Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocyte Growth Factor (HGF, also known as Scatter Factor) is a powerful mitogen or motility factor in different cells, acting through the tyrosine kinase receptor encoded by the MET protooncogene. Endothelial cells express the MET gene and expose at the cell surface the mature protein (p190MET) made of a 50 kD (alpha) subunit disulfide linked to a 145-kD (beta) subunit. HGF binding to endothelial cells identifies two sites with different affinities. The higher affinity binding site (Kd = 0.35 nM) corresponds to the p190MET receptor. Sub-nanomolar concentrations of HGF, but not of a recombinant inactive precursor, stimulate the receptor kinase activity, cell proliferation and motility. HGF induces repairs of a wound in endothelial cell monolayer. HGF stimulates the scatter of endothelial cells grown on three-dimensional collagen gels, inducing an elongated phenotype. In the rabbit cornea, highly purified HGF promotes neovascularization at sub-nanomolar concentrations. HGF lacks activities related to hemostasis-thrombosis, inflammation and endothelial cells accessory functions. These data show that HGF is an in vivo potent angiogenic factor and in vitro induces endothelial cells to proliferate and migrate.
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PMID:Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. 138 37

The Patch (Ph) mutation in mice is a deletion of the gene encoding the platelet-derived growth factor receptor alpha subunit (PDGFR alpha). Patch is a recessive lethal recognized in heterozygotes by its effect on the pattern of neural crest-derived pigment cells, and in homozygous mutant embryos by visible defects in craniofacial structures. Since both pigment cells and craniofacial structures are derived from the neural crest, we have examined the differentiation of other crest cell-derived structures in Ph/Ph mutants to assess which crest cell populations are adversely affected by this mutation. Defects were found in many structures populated by non-neuronal derivatives of cranial crest cells including the thymus, the outflow tract of the heart, cornea, and teeth. In contrast, crest-derived neurons in both the head and trunk appeared normal. The expression pattern of PDGFR alpha mRNA was determined in normal embryos and was compared with the defects present in Ph/Ph embryos. PDGFR alpha mRNA was expressed at high levels in the non-neuronal derivatives of the cranial neural crest but was not detected in the crest cell neuronal derivatives. These results suggest that functional PDGF alpha is required for the normal development of many non-neuronal crest-derived structures but not for the development of crest-derived neuronal structures. Abnormal development of the non-neuronal crest cells in Ph/Ph embryos was also correlated with an increase in the diameter of the proteoglycan-containing granules within the crest cell migratory spaces. This change in matrix structure was observed both before and after crest cells had entered these spaces. Taken together, these observations suggest that functional PDGFR alpha can affect crest development both directly, by acting as a cell growth and/or survival stimulus for populations of non-neurogenic crest cells, and indirectly, by affecting the structure of the matrix environment through which such cells move.
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PMID:A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non-neuronal subset of neural crest-derived cells. 163 76

The present study describes biochemical and morphological differences of pseudophakic bullous keratopathy (PBK) corneas as compared with normal corneas. At the ultrastructural level, all PBK corneas studied had abnormal fibrillar material posterior to the Descemet's membrane. In addition, two of the six PBK buttons had subepithelial fibrocellular materials disrupting the epithelial basement membrane and Bowman's layer. Aggregates of collagen fibrils with 110 nm periodicity were occasionally seen within the stroma of the PBK corneas. Isolation and purification of the collagen from the Descemet's membrane/posterior collagenous layer (DM/PCL) showed an increased amount of material with molecular weight in the range of 50-60K daltons (presumably type VIII collagen) and decreased amounts of higher molecular weight, disulfide-bonded collagenous materials (presumably type IV collagen) as compared with normals. Sugar-specific lectin studies showed an increased deposition of peanut agglutinin (PNA) and Ricinus communis agglutinin I (RCA120) in the DM/PCL of the PBK corneas. Our data suggest that the DM/PCL of PBK corneas have an increased accumulation of terminal B-galactose and B-D-galactose (1-3)-D-N-acetylgalactosamine residues and altered ratios of low and high molecular weight collagenous proteins.
Cornea 1990 Apr
PMID:Abnormal extracellular matrix in corneas with pseudophakic bullous keratopathy. 232 80

