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M McCartney

Publications and source records attributed to M McCartney.

At least 19 recordsLinked to original sources
PubMed2001

A model of activation of the protein tyrosine phosphatase SHP-2 by the human leptin receptor.

Signalling through the leptin receptor has been shown to activate the SH2 domain-containing tyrosine phosphatase SHP-2 through tyrosine phosphorylation. The human leptin receptor contains five tyrosine residues in the cytoplasmic domain that may become phosphorylated. We show here using BIAcore studies, wherein binding of peptides to SHP-2 was detected, that peptides corresponding to sequences containing phosphotyrosines 974 and 986 (LR974P and LR986P, respectively) from the leptin receptor cytoplasmic domain were the only two peptides that bound to the enzyme. Binding of LR974P to SHP-2 was inhibited in a dose-dependent fashion by orthovanadate, whereas binding of LY986P was not, indicating that the enzyme binds to these peptides through different sites. Only the leptin receptor-derived peptide corresponding to tyrosine 974 was dephosphorylated by recombinant purified SHP-2. Time courses of the reaction were complex, and fitted a two exponent rate equation. Preincubation of SHP-2 with LR986P markedly activated the enzyme at early time points and time courses of the activated enzyme fitted a single exponential first order rate equation. We propose that LR974P binds to the active site of SHP-2, whereas LR986P may bind to the N- and C-terminal SH2 domains of SHP-2, thus activating the phosphatase activity. These data support a model in which SHP-2 binds to phosphotyrosine 986 in the activated leptin receptor and is activated to dephosphorylate phosphotyrosine 974, downregulating signalling events emanating from SH2 domain-containing proteins that bind here.

Binding Sites↗
PubMed2000

Quantitative phase-sensitive imaging in a transmission electron microscope

This paper presents a new technique for forming quantitative phase and amplitude electron images applicable to a conventional transmission electron microscope. With magnetised cobalt microstructures used as a test object, we use electron holography to obtain an independent measurement of the phase shift. After a suitable calibration of the microscope, we obtain quantitative agreement of the phase shift imposed on the 200 keV electrons passing through the sample.

Journal Article↗
PubMed2000

Linkage analysis of candidate genes as susceptibility loci for osteoarthritis-suggestive linkage of COL9A1 to female hip osteoarthritis.

OBJECTIVE: To examine 11 candidate genes as susceptibility loci for osteoarthritis (OA). METHODS: A total of 481 families have been ascertained in which at least two siblings have had joint replacement surgery of the hip, or knee, or hip and knee for idiopathic OA. Each candidate gene was targeted using one or more intragenic or closely linked microsatellite marker. The linkage data were analysed unstratified and following stratification by sex and by joint replaced (hip or knee). RESULTS: The analyses revealed suggestive linkage of the type IX collagen gene COL9A1 (6q12-q13) to a subset of 132 families that contained affected females who were concordant for hip OA (female-hip) with a P-value of 0.00053 and logarithm of the odds (LOD) score of 2.33 [corrected P-value of 0. 0016, corrected LOD score of 1.85]. CONCLUSIONS: COL9A1 may therefore be a susceptibility locus for female hip OA. In addition, there was weak evidence of linkage to HLA/COL11A2 (6p21.3) in female hip OA with a corrected P-value of 0.016.

Arthroplasty, Replacement↗
PubMed2000

Linkage analysis of chromosome 2q in osteoarthritis.

BACKGROUND: In independent linkage studies chromosome 2q11-q24 and chromosome 2q23-35 have previously been implicated as regions potentially harbouring susceptibility loci for osteoarthritis (OA). OBJECTIVE: To test chromosome 2q for linkage to idiopathic osteoarthritis. METHODS: Using a cohort of 481 OA families that each contained at least one affected sibling pair with severe end-stage disease (ascertained by hip or knee joint replacement surgery), we conducted a linkage analysis of chromosome 2q using 16 polymorphic microsatellite markers at an average spacing of one marker every 8.5 cM. RESULTS: Our results provide suggestive evidence for a locus at 2q31 with a maximum multipoint logarithm of the odds score (MLS) of 1.22 which increased to 2.19 in those families concordant for hip-only disease (n = 311). This suggestive linkage was greater in male-hip families (MLS = 1.57, n = 71) than in female-hip families (MLS = 0.71, n = 132). CONCLUSIONS: Chromosome 2q is likely to contain at least one susceptibility locus for OA.

