PubMed Health⌕ Search

Biomedical subjects

G B van Setten

Publications and source records attributed to G B van Setten.

At least 19 recordsLinked to original sources
PubMed2003

Detection of connective tissue growth factor (CTGF) in human tear fluid: preliminary results.

PURPOSE: Connective tissue growth factor (CTGF) is one of the main regulators of fibrosis. We aimed to evaluate its presence in the human tear fluid of healthy individuals. METHODS: A total of 70 tear fluid samples were collected from eight volunteers prior to and after stimulation of reflex tears with onion vapour. Specific ELISA analysis was performed with goat IgG against human CTGF. RESULTS: Connective tissue growth factor was detected in seven samples (10%), with maximum levels of 17 ng/mL in basal tears. Induction of reflex tearing resulted in a fast and significant decrease of CTGF concentrations (r = - 0.95). No CTGF was detected in 90% of the samples. CONCLUSION: Connective tissue growth factor may occur in tear fluid in healthy human eyes. This indicates a possible role for tear fluid CTGF in ocular surface fibrosis and wound healing.

Connective Tissue Growth Factor↗
PubMed1997

Dry eye syndrome, tear film, pharmacology of eye drops, and toxicity.

Over the past years, the main parameters used for the diagnosis of dry eye have been outlined: there is now substantial effort to bring them into correlation with each other, resulting in easier diagnosis of the diseases that appear to cause dry eye. Although increasing awareness of the plethora of dry eye diseases makes the differential diagnosis and the treatment difficult, the increased availability of optimized artificial tears and tear substitutes, especially viscoelastics, does allow easier relief of the most serious symptoms of dry eye disease. Improved topical treatment, in turn, allows various treatments, such as excimer laser treatment, to be performed, even in dry eyes. This, together with the identification of tear substitutes as a major research target and a better understanding for the psychological tasks of chronic dry eye diseases, offers a good basis toward further improvements.

Dry Eye Syndromes↗
PubMed1997

Vascular endothelial growth factor (VEGF) in normal human corneal epithelium: detection and physiological importance.

PURPOSE: Corneal neovascularization is a major challenge following chemical burns and corneal inflammation. The factors triggering corneal neovascularization involve various growth factors. In the release and control of these factors the regenerating tissue plays a decisive role. Only recently has vascular endothelial growth factor been shown to be involved in the basic events of retinal neovascularization. From the cornea current knowledge allows only for the statement that corneal epithelium could be able to produce vascular endothelial growth factor. The present study was designed to show the presence of vascular endothelial growth factor-like substances in the corneal epithelium of the normal eye in vivo. METHODS: Using specific antibodies to the N-terminus of human vascular endothelial growth factor indirect immuno-histochemistry was applied to sections of normal human corneal epithelium and to five sections of enucleated human eyes with a morphologically normal anterior segment. RESULTS: In all sections specific staining for vascular endothelial growth factor was found over the entire epithelium. Staining was most intense in the basal layer of epithelial cells. Only a weak staining was detectable in the cell layers closer to the surface. Here, however, the samples of corneal epithelium having been subject to traumatic erosion showed a slightly more intense staining than the sections from the undisturbed corneal tissue of whole globe sections. CONCLUSION: It was shown that vascular endothelial growth factor-like protein is present in the human corneal epithelium. Observed differences in the staining pattern could suggest that the expression of vascular endothelial growth factor might be enhanced due to ocular surface trauma. It is suggested that corneal epithel vascular endothelial growth factor might be an important factor in the cascade leading to the onset of corneal neovascularization.

Endothelial Growth Factors↗
PubMed1996

Basic fibroblast growth factor in human tear fluid: detection of another growth factor.

BACKGROUND: Topical application of various growth factors have shown promising experimental data in speeding up corneal wound healing. Similar effects have been reported for another group of proteins, fibroblast growth factors (FGFs). One of them, basic FGF (bFGF), stimulates the proliferation of cells of mesodermal as well as of neuroectodermal origin and is highly angiogenic. The aim of the present study was to investigate the presence of bFGF in human tear fluid. METHODS: After establishing an advanced enzyme-linked immunosorbent assay technique, tear fluid was collected from 15 healthy individuals before and after stimulation of reflex tearing. RESULTS: In none of the tear fluid samples collected prior to induction of reflex tearing could FGF be detected. Of the 15 samples collected during reflex tearing, six (40%) contained measurable amounts of bFGF. The amount of bFGF appeared to decrease with increasing tear fluid flow, suggesting a dilution effect. CONCLUSION: This study gives strong evidence that bFGF, as previously shown for epidermal growth factor and transforming growth factor-alpha, may occur in human tear fluid of healthy individuals after induction of reflex tearing and, in very low concentrations, under normal conditions. Whether bFGF can to be considered a constant component of tear fluid, however, remains to be investigated.