A new endothelial cell growth factor (f-ECGF) was partially purified from the cultured medium of human fibroblast cells of embryonic lungs. The partially purified f-ECGF induced neovascularization in rabbit cornea. It showed a selective growth stimulatory activity on the endothelial cells in vitro, whereas acidic- and basic-fibroblast growth factors (a- and b-FGFs) showed a broad spectrum of growth stimulation among tissues or cells. f-ECGF did not compete with the binding of a-FGF to the cell surface receptor in HEP-G2 hepatoblastoma cell lines. These results indicated that f-ECGF is a new endothelial cell growth factor distinct from a- and b-FGFs which are known to be potent endothelial cell growth factors.
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PMID:Characterization of a new endothelial cell growth factor (f-ECGF) partially purified from the supernatant of human fibroblast cells. 248 61

Five patients with specific indications for photorefractive and phototherapeutic keratectomy (PRK and PTK) by excimer laser at 193 nm were treated successfully: they had presented with epithelial dystrophy of the cornea, amyloid, von Szilly's scleroperikartitis, myopia after cataract extraction and before secondary implantation of an intraocular lens in the other eye, and myopia. In all cases it was possible to avoid extensive surgical procedures such as lamellar keratoplasty or intraocular lens exchange. There were no recurrences in the patients with superficial corneal diseases, and the patients who had undergone PRK were within 0.25 Dpt of the target acuity. The follow-up was between 8 months and 1 year.
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PMID:[Special indications for photorefractive (PRK) and phototherapeutic (PTK) excimer laser keratotomies. A presentation of 5 cases]. 754 22

Forty-six pterygia were surgically removed using a modified "bare sclera" technique. Additionally, an excimer laser PTK was performed using the immersion method to smooth the irregular surface of the cornea. Follow-up was 6 to 10 months. We found 24 recurrences. In patients with pterygia of more than 4 mm who were from southern Europe, the Middle East, or Africa, the recurrence rate was 100%. In pterygia from 2 to 4 mm the recurrence rate was 50%; in pterygia up to the limbus no recurrences were noted. The excimer laser has no positive influence on pterygia recurrences that have been removed using the modified "bare sclera" technique.
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PMID:[Excimer laser phototherapeutic keratectomy (PTK) and modified bare sclera technique for treatment of pterygium]. 754 23

Signals transmitted from mesenchyme to epithelia or vice versa constitute the basis of reciprocal epithelial-mesenchymal interactions. As a first step toward understanding epithelial-mesenchymal interactions on the ocular surface where the transit amplifying cell-containing corneal epithelium is anatomically separated from the stem cell-containing limbal epithelium, we sought to characterize the expression patterns of cytokines and their receptors by primary epithelial and early-passaged fibroblast cultures of human cornea and limbus. Northern hybridization with oligonucleotide and cDNA probes to a total of 25 cytokines and 12 of their receptors revealed that the positively expressed cytokines could be divided into the following four patterns. Type I: TGF-alpha, IL-1 beta, and PDGF-B were expressed exclusively by epithelial cells but their respective receptors EGFR and IL-1R were predominantly and PDGFR-beta was exclusively expressed by fibroblasts. Type II: IGF-I, TGF-beta 1, -beta 2, LIF, and bFGF, and their receptors were expressed by both epithelial cells and fibroblasts. FGFR-1 (flg) and FGFR-2 (bek) were expressed more by fibroblasts and bFGF was expressed more by corneal than limbal epithelial cells. Type III: keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) were expressed exclusively by fibroblasts and their respective receptors, KGFR and c-met, were predominantly expressed by epithelial cells. Combined with RT-PCR, the quantity of KGF and KGFR transcripts was highest in limbal fibroblasts and epithelial cells, respectively. In contrast, the quantity of HGF and HGFR (c-met) transcripts was highest in corneal fibroblasts and epithelial cells, respectively. Type IV: M-CSF and IL-8 were expressed by fibroblasts and/or epithelial cells but their receptors were not expressed by epithelial cells nor fibroblasts, but by immune or inflammatory cells. In addition to these potential paracrine actions, autocrine actions mediated by TGF-alpha/EGFR, IL-1 beta/IL1-R, and bFGF/FGFR-1 were more expressed by corneal than limbal epithelial cells. Immunofluorescence staining on human corneoscleral cryosections confirmed that EGFR and bFGF were not expressed by the limbal basal epithelium, but expressed strongly by the corneal epithelium, a pattern consistent with Northern hybridization. These results indicate that ocular surface epithelial cells and fibroblasts can express a myriad of cytokines, among which the first three patterns constitute the network of potential epithelial-mesenchymal cytokine dialogues. The difference of certain cytokine expression between corneal and limbal regions suggests that this network participates in normal epithelial growth and differentiation, and plays an important role in wound healing.
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PMID:Three patterns of cytokine expression potentially involved in epithelial-fibroblast interactions of human ocular surface. 789 1