Adult↗
PubMed1999

Evaluation of the feasibility and use of a prototype remote drug delivery capsule (RDDC) for non-invasive regional drug absorption studies in the GI tract of man and beagle dog.

PURPOSE: Evaluate a prototype Remote Drug Delivery Capsule (RDDC) for use in beagle dogs and human volunteers for non-invasive drug absorption studies in different regions of the gastrointestinal tract. METHODS: The device was dual radiolabeled and GI transit of the RDDC was monitored by gamma scintigraphy. Beagles were used initially to demonstrate the functional utility of the device where a solution of ranitidine hydrochloride (150 mg) was non-invasively delivered to the stomach, proximal small intestine and distal small intestine. A subsequent first time in human study enrolled twelve healthy male volunteers where the intended site of release was the stomach, early small bowel, distal small bowel or colon. RESULTS: Preliminary studies conducted in beagles indicated that the RDDC operated successfully and the onset of ranitidine serum levels were dependent on the time of capsule activation and site of drug release. Results from the human study showed that all twelve subjects swallowed the device with no discomfort. Mean gastric emptying of the RDDC was 1.50 +/- 1.28 h (range = 0.25 to 4.25 h), and total small intestine transit was 4.79 +/- 1.82 h (range = 2.00 to 8.25 h). The capsule was retrieved from the feces at 30.25 +/- 15.21 h (range = 14.12 to 74.25 h) and there were no reported adverse events. The prototype RDDC operated successfully in nine of the twelve human volunteers and the cause for the three failures was attributed to mechanical failure while the electronics assembly performed favorably. CONCLUSIONS: This prototype remote control capsule was shown to be well tolerated and functional to use in human volunteers as well as beagles. The application of the device coupled with gamma scintigraphy has the potential to be a valuable and rapid method to non-invasively evaluate regional drug absorption in the gastrointestinal tract under conditions that are both pharmaceutically and physiologically meaningful.

Adult↗
PubMed1999

Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage.

We present a two-stage genomewide scan for osteoarthritis-susceptibility loci, using 481 families that each contain at least one affected sibling pair. The first stage, with 272 microsatellite markers and 297 families, involved a sparse map covering 23 chromosomes at intervals of approximately 15 cM. Sixteen markers that showed evidence of linkage at nominal P</=.05 were then taken through to the second stage, with an additional 184 families. This second stage confirmed evidence of linkage for markers on chromosome 11q. Additional markers from this region were then typed to create a denser map. We obtained a maximum single-point LOD score, at D11S901, of 2.40 (P=.0004) and a maximum multipoint-LOD score of 3.15, between markers D11S1358 and D11S35. A subset of 196 of the 481 families, comprising affected female sibling pairs, generated a corrected LOD score of 2.54 (P=.0003) for marker D11S901, with evidence for linkage extending 12 cM proximal to this marker. When we stratified for affected male sibling pairs there was no evidence of linkage to chromosome 11. Our data suggest that a female-specific susceptibility gene for idiopathic osteoarthritis is located on chromosome 11q.

Arthroplasty, Replacement↗
PubMed1997

An outbreak of Salmonella enteritidis phage type 4 infection in a rural community in Northern Ireland.

An outbreak of gastroenteritis arose in people who attended a charity barbecue at a hotel in a rural area of Northern Ireland in July 1995. About 120 people attended the barbecue, 98 of whom were identified. Fifty-one of them and seven members of hotel staff met the case definition. An epidemiological investigation showed that illness was significantly associated with eating foods containing mayonnaise that had been prepared using raw shell eggs and stored at too high a temperature. Salmonella enteritidis phage type 4 was cultured from 17 out of 24 faecal specimens received from people who attended the barbecue and in 17 out of 34 faecal specimens from staff, including all seven staff cases. The primary source of infection was not identified despite thorough investigation. This paper highlights the value of administering questionnaires by telephone when investigating community outbreaks of infection in rural areas, the important role of general practitioners in the identification of community outbreaks, and the need to periodically reiterate public health messages, in particular for food handlers and caterers.

Bacteriophage Typing↗
PubMed1997

Autoimmune hepatitis in childhood: a 20-year experience.

