Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The advantages of an endothelial cell surface on a prosthetic graft may be compromised by endothelial cell production of mitogens for smooth muscle cells. To study platelet-derived growth factor (PDGF) production by cells lining prosthetic grafts, 15 beagles underwent placement of 20 to 22 cm long, 8 mm inner diameter, expanded polytetrafluoroethylene thoracoabdominal aortic grafts, of which seven were seeded with autologous jugular vein endothelial cells, and eight were unseeded control grafts. Grafts and adjacent arteries were explanted after 4 weeks, divided into segments, and studied in organ culture. Platelet-derived growth factor production during a 72-hour incubation period was measured by radioreceptor assay. Midgraft segments of seeded grafts produced significantly more PDGF than control grafts, 43 +/- 8 pg/cm2 and 22 +/- 5 pg/cm2, respectively (mean +/- SEM), p less than 0.05. Platelet-derived growth factor production correlated directly with endothelial cell coverage on graft segments as measured by scanning electron microscopy (r = 0.63, p = 0.01), and inversely with platelet deposition (r = -0.48, p = 0.07). For all dogs, PDGF production by the distal aorta was significantly greater than that by the proximal aorta, 89 +/- 6 and 17 +/- 4 pg/cm2, respectively (p less than 0.0001). These results suggest that endothelial cells on prosthetic vascular grafts are a significant source of PDGF. Furthermore, the higher PDGF production by the distal arteries may offer an explanation for the clinical finding of more severe intimal hyperplasia adjacent to the distal anastomosis.
 ...
PMID:Platelet-derived growth factor production by canine aortic grafts seeded with endothelial cells. 156 May 61

Although platelet-derived growth factor (PDGF) is thought to be a major mediator of atherosclerotic disease, the pathophysiology of diabetic vasculopathy, including atherosclerosis, is unclear. By means of an enzyme immunoassay that used a monoclonal antibody against human PDGF-B chain, PDGF-like immunoreactivity was determined in serum, platelet-poor plasma, and platelet lysate of 28 patients with non-insulin-dependent diabetes mellitus and 11 control subjects. Growth-promoting activity was also measured by tritiated thymidine incorporation into DNA of cultured human fibroblasts. The PDGF-like immunoreactivity in serum was correlated (r = 0.42; p less than 0.01) with that in platelet lysate prepared from a fixed volume of blood. Furthermore, a correlation (r = 0.70; p less than 0.001) was found between the PDGF-like immunoreactivity and the growth-promoting activity in platelet lysate but not in serum. There was no significant difference between patients with diabetes and control subjects with respect to the PDGF-like immunoreactivity in serum or in platelet lysate (38.2 +/- 2.2 vs 42.8 +/- 3.1 ng/ml or 49.1 +/- 2.4 vs 56.2 +/- 3.4 ng/mg protein; mean +/- SEM). In contrast, the serum growth-promoting activity was lower (p less than 0.05) in patients with diabetes than in control subjects (88.1% +/- 7.1% vs 117.4% +/- 6.9%) and there was a negative correlation (r = -0.39; p less than 0.05) between the serum growth-promoting activity and the fasting plasma glucose level. The growth-promoting activity in platelet lysate of patients with diabetes did not differ from that of the control subjects (59.9% +/- 11.6% vs 65.9% +/- 11.2%).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Platelet-derived growth factor and growth-promoting activity in the serum samples and platelets of patients with non-insulin-dependent diabetes mellitus. 161 32

Growth factor-induced changes of cytosolic free calcium ion concentration ([Ca2+]i) and phosphatidylinositol (PI) turnover in cultured human retinal pigment epithelial (RPE) cells were studied, and their temporal relationship was compared. After a 24-hr serum depletion, RPE cells were loaded with fura-2/AM, and [Ca2+]i was analyzed using a digital imaging microscopy system. The resting [Ca2+]i in a single cultured human RPE cell was 153 +/- 1.5 nM (mean +/- the standard error of the mean [SEM], n = 105). The percentage of reactive cells that had Ca2+ transients induced by various growth factors were: epidermal growth factor, 18%; basic fibroblast growth factor (bFGF), 5%; nerve growth factor, 15%; platelet-derived growth factor (PDGF), 70%; insulin-like growth factor, 0%; fibronectin, 0%; insulin, 3%; and fetal bovine serum (FBS), 100%. The PDGF showed a peak concentration of 237 +/- 4.7 nM (mean +/- SEM, n = 67) and FBS, 774 +/- 34.5 nM (mean +/- SEM, n = 52). Chelation of the extracellular Ca2+ by EGTA made the resting and peak concentration lower. The Ca2+ transients occurred within 60 sec and lasted less than 5 min after the application of the growth factors. However, measurements of phosphoinositides in 24-hr serum-starved RPE cells revealed that growth factor-induced PI turnover was much slower than Ca2+ transients. In addition, FBS, bFGF, and PDGF increased the contents of inositol phosphate, inositol biphosphate, and inositol triphosphate (IP3) in RPE cells slowly up to 60 min except that PDGF showed a peak of IP3 at 15 min after stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Growth factor-induced cytosolic calcium ion transients in cultured human retinal pigment epithelial cells. 191 91

