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Biomedical subjects

D C Morris

Publications and source records attributed to D C Morris.

At least 55 records · Page 3Linked to original sources
PubMed1995

A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation.

Prostaglandins (PGs) of the J2 series form in vivo and exert effects on a variety of biological processes. While most of PGs mediate their effects through G protein-coupled receptors, the mechanism of action for the J2 series of PGs remains unclear. Here, we report the PGJ2 and its derivatives are efficacious activators of peroxisome proliferator-activated receptors alpha and gamma (PPAR alpha and PPAR gamma, respectively), orphan nuclear receptors implicated in lipid homeostasis and adipocyte differentiation. The PGJ2 metabolite 15-deoxy-delta 12,14-PGJ2 binds directly to PPAR gamma and promotes efficient differentiation of C3H10T1/2 fibroblasts to adipocytes. These data provide strong evidence that a fatty acid metabolite can function as an adipogenic agent through direct interactions with PPAR gamma and furthermore, suggest a novel mechanism of action for PGs of the J2 series.

Adipocytes↗
PubMed1995

Influence of diabetes mellitus on early and late outcome after percutaneous transluminal coronary angioplasty.

BACKGROUND: Although patients with diabetes mellitus constitute an important segment of the population undergoing coronary angioplasty, the outcome of these patients has not been well characterized. METHODS AND RESULTS: Data for 1133 diabetic and 9300 nondiabetic patients undergoing elective angioplasty from 1980 to 1990 were analyzed. Diabetics were older and had more cardiovascular comorbidity. Insulin-requiring (IR) diabetics had diabetes for a longer duration and worse renal and ventricular functions compared with non-IR subjects. Angiographic and clinical successes after angioplasty were high and similar in diabetics and nondiabetics. In-hospital major complications were infrequent (3%), with a trend toward higher death or myocardial infarction in IR diabetics. Five-year survival (89% versus 93%) and freedom from infarction (81% versus 89%) were lower, and bypass surgery and additional angioplasty were required more often in diabetics. In diabetics, only 36% survived free of infarction or additional revascularization compared with 53% of nondiabetics, with a marked attrition in the first year after angioplasty, when restenosis is most common. Multivariate correlates of decreased 5-year survival were older age, reduced ejection fraction, history of heart failure, multivessel disease, and diabetes. IR diabetics had worse long-term survival and infarction-free survival than non-IR diabetics. CONCLUSIONS: Coronary angioplasty in diabetics is associated with high success and low complication rates. Although long-term survival is acceptable, diabetics have a higher rate of infarction and a greater need for additional revascularization procedures, probably because of early restenosis and late progression of coronary disease. The most appropriate treatment for these patients remains to be determined.

Angina Pectoris↗
PubMed1995

Contemporary reperfusion therapy for cardiogenic shock: the GUSTO-I trial experience. The GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: This study sought to examine the incidence, temporal profile and clinical implications of shock in a large trial of thrombolytic therapy for acute myocardial infarction. BACKGROUND: Despite advances in the treatment of acute ischemic syndromes, cardiogenic shock remains associated with significant morbidity and mortality. METHODS: Patients who presented within 6 h of symptom onset were randomized to four treatment strategies: 1) streptokinase plus subcutaneous heparin; 2) streptokinase plus intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) plus intravenous heparin; or 4) streptokinase and rt-PA plus intravenous heparin. The primary end point was 30-day all-cause mortality. RESULTS: Shock occurred in 2,972 patients (7.2%): 315 (11%) had shock on arrival, and 2,657 (89%) developed shock after hospital admission. Reinfarction occurred in 11% of patients who developed shock compared with 3% of patients without shock. The mortality rate was significantly higher in patients who presented with (57%) or developed (55%) shock than in those without shock (3%) (p < 0.001). Shock developed significantly less frequently in patients receiving rt-PA. There were fewer deaths in patients who presented with shock and were treated with streptokinase plus intravenous heparin or who developed shock and were treated with streptokinase plus subcutaneous heparin. Patients who developed shock had a significantly lower 30-day mortality rate if angioplasty was performed. CONCLUSIONS: Because cardiogenic shock occurred most often after admission and with recurrent ischemia and reinfarction, recognizing signs of incipient shock may improve outcome. Fewer patients treated with rt-PA developed shock, yet those developing shock had the same high mortality rate as those presenting with shock, regardless of treatment. Only angioplasty was associated with a significantly lower mortality rate.

