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Biomedical subjects

A Tarkkanen

Publications and source records attributed to A Tarkkanen.

At least 73 records · Page 4Linked to original sources
PubMed1991

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↗
PubMed1991

Neuronal and glial properties of a murine transgenic retinoblastoma model.

Antigenic properties of a murine transgenic model for hereditary retinoblastoma, induced by a chimeric gene coding for Simian virus 40 large T antigen, an oncogene that inactivates the retinoblastoma susceptibility gene product, were studied by immunohistochemistry. All transgenic mice develop bilateral intraocular retinal tumors in the inner nuclear layer with Homer Wright-like rosettes, and one quarter develop midbrain tumors resembling trilateral retinoblastoma. Cell lines TE-1 and TM-1 were established from intraocular and metastatic tumors, respectively. Intraocular tumors reacted with antibodies to neuron-specific enolase and synaptophysin, while vimentin, glial fibrillary acidic, and S-100 proteins were detected only in reactive glia derived from adjacent retina. The midbrain tumors showed weak reactivity to synaptophysin, and they blended with reactive astrocytes positive for glial markers. The tumors were negative for cytokeratins. Finally both derived cell lines expressed synaptophysin and individual neurofilament triplet proteins in immunofluorescence and Western blotting, supporting their essentially neuronal nature. The antigenic profile resembles human retinoblastoma, but differences in morphology and antigen distribution suggest a more close relationship to neurons of the inner nuclear layer than to photoreceptor cells.

Animals↗
PubMed1991

Expression of tenascin and cellular fibronectin in the rabbit cornea after anterior keratectomy. Immunohistochemical study of wound healing dynamics.

Anterior keratectomy (AKE) was done on rabbits, and the appearance of immunohistochemically demonstrable tenascin (TN) or cellular fibronectin (cFN) was studied at different times (5 min to 14 months) after the operation. The substance TN was first observed 12 hr after wounding in the posterior stroma; cFN appeared with the same localization 12 hr later. During postoperative week 1, both TN and cFN immunoreactions shifted to more anterior parts of the cornea, and 9 days after wounding, they were localized in the most anterior part of the stroma only. Thereafter the reactions gradually decreased in intensity but still were visible 3 months after AKE. No reaction for TN or cFN was present 14 months postoperatively.

Animals↗
PubMed1991

Cytoskeleton in normal and reactive human retinal pigment epithelial cells.

The cytoskeleton of normal and reactive retinal pigment epithelium (RPE) was analyzed immunohistochemically in five light microscopically normal formalin-fixed, paraffin-embedded human eyes enucleated because of orbital tumor and in 44 eyes with a uveal melanoma. In 26 eyes, the RPE overlying the tumor was morphologically normal or atrophic; in 18 eyes, hyperplastic changes were present. Normal RPE cells lacked vimentin, but it was present in 35 of 44 eyes with uveal melanoma. Antibodies that recognize cytokeratins CK8 and CK18 labeled normal and reactive RPE cells in all specimens. Although CAM 5.2 and CY-90 detected RPE cells strongly and quantitatively, clones CK5, KS-B17.2, and pancytokeratin antibody lu-5 reacted weakly and did not label some specimens. Immunoblotting supported the presence of CK8 and CK18 in human RPE. Normal RPE cells did not express other simple epithelial cytokeratins, but both atrophic and hyperplastic reactive RPE cells were labeled with antibodies to CK7 or CK19 in 24 of the 44 eyes. Hyperplastic proliferating RPE cells that formed subretinal membranes reacted positively for alpha-smooth muscle actin in 13 of 18 eyes. Antibodies to CK8 and CK18 are valuable markers of normal and reactive human RPE cells, but a panel of reagents is necessary to document reactive changes in the cytoskeleton. Acquisition of alpha-smooth muscle actin by human RPE cells may be related to their ability to form periretinal membranes and contribute to intraocular proliferative diseases.

Adolescent↗
PubMed1991

Primitive neuroectodermal tumor of the midbrain in a murine model of retinoblastoma.

