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Biomedical subjects

J P Cooper

Publications and source records attributed to J P Cooper.

At least 37 records · Page 2Linked to original sources

Systemic sclerosis associated with right ventricular cardiomyopathy.

Systemic sclerosis is an uncommon multisystem disorder of unknown aetiology which predominantly affects the skin. Cardiac involvement, which is far more common than was originally realized, may affect any part of the heart but most frequently affects the left ventricular myocardium. Right ventricular dysfunction is usually associated with pulmonary vascular disease. We report a case of systemic sclerosis associated with right ventricular cardiomyopathy in whom pulmonary artery pressures were normal.

Adult↗

Permanent pacing in patients with tricuspid valve replacements.

OBJECTIVE: To assess the incidence and complications of permanent pacing in patients who undergo tricuspid valve replacement. DESIGN: A retrospective study of records of patients who had a tricuspid valve replacement between 1978 and 1993 at the Middlesex hospital. RESULTS: 45 patients with tricuspid valve replacements were followed up for a total of 104 patient years. Ten patients (22%) required permanent pacing, five with epicardial leads and five with endocardial. Endocardial leads had significantly lower initial implantation thresholds and were associated with fewer complications. CONCLUSION: Patients undergoing tricuspid valve replacement frequently require permanent pacing. Endocardial or epicardial lead insertion should be considered at the time of tricuspid valve replacement.

Aged↗

How do the clinical findings in patients with pericardial effusions influence the success of aspiration?

OBJECTIVE: To identify features associated with success or failure of aspiration of pericardial effusion. METHOD: A retrospective analysis of 36 drainage procedures in 30 patients with pericardial effusion was performed using patient records and echocardiograms. RESULTS: Unsuccessful aspiration was associated with pericardial loculation but not with the seniority of the operator or the size and position of the effusion. Pericardiocentesis relieved symptoms of breathlessness in 21 of 26 patients who had a pericardial effusion suspected of causing dyspnoea. These 21 patients had few clinical or echocardiographic signs of classic tamponade. CONCLUSION: The paucity of abnormal physical or echocardiographic signs of tamponade in breathless patients with pericardial effusion does not exclude symptomatic benefit being derived from pericardiocentesis. Pericardial aspiration is safe in appropriate hands, although aspiration of loculated effusions may not be as successful as aspiration of non-loculated effusions.

Adolescent↗

The global transcriptional regulators, SSN6 and TUP1, play distinct roles in the establishment of a repressive chromatin structure.

Repression of a-cell specific gene expression in yeast alpha cells requires MAT alpha 2 and MCM1, as well as two global repressors, SSN6 and TUP1. Previous studies demonstrated that nucleosomes positioned adjacent to the alpha 2/MCM1 operator in alpha cells directly contribute to repression. To investigate the possibility that SSN6 and TUP1 provide a link between MAT alpha 2/MCM1 and neighboring histones, nucleosome locations were examined in ssn6 and tup1 alpha cells. In both cases, nucleosome positions downstream of the operator were disrupted, and the severity of the disruption correlated with the degree of derepression. Nevertheless, the observed changes in chromatin structure were not dependent on transcription. Our data strongly indicate that SSN6 and TUP1 directly organize repressive regions of chromatin.

ATP-Binding Cassette Transporters↗

Electrophoretic evidence that single-stranded regions of one or more nucleotides dramatically increase the flexibility of DNA.

The influence of single-stranded nicks and gaps on the flexibility of DNA has been investigated by subjecting to gel electrophoresis sets of molecules containing single-stranded regions of defined position and length. The DNA molecules were produced by ligating together synthetic oligomers that contained either nicks or single-stranded gaps of 1-4 nucleotides; the oligomer repeat lengths were 20, 21, 22, 23, or 26 bp, in order to produce nicks or gaps that were either in- or out-of-phase with the helix repeat of DNA. Nick-containing DNA molecules displayed nearly normal electrophoretic behavior, with maximum reductions in gel mobility (41 degrees C; 12% polyacrylamide gels) of approximately 10% for 230-bp molecules containing 10 nicks. In contrast, molecules containing gaps of 2-4 nucleotides demonstrated dramatic reductions in mobility, approaching one-half of the values of their full-duplex counterparts; molecules containing 1-nucleotide gaps displayed intermediate behavior. The observed (relative) mobilities of molecules containing gaps of more than 1 nucleotide were remarkably insensitive to temperature and to the presence of magnesium ions in the electrophoresis buffer. The central conclusion of the current study is that single-stranded gaps represent points of swivel-like character, whereas nicks retain much of the rigid character of double-helical DNA.

Base Sequence↗

False aneurysm of the pulmonary artery associated with cardiac catheterisation.

A false aneurysm of the pulmonary artery developed in a 59 year old woman as a complication of right-sided cardiac catheterisation. This rare, life-threatening condition was successfully treated with coil embolisation of the feeding artery. Cardiologists and intensive care doctors should be aware of the possibility of the formation of false aneurysms of the pulmonary artery after Swan-Ganz and other right heart catheterisation. Appropriate therapy could be life-saving.

Aneurysm, False↗

Reversibility and benign recurrence of complete heart block in athletes.

In two patients, symptoms associated with complete heart block and physical training resolved with deconditioning. In one patient, symptoms recurred after resumption of training but she has remained well for 4 years without a pacemaker. This suggests that complete heart block induced by fitness is benign, even when symptomatic.

Adult↗

Monocyte adhesion to human saphenous vein in vitro.

