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Biomedical subjects

C K Moore

Publications and source records attributed to C K Moore.

11 recordsLinked to original sources

Stretch-induced membrane type matrix metalloproteinase and tissue plasminogen activator in cardiac fibroblast cells.

In the normal heart, cardiomyocytes are surrounded by extracellular matrix (ECM) and latent matrix metalloproteinases (MMPs), which are produced primarily by cardiac fibroblasts. An activator of latent MMPs might be induced by ischemic conditions or pressure-induced stretching. To test the hypothesis that an activator of latent MMP is induced in the ischemic heart during transformation of a compensatory hypertrophic response to a decompensatory failing response in cardiac fibroblast cells, we stretched the human cardiac fibroblasts at 25 cycles/min in serum-free or 5% serum culture condition. The membrane type (MT)-MMP activity in stretched cells was measured by zymography and immuno-blot analyses using MT-MMP-2 antibody. The MT-MMP activity was further characterized by transverse-urea gradient (TUG)-zymography. The results suggested that stretch induced a membrane MMP in the fibroblasts that was similar to the MT-MMP induced in ischemic heart. Furthermore, we observed that membrane MMP has distinct mobility in TUG-zymography. To localize the MT-MMP and tissue plasminogen activator (tPA) of latent MMPs, the membrane and cytosol were separated by a method employing a detergent and sedimentation. The MT-MMP and tPA activities of cytosol and membrane fractions were measured by gelatin- and plasminogen-zymography, respectively. Differential-display mRNA analysis was performed on control and stretched cells. In situ immuno-labelling was performed to localize the MT-MMP. The results indicate that induction of MT-MMP occurred in the membrane fractions. The secretion of tPA was elevated in the stretched cells. The MT-MMP activity was inhibited by prior incubation with an antibody generated to membrane MMP. The tPA activity was inhibited by using tPA antibody. These results suggest that, under stretched conditions, neutral transmembrane matrix proteinases are induced in the cardiac fibroblasts. This may lead to activation of adverse ECM remodeling, cardiac dilatation, and failure.

Blotting, Northern↗

Treatment of end stage dilated cardiomyopathy.

Patients should be referred for cardiac transplantation only after all other means of management of congestive heart failure have been attempted and have been unsuccessful (table 3). An adequate therapeutic trial of conventional and experimental agents including beta blockade and vesnarinone should be completed and be shown to be unsuccessful before transplantation is considered in patients in NYHA class III. Prospective clinical trials need to be completed to define the role of newer therapeutic options. The scarcity of donor organs will probably preclude the use of cardiac transplantation in all patients who may benefit. Alternative methods of cardiac replacement (such as dynamic cardiomyoplasty, permanent implantable mechanical circulatory assistance, and xenografting) must be developed. These methods coupled with better pharmacological treatment will greatly improve the outcome of patients with dilated cardiomyopathy.

Adrenergic beta-Antagonists↗

Acute effects of dobutamine on myocardial oxygen consumption and cardiac efficiency measured using carbon-11 acetate kinetics in patients with dilated cardiomyopathy.

OBJECTIVES: The aim of this study was to use positron emission tomography (PET)-derived carbon (C)-11 acetate kinetics to determine the effects of dobutamine on oxidative metabolism and its effects on myocardial efficiency in a group of patients with dilated cardiomyopathy. BACKGROUND: Dobutamine is known to improve myocardial function but may do so at the expense of myocardial oxygen consumption, which could be a potential deleterious effect. Carbon-11 acetate kinetics correlate with myocardial oxygen consumption as shown in animal models. Combining these scintigraphic measurements of oxygen consumption with estimates of cardiac work results in a work-metabolic index, which reflects cardiac efficiency. METHODS: Eight patients with nonischemic dilated cardiomyopathy underwent dynamic PET imaging, echocardiography and hemodynamic measurements. Seven of these patients were also studied while receiving dobutamine. Direct measurements of myocardial oxygen consumption using coronary sinus catheterization were obtained with eight of the PET studies to validate C-11 acetate in patients with cardiomyopathy. RESULTS: The mean (+/- SD) C-11 clearance rate significantly increased with dobutamine from 0.105 +/- 0.027 to 0.155 +/- 0.023 min-1 (p = 0.001). Directly measured myocardial oxygen consumption had a linear relation to the mean C-11 clearance rate (r = 0.8, p = 0.018). Dobutamine was noted to significantly reduce systemic vascular resistance as well as the severity of mitral regurgitation. The work-metabolic index determined using hemodynamic variables and PET data increased from 2 +/- 0.7 x 10(4) to 2.6 +/- 0.6 x 10(4) (p = 0.04). Efficiency, estimated by employing the oxygen consumption to k2 relation, also increased from 13 +/- 4.5% to 16.9 +/- 6.4% (p = 0.04). CONCLUSIONS: Despite an increase in myocardial oxygen consumption, dobutamine led to an increase in work-metabolic index in patients with dilated nonischemic cardiomyopathy. Dobutamine reduced systemic vascular resistance and mitral regurgitation, suggesting that in this group of patients, it had important vasodilatory action in addition to its inotropic effects. The use of the C-11 acetate PET for determining myocardial oxygen consumption and estimating efficiency could potentially complement existing clinical measures of ventricular performance and may allow improved and objective evaluation of therapy in patients with heart failure.

