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

We examined the effects of the tyrosine kinase (TK) inhibitors, genistein, and tyrphostin (RG-50864) on the contractile action of epidermal growth factor - urogastrone (EGF-URO), transforming growth factor-alpha (TGF-alpha), and other agonists in two smooth muscle bioassay systems (guinea pig gastric longitudinal muscle, LM, and circular muscle, CM). We also studied the inhibition by tyrphostin of EGF-URO stimulated protein phosphorylation in identical smooth muscle strips. The selective inhibition by genistein and tyrphostin of EGF-URO and TGF-alpha induced contraction, but not of carbachol- and bradykinin-mediated contraction, occurred at much lower concentrations (genistein, less than 7.4 microM (2 micrograms/mL); tyrphostin, less than 20 microM (4 micrograms/mL)) than those used in previously published studies with these TK inhibitors. In LM tissue, the IC50 values were for genistein 1.1 +/- 0.1 microM (0.30 micrograms/mL; mean +/- SEM) and 3.6 +/- 0.5 microM (0.74 micrograms/mL) for tyrphostin, yielding a molar potency ratio (GS: TP) of 1:3 in the longitudinal preparation. In CM tissue, the IC50 values were 3.0 +/- 0.3 microM (0.81 micrograms/mL) for genistein and 2.4 +/- 0.2 microM (0.49 micrograms/mL) for tyrphostin, yielding a molar potency ratio (GS:TP) of 1.0:0.8 in the circular strips. The inhibition by genistein and tyrphostin of EGF-URO and TGF-alpha mediated contraction was rapid (beginning within minutes) and was reversible upon washing the preparations free from the enzyme inhibitors. In intact tissue strips studied under bioassay conditions, tyrphostin (40 microM) also blocked EGF-URO triggered phosphorylation of substrates detected on Western blots using monoclonal antiphosphotyrosine antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine kinase inhibitors and the contractile action of epidermal growth factor-urogastrone and other agonists in gastric smooth muscle. 131 19

Somatostatin receptors (SS-R) were measured with in vitro receptor autoradiography using the SS analog 125I-[Tyr3]-SMS 201-995 as radioligand in 342 breast-tumor samples. In a group of 158 "small" tumor samples (mean section surface: 14 mm2 +/- 0.4; mean +/- SEM), 34 tumors (21%) were SS-R positive. In a group of 72 "large" tumor samples (mean size: 180 mm2 +/- 8; mean +/- SEM), 33 tumors (46%) were SS-R positive. In this second group, more than half of the tumors had a non-homogeneous distribution of SS-R, i.e., tumor regions within SS-R positive tumors were SS-R negative. In a group of 48 additional patients, we could show that primaries and their metastases, or double primaries from right and left breasts, or 2 primaries resected consecutively, could both occasionally be SS-R positive. Finally, in 71 SS-R-positive primary tumors, 18 tumor samples were found to have simultaneously Epidermal Growth Factor receptors (EGF-R); in 12 of these 18 cases, the 2 receptor types were not topographically overlapping. Whereas SS-R were located on tumor tissue, EGF-R were often seen on adjacent normal lobules and ducts. These results show that a subgroup of breast tumors contain SS-R, in several cases non-homogeneously distributed. Their location does not coincide with that of EGF-R. Metastasis of SS-R-positive primaries may be SS-R-positive, as are sometimes second primaries. For evaluation of SS-R incidence and distribution, autoradiography is of advantage, specially if it is performed on large tumor samples, since it allows precise identification of the tissue elements containing these receptors.
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PMID:Somatostatin receptor incidence and distribution in breast cancer using receptor autoradiography: relationship to EGF receptors. 216 44

