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Biomedical subjects

J R McCormick

Publications and source records attributed to J R McCormick.

11 recordsLinked to original sources

PMA-activated neutrophils decrease ectoenzyme activities in rabbit aortic endothelial cells in culture.

We have studied the effects of phorbol 12-myristate 13-acetate (PMA)-activated neutrophils [polymorphonuclear leukocytes (PMN)] on endothelial ectoenzyme [angiotensin-converting enzyme (ACE) and 5'-nucleotidase (NCT)] activities in cultured rabbit aortic endothelial cells (EC) with the use of [3H]benzoyl-Phe-Ala-Pro and 14C-labeled AMP as substrates, respectively, under first-order reaction conditions. PMA (1-1,000 ng/ml) or PMN alone had no effect on ACE activity. When PMA was incubated together with PMN (PMN/EC = 1.25:1 or 2.5 x 10(5) neutrophils/ml) for 4 h in Earle's salts, a PMA dose-dependent decrease in ACE activity was observed. Threshold PMA concentration was 2 ng/ml. At 8 ng PMA/ml, ACE activity was totally abolished, without any evidence of cytotoxicity, as inferred from release of 51Cr from prelabeled EC. The decrease in ACE activity was also dependent on PMN concentration and was detectable at PMN/EC values as low as 1.25:10 (0.25 x 10(5) PMN/ml). Inhibition of ACE occurred as early as 1 h after incubation (PMA 10 ng/ml, PMN/EC = 1.25:1). PMA alone caused a small but significant increase in NCT activity, whereas PMA coincubation with PMN produced a significant decrease in NCT activity (20-29%), which was PMA and PMN concentration independent. PMA increased PMN adherence to endothelial monolayers in a concentration-dependent manner. Pretreating PMN with monoclonal antibody 60.3 (raised against the adhesion glycoprotein CD18) or placing a 2-microns filter between PMN and EC, protected the decrease in ACE activity.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase

Intermediates in the degradation of mRNA from the lactose operon of Escherichia coli.

We have analyzed the processing of mRNA from the lac operon in an Escherichia coli strain carrying the lac on a multicopy plasmid. Messenger RNA was analyzed by hybridization and nuclease protection of pulse-labeled RNA and precursor-product relationships were determined by quantitating radioactivity in primary and processed transcripts at various times after induction of the lac promoter or inhibition of transcription with rifampicin. Our results support the existence of two types of processed transcripts with endpoints in the lacZ-lacY intercistronic region. One of these carries lacZ sequences and has a 3' endpoint about 30 bases downstream of this gene. The other carries lacY sequences and has a 5' end in the translation termination region of the lacZ gene. Finally, we have found evidence that transcription is continued at least 268 bases beyond the last gene (lacA) and that this 3' non-translated region is shortened by post-transcriptional processing.

Base Sequence

Left ventricular false aneurysm after coronary bypass surgery: radionuclide diagnosis and surgical resection.

A patient with left ventricular pseudoaneurysm formation resulting from myocardial infarction 4 years after coronary bypass surgery is described. The pseudoaneurysm was diagnosed with gated cardiac blood pool imaging and was subsequently successfully surgically repaired. Postoperative pericardial abnormalities predisposing to the possible development of a false aneurysm are discussed. Also, clinical situations in which pseudoaneurysm should be suspected are described, and appropriate diagnostic approaches are outlined.

Coronary Artery Bypass

Temporary left ventricular bypass: factors affecting patient survival.