The first heritable model of retinoblastoma was established by retina-specific expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice. Bilateral, multifocal ocular tumors were observed in 100% of transgene-bearing mice. Central nervous system neoplasms occurred at a lower rate (27%) and represented the murine counterpart of human trilateral retinoblastoma. The authors characterized the transgenic brain tumors and found them to be primitive neuroectodermal tumors (PNET) of the midbrain. Murine brain tumors do not involve the pineal gland and most closely resemble undifferentiated suprasellar or parasellar tumors occasionally observed in human trilateral retinoblastoma. The murine malignancies arose from the subependymal cells of the cerebral aqueduct. Immunohistochemical and ultrastructural examination revealed that the transgenic brain tumors were undifferentiated and lacked all antigens associated with normal murine neuronal, glial, and ependymal cells.

Animals↗
PubMed1990

Effects of the Schirmer test on the fibrinolytic system in the tear fluid.

Human tear fluid was collected with blunted glass capillaries before and after performing the Schirmer test (ST). The test caused an increase in the tear fluid (TF) plasmin concentration (from 0.40 +/- 0.29 microgram ml-1 (mean +/- S.E.M.) to 1.14 +/- 0.26 microgram ml-1; Mann-Whitney test P less than 0.001) and a decrease in plasminogen activator activity (from 2.04 +/- 0.24 IU ml-1 to 1.04 +/- 0.17 IU ml-1; Mann-Whitney test P less than 0.002). In the filter paper used for ST, that segment that had been in contact with the conjunctiva (5 mm) usually contained higher amounts of plasmin than the following 5 mm of the paper overhanging the lidmargin. The present results indicate that the TF collection may affect the plasminogen activator-plasmin system in TF, depending on the collection method used.

Fibrinolysin↗
PubMed1990

Long-term maintenance of therapeutic response to lovastatin in patients with familial and non-familial hypercholesterolemia: a 3-year follow-up.

The 3-year efficacy of lovastatin alone or in combination with colestipol was evaluated in 54 patients with type 2 hyperlipoproteinemia (22 non-familial and 32 familial hypercholesterolemic patients). A sufficient and sustained reduction in LDL cholesterol was achieved in non-familial hypercholesterolemia with lovastatin alone (average dose 74 mg/day, range 40-80 mg/d), whereas combination therapy with lovastatin 80 mg/d and colestipol (average dose 11.9 g/d, range 5-20 g/d) was required in familial hypercholesterolemia. The percentage changes from baseline at 3 years in serum LDL cholesterol, HDL cholesterol and total triglycerides were in the lovastatin-only group -53%, +10% and -15%, respectively, and in the two-drug group -58%, +22% and -18%, respectively. A subgroup analysis in patients with non-familial hypercholesterolemia indicated that the lipid-modifying effects of lovastatin were similar in type 2A and 2B phenotypes, except for a greater triglyceride lowering effect in type 2B. The lovastatin-alone regimen was well tolerated, whereas addition of colestipol caused subjective side effects in many patients. Serious side effects or discontinuations due to therapies did not occur. Both therapies caused slight but significant increases (within normal limits) in average serum transaminase levels. After 36 months a significant rise of 1.7 kg in mean body weight was observed in the lovastatin-only group. The ophthalmological follow-up did not reveal any cataractogenic effect attributable to treatment during the 3.8-year follow-up period.

Adult↗
PubMed1990

On the proteolytic activity of contact lenses and bacteria.

Contact lens wear (CLW) has been shown to cause an elevation in tear fluid (TF) plasmin levels. This study investigated whether the proteolytic activity assayed by a caseinolytic technique was also bound by CLs and whether certain bacterial species contribute to the production of plasmin. CLs worn by patients with corneal disease showed proteolytic activity in five out of nine cases when examined on casein agar. Histological and electron microscopic examination of the lenses revealed bacterial adherence and growth on both surfaces of the CLs. Strains of Staph. epidermidis, Staph. aureus, Pseudomonas aeruginosa and Branhamella catarrhalis, isolated from eyes with external infections, were cultured on a modified milk casein agar and examined for their proteolytic activity. Neither cultures of Branhamella catarrhalis nor Staph. aureus showed proteolytic activity when examined by direct caseinolytic assay. The proteolytic activity shown by Staph. epidermidis or Pseudomonas aeruginosa was not affected by a proteinase inhibitor aprotinin. However, when exogenous plasminogen was added into the casein agar, Staph. aureus was shown to produce caseinolytic activity. This activity was interpreted to be due to plasminogen activator (PA) activity. It was inhibited by aprotinin. Examination of culture fluids of the bacterial species mentioned above did not show caseinolytic activity. Culture fluid of Staph. aureus contained PA activity. The present study confirms the ability of certain bacterial species to adhere to CLs. Moreover, proteases such as plasmin and bacterial enzymes are present in TF during CL wear and may even adhere to the surface of CLs. Hence, bacterial growth probably contributes to the production of proteases on the ocular surface during CL wear.

