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E Mercer

Publications and source records attributed to E Mercer.

At least 19 recordsLinked to original sources
PubMed1998

EB1089, a synthetic analogue of vitamin D, induces apoptosis in breast cancer cells in vivo and in vitro.

1. Effects of the synthetic vitamin D analogue EB1089 on indices of apoptosis in cultured human breast cancer cells and in nitrosomethylurea-induced rat mammary tumours in vivo were investigated. 2. At a dose of 0.5 microg kg(-1) body weight, EB1089 caused significant inhibition of tumour progression over the 28 day treatment period in the absence of a significant increase in serum calcium concentration. Higher doses of EB1089 (1 and 2.5 microg kg(-1)) produced substantial regression of the experimental tumours which was accompanied by a striking change in the histological appearance of tumours consistent with induction of tumour cell death. 3. Fragmentation of genomic DNA is a characteristic feature of apoptosis. With the terminal transferase (TdT) assay, 3' DNA breaks indicative of DNA fragmentation were detected histochemically in mammary tumour cells from animals treated with EB1089 (2.5 microg kg(-1)) for 14 days. 4. Effects of the vitamin D analogue on induction of apoptosis were examined in vitro using the MCF-7 human breast cancer cell line. Using the TUNEL method, positive nuclear staining indicative of DNA fragmentation was detected in cells treated for 4 days with 10 nM EB1089. Apoptosis was also quantitated using a cell death ELISA which revealed a time and dose dependent induction of apoptosis by EB1089. 5. The effects of EB1089 on the expression of two oncoproteins which may regulate apoptosis, bcl-2 and bax were examined by Western analysis. In MCF-7 cell cultures treated with 1,25(OH)2D3 or EB1089 (1 x 10(-8) M), bcl-2 protein levels were decreased in a time-dependent manner relative to control levels. In contrast bax protein was not markedly regulated by these compounds. Densitometric analyses indicate that the vitamin D compounds lower the bcl-2/bax ratio favouring increased susceptibility of MCF-7 cells to undergo apoptosis. 6. These results suggest that the synthetic vitamin D analogue EB1089 may promote tumour regression by inducing active cell death.

Animals↗
PubMed1998

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Adolescent↗
PubMed1992

Percutaneous mitral valvotomy with the Inoue balloon catheter in children and adults: immediate results and early follow-up.

Percutaneous mitral balloon valvotomy (PMV) using the Inoue balloon catheter was attempted in 60 consecutive patients with severe symptomatic mitral stenosis. There were 10 children (mean age 13 years) and 50 adults (mean age 31 years). Forty patients were females and 20 were males; 53 were in sinus rhythm. The procedure was technically successfully performed in 57 (95%) patients. There were no deaths or thromboembolic complications. Balloon valvotomy was done using a 22 to 30 mm diameter catheter with the echo/Doppler guided stepwise mitral dilatation technique. After PMV the mean left atrial pressure decreased from 23.0 +/- 5.0 to 14.0 +/- 4.0 mm Hg (p less than 0.001). The mean mitral valve gradient (MVG) decreased from 15.0 +/- 4.0 to 6.0 +/- 2.0 mm Hg (p less than 0.001). The mitral valve area (Gorlin formula) increased from 0.7 +/- 0.2 to 1.6 +/- 0.4 cm2 (p less than 0.001). The mitral valve area as determined by echocardiography increased from 0.8 +/- 0.1 to 1.9 +/- 0.3 cm2 (p less than 0.001). Mild mitral regurgitation (MR) developed in six patients (11%) and increased by one grade in another five patients (9%). No patient developed severe mitral regurgitation. Mitral valve area at mean follow-up of 4.8 months remained unchanged at 1.9 +/- 0.3 cm2. We conclude that PMV, using the Inoue balloon catheter, is safe and effective in the treatment of severe mitral stenosis in children and adults, without inducing significant mitral regurgitation.

Adolescent↗
PubMed1992

Concurrent post-streptococcal carditis and glomerulonephritis: serial echocardiographic diagnosis and follow-up.

The two non-suppurative post-streptococcal events, acute rheumatic fever and acute glomerulonephritis, rarely occur simultaneously. We describe such a patient, a 16-year-old male who was admitted with fever, agitation and confusion. Blood work-up showed high antistreptolysin O titre, raised serum creatinine and low complement levels. Urinalysis showed RBC casts. Echocardiographic examination demonstrated markedly impaired left ventricular systolic and diastolic function and three large thrombi in the apex. Serial echocardiographic examinations revealed improvement of cardiac function and the resolution of the thrombi and both cardiac and renal function returned to normal after 3 weeks of treatment.

Acute Disease↗
PubMed1991

Mitral balloon valvotomy using the Inoue balloon technique for selected patients with severe pliable rheumatic mitral valve stenosis: immediate and short-term results.