Despite its abundance of cell culture growth factors, serum does not enhance growth of the in vivo test system, the chick chorioallantoic membrane (CAM). Previously we have also shown that fibrinogen (Kabi) and its degradation products do not display mitogenic activity on the CAM, but have now been surprised to find stimulation of DNA synthesis (up to 2.5-fold) 18 h after application of human plasma [incorporation of [3H]thymidine control mean +/- SEM 8442 +/- 1338 dpm/CAM (n = 8); test--20 199 = 3491 (n = 6); t-test P less than 0.01)]. Plasma (platelet-rich and platelet-poor) was freshly prepared by minicolumn removal of citrate at 16 degrees C; 0.3 ml aliquots of 10% human plasma were applied to the CAM and groups were fixed at various time intervals. Cross-sections were examined histologically, including immunoperoxidase studies with antihuman fibrinogen which does not cross react with chick fibrinogen, and autoradiography with [3H]thymidine. Initially, a layer of plasma was observed on the surface of the CAM. After 1 h a condensed fibrillar layer of fibrin was formed and was still present at 6 h. This was associated with increased [3H]thymidine labelling of the surface layer of the CAM. By 18 h the fibrin had disappeared, indicating that it had been lysed by the CAM, and widespread [3H]thymidine labelling was observed. No inflammatory cell infiltrate was apparent, but marked oedema developed. Oedema alone was observed in controls receiving serum or Dulbecco buffer. Both platelet-rich and platelet-free plasma gave stimulation of mitogenic activity, implying that platelet-derived growth factor is not involved in the stimulation of the CAM.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Artificial exudate: stimulation of cell proliferation by plasma not serum is associated with fibrinolysis. 213 31

Long-term bone marrow cultures are dependent on the formation in vitro of an adherent cell layer that supports hematopoiesis. We have grown bone-marrow-adherent cells, termed stromal colony-forming units, or CFU-ST, as isolated adherent colonies, and examined some of their growth requirements. Bone marrow mononuclear cells separated from aspirates by density centrifugation and cultured in medium supplemented with fetal calf serum or human plasma gave rise to adherent colonies (CFU-ST). An average of 23.4 +/- 2.1 (mean +/- SEM, n = 19) CFU-ST were produced by 10(5) bone marrow mononuclear cells. CFU-ST could not be cultured from similarly prepared peripheral blood mononuclear cells. The colonies were composed of spindle cells, flat cells, and fat-containing cells, with all three types often present in the same colony, suggesting derivation from a common progenitor. Cells were negative for nonspecific esterase and factor VIII antigen. Hydrocortisone added to the cultures at concentrations of 10(-7) M induced the formation of adipose cells in the center of one-third to one-half of the colonies but did not affect CFU-ST number. Human platelet-poor plasma and platelet-rich plasma were substituted for fetal calf serum in the medium. When all determinations for four experiments were averaged, platelet-rich plasma gave 17.8 +/- 1.2 (mean +/- SEM, n = 16) colonies, whereas platelet-poor plasma gave only 0.2 +/- 0.1 colonies (n = 15). When purified platelet-derived growth factor (PDGF) was added to platelet-poor plasma, growth of CFU-ST was enhanced, and a dose-response relationship was found between size of colonies and concentration of added PDGF. Granulocyte-macrophage colony stimulating factor added to cultures had no effect on the growth of CFU-ST.
 ...
PMID:Human bone marrow stromal cell colonies: response to hydrocortisone and dependence on platelet-derived growth factor. 301 48