Adolescent↗
PubMed1990

Immunohistochemical demonstration of epidermal growth factor in the lacrimal and submandibular glands of rats.

The extraorbital and intraorbital lacrimal glands, the Harderian glands, and the submandibular glands of five rats were excised after ethanol perfusion under general anesthesia. Indirect immunohistochemistry with antibodies specific to epidermal growth factor (EGF) was performed. EGF-like immunofluorescence (EGF-LI) was shown to be present both in the lacrimal glands (extra- and intraorbital) and in the submaxillary gland. In the lacrimal glands the specific immunoreaction appeared within the lumen of the acini and the cells of the tubular ducts close to the acini. Only faint EGF-LI was observed within the acinar cells. The submandibular glands showed intense EGF-LI only in the cells of the granular convoluted tubules. The Harderian gland did not show any EGF-LI. The results strongly support the idea that the lacrimal gland is a source of EGF in tear fluid (TF). Diseases of the lacrimal gland therefore may lead to decreased concentrations of EGF in tears. This may account in part for the pathophysiology of tear deficiency syndromes and may serve as the basis of a new rationale for the external application of EGF.

Animals↗
PubMed1990

Granular corneal dystrophy with early stromal manifestation. A clinical and electron microscopical study.

We describe a family tree from central Finland with 19 members of which 10 had typical granular corneal dystrophy (Bücklers 1938). This granular dystrophy seems to start from the subepithelial and anterior stromal region. In quite early ages the granules spread not only into the midstromal layers but also into the most posterior stroma between the stromal lamellae and Descemet's membrane. Corneal epithelial erosions were not noticed in this family. The central cornea was mostly affected and 2-3 mm of the corneal periphery was clear. No endothelial changes were found from the corneal midperiphery by specular microscopy. To date, two female patients have needed penetrating keratoplasty; one in her late thirties and the other in her early forties. Their corneal buttons were studied by electron microscopy and histochemically. Granular material was found between the stromal lamellae and also inside the stromal keratocytes. Bowman's membrane was disrupted and degenerated in the areas where the deposits were situated in the subepithelial region. Recurrence of the disease was observed in the corneal transplants of the two operated patients 3 years postoperatively, starting again in the subepithelial region and mostly in central areas of the transplant. This disease entity seems to be different from the granular dystrophy also reported from Finland by Forsius et al. (1983).

Adolescent↗
PubMed1990

Immunohistochemical demonstration of tenascin in the normal human limbus with special reference to trabeculectomy.

Sections from the anterior segment of the fetal and adult human eye and from limbal tissue excised during standard trabeculectomies were studied immunohistochemically with monoclonal antibodies against human tenascin or monoclonal antibodies against cellular fibronectin (cFN). In the fetal eye, tenascin-like immunoreactivity (TEN-LI) was observed in the area of the developing limbus. In the adult eye TEN-LI was most intense at the corneoscleral margin in the stromal tissue and decreased towards the posterior sclera. No reaction was observed in the corneal stroma, but the epithelium showed moderate immunofluorescence. All tissues obtained during trabeculectomy showed similarly strong TEN-LI. The sections from trabecular specimens incubated with antibodies against cFN were negative.

Anterior Eye Segment↗
PubMed1990

Plasmin and epidermal growth factor in the tear fluid of contact-lens wearers: effect of wearing different types of contact lenses and association with clinical findings.

The concentrations of plasmin and epidermal growth factor were determined in tear fluid (TF) samples from wearers of different types of contact lenses (CLs) during and after cessation of CL wear (CLW). TF samples of 50 healthy eyes served as controls. The plasmin concentrations in the control group (0.4 +/- 0.1 microgram/ml; mean +/- SEM) were significantly lower (p less than 0.001) than in the group of soft CL (SCL) wearers during CLW (1.2 +/- 0.2 microgram/ml). Cessation of CLW led to a decrease in TF plasmin concentrations from 1.2 +/- 0.2 to 0.6 +/- 0.1 micrograms/ml in the group of SCL wearers (p less than 0.001), from 1.5 +/- 1.1 to 0.3 +/- 0.2 micrograms/ml in the group of extended-wear SCL wearers (p greater than 0.05) and from 0.4 +/- 0.3 to 0.0 +/- 0.0 microgram/ml in the group of gas-permeable CL wearers (p greater than 0.05). After CLW cessation, TF plasmin levels of CL wearers did not differ from those of controls. The occurrence of plasmin in TF was associated with a higher degree of corneal neovascularization and with the presence of limbal injection. The concentrations of epidermal growth factor in TF were not significantly altered by the discontinuation of CLW.