Aged↗
PubMed1995

The mechanism of bone induction and bone healing by human osteosarcoma cell extracts.

Saos-2 cultured human osteosarcoma cells contain an extractable bone inducing agent that can induce heterotopic bone in the muscle of Nu/Nu mice. A semipurified GuHCl extract of Saos-2 cells also can promote healing and complete bony union in otherwise non-healing surgically induced defects of rat femur. Northern blot analyses indicate expression of mRNAs for bone morphogenetic proteins (BMP)-1, 2, 3, 4, 6 and transforming growth factor beta (TGF beta) in Saos-2 cells, and BMP-2, 3, 4, 5, 7 and TGF beta in nonosteoinductive U20S human osteosarcoma cells. Saos-2 cells exceeded U20S cells in expression levels of BMP-1, 3, 4 and TGF beta, whereas U20S cells expressed higher levels of BMP-2, 6 and also expressed trace amounts of BMP-5 and 7 not seen in Saos-2 cells. The authors hypothesize that Saos-2 cells contain an optimal admixture of known bone growth factors plus possible other unknown components that, acting alone or in combination with bone morphogenetic protein and/or TGF beta, can induce bone. Although bone inducing agent-induced heterotopic bones have half lives of only a few weeks, the reparative bone induced by bone inducing agent in femoral defects gives every indication of being permanent and self-sustaining. This suggests a fundamental difference between heterotopic and orthotopic osteoprogenitor cells with those involved in orthotopic bone repair more closely resembling the committed or determined osteoprogenitor cells of marrow as described by Friedenstein.

Animals↗
PubMed1995

Treatment of acute myocardial infarction by invasive cardiology techniques.

The role of coronary angioplasty as a means of reperfusion therapy in the patient who suffered an acute myocardial infarction has continued to evolve. Adjunctive angioplasty immediately after thrombolytic therapy has been discarded as a routine therapeutic approach. Rescue angioplasty after failed thrombolysis has limited applicability due to the inability to readily diagnose a failure of thrombolysis. Primary angioplasty is the appropriate reperfusion approach in those patients ineligible for thrombolysis and perhaps offers advantages over thrombolysis in the elderly patients, in the patients with a large anterior infarction, and in patients in cardiogenic shock secondary to the acute infarction.

Angioplasty, Balloon, Coronary↗
PubMed1994

Hepatic artery interruption followed by portal vein thrombosis in an adult liver transplant.

Vascular complications following liver transplantation result in significant morbidity and mortality. We report a 28-year-old man who, because of a mycotic false aneurysm, underwent ligation of the hepatic artery 4.5 weeks post-transplantation and who, 4.5 months later, suffered a portal-mesenteric vein thrombosis. Adverse hepatic sequelae did not follow these events, demonstrating the capacity of the collateral circulation to perfuse the transplanted liver.

Adult↗
PubMed1994

Percutaneous transluminal coronary angioplasty in women compared with men.