Adult↗

Aspergillus terreus as a cause of invasive pulmonary aspergillosis.

A 70-year-old woman with nodular, poorly differentiated lymphocytic lymphoma is the third reported patient with invasive pulmonary aspergillosis caused by Aspergillus terreus. This case differs from the two previously reported in that neither neutropenia nor broad spectrum antibiotics preceded the infection. A terreus should not be dismissed as a laboratory contaminant in pulmonary specimens, especially those from immunosuppressed patients.

Aged↗

Hyperactivity and child abuse.

The role of a child in his/her physical abuse was reviewed with particular attention to hyperactive children. A retrospective analysis of the records of children referred to a university-based hyperactive children's clinic revealed that children both with and without Attention Deficit Disorder (ADD) were more often physically abused than children in the general population. The period prevalence of physical abuse in children with ADD did not differ significantly from that in children without ADD. This suggests that hyperactivity may either contribute to, or result from, physical abuse.

Adolescent↗

Nitrogen balance, abomasal crude protein and amino acids in wethers fed formaldehyde-treated coastal bermudagrass and infused with methionine, glucose or monensin.

A 5 X 5 Latin square design was used to study the effects on nitrogen balance, wool growth and plasma amino acids of infusing methionine and (or) glucose into the abomasum of growing wethers fed formaldehyde-treated Coastal bermudagrass (F-CBG) or untreated Coastal bermudagrass hay. Daily treatments were: (1) CBG; (2) F-CBG + 3 g methionine (met); (4) F-CBG + 96 g glucose and (5) F-CBG + 3 met + 96 g glucose. Glucose infusion decreased (P < .005) moles/100 g of total essential amino acids in plasma; moles/100 g of lysine, valine, leucine and isoleucine were also reduced (P < .005). Moles/100 g of methionine in plasma were increased significantly by methionine infusion, but nitrogen retention was not affected (P > .10). The grams digestible protein to megacalorie digestible energy (DE) ratio was 36.6, 35.9 and 32.4 for CBG, F-CBG and F-CBG + glucose, respectively. The decrease (36.6 to 32.4) resulted in increased nitrogen retained (P < .05), increased percentage nitrogen intake retained (P < .05) and increased percentage digested nitrogen retained (P < .01). Urinary nitrogen excretion was lower (P < .01) in wethers receiving the F-CBG + glucose treatment than in those receiving the F-CBG treatment (3.60 vs 5.09 g/day). Effects of formaldehyde treatment of CBG and rumen infusion of monensin on quantities of various crude protein (CP) components reaching the abomasum were also determined in a 4 X 4 Latin square design experiment. Total CP reaching the abomasum increased (P < .01) with formaldehyde treatment and resulted in increased quantities of amino acids reaching the abomasum (P < .05). Monensin had no effect on these two parameters, and no interaction between monensin and formaldehyde was observed. Dietary CP reaching the abomasum increased with formaldehyde treatment (P < .005) and with infusion of monensin (P < .025). Total microbial protein (MP) and MP reaching the abomasum per 100 g dry matter digested were not influenced by either formaldehyde or monensin.

Abomasum↗