and borderline significance of the CT60(A) alleles (P = 0.055, OR 1.51, 95% CI 1-2.38). Significant association of the +49(A)/CT60(A) haplotype was detected (P = 0.002, OR 1.78, 95% CI 1.2-2.65). CONCLUSIONS: Polymorphisms within the gene encoding CTLA4 were associated with early onset infant AD. This is in agreement with findings from asthmatic cohorts, suggesting that the +49(A)/CT60(A) haplotype is a genetic risk factor common to asthma and AD.

Adolescent↗
PubMed2005

Preoperative radiotherapy for esophageal carcinoma.

BACKGROUND: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. OBJECTIVES: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy SEARCH STRATEGY: MEDLINE and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. The search strategy was run again in MEDLINE, EMBASE and the Cochrane Library on 30th April 2001, two years after original publication. No new trials were found. The search strategy was re-run August 2002 and August 2003 on MEDLINE, EMBASE , CancerLit and The Cochrane Library, and July 2004 and 2005 on MEDLINE, EMBASE and the Cochrane Library. No new relevant trials were identified on any of these occasions. SELECTION CRITERIA: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. MAIN RESULTS: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. AUTHORS' CONCLUSIONS: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Esophageal Neoplasms↗
PubMed2005

Increased risk of hemorrhagic complications in renal allograft recipients receiving systemic heparin early posttransplantation.

UNLABELLED: The aim of this paper is to document the risk of hemorrhagic complications in renal allograft recipients requiring systemic heparinisation within the first 2 weeks posttransplantation. METHODS: A retrospective chart review of 326 RA recipients from January 1998 to July 2003 was subjected to statistics by SPIDA with P values <.05 considered significant. RESULTS: 16/326 (4.9%) recipients were initiated on intravenous (IV) heparin within the study period. Enoxaparin was subsequently used in 10/16 (62.5%) of these recipients. Intravenous heparin was instituted at a median 8 (1-14) days posttransplantation. Hemorrhagic complications occurred in 10/16 (62.5%) recipients on IV heparin versus 11/310 (3.5%) nonanticoagulated RA recipients (P = .0001). Hemorrhage occurred at a mean 9.75 (2-43) days into the course of IV heparin. The median peak APTT 24 hours prior to hemorrhage in RA recipients on heparin was 68.5 (58-180) versus a median peak APTT of 70 (50-140) among recipients on heparin who did not sustain a hemorrhagic complication (P = .30). A major intervention (predominantly surgery) was required in 6/16 (37%) recipients on IV heparin versus 7/310 (2.2%) nonheparinised RA recipients (P < .0001). Enoxaparin was instituted at a mean 22.5 (4-55) days posttransplantation. Delayed hemorrhage subsequently occurred in 4/10 (40%) recipients on enoxaparin. In conclusion, major and minor hemorrhagic complications occur more commonly among recipients requiring early post transplant IV heparin. Hemorrhage occurred despite APTT monitoring with APTT levels tending to be similar in RA recipients with versus without complications. Delayed hemorrhage was also seen with the subsequent use of enoxaparin.

Anticoagulants↗
PubMed2005

Effects of immediate post-game recovery procedures on muscle soreness, power and flexiblity levels over the next 48 hours.

This study investigated whether or not immediate post-game recovery procedures could enhance the rate of recovery in Australian football players in the first 48 hr after a game. Control, stretch, pool walking and hot/cold recoveries were trialled. Typical next day recovery training (25 min of pool exercise) was also performed after each game. Muscle soreness ratings and measures of flexibility (sit and reach) and power (6-s cycling sprint and vertical jump) were obtained 45 hr pre-game (Thursdays) (baseline), 15 hr post-game (Sundays, prior to "next day" recovery) and 48 hr post-game (Mondays). Performance ratios (Sunday and Monday scores divided respectively by the Thursday score) were used as the primary index of recovery. Muscle soreness was significantly greater (p<0.01) than baseline on both Sunday and Monday in all conditions, but no differences between the three recoveries and control were evident. On Sunday, vertical jump and 6-s work and power scores were only significantly lower than baseline values in control and performance ratios recorded two significant differences (vertical jump: pool walking > control, p<0.01; 6-s power: stretch > control, p<0.01) and moderate to large effect sizes (>0.3). No differences were found between the three experimental recoveries. On Monday no significant differences were recorded in performance between the recoveries and the effect sizes were of lower magnitude. In conclusion, recovery of muscle soreness, flexibility and power at 48 hr post-game was not significantly enhanced by performing an immediate post-game recovery beyond that achieved by performing only next day recovery training.

