Search PubMed⌕ Search

Biomedical subjects

R Grose

Publications and source records attributed to R Grose.

At least 19 recordsLinked to original sources
PubMed2005

Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling.

The upregulation of TGF-beta1 and integrin expression during wound healing has implicated these molecules in this process, but their precise regulation and roles remain unclear. Here we report that, notably, mice lacking beta(3)-integrins show enhanced wound healing with re-epithelialization complete several days earlier than in wild-type mice. We show that this effect is the result of an increase in TGF-beta1 and enhanced dermal fibroblast infiltration into wounds of beta(3)-null mice. Specifically, beta(3)-integrin deficiency is associated with elevated TGF-beta receptor I and receptor II expression, reduced Smad3 levels, sustained Smad2 and Smad4 nuclear localization and enhanced TGF-beta1-mediated dermal fibroblast migration. These data indicate that alpha(v)beta(3)-integrin can suppress TGF-beta1-mediated signaling, thereby controlling the rate of wound healing, and highlight a new mechanism for TGF-beta1 regulation by beta(3)-integrins.

Animals↗
PubMed2000

Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes.

beta 1 integrins are ubiquitously expressed receptors that mediate cell-cell and cell-extracellular matrix interactions. To analyze the function of beta1 integrin in skin we generated mice with a keratinocyte-restricted deletion of the beta 1 integrin gene using the cre-loxP system. Mutant mice developed severe hair loss due to a reduced proliferation of hair matrix cells and severe hair follicle abnormalities. Eventually, the malformed hair follicles were removed by infiltrating macrophages. The epidermis of the back skin became hyperthickened, the basal keratinocytes showed reduced expression of alpha 6 beta 4 integrin, and the number of hemidesmosomes decreased. Basement membrane components were atypically deposited and, at least in the case of laminin-5, improperly processed, leading to disruption of the basement membrane and blister formation at the dermal-epidermal junction. In contrast, the integrity of the basement membrane surrounding the beta 1-deficient hair follicle was not affected. Finally, the dermis became fibrotic. These results demonstrate an important role of beta 1 integrins in hair follicle morphogenesis, in the processing of basement membrane components, in the maintenance of some, but not all basement membranes, in keratinocyte differentiation and proliferation, and in the formation and/or maintenance of hemidesmosomes.

Animals↗
PubMed2000

The angiogenesis inhibitor endostatin impairs blood vessel maturation during wound healing.

Endostatin is a cleavage product of collagen XVIII that strongly inhibits tumor angiogenesis. To determine if endostatin affects other angiogenic processes, we generated full-thickness excisional wounds on the back of mice that were systemically treated with recombinant murine endostatin. No macroscopic abnormalities of the wound healing process were observed. Histological analysis revealed normal wound contraction and re-epithelialization, but a slight reduction in granulation tissue formation and reduced matrix deposition at the wound edge. The blood vessel density in the wounds of endostatin-treated mice was not affected. However, ultrastructural analysis demonstrated severe abnormalities in blood vessel maturation. The wound vessels in the endostatin-treated mice were narrowed or closed with an irregular luminal surface, resulting in a severe reduction in the number of functional vessels and extravasation of erythrocytes. Endostatin treatment did not affect the expression level and localization of collagen XVIII mRNA and protein. Furthermore, the angiogenesis regulators vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 were normally expressed in the wounds of endostatin-treated mice. However, expression of the major wound matrix proteins fibronectin and collagens I and III was significantly reduced. This reduction is likely to explain the reduced density of the wound matrix. Our results demonstrate that endostatin treatment reduces the number of functional blood vessels and the matrix density in the granulation tissue, but does not significantly affect the overall wound healing process.

Angiogenesis Inhibitors↗
PubMed1996

Early postoperative angiographic assessment of radial grafts used for coronary artery bypass grafting.