Monocyte adhesion to endothelium is believed to be an initiating event in atherosclerosis both in arteries and in saphenous vein coronary artery bypass grafts. We have developed a method to quantify adhesion of 51Cr-labelled human blood monocytes to saphenous vein. Adhesion to the intimal surface was measured to uniform 6 mm diameter discs, the adventitia of which was embedded in a layer of inert silicone grease. The identity, number and location of bound cells was further defined by scanning electron microscopy. The proportion of monocytes adhering to discs of freshly-isolated vein was 7.1 +/- 1.2% (SE, n = 8), which was equivalent to 500 +/- 80 monocytes/mm2. The percentage of monocytes adhering was independent of the number of monocytes added in the range 5-50 x 10(4). Scanning micrographs showed 80% endothelial coverage with monocytes adhering preferentially but not exclusively to subendothelium. Endothelial removal increased monocyte adhesion by 1.60 +/- 0.15-fold (n = 8, P less than 0.01). Vein surgically prepared for use in coronary bypass surgery, had a 50% reduction in endothelial coverage and a small but non significant (1.14 +/- 0.13-fold, n = 8) increase in monocyte adhesion. Treatment of freshly-isolated vein for 4 h at 37 degrees C with 1 micrograms/ml of E. Coli endotoxin followed by extensive washing did not remove endothelium but increased monocyte adherence by 1.46 +/- 0.18-fold (n = 8, P less than 0.05). The proportion of monocytes adhering to veins which had been cultured for 14 days was similar to freshly isolated veins (6.4 +/- 0.8%, n = 7), but in cultured veins, monocytes adhered preferentially to cells with typical endothelial morphology. Endotoxin treatment of cultured freshly-isolated veins increased monocyte adhesion by 1.77 +/- 0.23-fold (n = 8, P less than 0.05). The data show that both endothelial activation, and exposure of subendothelium promote monocyte adhesion to human saphenous vein.

Cell Adhesion↗

Analysis of fluorescence energy transfer in duplex and branched DNA molecules.

Nonradiative fluorescence energy transfer (FET) is thought to be a highly sensitive measure of distance, occurring through a dipole coupling (Forster) mechanism in which the efficiency of FET depends on the inverse sixth power of the distance between fluorophores. The current work assesses the utility of FET for measuring distances in duplex and branched DNA molecules. The apparent efficiencies of FET between donor (fluorescein) and acceptor (eosin) fluorophores attached to opposite ends of oligonucleotide duplexes of varying length were determined; the results suggest that FET is a useful qualitative indicator of distance in DNA molecules. However, the apparent FET efficiency values cannot be fit to the Forster equation without the specification of highly extended DNA-to-fluorophore tethers and motionally restricted fluorophores, conditions that are unlikely to coexist. Three other lines of evidence further suggest that factors in addition to Forster transfer contribute to apparent FET in DNA: (1) The efficiency of FET appears to depend on the base sequence in some instances. (2) Donor fluorescence changes with the extent of thermally induced DNA melting in a sequence-dependent fashion, indicating dye-DNA interactions. (3) The distances between the ends of various pairwise combinations of arms of a DNA four-way junction do not vary as much as expected from previous work. Thus, the occurrence of any nondipolar effects on energy transfer in oligonucleotide systems must be defined before distances in DNA molecules can be quantified by using FET.

Base Sequence↗

Geometry of a branched DNA structure in solution.

An approximate geometry of a stable, four-way DNA junction has been determined in free solution by applying the technique of transient electric birefringence. The current approach consists of (i) construction of a set of six molecules in which two of the four arms of a synthetic junction are elongated by approximately 9-fold (in each of the six possible two-arm combinations), (ii) determination of the ratios of the longest birefringence decay time of each elongated junction to the decay time of a linear control molecule, and (iii) comparison of the experimental ratios with corresponding ratios computed as a function of the junction interarm angle. The result is a set of six angles that define the geometry of the junction. In the presence of magnesium ions, the junction adopts a geometry in which particular pairs of arms approach colinearity. Furthermore, the geometry of the junction is significantly altered in the absence of magnesium, adopting a more uniform structure, although such an effect is not apparent on gels. The application of transient electric birefringence, as described in the current study, should be useful for the characterization of a broad range of tertiary structures in both DNA and RNA.

Base Sequence↗

Simple three-program implantable muscle stimulator with optical control.

We describe an implantable stimulator which is capable of producing both continuous and intermittent patterns of indirect muscle stimulation. Switching between modes is achieved remotely via a percutaneous optical link and only standard laboratory techniques are employed in the construction of the device. It has been used to assess the influence of the pattern of stimulation on type transformation of mammalian skeletal muscle.

Animals↗

Gel electrophoretic analysis of the geometry of a DNA four-way junction.

Branched DNA molecules (Holliday structures) are believed to be key intermediates in the process of homologous genetic recombination. However, despite the importance of such structures, their transient nature makes it difficult to analyze their physical properties. In an effort to evaluate several models for the geometry of such branched molecules, a stable, synthetic DNA four-way junction has been constructed. The geometry of the synthetic junction has been probed by gel electrophoresis, utilizing the fact that bent DNA molecules demonstrate reduced mobilities on polyacrylamide gels to an extent that varies with the degree of the bend angle. From the synthetic four-way junction, we have produced a set of molecules in which all combinations of two junction arms have been extended by 105 base-pairs. The electrophoretic mobilities of the extended junctions differ in a manner which indicates that the junction is not a completely flexible structure; nor is it tetrahedral or planar-tetragonal. Instead, the four strands that comprise the DNA four-way junction are structurally non-equivalent. The significance of these observations with regard to previous models for four-way junction geometry is discussed.

Base Sequence↗