Adult↗
PubMed2005

Physiological and anthropometric characteristics of starters and non-starters and playing positions in elite Australian Rules Football: a case study.

A purpose of this study was to determine if pre-season anthropometric and physiological measures were significantly different for the players from one Australian Football League (AFL) club selected to play in the first game of the season compared to the players not selected. Another purpose was to compare fitness test results for defenders, forwards and mid-fielders in the same AFL club. Thirty-four players were tested for isolated quadriceps and hamstrings strength, leg extensor muscle strength and power, upper body strength, sprinting speed, vertical jump (VJ), endurance, skinfolds and hamstring flexibility. The starters who were selected to play the first game were a significantly older and more experienced playing group, and were significantly better (p < 0.05) in measures of leg power, sprinting speed and the distance covered in the Yo Yo intermittent recovery test compared to the non-starters. Although there were trends for the superiority of the starters, the differences in lower and upper body strength, VJ and predicted VO2max were non-significant. The forwards generally produced the worst fitness scores of the playing positions with the midfielders having significantly lower skinfolds and the defenders possessing better hamstring strength and VJ compared to the forwards. It was concluded that some fitness qualities can differentiate between starters and non-starters, at least in one AFL club. Comparisons of playing positions and the development of fitness norms for AFL players require further research.

Adult↗
PubMed2005

Polymorphisms within the PHF11 gene at chromosome 13q14 are associated with childhood atopic dermatitis.

Atopic dermatitis is an increasingly common and debilitating childhood disorder that is often accompanied by asthma and allergic rhinitis. Although the pathology of these disorders is distinct, the majority of cases are atopic, typified by elevated serum IgE. A new locus at chromosome 13q14 centred on the genes SETDB2 and PHF11 and associated with increased total serum IgE has recently been identified. Although the precise functions of SETDB2 and PHF11 are not known, both proteins are expressed in cells of the immune system and include conserved domains that suggest a role in chromatin remodelling or transcriptional regulation, respectively. In a family-based association study across the SETDB2 and PHF11 genes, we have identified two single-nucleotide polymorphisms in the PHF11 gene significantly associated with childhood atopic dermatitis in an Australian cohort. These results provide further evidence that this locus is a novel and important regulator of human atopic disease.

Chromosomes, Human, Pair 13↗
PubMed2005

Evaluation of detection methods for genetically modified traits in genotypes resistant to European corn borer and herbicides.

Detection of genetically modified (GM) traits in corn (Zea mays L.) is urgently needed for preservation of genetic identity and marketing GM products. A laboratory study was conducted to evaluate the efficiency, accuracy, and reliability of different analytical methods to detect GM traits in corn. Samples with known fractions of GM concentrations (Bacillus thuringiensis [Bt], Liberty Link [LL] and stacked [Bt/LL] genes) from commercial seed companies and those derived from yellow kernels in a white corn ear, outcrossed by pollen of neighboring Bt hybrid, were tested by lateral flow quick test kits and by enzyme-linked immunosorbent assay (ELISA)-based test strips purchased from different companies. Liberty Link hybrids are resistant to glufosinate (Liberty or Basta) herbicides, whereas Bt corn is developed for the control of European corn borer (Ostrinia nubilalis). Selected samples of GM concentrations were also tested in a commercial laboratory using DNA-based polymerase chain reaction (PCR) test. The results demonstrated that qualitative lateral flow quick tests could detect samples containing 1% or higher Bt and 2% or higher LL concentrations within the recommended time limit of the test. Faint test lines for samples containing 0.5 to 1% Bt or 1 to 2% LL concentrations appeared if samples remained in the test cup overnight. ELISA test strips detected the Bt content semiquantitatively in the range of 0.5 to 2.0%. Grain samples derived from non-Bt corn outcrossed by neighboring Bt pollen had usually lower GM concentrations than commercial GM seed samples. Both ELISA- and DNA-based PCR tests distinguished samples with GM concentrations between 0.1 to 0.5%, but the precision of quantification at this range was very low and results were highly inconsistent.

Enzyme-Linked Immunosorbent Assay↗
PubMed2004

A case-control study of sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of clustering.