UNLABELLED: Despite a revival of interest in using the radial artery as an alternative conduit for myocardial revascularization, little angiographic documentation of early postoperative results has been presented, particularly in North America. Accordingly, 60 of 150 patients who underwent coronary artery bypass with radial arteries from November 1993 to July 1995 have had postoperative cardiac catheterization at our institution. The patency rate of the radial artery grafts was 95.7% (90 of 94 grafts patent) with an average internal diameter of 2.51 mm. Four radial artery grafts showed diffuse narrowing. The patency rate of the internal thoracic artery grafts was 100% with an average internal diameter of 2.25 mm. Three of 62 grafts demonstrated diffuse narrowing. Two of 24 (7.7%) saphenous vein grafts were occluded; the average internal diameter was 3.23 mm. The internal thoracic artery, the radial artery, and saphenous vein grafts were, respectively, 7.5%, 19.5%, and 53.3% larger than the anastomosed native coronary arteries. Graft-dependent flow was found in 81.1% of the radial artery grafts. CONCLUSION: The results of this study demonstrate that the short-term patency rate of radial artery grafts is excellent.

Adult↗
PubMed1993

Coronary angioplasty of anomalous right coronary arteries.

We report 2 cases of successful angioplasty of anomalous right coronary arteries originating above the sinotubular line at the junction of the right and left sinus of Valsalva. The use of Amplatz left guiding catheters provided optimal support for performing angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1987

The Thrombolysis in Myocardial Infarction (TIMI) phase II pilot study: tissue plasminogen activator followed by percutaneous transluminal coronary angioplasty.

The Thrombolysis in Myocardial Infarction (TIMI) Study Group is investigating whether percutaneous transluminal coronary angioplasty or intravenous beta-receptor blockers, or both, are useful adjuncts to recombinant tissue-type plasminogen activator (rt-PA) in the treatment of patients with acute myocardial infarction (TIMI II study). A total of 317 patients with acute myocardial infarction were treated an average of 2.7 hours after the onset of chest pain during the course of a nonrandomized pilot investigation with 150 mg of rt-PA given over 6 hours. This dose of rt-PA resulted in a high rate of infarct-related coronary artery patency (82 and 87% of patients catheterized an average of either 1 or 32 hours after entry, respectively) and a low 21 day mortality rate of 4.4%. Coronary angioplasty was performed successfully in greater than 90% of patients with appropriate anatomy and in greater than 50% of those treated with rt-PA. In 75 patients treated within 2 hours of the onset of chest pain only 2 (2.7%) were dead by 6 weeks. However, five cases of intracranial hemorrhage were noted, and the rt-PA dose was subsequently reduced to 100 mg given over 6 hours. The TIMI II design and the results of the TIMI II pilot study are discussed.

Adrenergic beta-Antagonists↗
PubMed1986

Angiographic and hemodynamic correlations in hypertrophic cardiomyopathy with intracavitary systolic pressure gradients.

To correlate angiographic and hemodynamic events in hypertrophic cardiomyopathy (HC), 14 patients with HC were investigated using pressure recordings and caudocranial left anterior oblique contrast angiography. Patients were separated into 2 groups on the basis of the presence (group I) or absence (group II) of systolic anterior motion of the anterior mitral leaflet on caudocranial angiography. In group I (10 patients), the pressure gradient could be recorded with the left ventricular (LV) catheter in the nonobliterated inflow region of the left ventricle. Simultaneous micromanometer tracings and caudocranial angiography revealed that contact between the anterior mitral leaflet and the ventricular septum was an early systolic event (occurring 136 +/- 33 ms after the R wave of the electrocardiogram) and was coincident with the onset of the pressure gradient. Cavitary obliteration was present in only 7 of 10 patients in group I, and occurred late in systole well after the peak gradient (292 +/- 28 ms after the R wave). In group II (4 patients), the pressure gradients could be recorded only from the obliterated portion of the ventricle distal to the level of the papillary muscles. Total LV cavitary obliteration was present in all group II patients. In 1 patient, simultaneous micromanometer pressure recording and caudocranial angiography revealed that cavitary obliteration preceded the peak gradient by 40 ms. Thus, in group I patients the onset of the pressure gradient is coincident with mitral leaflet-septal contact, while cavitary obliteration is an inconsistent late systolic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1986

Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure.

