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Biomedical subjects

T Tervo

Publications and source records attributed to T Tervo.

At least 19 recordsLinked to original sources

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

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

Pseudomembranous and membranous conjunctivitis. Immunohistochemical features.

A 63-year-old man, who had for one month been on sulfasalazine therapy, developed general malaise, high fever, severe stomatitis, and bilateral necrotizing pseudomembranous conjunctivitis with corneal erosion, identical to that seen in the Stevens-Johnson syndrome. Topical therapy with antibiotics and aprotinin rapidly healed the corneal surfaces, while densely adherent true membranes developed on the conjunctiva, and were removed surgically several times during the next week. After the acute stage, subtle subepithelial conjunctival scarring, superficial punctate keratitis, dry eye syndrome and fluctuating irregular corneal astigmatism became evident, but good visual acuity, lid function and ocular motility were retained. Histopathologic study of conjunctival membranes from two cases of membranous conjunctivitis revealed polymorphonuclear leukocytes within a matrix composed of fibrin, tenascin and fibronectin. In older membranes, histiocytes were additionally found. Surgical debridement of such membranes removes a substratum of inflammatory debris that is likely to promote secondary infection, fibrosis and symblepharon formation, and may decrease rather than increase subsequent scarring of the necrotized conjunctiva.

Adult

Integrins as receptors for extracellular matrix proteins in human cornea.

Extracellular matrix (ECM) proteins form distinct protein families that play a role during tissue maturation, wound healing and maintenance of tissue architecture. Recent studies show that there are tissue type-specific variations in their expression. ECM proteins function by complexing with each other and also by interacting with their cellular receptors, called integrins. Integrins are heterodimeric membrane glycoproteins that are partly cell type-specifically expressed in human tissues. Like other stratified epithelia, corneal epithelium expresses alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, 4, and alpha v beta 1 integrins that mediate attachment to the basement membrane and cell-cell interactions.

Basement Membrane

Integrins in the normal and healing corneal epithelium.

Integrins are heterodimeric plasma membrane glycoproteins involved in cell-matrix and cell-cell interactions. The present communication reviews the distribution of several of the currently known integrin subunits in the corneal epithelium. The corneal epithelium contains the following integrin heterodimers: alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 4. The expression of alpha v with an unknown beta subunit is also recognized, whereas the expression of alpha 4 and alpha 5 subunits remains controversial. Some of the changes occurring in the distribution of integrins in response to wounding will also be discussed.

Basement Membrane

Surface-associated activation of plasminogen on gram-positive bacteria. Effect of plasmin on the adherence of Staphylococcus aureus.

In this article we review a novel type of plasminogen activation on staphylococcal and streptococcal cells. The activation mechanism implies a specific binding of glu-plasminogen to bacterial surface via the lysine-binding sites of plasminogen. Association of plasminogen with bacterial surfaces greatly enhances the t-PA mediated activation which takes place only poorly in solution. The end product, surface-associated plasmin, is enzymatically active, protected against high molecular weight plasmin inhibitors and capable of converting itself from glu-plasmin to the lys-form. The modification is associated with an increased affinity of the bound lys-plasmin towards the binding molecules on bacterial surface. This novel way of retaining plasmin on the surface may be important for the bacteria to invade and penetrate surrounding tissues. Our data on the effect of plasmin on staphylococcal adherence indicate that plasmin is not very effective in cleaning bacteria from surfaces coated with extracellular matrix components, fibronectin and fibrinogen.

Bacterial Adhesion

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

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

Epidermal growth factor in human tear fluid: a minireview.

This minireview deals with the presence of epidermal growth factor (EGF) in human tear fluid. It explains the occurrence of EGF in tear fluid, the origin of EGF and its dependency on tear fluid dynamics. The alterations in tear fluid EGF concentrations that occur during diseases of the ocular surface are described and discussed in the context of the current knowledge about the interaction between EGF and EGF receptors. The possible clinical implications of topical treatment with EGF are considered.

Epidermal Growth Factor

Integrins in human corneal epithelium.

Monoclonal antibodies (Mabs) were used for immunohistochemical location of integrin beta- (beta 1,3, and 4) and alpha subunits (alpha 1-6 and alpha v) in the epithelium of both normal and tissue-cultured human cornea. Immunoreaction for the beta 1 integrin subunit was the most intense at the membranes of the basal epithelial cells and weaker at the superficial cell membranes. Anti-beta 4 immunofluorescence appeared in the basal part of the epithelium only, apposing the basement membrane. Both anti-alpha 2 and anti-beta 3 Mabs showed an immunoreaction with distribution similar to the beta 1 integrin subunit. Immunoreaction for the alpha 6 integrin subunit resembled the distribution of the beta 4 subunit. Anti-alpha v showed a faint immunoreaction at the basal and lateral aspects of the basal cell layer. Antisera against beta 3, alpha 1, alpha 4, and alpha 5 integrin subunits showed no specific reactions. The present results suggest that both the normal and tissue-cultured human corneal epithelium contain alpha 2 beta 1, alpha 3 beta 1, and probably also alpha v beta 1 and alpha 6 beta 4 integrin dimers or complexes. We discuss their role as possible receptors for some known ligands.