BACKGROUND: The authors investigated whether cases of sporadic Creutzfeldt-Jakob disease (CJD) had lived closer to one another at some time in life than individuals without sporadic CJD. Such a phenomenon would be compatible with some cases resulting from transmission. METHODS: UK sporadic CJD cases occurring from 1990 to 1998 were identified. Age-, sex- and hospital-matched controls were recruited. Lifetime residential histories were obtained by interview, usually with a proxy respondent. With use of Monte Carlo simulation, the residential proximity of cases during various time periods was compared with that expected in the absence of any clustering, using the information collected on the controls. RESULTS: Two hundred twenty sporadic CJD disease cases and 220 controls were included. Cases lived closer together than might be expected in the absence of any disease-clustering mechanism. This evidence became stronger as the critical period during which residential proximity was required to have occurred extended further into the past. CONCLUSIONS: These findings are consistent with some sporadic Creutzfeldt-Jakob disease (CJD) cases resulting from exposure to a common external factor. The rarity of sporadic CJD suggests that repeated point-source outbreaks of infection are more likely to explain our observations than direct case-to-case transmission. Identifying sources of such outbreaks many years after the event will be extremely difficult.

Adult↗
PubMed2004

Elderly patients with fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy.

Elderly patients are recommended to have a reduced starting dose (300 mg m(-2) once every 3 weeks) of irinotecan monotherapy. The aims of this analysis are to compare toxicity and survival according to age, performance status (PS), gender and prior radical pelvic radiotherapy (RT). The primary end points were overall survival and an irinotecan-specific toxicity composite end point (TCE) defined as the occurrence of grade 3 or 4 diarrhoea, neutropenia, febrile neutropenia, fever, infection or nausea and vomiting. Between 1997 and 2003, 339 eligible patients with advanced colorectal cancer (CRC) progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered in a multicentre randomised trial. All patients commenced irinotecan at 350 mg m(-2) once every 3 weeks. There were no differences in proportions of patients developing TCE by age (<70 vs > or =70 : 37.8 vs 45.8%; P=0.218), PS (0-1 vs 2 : 39.3 vs 41.5%; P=0.793) or prior RT (RT vs no RT : 45.1 vs 38.5%; P=0.377). Males experienced more toxicity than females (44.3 vs 32.6%; P=0.031), but this was not significant after controlling for other co-variates (P=0.06). Patients aged > or =70 had similar objective responses (11.1 vs 9%; P=0.585) and survival (median 9.4 vs 9 months; log rank P=0.74) compared to younger patients. Elderly patients derive the same benefit without experiencing more toxicity with second-line irinotecan treatment for advanced CRC. Our data do not support the recommendation to reduce the starting dose for the elderly patients.

Adult↗
PubMed2004

Player movement patterns and game activities in the Australian Football League.

In the Australian Football League (AFL), specific game movements and activities have not been studied since the 1970s and 1980s and the game is now much faster than it was 20-30 years ago. Using lapsed-time video analysis, AFL players from five different positions (full forward/full back, centre half forward/centre half back, small forward/small back, mid fielders and ruckmen) had their movement patterns (stand, walk, jog, fast-run, sprint, change of direction) and game activities (possessions, ruck duels, ground ball contests, shepherds, spoils, bumps and tackles) recorded in two games each in the 2000 season. A descriptive analysis of the results was undertaken. The main findings were: full forward/full back were most different from the other positions, as they were seen to stand more and jog and fast-run less: ruckmen and midfielders were involved in more game activities than the other positions; for all positions, there were more than 150 high intensity movements (fast-run plus sprint) in the game, but these accounted for only 4-6% of total movement time: virtually all of the high intensity movements lasted for <6 secs; more than half of all sprints involved at least one change of direction, mostly within the 0-90 degrees arc (left or right) and all ground ball contests took <6 secs, with midfielders having 2-3 times as many as the other positions. Improvements in specific pre-season and in-season training practices for different positions should be possible after careful interpretation of these findings.

Australia↗
PubMed2004

Comparison of training activities and game demands in the Australian Football League.

his paper serves as a companion to our recent study of the movement patterns and game activities of players (from five different positions) during matches in the 2000 Australian Football League season. Using lapsed-time video analysis, the same individual players (n= 11) as filmed in matches were also monitored during 21 in-season, main training sessions conducted by their clubs in order to assess the degree to which training activities matched game demands. In general, the training sessions did not involve physical pressure; therefore there were very few contested marks and ground balls or tackles, shepherds and spoils, thereby not matching these game demands. Players typically had more possessions (kicks and handballs) at training than in games. They also spent a greater percentage of total time standing and less time walking at training than in games. Fast-running and sprinting efforts at training were almost all for durations of <6 secs, which matched game demands, as did changes of direction when sprinting, which were almost all in a 0-90 degrees arc. However, across all players filmed, high intensity (fast-running and sprinting) movements were not performed as frequently at training (one every 76 secs) as in games (one every 51 secs). Therefore, while some game demands were adequately replicated at training, others were not closely simulated, suggesting that, after careful interpretation of these results, some improvements in training practices could be made.

Australia↗
PubMed2002

Active management of term prelabour rupture of membranes with oral misoprostol.