Exposure of porcine vascular smooth muscle cells to platelet-derived growth factor (PDGF; 18-180 ng/ml) but not epidermal growth factor (EGF; 30 ng/ml), somatomedin C (SmC; 30 ng/ml), or insulin (10 microM), results in a rapid, reversible, time- and concentration-dependent disappearance of vinculin staining in adhesion plaques; actin-containing stress fibers also become disrupted following exposure of cells to PDGF. Disappearance of vinculin staining from adhesion plaques is also caused by 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 200-400 nM), though the time course of the disappearance of vinculin staining under these conditions takes longer than in cells exposed to PDGF. The PDGF-induced removal of vinculin from adhesion plaques was inhibited in a concentration-dependent fashion by 8-(N,N-diethylamino) octyl-3,4,5-trimethoxybenzoate (TMB-8; 0.25-4 microM) and leupepetin (2-300 microM), and by n-alpha-tosyl-L-lysine chloromethylketone (TLCK; 100 microM) and trifluoperazine (TFP; 2.5 microM). Addition of PDGF to vascular smooth muscle cells caused a rapid, transient increase in cytosolic free calcium, from a basal resting level of 146 +/- 6.9 nM (SEM, n = 62) to 414 +/- 34 nM (SEM, n = 22) as determined using the calcium-sensitive indicator Fura-2 and Digitized Video Microscopy. This increase in cellular calcium preceded the disappearance of vinculin from adhesion plaques and was partially blocked by pretreatment of cells with TMB-8 but not leupeptin. This rise in cytosolic free calcium was found to occur in approximately 80% of the sample population and displayed both spatial and temporal subcellular heterogeneity. Exposure of cells to TPA (100 nM) did not result in a change in cytosolic free calcium. Both PDGF (20 ng/ml) and TPA (100 nM) caused cytosolic alkalinization which occurred after PDGF-induced disruption of vinculin from adhesion plaques, as determined using the pH-sensitive indicator BCECF and Digitized Video Microscopy. PDGF stimulated DNA synthesis and vinculin disruption in a similar dose-dependent fashion. Both could be inhibited by leupeptin or TMB-8. These results suggest that 1) exposure of vascular smooth muscle cells to PDGF is associated with the disruption of vinculin from adhesion plaques, 2) PDGF-induced vinculin disruption is regulated by an increase in cytosolic calcium (but not cytosolic alkalinization), and involves proteolysis; 3) activation of protein kinase C also causes vinculin removal from adhesion plaques but by a calcium-independent mechanism, and 4) the cellular response to PDGF-stimulated increases in cytosolic free calcium is heterogeneous.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Platelet-derived growth factor-induced alterations in vinculin distribution in porcine vascular smooth muscle cells. 312 Nov 90

Cultured endothelial cells secrete a platelet-derived growth factor-like molecule (PDGFc). We examined the effects of purified human alpha-thrombin on the production of PDGFc in cultures of human umbilical vein endothelial cells (HUVE) using a specific radioreceptor assay for PDGF. Addition of physiologically relevant concentrations of alpha-thrombin (0.1 to 10 U/ml) induced a time- and dose-dependent increase in the release of PDGFc into the culture medium. Significant stimulation of PDGFc release was observed as early as 1.5 h after addition of alpha-thrombin (10 U/ml) with a 4.9 +/- 1.1 fold increase at 24 h (mean +/- SEM of nine experiments, P less than 0.01). alpha-Thrombin treatment of HUVE did not affect cell viability as assessed by trypan blue dye exclusion. The receptor binding of PDGFc secreted by HUVE in response to alpha-thrombin was inhibited by monospecific antibody to purified human PDGF indicating that the molecule(s) is closely related to PDGF. alpha-Thrombin inactivated with diisopropylfluorophosphate was without stimulatory effect. Lysis of HUVE by repeated cycles of freeze/thaw released minimal PDGFc (less than 0.3 ng per 10(6) cells) compared to levels of PDGFc released into supernatant medium in response to alpha-thrombin (greater than 5.0 ng per 10(6) cells after a 24-h incubation with 10 U/ml alpha-thrombin). Moreover, incubation of freeze/thaw lysates of HUVE with alpha-thrombin failed to release PDGFc. Over a 3-h time course, however, alpha-thrombin-induced secretion of PDGFc was not prevented by cycloheximide. We conclude that alpha-thrombin induces secretion of PDGFc from HUVE by a nonlytic mechanism requiring the serine esterase activity of the enzyme. Although this effect does not initially require de novo protein synthesis, it does require cell-mediated conversion of PDGFc from an inactive to an active form.
 ...
PMID:Alpha-thrombin induces release of platelet-derived growth factor-like molecule(s) by cultured human endothelial cells. 374 65