Adult

Immunohistochemical demonstration of cellular fibronectin and tenascin in human epiretinal membranes.

The occurrence of fibronectin, cellular fibronectin and tenascin was studied immunohistochemically in epiretinal membranes from 5 patients with retinal detachment and 3 patients with macular pucker, and in preretinal membranes from 3 patients with proliferative diabetic retinopathy. Positive immunofluorescence for these proteins was seen in all specimens studied. The presence of cellular fibronectin suggests that local production of fibronectin occurs in these membranes. The expression of tenascin, an extracellular matrix glycoprotein, originally found to modulate organosenesis in tendinous and glial tissue, suggests that this glycoprotein also participates in the regulation of cellular growth in these membranes.

Adolescent

Ocular irritation leads to the appearance of proteolytic activity in the aqueous humor.

Aqueous humor (AH) collected from healthy eyes of man and rabbit was analysed for proteolytic activity using a casein-agar assay. Normal AH collected during surgery or rabbit AH aspirated before ocular irritation contained no caseinolytic activity. In rabbits, mechanical irritation of the iris and subconjunctival as well as intracameral injection of capsaicin led to ocular irritative response. AH samples collected after such manipulation contained a considerable caseinolytic activity. On the other hand, anterior chamber puncture alone did not seem to induce elevation of caseinolytic activity in AH. The clinical significance of this phenomenon and the mechanisms behind it are discussed.

Animals

Immunocytochemical localization of carbonic anhydrase, NaK-ATPase and the bicarbonate chloride exchanger in the anterior segment of the human eye.

We examined immunohistochemically the localization of three transport enzymes (carbonic anhydrase, Ca-II; sodium-potassium-activated adenosine triphosphatase, NaK-ATPase; bicarbonate-chloride exchanger, band III) in the anterior segment of the human eye. In accord with earlier studies, NaK-ATPase was primarily found in the corneal endothelium, but also in the corneal basal epithelial cell membranes. In addition, immunoreactivity for NaK-ATPase was observed in the non-pigmented epithelium of the ciliary processes and between the two epithelial cell layers. Ca-II immunoreactivity was found in the corneal endothelium as well as in the non-pigmented epithelial layer of the ciliary processes. Interestingly, band III immunoreactivity was found in the corneal endothelium, as similar to Ca-II, but not in the ciliary processes. These results show that, similar to many other tissues, Ca-II and band III immunoreactivities colocalize in the same cytologic site in the human corneal endothelium. Immunocytochemical detection of these key transport enzymes not only gives their accurate and reliable anatomical distribution, but also provides information on the electrolyte transport at these sites.

Anion Exchange Protein 1, Erythrocyte

Ocular disease leads to decreased concentrations of epidermal growth factor in the tear fluid.

The concentration of epidermal growth factor (EGF) in tear fluid (TF) was recently shown to decrease with increasing tear fluid flow (TFF). The purpose of the present study was to clarify the effects of ocular surface disease on the TF EGF concentrations. Tear fluid samples (n = 243) were collected from diseased eyes by means of blunted glass capillaries. The time of collection was measured for each sample, and the tear fluid flow in the capillaries (TFFc) was calculated. The concentration of human EGF (hEGF) was determined using a time-resolved immunofluorometric assay (TR-IFMA). For statistical analysis diagnosis-dependent multigrouping was performed and the data of the patient groups were compared to the data for a control group. The control material consisted of 271 TF samples collected from healthy eyes before (n = 59) and after stimulation of reflex tearing (n = 212). It was shown that TF specimens of patients (n = 243) contained significantly (p less than 0.001) less EGF (mean 952 pg/ml) than the TF of healthy control individuals before (n = 59 samples; mean 6589 pg/ml) or after stimulation of reflex tearing (n = 212 samples; mean 2762 pg/ml). The EGF concentration of every patient group was significantly lower than that found in the TF of control individuals both before and during reflex tearing (p less than 0.001). The rate of EGF released with TF during collection did not differ significantly between the various groups of patients or from that released with the TF of normal individuals before induction of reflex tearing.(ABSTRACT TRUNCATED AT 250 WORDS)

Corneal Diseases