The Argon Fluoride (ArF) Excimer laser is currently used for experimental reshaping of the front surface of the cornea for the correction of myopic refractive error (photorefractive keratectomy, PRK) and for smoothing corneal irregularities (phototherapeutic keratectomy, PTK). Both PRK and PTK are in FDA clinical trials, but are more readily available outside the U.S.A. These techniques have achieved reasonable success in spite of early reports that deeper ablation procedures can cause reduced corneal clarity (haze) or a result which is less accurate or tends to regress. We studied how different depths of excimer tissue removal affect the smoothness of the ablation zone of the rabbit cornea. Dutch belted rabbits were immediately sacrificed by pentobarbital overdose. Their corneas were de-epithelialized with a knife or by the excimer laser and then were photoablated. A 4.5-mm circular ablation beam was delivered to each denuded area, but the beam was masked by positioning a steel blade to partially block the laser beam, thus creating variable ablation depths corresponding to 0.0, 12.5, 37.5, and 62.5 microns. The eyes were fixed in situ by topical and anterior chamber application of glutaraldehyde and the corneas were excised after 5 min and placed in glutaraldehyde for tissue processing. The corneas were whole-mounted and examined by scanning electron microscopy (SEM). The resultant micrographs show increasing irregularity of the ablated surface as a function of depth. The irregularity appeared to be due largely to the inhomogeneities of the anterior stroma, which is known to be layered by alternately directed collagen fibrils.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of depth upon the smoothness of excimer laser corneal ablation. 815 41

The objective of this study was to compare four methods of counting corneal endothelial cell density using the Topcon SP 1000 microscope and Image-NET digital graphic software. Two independent observers quantified cell density from 63 endothelial photomicrographs using the various standardized techniques. The first method was that suggested for use with Topcon SP 1000, employing five different reference grids to compare subjectively with the endothelial cell density of the unknown sample. The other three methods involved the automated, semiautomated, and manual procedures developed for use with the Image-NET system software. The manual Image-NET system is presently considered to yield accurate cell morphology data. Confidence limits and standard errors of mean differences between values obtained by different methods were used to evaluate agreement and reproducibility of computerized methods. Sensitivity and specificity were calculated for two different threshold limits of endothelial cell density. Results showed that the automated Image-NET system is not reliable for clinical use because of its poor agreement with other methods and its lack of sensitivity and specificity at the selected threshold limits of endothelial cell density. The comparative Topcon method of using reference grids, although inexpensive and accurate for 500 cell/mm2 increments, was considered too imprecise for most clinical situations. The semiautomated Image-NET system, in half the analysis time required by the manual method, provided endothelial cell count estimates that were not clinically different from those obtained with manual counting.
Cornea 1996 May
PMID:The Topcon SP 1000 and Image-NET systems. A comparison of four methods for evaluating corneal endothelial cell density. 871 30

Earlier experiments in this laboratory identified a highly expressed 65-68-kDa protein in both mouse and human corneas (Cuthbertson, R. A. , Tomarev, S. I., and Piatigorsky J. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 4004-4008). Here, we demonstrate that this protein is transketolase (TKT; EC 2.2.1.1), an enzyme in the nonoxidative branch of the pentose-phosphate pathway, based on peptide and cDNA isolation and sequence analysis of mouse cornea protein and RNA samples, respectively. While expressed at low levels in a number of tissues, the 2.1-kilobase TKT mRNA was expressed at a 50-fold higher level in the adult mouse cornea. The area of most abundant expression was localized to the cornea epithelial cell layer by in situ hybridization. Western blot analysis confirmed TKT protein abundance in the cornea and indicated that TKT may comprise as much as 10% of the total soluble protein of the adult mouse cornea. Soluble cornea extracts exhibited a correspondingly high level of TKT enzymatic activity. TKT expression increased progressively through cornea maturation, as shown by Northern blot, in situ hybridization, Western blot, and enzymatic analyses. TKT mRNA and protein were expressed at low levels in the cornea prior to eye opening, while markedly increased levels were observed after eye opening. Taken together, these observations suggest that TKT may be a cornea enzyme-crystallin, and suggest that the crystallin paradigm and concept of gene sharing, once thought to be restricted to the lens, apply to other transparent ocular tissues.
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PMID:Transketolase is a major protein in the mouse cornea. 896 23


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