Several studies have focused on retinal pigment epithelial (RPE) cell proliferation as an important event in proliferative vitreoretinopathy (PVR). Little attention has been given to the question of how RPE cells gain access to the vitreous cavity where proliferation occurs. We have recently demonstrated that the serum components fibronectin and platelet-derived growth factor stimulate and direct RPE migration in vitro. In this study, we used this same in vitro technique to examine vitreous aspirates from 13 eyes with PVR, five eyes with macular puckers, and three eyes with uncomplicated retinal detachments for their ability to stimulate RPE migration. We found that aspirates from eyes with PVR stimulated RPE migration to a much greater extent than aspirates from eyes with macular pucker and uncomplicated retinal detachments. The ability to stimulate RPE cell migration correlated with high levels (mean +/- SEM, 178 +/- 67 mg/L) of immunoreactive fibronectin.
 ...
PMID:Vitreous aspirates from patients with proliferative vitreoretinopathy stimulate retinal pigment epithelial cell migration. 403 35

Chronic hypoxia produces pulmonary artery hypertension and remodeling of pulmonary arteries with hypertrophy of smooth muscle in the media and extension of smooth muscle into more distal small precapillary arteries. The present study investigated the influence of heparin, an inhibitor of platelet-derived growth factor, and of the clotting cascade on this remodeling. Mice maintained in room air or 10% O2 for 26 days were treated with low-dose heparin at 75 units/kg or high dose heparin at 300 units/kg. Pulmonary hypertension and right ventricular hypertrophy developed in the hypoxic mice compared with the room air mice as evidenced by the greater (p less than 0.05) right ventricular systolic pressure (36 +/- 4 SEM versus 21 +/- 1 mmHg) and the increase (p less than 0.05) in right heart weight/left ventricular plus septal weight (35 +/- 1.6 SEM versus 25.2 +/- 1.3). Hypoxia also induced smooth muscle hypertrophy in small pulmonary arteries, with an increase (p less than 0.05) in the percent media thickness/vascular diameter from 5.7 +/- 1 SEM to 13.3 +/- 3 and an apparent decrease (p less than 0.05) in distal small pulmonary arteries from 4.4 +/- 0.2 SEM to 2.05 +/- 0.1 per 100 alveoli. High-dose heparin partially but significantly (p less than 0.05) prevented the pulmonary artery hypertension (right ventricular systolic pressure of 28 +/- 2 mmHg), the right ventricular hypertrophy (right ventricular weight/left ventricular plus septal weight of 30.1 +/- 1) and remodeling of distal small pulmonary arteries (media thickness/vascular diameter of 8.4 +/- 1%, small pulmonary artery/100 alveoli of 3.63 +/- 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Impairment of hypoxic pulmonary artery remodeling by heparin in mice. 622 26

Acromegaloidism is a syndrome characterized by features of acromegaly without biochemical evidence of excessive GH or somatomedin production. We searched for a growth factor in the serum of patients with this syndrome. Growth-promoting activity was measured by determining the stimulatory effect of whole and fractionated serum on colony formation by human erythroid progenitors in vitro. Sera from five subjects with acromegaloidism gave a mean (+/- SEM) stimulated colony growth of 211 +/- 4.0 colonies, in contrast to normal sera which yielded a mean colony growth of 100 +/- 11.0 (n = 9; P less than 0.001). When serum was chromatographed on a Sephadex G-200 column, the maximal stimulation of colony growth was found in the fractions coinciding with the descending slope of the second protein peak. Based on gel filtration chromatography, the estimated molecular weight was 70,000 daltons. Epidermal growth factor, nerve growth factor, fibroblast growth factor, and platelet-derived growth factor resulted in no substantial stimulation of colony growth under the conditions used. Although the erythroid progenitor cells of a Laron dwarf were unresponsive to 200 ng/ml human GH, they were clearly stimulated by serum from a patient with acromegaloidism. The present study describes the presence of a heretofore unidentified growth factor in the serum of subjects with acromegaloidism. This factor also stimulated the erythroid precursor cells of a Laron dwarf whose cells were unresponsive to GH. The physiological role of this growth factor in normal man as well as its pathogenic role in subjects with acromegaloidism remain to be established.
 ...
PMID:A unique growth factor in patients with acromegaloidism. 686 75


1 2 3 Next >>