We selected 40 patients with severe symptomatic rheumatic mitral stenosis for balloon valvotomy using the Inoue balloon technique. The patients' mean age was 31 +/- 14 years and there were 24 females and 16 males. The patients were selected according to the following echo/Doppler criteria; 1. Severe mitral stenosis, i. e. mitral valve area (MVA) less than 1.1 cm2; 2. pliable anterior mitral valve leaflet; 3. absence of calcification of the mitral commissures and 4. absence of significant subvalvular mitral valve disease (Block echo score less than 8). We failed to cross the mitral valve in three cases and repeat attempts in two patients with higher transeptal puncture was successful. Thirty-nine procedures were technically successful (98%). There were no complications. We used an Inoue balloon size 24-30 mm using echo/Doppler guided stepwise mitral dilatation. After mitral balloon valvotomy, the MVA increased from 0.8 +/- 0.2 to 1.7 +/- 0.5 cm2 (p less than 0.001). Five patients developed mild mitral regurgitation and in one patient the degree of mitral regurgitation increased from mild to moderate. The mean mitral valve area 48 hours after the procedure measured 1.9 +/- 0.4 cm2 (echo/Doppler); one patient (2.5%) had residual mitral stenosis (MVA less than 1.5 cm2). At six weeks follow-up study the mean mitral valve area was 1.9 +/- 0.5 cm2 (Echo/Doppler), with no restenosis. We conclude that in selected cases of severe pliable mitral stenosis, the Inoue balloon technique achieves a greater than 100% increase of the MVA, without inducing significant iatrogenic mitral regurgitation or residual stenosis.

Catheterization↗
PubMed1988

Synovial fluid collagenase in patients with destructive arthritis of the shoulder joint.

We studied synovial fluid (SF) collagenase in 10 women with severe rheumatoid arthritis (RA), 10 with pyrophosphate arthropathy, and 10 with idiopathic destructive disease of the shoulder conforming to a pattern recently described. SF cell counts were highest in the RA group. Particles were detected by polarized light microscopy and alizarin red staining. Crystals were seen in fluids from all 3 groups; pyrophosphate predominated in the pyrophosphate arthropathy group and alizarin red-positive particles in the idiopathic disease group. Collagenase and tissue inhibitor of metalloproteinase levels were estimated in SF after gel filtration. Tissue inhibitor of metalloproteinase activity was detected in all fluids, but tended to be highest in the RA group. Collagenase activity was detected in 3 RA fluids only. In no sample was collagenase found in an active form. These findings support the clinical concept of an aggressive destructive process which sometimes occurs in the shoulder joints of elderly women. Because we were not able to detect free collagenase in SF from any of the patients with idiopathic shoulder disease, the data suggest that high levels of active collagenase are not characteristic of this group of patients.

Apatites↗
PubMed1987

Hemodynamic evaluation of porcine bioprostheses in the mitral position by Doppler echocardiography.

Twenty-four patients with porcine bioprostheses in the mitral position were studied by Doppler echocardiography followed by cardiac catheterization within 24 hours. Doppler mean diastolic mitral valve gradient was calculated by a 3-point method and mitral valve area was determined by the pressure half-time method. Data from Doppler echocardiography and cardiac catheterization were compared. There was a strong correlation between Doppler echocardiography and catheterization-determined mean diastolic gradient: r = 0.9, standard error of estimate (SEE) = 1.4 mm/Hg (regression equation y = 0.63x + 1.41), p less than 0.001. There was also a strong correlation between Doppler echocardiography and catheterization-determined mitral valve area: r = 0.86, SEE = 0.18 cm2 (regression equation y = 0.64x + 0.52), p less than 0.001. Fourteen patients whose valvular function was considered normal by clinical evaluation had Doppler-calculated mean diastolic gradients of 4.5 to 9.5 mm Hg (mean 6.5 +/- 1.4); the Doppler-determined valve area was 1.15 to 2.0 cm2 (mean 1.54 +/- 0.3). Ten patients had a malfunctioning bioprosthesis, 7 had severe mitral regurgitation and 3 had stenosis. Valvular malfunction in all 10 patients was detected by Doppler echocardiography and confirmed by catheterization and angiocardiography. Nine patients underwent reoperation. Doppler hemodynamic evaluation of porcine bioprostheses in the mitral position provided noninvasive information comparable to that obtained by cardiac catheterization.

Adult↗
PubMed1986

Preferential binding of collagenase to alpha 2-macroglobulin in the presence of the tissue inhibitor of metalloproteinases.

The binding of collagenase to both alpha 2-macroglobulin and the tissue inhibitor of metalloproteinases was studied using purified materials. Collagenase bound preferentially to alpha 2-macroglobulin although no transfer of collagenase to alpha 2-macroglobulin occurred if the enzyme was first mixed with the tissue inhibitor of metalloproteinases. The sequences of amino acids in both inhibitors likely to be responsible for the binding of collagenase are discussed and compared to the cleavage site in the collagen molecule.

Animals↗
PubMed1986

Expression and structure of the human NGF receptor.