Adult↗
PubMed1996

The clinical use of contact lenses and collagen shields.

Contact lens wear before and after photorefractive or phototherapeutic keratectomy with excimer lasers has become an increasingly interesting subject. No negative side effects of contact lens wear prior to photorefractive keratectomy have yet been shown and refractive errors postoperatively do not seem to constitute a major practical problem. Normal side effects include the risk of bacterial infection and keratitis. The major pathogen in this context is still Pseudomonas aeruginosa, although increased insight into the mechanisms of bacterial adhesion and improvements in cleaning procedures now allow more effective preventive care of contact lenses themselves and of contact lens cases. Tear fluid research using leucotriene C4 as a possible indicator for subclinical inflammation has led to interesting results, and the importance of the arachidonic pathway and its metabolites has become more evident. These advances contribute considerably to the safe use of contact lenses in clinical ophthalmology, although major innovations such as the multifocal contact lenses have not reached the stage of perfection.

Animals↗
PubMed1996

Growth factors and their receptors in the anterior chamber. Absence of epidermal growth factor and transforming growth factor alpha in human aqueous humor.

The involvement of growth factors such as epidermal growth factor (EGF) in regenerative processes of corneal endothelium and lens epithelium has recently been suggested. However, knowledge on the presence of growth factors in anterior chamber fluid (ACF) is still very restricted. Although we have previously shown that EGF is undetectable in the ACF of normal eyes undergoing cataract surgery even by the use of high-sensitivity assays, this does not exclude the possible presence of other, EGF-like proteins in ACF such as transforming growth factor alpha (TGF-alpha). In the present study, we have hence determined in ACF samples of 70 human eyes the concentrations of both EGF and TGF-alpha. As assays served ELISA techniques and RIA. In none of all the samples investigated could detectable amounts of EGF, i.e. above 0.2 pg/ml (detection limit of the assay), be found, confirming earlier results. Interestingly, however, also no TGF-alpha could be detected in ACF. If present at all, the level of any TGF-alpha concentration in ACF was hence below the detection limit, i.e. less than 20 pg/ml. Based on the results of this study, it seems therefore that under physiological conditions there is no measurable presence of free EGF or TGF-alpha in human ACF. Existing receptors in the structures of the anterior segment must hence have ample binding capacity which could explain the effect of externally applied growth factors. The physiological and clinical importance of this result is briefly outlined.

Adult↗
PubMed1996

Detection of transforming growth factor-alpha mRNA and protein in rat lacrimal glands and characterization of transforming growth factor-alpha in human tears.

PURPOSE: To assess whether the lacrimal gland is a possible site of synthesis of transforming growth factor-alpha (TGF-alpha) and to characterize TGF-alpha biochemically in human tears. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) amplification was used to analyze rat lacrimal glands for the presence of TGF-alpha mRNA. Specific monoclonal antibodies were used to localize TGF-alpha immunohistochemically in lacrimal gland tissue of rats. Human tears were analyzed for immunoreactive TGF-alpha protein using a specific radioimmunoassay, and the molecular weight of TGF-alpha in tears was characterized by Western blot analysis. RESULTS: RT-PCR amplification of rat lacrimal gland RNA generated a band of the predicted 492 base pairs for TGF-alpha mRNA. Immunohistochemical staining of rat lacrimal gland localized TGF-alpha protein to lacrymocytes constituting acini but not to interacinar and intraacinar ducts of lacrimal glands. Western blot analysis of human tears detected a single band at MWt 16,000. Logit transformation of radioimmunoassay data for tears and TGF-alpha standard generated parallel displacement lines, indicating the presence of immunoreactive TGF-alpha levels in human tears with an average concentration of 100 +/- 20 pg/ml (mean +/- SEM). CONCLUSIONS: Rat lacrymocytes synthesize TGF-alpha mRNA and protein, and human tears contain immunoreactive TGF-alpha, suggesting that the lacrimal gland may be an exocrine source for TGF-alpha in tears. The single MWt 16,000 form of TGF-alpha in human tears appears to be generated by an unusual proteolytically processing of the pro-TGF-alpha transmembrane precursor protein.

Adult↗
PubMed1996

Inhibition of pseudomonal ulceration in rabbit corneas by a synthetic matrix metalloproteinase inhibitor.