The effects of dobutamine and intravenous milrinone on systemic hemodynamics, coronary blood flow and myocardial metabolism were studied in 11 patients with severe congestive heart failure. Although milrinone and dobutamine similarly increased cardiac index from 1.9 +/- 0.4 to 2.5 +/- 0.4 liters/min per m2 (p less than 0.001) and from 1.9 +/- 0.4 to 2.8 +/- 0.8 liters/min per m2 (p less than 0.001), respectively, milrinone decreased left ventricular end-diastolic pressure to a greater extent than dobutamine, that is, from 26 +/- 6 to 12 +/- 8 mm Hg (p less than 0.001) versus 26 +/- 8 to 20 +/- 8 mm Hg (p less than 0.001). In contrast to dobutamine, milrinone significantly reduced mean systemic arterial and right atrial pressures. Dobutamine increased the first derivative of left ventricular pressure (dP/dt) from 1,013 +/- 309 to 1,360 +/- 538 mm Hg/s (p less than 0.01) but milrinone did not. Similarly, blood flow and myocardial oxygen consumption were increased by dobutamine from 152 +/- 87 to 187 +/- 118 ml/min (p less than 0.05) and from 17.7 +/- 10.9 to 21.5 +/- 14.9 ml O2/min (p less than 0.05), respectively, but were unchanged by milrinone. Both drugs significantly decreased coronary vascular resistance and myocardial oxygen extraction but did not change myocardial lactate extraction. Thus, dobutamine and milrinone produce similar improvement in cardiac index. However, dobutamine increases myocardial oxygen consumption, whereas milrinone does not. This difference can probably be explained by the substantial vasodilating properties of milrinone.

Aged↗
PubMed1986

Effects of milrinone on left ventricular performance and myocardial contractility in patients with severe heart failure.

The potent vasodilating properties of the bipyridine derivatives confounds the assessment of changes in contractility as measured by peak positive left ventricular dP/dt and explains why the positive inotropic action of these agents has not been consistently demonstrated in patients with ventricular dysfunction. Therefore we studied the individual dose-response effects of intravenous milrinone on myocardial contractility as measured by peak positive left ventricular dP/dt in the context of concurrent changes in ventricular filling pressure. Incremental doses of milrinone caused a dose-related increase in peak positive left ventricular dP/dt in six of 11 patients. Peak positive left ventricular dP/dt was unchanged in four patients and reduced in one patient, all of whom experienced a substantial fall in left ventricular filling pressure. Thus milrinone has a definite inotropic effect in addition to its potent vasodilating properties.

Animals↗
PubMed1985

Effects of a new cardiotonic agent, MDL-17,043, on myocardial contractility and left ventricular performance in congestive heart failure.

MDL-17,043, a newly synthesized imidazole derivative, has been shown to manifest both inotropic and peripheral vasodilating properties in experimental animals and to be effective when administered orally. Although MDL-17,043 has been demonstrated to inhibit cyclic adenosine monophosphate (AMP) phosphodiesterase activity in vitro, whether its inotropic activity derives from increased myocellular levels of cyclic AMP is not yet known. After intravenous administration of MDL-17,043 to seven patients with severe congestive heart failure (CHF) at the time of cardiac catheterization, the rate of left ventricular (LV) pressure rise increased almost immediately from a control of 878 +/- 161 to a peak of 1010 +/- 217 mm Hg/sec (p less than 0.01), while cardiac index tended to increase but not significantly. Subsequently, as mean aortic pressure decreased from 86.4 +/- 15.9 at control to 75.6 +/- 16.4 mm Hg (p less than 0.01), cardiac index rose from 1.87 +/- 0.35 at control to 2.30 +/- 0.27 L/min/m2 at peak effect (p less than 0.01), while pulmonary capillary wedge pressure fell from 23.7 +/- 5.1 to 13.1 +/- 4.6 mm Hg (p less than 0.01). Concomitantly, the rate of LV pressure rise returned to control value. Thus, intravenous administration of MDL-17,043 improves myocardial contractility and LV performance in patients with severe CHF. This manifest improvement in LV performance most probably results from both the positive inotropic and direct vasodilating effects of MDL-17,043.