The nucleotide sequence for the human nerve growth factor (NGF) receptor has been determined. The 3.8 kb receptor mRNA encodes a 427 amino acid protein containing a 28 amino acid signal peptide, an extracellular domain containing four 40 amino acid repeats with six cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155 amino acid cytoplasmic domain. The sequence of the extracellular domain of the NGF receptor predicts a highly ordered structure containing a negatively charged region that may serve as the ligand-binding site. This domain is conserved through evolution. Transfection of a full-length cDNA in mouse fibroblasts results in stable expression of NGF receptors that are recognized by monoclonal antibodies to the human NGF receptor and that bind [125I]NGF.

Amino Acid Sequence↗
PubMed1985

Purification of a metalloproteinase inhibitor from human rheumatoid synovial fluid.

A metalloproteinase inhibitor present in human rheumatoid synovial fluid was purified by a combination of heparin-Sepharose chromatography, concanavalin A-Sepharose chromatography, ion-exchange chromatography and gel filtration. The Mr of the purified inhibitor was 28000 by SDS/polyacrylamide-gel electrophoresis and 30000 by gel filtration. The inhibitor blocked the activity of the metalloproteinases collagenase, gelatinase and proteoglycanase, but not thermolysin or bacterial collagenase. The serine proteinase trypsin was not inhibited. The inhibitory activity was lost after treatment with trypsin (0.5 micrograms/ml) at 37 degrees C for 30 min, 4-aminophenylmercuric acetate (1 mM) at 37 degrees C for 3 h, after incubation for 30 min at 90 degrees C and by reduction and alkylation. These properties suggest that the inhibitor closely resembles the tissue inhibitor of metalloproteinases ('TIMP') recently purified from connective-tissue culture medium.

Arthritis, Rheumatoid↗
PubMed1984

Metalloproteinases and collagenase inhibitors in rheumatoid synovial fluid.

The levels of metalloproteinases and metalloproteinase inhibitors were measured in rheumatoid synovial fluid. Reliable estimates of total enzyme and inhibitor levels in the synovial fluids were obtained only after hyaluronidase treatment and gel filtration. Three latent metalloproteinases were found which, after activation, degraded collagen, proteoglycan, and gelatin. These enzymes closely resembled the metalloproteinases secreted into connective tissue culture medium. In addition to alpha 2 macroglobulin, an Mr 30,000 collagenase inhibitor was detected which closely resembled the tissue inhibitor of metalloproteinase found in tissue culture medium.

Arthritis, Rheumatoid↗
PubMed1983

The interaction of purified rabbit bone collagenase with purified rabbit bone metalloproteinase inhibitor.

1. Pure rabbit bone metalloproteinase inhibitor (TIMP) bound tightly to pure rabbit bone collagenase with an apparent Kd of 1.4 X 10(-10) M. 2. The molecular weight of the enzyme-inhibitor complex was found to be 54 000, but no enzyme activity could be recovered from the complex after treatment with either mercurials or proteinases. The complex thus differed from latent collagenase in terms of size, susceptibility to mercurials and behaviour on concanavalin A-Sepharose. 3. The interaction of the purified components was compared with that of crude collagenase and crude inhibitor in culture medium. Mercurial treatment partially reversed the inhibition in the crude system, but not when the purified components were used. 4. The significance of the results is discussed in relation to the extracellular control of the activity of collagenase.

Animals↗
PubMed1982

A nosocomial outbreak of diarrheal disease due to Yersinia enterocolitica serotype 0:5, biotype 1.

An outbreak of diarrheal disease due to Yersinia enterocolitica serotype 0:5 , biotype 1, involved nine hospitalized patients. The possible source of this infection was two patients who were both hospitalized with a history of several weeks of intermittent diarrhea. Person-to-person contact was the probable mode of transmission of the disease. The present report describes the second known nosocomial outbreak of infection due to Y. enterocolitica, Serotype 0:5 of Y. enterocolitica is not commonly encountered, and its involvement in an outbreak of gastroenteritis has not been previously reported. The importance of the enrichment technique in the isolation of Y. enterocolitica is demonstrated.

Adult↗
PubMed1981

Metalloproteinases from rabbit bone culture medium degrade types IV and V collagens, laminin and fibronectin.

Gel-filtration chromatography of culture medium from rabbit bone explants separates three latent metalloproteinases with activities against collagen, proteoglycan and gelatin respectively. The fractions degrading proteoglycan also degrade laminin, fibronectin and the polymeric products of pepsin-solubilized type IV collagen and can also solubilize insoluble type IV collagen. The fractions degrading gelatin are capable of degrading solubilized type V and 1 alpha,2 alpha,3 alpha (cartilage) collagens, as well as the lower-molecular-weight products of pepsin-solubilized type IV collagen. All activities can be inhibited by 1,10-phenanthroline and occur in either partially or totally latent forms that can be activated by 4-aminophenylmercuric acetate.

Animals↗