OBJECTIVE: To compare the active management of term prelabour rupture of membranes with oral misoprostol with conservative management for 24 hours followed by induction with oxytocin or prostaglandin E(2) (PGE(2)) gel. DESIGN: A non-blinded randomised controlled trial. SETTING: Induction and labour wards, Aberdeen Maternity Hospital. POPULATION: Sixty-one women with confirmed prelabour rupture of the membranes at > or =36 weeks of gestation. METHODS: The women were randomised to 50 microg of oral misoprostol repeated every 4 hours, if required, to a maximum of five doses (active group), or to induction of labour with PGE(2) gel or oxytocin only if not in spontaneous labour 24 hours after prelabour rupture of membranes (conservative group). MAIN OUTCOME MEASURES: Number of women in active labour within 24 hours of the prelabour rupture of membranes, preference of women for any one particular method of management in any subsequent pregnancy with prelabour rupture of membranes. RESULTS: 93.3% of the active group and 54.8% of the conservative group were in spontaneous labour within 24 hours of the prelabour rupture of membranes (RR 1.7, 95% CI 1.2 to 2.4). Of those achieving a vaginal delivery, 72% of the active group did so within 24 hours of the prelabour rupture of membranes as compared with 26.9% of the conservative group (RR 2.7, 95% CI 1.4 to 5.3, P = 0.002). There were no significant differences in the neonatal or maternal outcomes. In the active group, 78% felt they would have the same method of induction as compared with 40% in the conservative group (RR 1.9, 95% CI 1.1 to 3.3, P = 0.03). CONCLUSIONS: Active management with oral misoprostol resulted in more women going into labour and delivering within 24 hours of the prelabour rupture of membranes with no increase in maternal or neonatal complications. Women tended to view active management of prelabour rupture of membranes more positively. Oral misoprostol might be an option to consider in those wishing active management.

Administration, Oral↗
PubMed2002

Barmah-Millewa forest environmental water allocation.

The formal allocation of water for the environment is a developing area of river management both scientifically and in terms of community participation. This case study, illustrating the recent use of the Barmah-Millewa Forest Environmental Water Allocation (EWA), provides a practical demonstration of community participation in environmental water management, the application of hydrological and biological "triggers" and a positive, demonstrable biological outcome from an environmental water allocation. The Barmah-Millewa Forest covers an area of 70,000 ha across the floodplain of the Murray River, upstream of the town of Echuca. About half the forest is in NSW (Millewa) and half is in Victoria (Barmah). The Barmah Forest is a Wetland of International Importance listed under the Convention on Wetlands - Ramsar Convention. The forest is the largest river redgum forest in the world. The natural flooding cycle associated with the forest has been significantly altered by regulation of the Murray River--impacting upon the overall health of the forest ecosystem. Recognising this, the Murray Darling Basin Commission developed a water management strategy for the forest to enhance forest, fish and wildlife values. To implement this strategy, between 1990 and 1993 reports were completed and community consultation took place. In 1993 the Murray Darling Basin Ministerial Council approved allocation of 100 Gigalitres of water per year, provided in equal shares by NSW and Victoria, to meet the needs of the forest ecosystem and in 1994 the Barmah-Millewa Forum was established under the Murray-Darling Basin Agreement. The vision for the Forum is to maintain and, where possible, improve the ecological and productive sustainability of the Barmah-Millewa Forest and to establish a planning and operational framework to better meet the flooding and drying requirements of the riparian forests and wetlands. Between October 2000 and January 2001 the Barmah-Millewa Forest Environmental Water Allocation was used for the second time. A total of 341 GL was released as an EWA. This amount represented only 8% of the total flows downstream of Yarrawonga Weir from September 2000 and January 2001. The strategic use of the relatively small amount of water enabled flooding to be maintained and ensured significant breeding success for water birds and other biota in the Forest.

Australia↗
PubMed2001

p53 dysfunction in B-cell chronic lymphocytic leukemia: inactivation of ATM as an alternative to TP53 mutation.