EGF receptor was identified and its binding characteristics were determined. Buccal mucosa was obtained from 12 healthy volunteers (6 males and 6 females) and assayed individually for [125I]-EGF binding. The specific binding of [125I]-EGF to the receptor ranged from 2.85 to 6.12 fmol/mg protein. There was no significant difference in binding between male and female (4.31 +/- 0.61 versus 3.94 +/- 0.53 fmol/mg protein; mean +/- SEM). Individual tissue homogenates were pooled for Scatchard analysis and cross-linking experiments. Scatchard analysis produced curvilinear plots with a Kd of 0.71 nM and Bmax of 0.024 pmol/mg protein for the high-affinity binding sites, and Kd of 435 nM and Bmax of 9.92 pmol/mg protein for the low-affinity binding sites. To determine the molecular weight of the EGF receptor, the [125I]-EGF and receptor complex were cross-linked by DSS and subjected to SDS-PAGE. The autoradiogram of the gel revealed one major protein band of 160K and a minor band of 170 K, characteristics shared with the EGF receptors in other tissues. The study is thought to be the first to demonstrate the presence of the EGF receptor in human buccal tissue and to show its biochemical features.
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PMID:Identification of epidermal growth factor receptor in human buccal mucosa. 226 99

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)
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PMID:Platelet-derived growth factor-induced alterations in vinculin distribution in porcine vascular smooth muscle cells. 312 Nov 90

To evaluate further the action of epidermal growth factor - urogastrone (EGF-URO) in smooth muscle systems, we examined the effect of the peptide on guinea pig tracheal strips. The cumulative addition of EGF-URO to the organ bath resulted in a concentration-dependent tonic contraction without tachyphylaxis. The half-maximal contraction was obtained at 13 +/- 3 ng/mL EGF-URO (2 nM). The maximum contraction at 100 ng/mL approached 60% of that induced by 1 microM histamine. No significant difference in the EGF-URO-induced contraction was observed in the presence or absence of a functional epithelium. Preincubation with 1 microM indomethacin for 20 min abolished the action of EGF-URO. The contractile effect of EGF-URO was not affected by yohimbine, propranolol, atropine, tetrodotoxin, and esculetin. However, mepacrine caused inhibition by 37 +/- 7% (mean +/- SEM for n = 3). Verapamil (10 microM) inhibited the EGF-induced response by 62 +/- 5% (mean +/- SEM for n = 4); the response was also absent in Ca-free (1 mM EGTA) buffer. However, the response was restored after the readdition of calcium. Our results suggest that EGF-URO can modulate tracheal smooth muscle contractility via a cyclooxygenase product and raise the possibility that EGF-URO might play a role in controlling pulmonary smooth muscle tone in vivo.
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PMID:Contraction of guinea pig trachea by epidermal growth factor--urogastrone. 314 4

To clarify the source of human urine EGF, we studied EGF renal clearance in 20 healthy, young adult subjects. Immunoreactive EGF was measured hourly in EDTA plasma, heparin plasma, serum and urine of 12 males and 8 females during a 3 h study period. Plasma and urine creatinine and creatinine clearance were measured and calculated hourly. Mean (and SEM) creatinine clearance was similar in males and females (118 +/- 12 vs 105 +/- 6 ml/min). EGF was not detectable in plasma, whereas relatively high levels were measured in serum (2.5 +/- 0.25 vs 1.5 +/- 0.18 ng/ml in males and females respectively p less than 0.05). Urine EGF excretion averaged 1641 +/- 233 ng/h in males and 1507 +/- 191 ng/h in females (p greater than 0.05). A significant correlation was observed between urine creatinine and urine EGF concentrations in both male (r = 0.98, p less than 0.01) and female (r = 0.94, p less than 0.01) subjects. EGF immunoreactivity in urine and serum eluted from G-75 sephadex columns similarly to recombinant 6000 Mr hEGF. Urine excretion of EGF approximated 1.5 micrograms/h or 25 ng/mg creatine. The high concentrations of EGF found in urine in the face of non-detectable levels of EGF in plasma favor the hypothesis that EGF in urine is derived from kidney synthesis and secretion. The significant positive correlation between urine creatinine and urine EGF suggests a functional correlation between glomerular filtration and the process of tubular EGF excretion.
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PMID:The source of urinary epidermal growth factor in humans. 326 26