OBJECTIVES: This study compares in-hospital and long-term outcome after angioplasty in women and men. BACKGROUND: The recognition that coronary artery disease is the most common cause of death in women has increased interest in outcome studies of coronary artery disease in women. METHODS: Patients who had previous coronary revascularization and those who underwent angioplasty in the setting of acute myocardial infarction were excluded. Angioplasty was performed with standard methods. Clinical data were retrieved from a clinical data base and analyzed with standard statistical methods. RESULTS: There were 2,845 women and 7,940 men. The women were older (62 +/- 11 vs. 57 +/- 10 years) and had more hypertension (54.5% vs. 40.1%), diabetes (19.3% vs. 11.7%), grade III to IV angina (71.5% vs. 58.4%) and congestive failure (4.3% vs. 2.1%) than men (all p < 0.0001). More men had a previous myocardial infarction (35.4% vs. 31.0%) and were taller and weighed more (all p < 0.0001). The men had lower ejection fractions and more multivessel disease (31.0% vs. 25.2%) (both p < 0.0001). In women there was a trend toward more Q wave myocardial infarctions (1.1% vs. 0.75%, p = 0.10), and hospital mortality was higher (0.7% vs. 0.1%, p < 0.0001). Angina at follow-up was more common in women 40.2% vs. 26.7%, p < 0.0001). The multivariate correlates of in-hospital death were short stature, reduced ejection fraction and multivessel disease, with trends for older age and female gender. Five-year survival was 95% in men and 92% in women (p = 0.0002). However, female gender was not a multivariate correlate of long-term survival and was accounted for by other characteristics, primarily age. The multivariate correlates of long-term survival were older age, congestive failure, reduced ejection fraction, multivessel disease, diabetes, hypertension and a trend for severe angina. No difference between women and men was noted in long-term freedom from myocardial infarction. There were more additional procedures in men than in women. CONCLUSIONS: Despite higher in-hospital mortality, long-term mortality and clinical outcome were similar in both genders when age and body habitus were accounted for.

Age Distribution↗
PubMed1993

Effect of restenosis at one previously dilated coronary site on the probability of restenosis at another previously dilated coronary site.

The purpose of this study was to determine whether in patients with 2 sites dilated by percutaneous transluminal coronary angioplasty (PTCA), the sites undergo restenosis independently. Although restenosis remains a critical limitation after PTCA, there is little information separating site- and patient-dependent determinants of restenosis. In particular, if patients with 2 sites dilated have restenosis at 0 or 2 sites more frequently and at 1 site less frequently than expected by random chance, then patient-related factors may be important in the restenosis process. The source of data was the clinical data base at Emory University. Patients who had previously coronary surgery or PTCA, and those who underwent PTCA in the setting of acute myocardial infarction were excluded. In all, 515 patients with 2 sites dilated undergoing angiographic restudy at 4 months to 1 year after PTCA formed the study population. Site 1 was the first site dilated. At site 1, 224 of 515 sites (45%) were restenotic, and at site 2, 193 (33%) were restenotic. Multiple clinical and angiographic variables were analyzed as possible correlates of restenosis. The most powerful univariate and multivariate correlate of restenosis at either site 1 or 2 was the behavior of the other site. If site 2 was patent, then site 1 was restenotic 28% of the time compared with 69% if site 2 was restenotic. If site 1 was patent, site 2 was restenotic 20% of the time compared with 60% if site 1 was restenotic. This relation was stronger if the 2 sites were in the same coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Coronary surgery and coronary angioplasty in patients with two-vessel coronary artery disease.

There is uncertainty regarding the selection between coronary artery surgery and angioplasty in many patients with coronary artery disease, especially in those with 2-vessel disease. Whereas randomized trials will provide the best possible and most detailed data comparing therapy in these patients, clinical data bases may be used to provide a current perspective. The purpose of this study was to compare the long-term outcome of patients with 2-vessel coronary artery disease undergoing coronary surgery or angioplasty at Emory University hospitals in the years 1984 and 1985. Data on all patients with 2-vessel disease diagnosed at Emory University who underwent elective angioplasty or coronary surgery in the years 1984 and 1985 were compared. Categoric variables were analyzed by chi-square and continuous variables by unpaired t test. Survival was determined by the Kaplan-Meier method and differences in survival by the Mantel-Cox method. Determinants of survival were determined by Cox model analysis. There were 415 angioplasty patients and 454 surgical patients. Surgical patients were older and had more frequent systemic hypertension, diabetes mellitus, prior myocardial infarction, severe angina and congestive failure, and more significant narrowing in the left anterior descending coronary artery, totally occluded vessels and left ventricular dysfunction than did angioplasty patients. Complete revascularization was achieved more often in surgical patients. There was no difference in Q-wave myocardial infarction in the hospital. No angioplasty patient died compared with 1.1% of surgical patients (p = 0.03). Whereas 5-year survival was 93% in angioplasty patients and 89% in surgical patients (p = 0.11), there was no difference in risk-adjusted survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