The well-established association between TP53 mutations and adverse clinical outcome in a range of human cancers reflects the importance of p53 protein in regulating tumor-cell growth and survival. Although it is theoretically possible for p53 dysfunction to arise through mechanisms that do not involve TP53 mutation, such a phenomenon has not previously been demonstrated in a sporadic tumor. Here, we show that p53 dysfunction in B-cell chronic lymphocytic leukemia (CLL) can occur in the absence of TP53 mutation and that such dysfunction is associated with mutation of the gene encoding ATM, a kinase implicated in p53 activation. Forty-three patients with CLL were examined for p53 dysfunction, as detected by impaired up-regulation of p53 and of the p53-dependent protein p21(CIP1/WAF1) after exposure to ionizing radiation (IR). Thirty (70%) patients had normal p53 responses and underwent progressive IR-induced apoptosis. In 13 (30%) patients, p21 up-regulation was markedly impaired, indicating p53 dysfunction. Six (14%) of these patients with p53 dysfunction had increased baseline levels of p53, were found to have TP53 mutations, and were completely resistant to IR-induced apoptosis. In the other 7 (16%) patients with p53 dysfunction, IR-induced p53 up-regulation and apoptosis were markedly impaired, but baseline levels of p53 were not increased, and no TP53 mutations were detected. Each of these patients was found to have at least one ATM mutation, and a variable reduction in ATM protein was detected in all 4 patients examined. This is the first study to provide a direct demonstration that p53 dysfunction can arise in a sporadic tumor by a mechanism that does not involve TP53 mutation. (Blood. 2001;98:814-822)

Ataxia Telangiectasia Mutated Proteins↗
PubMed2001

Geographical distribution of variant Creutzfeldt-Jakob disease in Great Britain, 1994-2000.

BACKGROUND: Geographical variation in the distribution of variant Creutzfeldt-Jakob disease (vCJD) might indicate the transmission route of the infectious agent to man. We investigated whether regional incidences of vCJD were correlated with regional dietary data. METHODS: The National CJD Surveillance Unit prospectively identified 84 people with vCJD up to Nov 10, 2000, in Great Britain. Their lifetime residential histories were obtained by interviews with a close relative. Cumulative incidences of vCJD by standard region were calculated. Grid references for places of residence in 1991 were identified and evidence of geographical clusters were sought. Data on diet in the 1980s were analysed for regional correlations with vCJD incidence. The socioeconomic status of the places of residence of people with vCJD was compared with that of the general population. FINDINGS: vCJD incidence was higher in the north of Great Britain than the south. The rate ratio (north vs south) was 1.94 (95% CI 1.27-2.98). The mean Carstairs' deprivation score for areas of residence of people with vCJD was -0.09 (-0.73 to 0.55), which is close to the national average of zero. Regional rates of vCJD were correlated with consumption of other meat or meat products as classified and recorded by the Household Food Consumption and Expenditure Survey (r=0.72), but not with data from the Dietary and Nutritional Survey of British Adults. Five people with vCJD in Leicestershire formed a cluster (p=0.004). INTERPRETATION: Regional differences in vCJD incidence are unlikely to be due to ascertainment bias. We had difficulty determining whether regional variations in diet might cause these differences, since the results of dietary analyses were inconsistent.

Adult↗
PubMed2001

Characterization of the mouse metal-regulatory-element-binding proteins, metal element protein-1 and metal regulatory transcription factor-1.

Metal activation of metallothionein gene transcription depends mainly on the presence of regulatory DNA sequences termed metal-regulatory elements (MREs) and involves MRE-binding transcription factor-1 (MTF-1) interacting with the MREs in a Zn(2+)-dependent manner. We previously identified and characterized a nuclear protein, termed metal element protein-1 (MEP-1), specifically binding with high affinity to MRE elements. The precise relationship between MTF-1 and MEP-1 was unclear, and to determine whether MEP-1 and MTF-1 were distinct protein species, we performed DNA binding analyses to characterize the binding properties of both proteins. Electrophoretic mobility-shift assays showed that MTF-1, produced in COS cells, produces a slower-migrating band compared with that obtained with purified MEP-1. Using an anti-MTF-1 antibody, we showed that both the MTF-1-MRE and the MEP-1-MRE complexes are supershifted by an anti-MTF-1 antibody, thus demonstrating that MEP-1 is antigenically related to MTF-1. RNase protection analyses carried out with RNA prepared from different tissues and cell lines failed to reveal the presence of MTF-1 splicing variants. This indicates that MEP-1 may be a proteolytic fragment of MTF-1. MTF-1 DNA-binding activity was rapidly activated in vivo by Zn(2+) ions but not by Cd(2+), UV irradiation or PMA, and occurred on ice as well as at 21 degrees C. In control and Zn(2+)-treated cell extracts, DNA-binding activity was not enhanced in vitro following the addition of exogenous Zn(2+) or a preincubation at 37 degrees C. However, recombinant MTF-1 produced in vitro required Zn(2+) activation for DNA binding. Interestingly, treatment of nuclear extracts with calf intestine phosphatase completely abrogated MTF-1 DNA-binding activity, thus suggesting that phosphorylation is involved in the regulation of MTF-1 activity.

Animals↗