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Biomedical subjects

W Casscells

Publications and source records attributed to W Casscells.

51 records · Page 3Linked to original sources
PubMed1990

Immunohistochemical study of fibronectin in experimental myocardial infarction.

Light microscopic immunohistochemical studies were performed to evaluate the distribution of fibronectin in paraffin sections of p-formaldehyde-fixed normal rat hearts and the hearts of rats that had undergone ligation of the left coronary artery. A peroxidase-labeled antibody technique was used, together with appropriate immunohistochemical control procedures, for the localization of fibronectin in normal hearts and in the hearts of sham-operated animals. Fibronectin was localized in the interstitial space between myocytes, and beneath arterial, venous, and capillary endothelium. At 4 hours after coronary ligation, fibronectin was localized in a patchy fashion in the cytoplasm and interstitial space of some of the myocytes in the area supplied by the ligated vessel. At 24 hours, there was more intense, homogeneous staining in necrotic myocytes in the infarcted area and in the capillary endothelium in the border zone. At 48 hours, the intensity of staining for fibronectin was maximal in and between the necrotic myocytes in the center of the infarct and in proliferating and migrating capillaries and fibroblasts in the border zone. Similar patterns of localization were observed at 3 and 7 days after coronary ligation, but with progressive decreases in the intensity of staining. Two sources of fibronectin appeared to have contributed to these changes: plasma fibronectin diffusing through damaged blood vessels would account for the early staining observed in necrotic myocytes in the center of the infarct, whereas de novo synthesis of fibronectin by connective tissue cells and endothelial cells in sprouting capillaries would be responsible for the subsequent staining observed in viable capillaries in the border zone of the infarct. Known properties of fibronectin in vitro, combined with these in vivo observations, indicate that fibronectin may influence the thrombotic, inflammatory, angiogenic, and fibrotic processes involved in infarct healing.

Animals↗
PubMed1989

Fibroblast growth factors are present in adult cardiac myocytes, in vivo [corrected and issued with original paging in Biochem Biophys Res Commun 1988 Dec 30;157(3)].

We have previously shown that the adult heart contains mitogens immunologically identical to acidic and basic fibroblast growth factors. To determine whether these proteins are present in myocytes, we subjected lysates of freshly isolated myocytes to heparin-affinity chromatography. The 1.1 M - 3 M NaCl eluates stimulated incorporation of thymidine into DNA in quiescent Balb/c 3T3 fibroblasts, caused proliferation of vascular endothelial cells, and cross-reacted with antisera raised against acidic (1.1 M) and basic FGF's (1.5 M) by Western blotting and by RIA. These proteins may be involved in cellular differentiation and proliferation and may play an important role in regenerative and repair processes in the heart.

Animals↗
PubMed1988

Transforming growth factor beta-1 in acute myocardial infarction in rats.

TGF-beta 1 has been examined in the heart during myocardial infarction caused by ligation of the left coronary artery. Infarcted and uninfarcted myocardium have been compared by immunohistochemical staining of TGF-beta 1 and by Northern blot analysis of mRNA. Normal ventricular myocytes are strongly stained by an antibody to TGF-beta 1. Progressive loss of staining of these myocytes begins within 1 hr after coronary ligation. However, by 24-48 hr after ligation, intense staining of myocytes at the margin of infarcted areas is seen. Northern blots of infarcted myocardium 48 hr after ligation show a 3- to 4-fold increase in the principal 2.4 kb TGF-beta 1 mRNA; there is also a marked increase in a minor 1.9 kb transcript. In the same tissue samples, there is a 2-fold decrease in the mRNA for the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase. The results indicate a significant role for TGF-beta in the response of the heart to injury.

Animals↗
PubMed1988

Heparin-binding growth factor-I (endothelial cell growth factor) binds to endothelium in vivo.

Heparin-binding growth factor-I (HBGF-I) produces a significant increase in endothelial cell replication in vitro and may prove useful for endothelial regeneration and endothelial seeding in vivo. Heparin enhances the mitogenic effects of HBGF-I in vitro and may be an important adjunct to its pharmacologic use. Binding studies in the rat were undertaken to determine the feasibility of use of HBGF-I in vivo. For saturation studies, 125I-labeled HBGF-I was administered intravenously at various concentrations with heparin (approximately 5 U/ml blood volume). Further binding studies were conducted with the use of a constant concentration of 125I-labeled HBGF-I (40 ng) with or without heparin (2.5 U/ng HBGF-I). In each case, the rat was perfused with ice-cold saline solution 5 minutes after drug administration and the aorta or carotid arteries were harvested. 125I-labeled HBGF-I with heparin demonstrated saturation binding to rat aortic endothelium at an approximate blood concentration of 10 ng/ml. Scatchard plot analysis of in vivo data revealed a binding constant (KD) of 1.60 +/- 0.004 x 10(-9) mol/L compared with 2 to 8 x 10(-10) mol/L obtained for in vitro binding. Receptor number per cell was approximately 3000 for rat aortic endothelium, compared with a receptor number of 2000 to 20,000 for several endothelial cell lines, including bovine aortic endothelial cells, determined in vitro. 125I-labeled HBGF-I binding to uninjured rat carotid endothelium was significantly increased (p = 0.0001) by heparin (463 +/- 302 cpm to 1172 +/- 403 cpm).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Lignocaine prophylaxis in acute myocardial infarction: an evaluation of randomised trials.

Although lignocaine has been used in coronary care units for almost two decades, its role in preventing ventricular fibrillation (VF) during acute myocardial infarction (MI) is still debated. Of fifteen randomised trials of lignocaine prophylaxis, most showed no apparent benefit. When the data from all fifteen trials were pooled and a summary relative risk estimate calculated, there was a significant benefit of lignocaine treatment in preventing VF. However, the trials had widely differing treatment schedules, modes of drug administration, and doses of lignocaine; to decrease the clinical heterogenity, minimum criteria for adequacy of treatment were established and the data from six trials which fulfilled these requirements were pooled. The summary relative risk estimate calculated from the pooled data of these six trials also demonstrated a significant prophylactic effect of lignocaine that was even greater when the two trials which treated patients with left ventricular failure and shock were excluded. From these analyses, it is concluded that lignocaine treatment provides prophylaxis against VF in acute MI. The failure of most trials to demonstrate such a prophylactic effect is due to small sample sizes and inadequate treatment protocols.

Clinical Trials as Topic↗
PubMed1980

Retirement and coronary mortality.

Information on several variables, including occupational history and various coronary risk factors, was collected from the wives of 568 married men who died of coronary heart-disease (CHD) and an equal number of matched control subjects. The crude matched-pair relative risk of fatal CHD among men who retired compared with non-retirees was 2.9 (95% confidence limits from 1.9 to 4.9). After adjustment for age and history of hospitalisation for myocardial infarction by means of a paired multiple-logistic regression analysis the relative risk was reduced to 1.8 (range 1.0 to 3.3). These data suggest that retirement and subsequent coronary mortality may be linked.

Adult↗