In vitro Ca deposition by rat matrix vesicles: is the membrane association of alkaline phosphatase essential for matrix vesicle-mediated calcium deposition?

1. Phosphatidylinositol phospholipase C (PI-PLC) treatment of rachitic rat matrix vesicles (MVs) released about 80% of membrane-bound alkaline phosphatase (ALP), AMPase, PPiase into the media. 2. About 20% hydrolytic activity was not released from MV membranes by PI-PLC treatment. 3. SDS-polyacrylamide gel electrophoresis and Western blot analysis showed only one immunoreactive protein corresponding to the molecular weight of ALP present in the soluble fraction after PI-PLC treatment. 4. The specific activity of the released ALP was at least 5-fold higher than the residual activity. 5. After PI-PLC treatment, MVs also demonstrated an 80% reduction of AMP- or beta GP-dependent calcium deposition. 6. The soluble fraction containing 80% of ALP activity was unable to support calcium deposition. The mixing of the soluble and insoluble fractions after PI-PLC treatment failed to fully restore calcium-depositing activity.

Alkaline Phosphatase↗
PubMed1993

Long-term clinical follow-up in patients with angiographic restudy after successful angioplasty.

BACKGROUND: Restenosis remains a critical limitation after coronary angioplasty. There is little information comparing long-term prognosis in patients who suffer from restenosis and others who do not. The purpose of this paper is to determine the clinical events in patients with restenosis or continued patency documented by restudy coronary arteriography. METHODS AND RESULTS: The source of data was the clinical data base at Emory University. Patients who had previous coronary surgery and patients who underwent angioplasty in the setting of acute myocardial infarction were excluded. A total of 3,363 patients undergoing angiographic restudy 4 months to 1 year after angioplasty were compared with 3,858 not undergoing restudy. In the restudy population, 1,570 had restenosis and 1,793 had patent arteries at all sites dilated. The restenosis patients were older and had more hypertension, more diabetes, more severe angina, more multivessel coronary artery disease, more severe stenoses, and less satisfactory original results. At restudy, in patients without restenosis, 38.7% had angina versus 70.7% in patients with restenosis (p < 0.0001). There were few deaths in the first 6 months. At 6 years, the survival rate was 0.95 without restenosis and 0.93 with restenosis (p = 0.16). At 6 months and 6 years, freedom from myocardial infarction was 0.97 and 0.88 without restenosis and 0.93 and 0.85 with restenosis (p = 0.0001). On multivariate analysis, restenosis was an independent correlate of myocardial infarction but not mortality. At 6 months and 6 years, freedom from coronary bypass surgery was 0.99 and 0.94 without restenosis and 0.91 and 0.78 with restenosis (p < 0.0001). At 6 months and 6 years, freedom from repeat angioplasty was 0.96 and 0.76 without restenosis and 0.44 and 0.20 with restenosis (p = 0.0001). The highest event rates were noted in the patients with restenosis with recurrent chest pain. Patients not undergoing restudy differed somewhat from the study group, and there were far fewer repeat revascularization procedures in the group not undergoing restudy. CONCLUSIONS: Patients with restenosis are more likely to have recurrent angina pectoris. Although there is no or little difference in survival, there is a difference in myocardial infarction rate in the patients with and without restenosis. The low myocardial infarction and death rates in the group suffering restenosis may be related to repeat revascularization in these patients; the principal events in the restenosis population are frequent repeat revascularization procedures.