To determine the clinical, biochemical, and histological features, and outcome of childhood autoimmune hepatitis (AIH), we reviewed the medical records of 52 children with AIH, 32 (median age: 10 [2-15] years) anti-nuclear and/or smooth muscle antibody (ANA/SMA) positive, 20 (7 [0.8-14] years) liver/kidney microsomal antibody (LKM-1) positive, with median follow-up of 5 years (range 0.3-19). At presentation: 56% had symptoms of prolonged acute hepatitis; LKM-1 positive were younger (P = .011), with higher bilirubin (P = .007), and AST (P = .047); ANA/SMA positive had lower albumin (P = .023); 69% ANA/SMA positive, and 38% LKM-1 positive were cirrhotic (P = .080). ANA/SMA positive had increased frequency of HLA haplotype A1/B8/DR3/DR52a compared with controls (53% vs. 14%, P < .001). Of six (5 LKM-1 positive) with fulminant hepatitis, four were transplanted, one died, and one ANA/SMA positive improved with immunosuppression. Of 47 treated with immunosuppression, 2 (1 LKM-1 positive) died with no remission and 4 (2 LKM-1 positive) were transplanted 8 to 14 years after diagnosis. Immunosuppression was stopped successfully in 19% of ANA/SMA positive after a median of 3 years of treatment, but in none of LKM-1 positive. Baseline bilirubin and international normalized prothrombin ratio (INR) were independent variables predictive of outcome. In conclusion, ANA/SMA positive and LKM-1 positive AIH in childhood have clinical, biochemical, and histological differences, but similar severity and long-term outcome.

Adolescent↗
PubMed1993

Oligodendroglioma. The Princess Margaret Hospital experience (1958-1984).

BACKGROUND: Oligodendrogliomas are rare central nervous system (CNS) tumors. Although surgery remains the primary treatment, the role of postoperative radiation treatment remains a matter of controversy. This study assesses whether postoperative radiation improves survival and local tumor control when compared with surgical treatment alone. METHODS: The medical records of 72 patients with the diagnosis of oligodendroglioma, registered at the Princess Margaret Hospital (PMH) between 1958 and 1984, were reviewed retrospectively. The data of 68 patients were evaluated, but 4 patients were excluded from the analysis because of inadequate follow-up. The median follow-up period at the time of analysis was 7.5 years. Tumors were classified as oligodendrogliomas, malignant oligodendrogliomas, or mixed oligoastrocytomas. Fifty-eight (85%) patients received postoperative irradiation at initial diagnosis, and 10 (15%) patients were treated with surgery alone. In most patients (76%), the radiation dose was 5000 cGy in 25 fractions given during a period of 5 weeks. RESULTS: Five- and 10-year overall survival was 66% and 30%, respectively. Forty-two (62.0%) patients experienced disease relapse during the follow-up period. The median time to relapse from initial diagnosis was 2.6 years. Most tumor recurrences were at the primary site. Two patients developed distant metastasis within the CNS axis. Histologic subtype was the only significant prognostic factor for survival. The patients with oligodendroglioma and malignant oligodendroglioma had 5-year survival rates of 73% and 32%, respectively (P = 0.033). CONCLUSIONS: The authors drew three conclusions. (1) Most patients eventually died with this tumor from local recurrence without distant metastasis. Local tumor control remains the major problem. (2) Tumor histologic subtype is a significant prognostic factor. (3) No statistically significant benefit can be attributed to postoperative irradiation; however, the number of patients not receiving radiation therapy was small (10). Thus, the role of radiation therapy remains a matter of controversy.

Adult↗
PubMed1989

Examining nursing personnel costs: controlled versus noncontrolled oral analgesic agents.

To date, few evaluations have focused on nursing personnel costs generated by practices of other clinicians. The authors used traditional industrial engineering and cost accounting techniques to determine nursing personnel costs generated by the use of controlled versus noncontrolled oral analgesic agents. The findings indicate that additional nursing labor costs are generated for drug administration and inventory activities for controlled agents when compared with noncontrolled agents. On an annual basis, the additional costs for drug administration generate approximately +34,000 in hospital expenses for the three nursing units included in this evaluation. This type of interdisciplinary investigation may be valuable as nursing departments face increasing pressures to decrease costs by reducing overtime and eliminating positions.

Algorithms↗
PubMed1985

Carcinogenic N-hydroxylaminopurine derivatives do not act as base analog mutagens in Salmonella typhimurium.

N-Hydroxylaminopurines are highly mutagenic for growing as well as resting Salmonella typhimurium strain TA100 and to a lesser extent for strain TA98. Aminopurines, under similar conditions, are not mutagenic. N-Methylhydroxylaminopurine, under similar conditions, exhibits only minimal activity. The results are taken to indicate that unlike non-hydroxylated aminopurines, N-hydroxylaminopurines exert their mutagenicity not by acting as base analogs but by direct covalent binding with DNA-guanine.

Adenine↗