Conjunctiva↗
PubMed1989

Epidermal growth factor is a constant component of normal human tear fluid.

Epidermal growth factor (EGF) is a mitogenic polypeptide, which was first isolated from mouse submaxillary gland. Since EGF also stimulates the growth of corneal epithelial cells and only preliminary data exist on its presence in tear fluid, we studied the occurrence of human EGF (hEGF) in the tear fluid of 36 healthy persons (31 women and 5 men from 20 to 59 years of age; 60 eyes). hEGF, as measured by an immunofluorometric assay, was present in all tear fluid samples investigated. Its concentration varied from 200 to 2860 pg/ml (median, 705 pg/ml). The tear fluid hEGF concentrations differed less between the eyes of one individual than between individuals. The total amount of hEGF released to the tear fluid increased with fluid flow, but the higher the flow was, the lower the concentration of hEGF. We could not find any evidence of sex dependency in the hEGF concentrations. In demonstrating that hEGF is a normal component of human tear fluid, the results of this study suggest that hEGF may be important for conjunctival and corneal epithelial integrity.

Adult↗
PubMed1989

Contact lens wear is associated with the appearance of plasmin in the tear fluid--preliminary results.

We determined biochemically the plasmin concentration in tear fluid from 50 externally healthy eyes and from 49 eyes during contact lens (CL) wear. After cessation of CL wear, samples were collected again from 41 of the 49 eyes. Plasmin was detected more frequently (P less than 0.0001) in the CL-wearing group (75.5%) than in the control group (20%). After the cessation of CL wear (3-21 days), the frequency of plasmin detection in tear fluid decreased significantly (P less than 0.0006) but was still higher (39%) than in the control group. We conclude that the occurrence of plasmin in tear fluid is correlated with CL wear. The proteolytic activity of plasmin may contribute to the development of corneal epithelial pathology associated with CL wear.

Contact Lenses↗
PubMed1989

Plasminogen activator and its inhibitor in the experimental corneal wound.

Anterior keratectomy was performed to 10 eyes of 8 adult rabbits. The animals were killed 3-24 hr after wound closure. The corneas were excised and subjected to histochemical demonstration of urokinase-type plasminogen activator (u-PA), tissue-type PA (t-PA) and plasminogen activator inhibitor [PAI-1) using commercial antibodies. A strong immunoreaction for u-PA, a weaker reaction for PAI-1 and a very weak t-PA-like immunoreaction appeared in the anterior stroma of the wounded area. None of the antisera used showed any immunostaining in the cornea outside the wound. The role of the plasminogen activator-plasmin system in the healing of the corneal wound is discussed.

Animals↗
PubMed1989

Glioneuroma associated with colobomatous dysplasia of the anterior uvea and retina. A case simulating medulloepithelioma.

The left eye of an otherwise healthy child was enucleated at the age of 2 months because of an enlarging mass involving the temporal iris, ciliary body, and anterior retina. The initial histopathologic diagnosis was malignant medulloepithelioma with orbital extension. Closer study revealed a superotemporal chorioretinal and ciliary body coloboma; dysplasia of the adjacent retina; a glioneuromatous mass replacing the temporal ciliary body, chamber angle structures, and iris and extending through the sclera to involve the insertion of the lateral rectus muscle; neuroepithelial elements resembling medulloepithelioma; and abnormally developed iris pigment epithelium, and dilator and sphincter muscles. Immunohistochemistry demonstrated that the main mass consisted of neurons positive for neuron-specific enolase (NSE), synaptophysin and neurofilaments, and glial cells expressing vimentin, glial fibrillary acidic protein, and S-100 protein. The neuroepithelial elements reacted positively for cytokeratins and S-100 protein, in addition to NSE and vimentin, suggesting ciliary epithelial rather than embryonic retinal origin. The tumor was rediagnosed as glioneuroma, which in this case was part of a widespread colobomatous dysplasia of the anterior uvea and retina. The patient is alive without metastases or local recurrence 2 years following enucleation and subtotal removal of the lesion.

Ciliary Body↗