Saliva samples were obtained from volunteers either by spontaneous expectoration or after stimulation with citric acid (5%) and EGF was measured by a homologous radioimmunoassay. The mean +/- SEM of salivary human epidermal growth factor (hEGF) concentration in 70 males (aged 19-41) was 368.71 +/- 28.55 pmol/1 and 417.67 +/- 37.61 pmol/1 in 55 females (aged 19-45), P0.5. Values were found undetectable (32 pmol/1 in 6 prepubertal children. There was a tendency for hEGF to rise with age from about middle age but no significant racial or pregnancy related changes were observed. Stimulated sallivation with citric acid caused a fall in hEGF through a dilution effect. These results show that age has an important influence on the hEGF concentration of resting saliva.
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PMID:Epidermal growth factor EGF in human saliva: effect of age, sex, race, pregnancy and sialogogue. 350 91

Epidermal growth factor-like activity (EGF-LA) has been detected in human seminal plasma in concentrations of 5-150 ngeq/ml (36.4 +/- 2.1, mean +/- SEM), using a heterologous RRA with murine EGF. The samples were obtained from normal, subfertile and azoospermic men, aged 21-50 yr. No correlation was found between EGF concentration and age of donor, sperm count, sperm motility, or period of sexual abstinence before sample collection. High performance liquid chromatography of the seminal plasma resulted in a main peak of EGF-LA which eluted at 29% acetonitrile, compared to 33% for murine EGF. Microsomal membranes were prepared from several tissues from the human male reproductive tract and were tested for their ability to bind radioiodinated murine EGF. Specific EGF binding activity was detectable in testicular membrane preparations but was not detectable in membranes prepared from human prostate, seminal vesicle, epididymis, or spermatozoa. Endogenous EGF-LA was detectable in human testis, seminal vesicle, prostate, and epididymis.
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PMID:Identification of epidermal growth factor-like activity in human male reproductive tissues and fluids. 632 31

Epidermal growth factor is a polypeptide that stimulates proliferation and differentiation of a variety of cell types, including the developing intestinal epithelium; it is the agent in human milk that induces mitosis in human fibroblast culture. We systematically evaluated the EGF content of milk from 20 women delivering prematurely and from 11 women delivering at term. In preterm mothers, the concentration of EGF was 70 +/- 5 ng/ml (mean +/- SEM), with no significant change during seven weeks of lactation. EGF concentration in milk of term mothers was 68 +/- 19 ng/ml (mean +/- SEM). No diurnal variation in the concentration was found. Total EGF content was closely correlated with the volume of milk expressed, suggesting a passive transport from the circulation. These observations confirm that a substantial amount of EGF is present in human milk and that EGF concentrations are not affected by duration of gestation, time of day, or duration of lactation.
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PMID:Epidermal growth factor in human milk: daily production and diurnal variation during early lactation in mothers delivering at term and at premature gestation. 660 47

Porcine thyroid follicle cells, cultured in suspension, were employed to investigate the effects of immunoglobulin preparations from patients with colloid goitre, Graves' disease or Hashimoto's thyroiditis on thyroid growth in vitro. Epidermal growth factor (EGF, 19 ng/ml) was used as a reference for maximum growth stimulation and produced a 9-fold increase in [3H]thymidine incorporation. Immunoglobulins (1000 micrograms/ml) were found to increase [3H]thymidine incorporation compared to control: from 10 normal individuals 32 +/- 4% (mean +/- SEM, % of EGF response), from 10 patients with colloid goitre 26 +/- 4% (not significantly different from normal), from 10 patients with Graves' disease 19 +/- 3% (P less than 0.05) and from 15 patients with Hashimoto's thyroiditis 11 +/- 2% (P less than 0.001). No patient immunoglobulin preparation showed activity greater than that of normal individuals. The lower growth stimulatory activity in Graves' disease and Hashimoto's thyroiditis remained after heat inactivation of serum and is thought to reflect surface binding of thyroid autoantibodies.
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PMID:Influence of thyroid autoantibodies on thyroid cellular growth in vitro. 660 95


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