Circulatory support (range, 2 hours-8 days) was undertaken in eight cardiac surgical patients (with two survivors) exhibiting intractable cardiogenic shock. A paracorporeal, pneumatic, xenograft-valve pump was interposed between the left ventricular apex and ascending aorta. Pumping lowered left atrial and ventricular pressure while maintaining cardiac output (1.8--2.6 l/min/m2). Following implantation, plasma hemoglobin and erythrocyte mechanical fragility values were elevated but decreased to normal when renal function was not impaired. Mild thrombocytopenia was noted in three patients and was severe in five others with persistent hemorrhage. Anticoagulation agents were used during tapering of pump flow (three patients) after 100, 105 and 120 hours of bypass. Otherwise, for the major portion of the interval of mechanical circulatory support, anticoagulants were not administered. Despite this fact, no systemic embolization was detected in any of the patients. It appears that assist pump support can be life-saving in acute left ventricular failure in patients following cardiac surgery.

Adult

Suppression of immune complex vasculitis in rats by prostaglandin.

Immune complex-induced vascular damage can be markedly suppressed by treatment of rats with either prostaglandin (PG)E1 or its stable derivative, 15-(S)-15-methyl PGE1, but not with PGF2 alpha. In addition, PGD2 and PGE2 also show suppressive effects. The PGE1 derivative is considerably more effective than PGE1 and shows potent anti-inflammatory activity even after oral administration. Suppression of the vasculitis reaction is reflected by a greatly diminished increase in vasopermeability, indicating little or no vascular damage. In suppressed animals, the infiltration of neutrophils is greatly reduced, and those leukocytes that have appeared at tissue sites fail to show phagocytic uptake of immune complexes. In suppressed animals, the skin sites nevertheless show deposits of immune complexes and C3 fixation in vascular walls. Neutrophils harvested from the blood of rats treated with PGE1 show depressed responsiveness in chemotaxis and in enzyme secretion after incubation with chemotactic peptide. These studies indicate that certain PG have potent anti-inflammatory activity, which may be related to their effects on leukocytes.

Administration, Oral

Simple method for measurement of cardiac output by thermodilution after cardiac operation.

Cardiac output by the thermodilution technique was measured by a new No. 2 Fr. transthoracic (2F-TT) thermistor catheter placed at cardiac operation into the pulmonary artery directly through the right ventricular outflow tract. Cold (0 degree C) 5% dextrose in water (D5W) was used as indicator and injected through a percutaneously placed central venous pressure (CVP) catheter in the jugular vein. Comparison to the No. 7 Fr. Swan-Ganz (7F-SG) catheter demonstrated a close correlation (r = 0.87) and almost identical mean thermodilution cardiac output values during 530 determinations in 10 patients. No difficulty was experienced in insertion or removal of the 2F-TT catheter and no bleeding complications were noted. Experiments in six dogs showed that variation in position of the tip of the CVP catheter within the superior vena caval venous system and right atrium was not a critical factor in measurement of thermodilution cardiac output. The thermodilution cardiac output technique in general and the ease of insertion, as well as the small size of the 2F-TT catheter, should make this method especially advantageous in infants and small children.

Cardiac Output

Bleomycin-induced pulmonary fibrosis in the rat: inhibition by indomethacin.

A model for pulmonary fibrosis in the rat has been developed using intratracheal administration of bleomycin. The histopathologic features of the reaction are similar to those reported in the hamster model. Increases in vascular permeability are seen in the lung within 24 hours and persist over a 2-month period. Extractable collagen, as measured by hydroxyproline, increases during this time by a factor greater than 1.5 times the reference control values of normal lung. During this same period, a prominent eosinophilia develops. The continued treatment of bleomycin-injected rats with indomethacin markedly diminishes the amount of extractable lung collagen at 60 days and the histopathologic evidence of pulmonary fibrosis. The eosinophilia over the first 3 weeks is also markedly suppressed. Less dramatic effects were seen with the permeability changes. These findings indicate that the rat is a reliable and useful model for the study of blemoycin-induced pulmonary fibrosis and that treatment with indomethacin ameliorates the lung changes.

Animals

Surgical treatment of unstable angina by saphenous vein and internal mammary artery bypass grafting.