Aged↗
PubMed1992

Initial management and long-term clinical outcome of restenosis after initially successful percutaneous transluminal coronary angioplasty.

Restenosis remains a critical limitation after percutaneous transluminal coronary angioplasty (PTCA). The clinical experience with restenosis was reviewed in 1,490 patients who had restenosis of at least 1 site within 1 year of their PTCA. The source of data was the clinical database at Emory University. Patients who had previous coronary bypass surgery or PTCA and patients who underwent PTCA in the setting of acute myocardial infarction were excluded. When restenosis was angiographically documented, 363 were treated medically, 1,051 with repeat PTCA, and 76 with coronary bypass surgery. In the repeat PTCA group there were 778 patients who originally had 1-vessel disease and 273 with multiple vessel disease. Re-dilatation of restenotic sites was performed in 95%. Angiographic success of all lesions dilated was achieved in 99%. Coronary bypass surgery was required in 2.5% of patients with restenosis first treated with repeat PTCA. One patient with multiple vessel disease died. Coronary bypass surgery was performed in fewer patients aged greater than or equal to 65 years, but more patients with multiple vessel disease. Two (2.6%) of the coronary bypass surgery patients had Q-wave myocardial infarction and there were no deaths. In the PTCA group, 5-year actuarial survival was 95%, and cardiac survival 96%. Freedom from cardiac events or further revascularization procedures was 51% at 5 years. Patients treated with PTCA and medically treated patients had similar cardiac survival rates. The most important correlates of cardiac survival were age and the presence of diabetes mellitus. At 5 years, cardiac survival without diabetes was 97 and 83% with diabetes (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Comparison of normal and rachitic rat matrix vesicles.

Accumulated information about MVs in PO4-deficient rachitic rats shows them to be normal in most aspects. Both normal and rachitic MVs show the same ultrastructural features and selective spatial distribution in the growth plate, and both contain a nearly identical array of major proteins. Rachitic and normal MVs show the same avidity to calcify in vivo and in vitro. A slightly greater specific activity of ALP in rachitic MVs may enhance their calcifiability. We conclude that rachitic rat MVs are essentially 'normal' and can be used as an adequate model to study the mechanism of biological calcification.

Alkaline Phosphatase↗
PubMed1992

Presence and specific concentration of carbonic anhydrase II in matrix vesicles.

Matrix vesicles were isolated from the epiphyseal growth plates of normal weanling rats, and the presence of carbonic anhydrase II was demonstrated by Western blotting and ultrastructural immunolocalization using the immunogold technique. Total carbonic anhydrase activity was assayed and showed a statistically significant increase in matrix vesicles as compared to normal rat chondrocytes derived from the same growth plates. These results are the first to establish the presence of carbonic anhydrase in matrix vesicles.

Animals↗
PubMed1992

Bone-inducing agent (BIA) from cultured human Saos-2 osteosarcoma cells.

The Saos-2 line of human osteosarcoma cells was established in culture in 1975. These cells produce a large amount of alkaline phosphatase but little or no matrix in vitro, and are unable to grow when transplanted into athymic mice. We decided to test our local strain of Saos-2 cells for bone-inducing ability in the skeletal muscle of athymic mice by implanting freeze-dried, acetone-defatted cells, with and without a collagen carrier. A bone-inducing activity (BIA) thus was demonstrated in 88% of 90 implants of devitalized Saos-2 cells. In further studies, we have used guanidinium hydrochloride (Gu-HCl) to extract, solubilize, and remove the Saos bone-inducing agent(s) in an active state which when reprecipitated by aqueous dialysis was able to induce ultrastructurally typical endochondrial bone formation in nude mouse muscle in 92% of 48 implants. This preliminary report is offered to alert investigators to the presence of an extractable BIA in Saos-2 cells.

Animals↗