PURPOSE: To evaluate the effect of the synthetic matrix metalloproteinase inhibitor, Galardin, on proteases produced by Pseudomonas aeruginosa (PA) and on a rabbit model of Pseudomonas keratitis. METHODS: Protease activities of culture broths from Pseudomonas strains PA-28 and W-186 were characterized in vitro by gelatin zymography and by digestion of Azocasein in the presence and absence of Galardin and the serine protease inhibitor, aprotinin. In a noninfectious in vivo experiment, sterile PA culture broth from W-186 was injected intrastromally into rabbit corneas that were treated topically with Galardin or vehicle, then evaluated clinically and histologically. In an infectious in vivo experiment, rabbit corneas were injected with washed PA-28, then treated topically with Galardin or vehicle and clinically scored. RESULTS: Gelatin zymography of culture broth from W-186 and PA-28 detected two proteases that were both inhibited by Galardin. Galardin reduced the digestion of Azocasein by both PA culture broths by 99%, whereas aprotinin did not significantly reduce the protease activity of PA-28 conditioned broth. Intrastromal injection of sterile W-186 culture broth caused rapid corneal destruction that was prevented by topical treatment with Galardin. Intrastromal injection of washed PA-28 bacteria resulted in progressive corneal melting that was significantly (P < 0.005) delayed, but ultimately not prevented, by topical treatment with Galardin. CONCLUSIONS: Pseudomonal protease activity in culture broth consisted predominantly of metalloproteinases and were effectively inhibited by Galardin in vitro. Topical treatment with Galardin prevented destruction of rabbit corneas by bacterial products present in culture broth, and it delayed corneal destruction after injection of PA bacteria. Galardin may be a useful adjuvant when corneal destruction proceeds despite prompt antibiotic treatment.

Administration, Topical↗
PubMed1995

Basic fibroblast growth factor in human saliva: detection and physiological implications.

After the detection of epidermal growth factor and transforming growth factor alpha in various body fluids and human saliva the current study aimed to investigate the presence of basic fibroblast growth factor (bFGF) in human saliva. Basic FGF is stimulating the proliferation of cells of mesodermal and neuroectodermal origin and is highly angiogenetic. After ELISA technique was established, saliva was collected from eight healthy individuals. Run in duplicate, 14 (87.5%) of the 16 samples investigated contained measurable amounts of bFGF. In the samples containing bFGF the concentration varied between 0.1 pg/mL and 8.4 pg/mL (mean concentration, 3.8 pg/mL; SD, 3.5). There was no correlation between age and sex and bFGF concentrations. It is therefore concluded that bFGF is present in human saliva and may even constitute a constant component. The physiological importance of this finding is discussed.

Adult↗
PubMed1994

Growth factors in human tear fluid and in lacrimal glands.

EGF has been shown to be a constant component of human tear fluid. Its concentration depends on the actual tear fluid flow, as shown for other proteins secreted by the lacrimal gland. This organ has also been considered to be the origin of tear fluid EGF and immunohistochemical evidence for this hypothesis was found. During corneal disease the concentration of EGF in tear fluid considerably decreases to levels even lower than those found during short time stimulation of reflex tearing. Other members of the EGF family, such as TGF-alpha, have considerable similarity with the EGF molecule and even bind to the same receptor. Currently it is thought that TGF-alpha may be, in certain phases of cell life, even more important in the regulation of cell metabolism than EGF. In the present study we have investigated the presence of TGF-alpha in tear fluid and the lacrimal gland. The initial results presented here, show for the first time that TGF-alpha like EGF, seems to be constant component of human tear fluid and to originate, at least partially, from the lacrimal gland.

Epidermal Growth Factor↗
PubMed1994

A rapid fluorometric assay for tear fluid plasmin activity.

A rapid (5- to 10-min), sensitive (detection limit 0.6 IU/L), and moderately specific fluorometric plasmin assay for small volume tear fluid samples was developed. Addition of albumin (up to 0.1% final concentration) to the assay buffer improved the sensitivity of the test so that plasmin activity in healthy controls could be detected. pH in the reaction buffer was 8.0, Michaelis-Menten constant for the substrate, H-D-Val-Leu-Lys.7-amido-4-methyl-coumarin (AMC), was 0.28 mM, and final substrate concentration in the reaction buffer was 1 mM. Intra- and interassay imprecisions were 1.6 and 4.4%, respectively at a plasmin level of 10 IU/L. Tear fluid flow was significantly higher in the patients than in the healthy controls, and this dilatory effect must be considered when using plasmin determination for diagnostic purposes. This effect was counteracted by correcting the plasmin activity values by tear fluid flow. Plasmin flux is plasmin activity (microIU) secreted in units of time (min). This parameter showed highly significant differences between the patients and controls. All patients with microbial keratitis, corrosive trauma, ocular trauma, herpetic infection, and other diseases showed highly significant elevation of plasmin flux compared with controls. The highest plasmin flux values (several hundredfold that of controls) were recorded in patients with severe corneal ulcers. Few patient samples showed some involvement of other proteases, which were not inhibited by aprotinin.