Cardiotonic Agents↗
PubMed1984

Pulmonary arterial V waves in mitral regurgitation: clinical and experimental observations.

Pulmonary arterial early diastolic waves (V waves) were investigated in patients and experimental animals with mitral regurgitation. V waves exceeding systolic pressure in the pulmonary artery were recorded in the main pulmonary artery with micromanometer catheters both in patients and animals, eliminating the possibility of catheter artifact. In experimental animals, aortic closure preceded pulmonic closure by 33 +/- 12 msec at baseline. With the creation of acute mitral insufficiency, a pulmonary arterial V wave occurred in six of eight animals. Early pulmonic valve closure occurred only in the six animals with a pulmonary arterial V wave. In these animals, pulmonic closure preceded aortic closure by 28 +/- 7 msec during mitral insufficiency (p less than .05). Of 70 patients with severe mitral regurgitation at cardiac catheterization, 14 had a pulmonary arterial V wave. In five patients recordings with micromanometer catheters were made and early pulmonic closure was also observed in four of these patients who had pulmonary arterial V waves at rest or upon provocation. Patients with pulmonary arterial V waves had a more acute onset of symptoms, shorter duration of mitral regurgitation, higher pulmonary capillary wedge V waves, and lower pulmonary arterial resistances than patients without them and were more likely to have nonrheumatic mitral regurgitation.

Adult↗
PubMed1983

Dual left anterior descending coronary artery: angiographic description of important variants and surgical implications.

Twenty-three cases of an anatomic variant of the left anterior descending artery (LAD) are described. This variant is termed "dual LAD" and consists of two branches which supply the usual distribution of the LAD. One branch (short LAD) terminates in the proximal aspect of the anterior interventricular sulcus (AIVS). A second, longer branch has a variable course outside the AIVS and returns to the AIVS distally. The long LAD arose from the LAD proper in 21 cases and from the RCA in two cases. The initial course of the long LAD was on the epicardial surface of the left ventricle (17 cases), right ventricle (three cases), or within the interventricular septum (three cases). Recognition of these variants is important for correct surgical identification of the short and long LADs.

Adult↗
PubMed1983

Right ventricular function in valvular heart disease: relation to pulmonary artery pressure.

Right ventricular angiography was performed in 46 patients with acquired valvular heart disease and 8 normal subjects. Right ventricular ejection fraction (RVEF) correlated highly only with right ventricular peak systolic pressure (RVPSP) and mean pulmonary artery pressure, both in patients with and without tricuspid insufficiency. For the group, RVEF = -0.33 RVPSP + 63 (correlation coefficient [r] = -0.76, probability [p] less than 0.001). Of 20 patients with moderate or severe elevation of pulmonary artery pressure, 17 (85%) had an abnormally low ejection fraction (less than 47%), while 19 (73%) of 26 patients with normal or mildly elevated pulmonary artery pressure had a normal right ventricular ejection fraction. In seven patients with elevated pulmonary artery pressure, a second ventriculogram was performed during intravenous nitroglycerin administration. Nitroglycerin produced a significant decrease in right ventricular peak systolic pressure (59 +/- 22 to 49 +/- 18 mm Hg, mean +/- standard deviation) (p less than 0.05) and in end-systolic volume (71 +/- 16 to 59 +/- 11 m1/m2) (p less than 0.05), and an increase in ejection fraction (43 +/- 9 to 48 +/- 7%) (p less than 0.05). Thus, at least part of the depression of ejection fraction in patients with elevated pulmonary pressure is reversible with a decrease in pulmonary artery pressure.

Adult↗