During a 3 year period, direct myocardial revascularization was performed on an urgent basis in 48 patients with intermittent resting chest pain which persisted more than 24 hours despite in-hospital medical therapy and was accompanied by electrocardiographic changes representative of ischemia. Sixteen patients had saphenous vein (SV) grafts exclusively, and 32 patients each had one or two internal mammary artery (IMA) grafts with or without additional vein grafts. Follow-up ranges from 5 to 41 months (mean, 22 months). Twelve patients had single grafts to the left anterior descending coronary artery (LAD), 18 had double grafts, 16 had triple grafts, and 2 had quadruple grafts. The LAD required grafting in every patient. There was one operative death (2 per cent) and one late death from noncardiac causes. There were two (4 per cent) early postoperative myocardial infarcts and no late infarcts. Actuarial analysis projects a survival rate of 96 per cent 3 years postoperatively. Eighty-one per cent of the survivors are in Functional Class I, 17 per cent are in Class II, and 2 per cent are in Class III. All patients had postoperative angiography 2 weeks after operation. Eighty-six per cent of the SV grafts and all IMA grafts were open. No significant differences were observed between mean preoperative and postoperative left ventricular end-diastolic pressures or ejection fractions, but these parameters were noted to improve after operation in several patients. The remarkably high early and late survival rates, the low incidence of myocardial infarction, and the excellent functional results after rather long follow-up indicate that emergency coronary revascularization provides an effective therapy for unstable angina. The use of IMA grafts, when feasible, is a safe and possibly preferable approach in these patients.

Adult

Blood flow and vasoactive drug effects in internal mammary and venous bypass grafts.

Cardiac output and pressure-flow measurements were made in left internal mammary artery-to-left anterior descending coronary artery grafts and left subclavian artery-to-left circumflex coronary artery vein grafts after proximal coronary artery ligation. Similar measurements were also made in left internal mammary artery-to-left anterior descending coronary artery grafts and aortocoronary saphenous vein grafts in patients with coronary artery disease. Hemodynamic parameters and graft blood flows were measured during control baseline conditions and after pharmacological interventions using isoproterenol, phenylephrine, and epinephrine in random order. Blood flow through vein grafts and internal mammary artery grafts was similar under basal conditions and increased similarly with each of these vasoactive agents. Other hemodynamic parameters changed variably with the various pharmacological agents used. There was no close correlation between mammary artery or vein graft blood flow and arterial mean pressure and cardiac output over the wide range observed with the different drugs was associated with either an increase in perfusion pressure or a decrease in coronary vascular resistance. If the percentage increase in coronary blood flow above the basal control value in response to pharmacological stress is considered as a reflection of coronary vascular reserve, these studies suggest that coronary vascular reserve in patients with coronary artery disease is less than that of the normal dog heart.

Adrenergic Agonists

Selection of coronary bypass. Anatomic, physiological, and angiographic considerations of vein and mammary artery grafts.

Results of direct coronary revascularization with 511 grafts in 213 patients from 1971 to 1974 are reviewed. To improve an early saphenous vein graft (SVG) patency of 84 per cent in the first 85 patients, we have used internal mammary artery grafts (IMAG), when possible, since January, 1973. In 1973 to 1974, 15 patients had SVG's only (36 grafts) and 113 received one or two IMAG's with or without additional SVG's (total 282 grafts); in 26 we used a crossed double IMAG. Forty-seven of 48 patients with unstable angina survived and did well. Flows in SVG's and IMAG's were comparable. Flows in right IMAG's to diagonal or marginal vessels were higher than in right IMAG's to right or left anterior descending (LAD) vessels. In 12 patients with both SVG and IMAG, there was no difference in flow response of either graft to vasoactive drugs. Survival, functional, and patency results with IMAG's were as good as or better than results with SVG's. We conclude that IMAG's yield higher patency and comparable flow rates to SVG's and should be used when the IMA approximates the recipient artery in size and when a high pulsatile free flow is measured from the end of the graft. IMAG's are also safe and feasible for unstable angina.

Adult