Adult↗
PubMed1994

C-reactive protein serum levels in patients with ocular disease.

Hepatocyte derived C-reactive protein (CRP) is a sensitive indicator for inflammatory or infectious processes in a variety of tissues. As several other plasma proteins it is regarded as part of the acute phase response to a variety of tissue damage. CRP is commonly used in general medicine as a tool for the follow-up of especially bacterial infections. However, it has not been widely used in ophthalmology. In the present study CRP values in serum samples from 51 patients with various acute ocular diseases were determined semiquantitatively. High CRP levels were found most frequently in patients with either preseptal cellulitis (83.3%) or endophthalmitis (25.8%) whereas in the serum of patients with keratitis and uveitis, CRP exceeded 20 mg/l in only 18.7% of the cases. In a control group of 10 patients with retinal detachment the mean CRP level was 2.3 mg/l (SD +/- 0.98 mg/ml). The clinical significance and the prognostic value of CRP determinations during ocular diseases are discussed.

C-Reactive Protein↗
PubMed1992

Expression of tenascin and fibronectin in the rabbit cornea after excimer laser surgery.

In order to investigate the effects of excimer laser surgery on corneal wound healing, 25 rabbits underwent anterior keratectomy at a depth of 100 or 300 microns with a Meditec MEL 50 excimer laser. After various intervals the animals were killed and the cornea excised and investigated immunohistochemically for the expression of extracellular matrix (ECM) proteins, fibronectin and tenascin. Fibronectin was shown to occur earlier than tenascin, and the two also had different distribution patterns. Wound depth showed no clear effect on the localization and time of ECM protein expression. This study indicates that corneal wounds caused by excimer laser radiation and those caused by mechanical surgery differ as to healing mechanisms.

Animals↗
PubMed1992

Distribution of integrins alpha 6 and beta 4 in the rabbit corneal epithelium after anterior keratectomy.

Integrins are heterodimeric cell-surface receptor glycoproteins involved in cell-matrix and also in cell-cell interactions. The alpha 6 beta 4 integrin heterodimer has been shown to be a component of the hemidesmosome. In response to wounding, hemidesmosomes are disassembled, the epithelium migrates to cover the denuded area, and eventually the hemidesmosomes reappear. In the present investigation the distribution of the integrin alpha 6 and beta 4 subunits after anterior keratectomy was studied by indirect immunohistochemistry. Labeling for the alpha 6 subunit was observed around the entire cell surface, right to the leading edge. The immunoreaction for the beta 4 subunit was confined to the basal cell membrane facing the basement membrane as in the normal cornea. Cells at the leading edge of the migrating epithelium did not show any labeling for beta 4. Patchy labeling for beta 4 was first observed in the region midway between the wound margin and the leading edge. Because integrins are only expressed as heterodimers, the alpha 6 subunit may be complexed with the beta 1 subunit, instead of with beta 4, at the leading edge of the migrating epithelium. We also suggest that this alpha 6 beta 1 heterodimer may play a role in the reformation of the adhesion complex.

Animals↗
PubMed1992

Experience with plasmin inhibitors.

The involvement and role of the plasminogen activator-plasmin system in normal and pathological wound healing is reviewed. The methods currently available for demonstrating plasmin activity are briefly described. The article also reviews some other serine proteases potentially involved in pathological wound healing processes. The current ophthalmological therapeutic measures used to regulate tissue proteolysis are also described.

Cornea↗
PubMed1992

Wound healing of the ocular surface.

Wound healing is a complex, long-lasting regulatory sequence that involves expression of a number of genes, which are active during the individual's development. Some of the phenomena differ from normal tissue turnover and growth only quantitatively. This article reviews the current data on corneal wound healing, with particular reference to mesenchymal matrix proteins and their integrin receptors, to growth factors and to proteolytic enzymes. Some inflammatory mediators are also discussed. The theoretical basis for therapeutic interventions is also discussed briefly, in the light of present knowledge.

Cell Adhesion↗