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Biomedical subjects

T Kivelä

Publications and source records attributed to T Kivelä.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1989

Prognosis of conjunctival melanomas in relation to histopathological features.

Twenty-six patients (age 29-85 years) with primary malignant melanoma of the conjunctiva were analysed for usefulness of various histopathological and immunohistochemical features of the primary, recurrent and metastatic tumours in evaluating their prognosis. The mean follow-up time was 5.5 years, ranging from 8 months to 17 years. Eight patients developed metastases and seven have died. The mean time from diagnosis to death due to metastasis was 3.8 years (range 1-6 years). The site of the primary tumour seemed to be most closely correlated to high metastatic risk. Only two of the sixteen limbal melanomas metastasised, whereas two of the four bulbar, all three tarsal and the only diffuse primary tumour caused metastatic disease. Two of the metastasising primary tumours were less than 1.5 mm thick, but all exceeded 0.8 mm in thickness. The mitotic rate, the amount of inflammatory infiltrate, the cell type or the presence of adjacent intraepithelial involvement did not obviously correlate to treatment outcome. Furthermore, the expression of S-100 protein and neuron-specific enolase (NSE), both suggested to be prognostic indicators in cutaneous melanoma, did not correlate to the tendency of the conjunctival melanomas to recur or metastasise.

Adult↗
PubMed1989

Rabies: ocular pathology.

Ocular pathology in the first European case of human bat-borne rabies is described. The patient was a 30-year-old bat scientist who seven weeks after bat bite developed neurological symptoms and died 23 days later. Rabies virus antigens were detected in brain smears. After extensive virological studies the virus turned out to be a rabies-related virus, closely resembling the Duvenhage virus isolated from bats in South Africa in 1980. By light microscopy focal chronic inflammatory infiltration of the ciliary body and of the choroid was found. PAS-positive exudate was seen in the subretinal and in the outer plexiform layers of the retina, and retinal veins showed endothelial damage and perivascular inflammation. Many of the retinal ganglion cells were destroyed. The presence of rabies-related viral antigen in the retinal ganglion cells was shown by positive cytoplasmic immunofluorescence, though electron microscopy failed to identify definite viral structures in the retina. By immunohistochemistry glial fibrillary acidic protein was observed in the Müller's cells, which are normally negative for this antigen but express it as a reactive change when the retina is damaged. Synaptophysin, a constituent of presynaptic vesicles of normal retinal neurons, was not detected in the retina.

Adult↗
PubMed1989

Synaptophysin in the human retina and retinoblastoma. An immunohistochemical and Western blotting study.

Fifty-four formalin-fixed and paraffin-embedded intraocular retinoblastoma specimens and three human eyes enucleated because of orbital tumors were studied for the presence of synaptophysin, a neuron-associated integral membrane glycoprotein of presynaptic vesicles, by using the monoclonal antibody SY38. Normal human brain was used as control. In the human retina, synaptophysin-like immunoreactivity was present in both plexiform layers, but could not be detected in neuronal perikarya. However, in reactive retinas present in retinoblastoma eyes, synaptophysin was often observed in perikarya and processes of photoreceptors. Positive neoplastic cells were found in 45 of the 54 retinoblastomas. Differentiated tumors tended to contain greater numbers of positive cells than undifferentiated ones, a third of which were entirely negative. Identical immunoreactivity was seen in frozen specimens from human retina and from three retinoblastomas. Using Western blotting, a major polypeptide comigrating with human brain synaptophysin was detected in human retina, and a similar but slightly slower migrating band in retinoblastoma. The results support a primarily neuronal origin for this tumor and point to the possibility that synaptic elements, previously observed in a few cases, may be more frequent in retinoblastoma than had been thought.

Blotting, Western↗
PubMed1989

Expression of intermediate filaments (IF) in tissues and cultured cells.

Intermediate filaments are found in most nucleated cells as part of their cytoskeleton. Intermediate filaments are formed by different proteins in cells of major tissues types. Therefore, antibodies against intermediate filaments can be used in tissue typing, in the analysis of cell lineages during development and in the elucidation of the origin of unknown tumors.

Animals↗
PubMed1988

Recurrent medulloepithelioma of the ciliary body. Immunohistochemical characteristics.

A predominantly benign medulloepithelioma of the ciliary body was diagnosed in an 8-year-old girl and resected by iridocyclectomy. It recurred twice during 30 months. Highly malignant histopathologic features developed, and the eye finally perforated and had to be enucleated. No recurrence or metastases have subsequently developed. Histologically, the tumor was a nonteratoid medulloepithelioma consisting of elements resembling embryonic retina, nonpigmented ciliary epithelium, and neuroblasts, but had also areas of obvious glial and neuronal differentiation as judged by immunohistochemistry. The neuroepithelial tumor cells were positive for neuron-specific enolase, vimentin, and often for S-100 protein. The neuroblastic cells were generally positive for neuron-specific enolase and synaptophysin, but were intermixed with glia-like tumor cells positive for vimentin, glial fibrillary acidic protein, and S-100 protein. The results suggest that even a nonteratoid medulloepithelioma may be, unlike retinoblastoma, a truly multipotential tumor.

Child↗
PubMed1988

Histopathology of enucleated intraocular melanomas irradiated with cobalt and ruthenium plaques.

Eight malignant uveal melanomas irradiated with Stallard's 60Co applicator or Lommatzsch's 106Ru/106Rh applicator were studied by light microscopy and immunohistochemistry to analyse tumour cell morphology, antigenic expression and inflammatory cell infiltration in relation to radiation dose. The tumours were enucleated 1 to 24 months after irradiation because they did not regress or continued to grow. One patient has later died of metastatic disease. Eight uveal melanomas that were not irradiated were studied for comparative purposes. Radiation necrosis was found only in two cases. In four irradiated and in one control melanoma conspicuous collagen fibres were present in the basal part of the tumour. No difference was noted between the two groups in the number of mitotic figures or in the morphology of tumour cells. In all cases but one, more than half of the tumour cells were variably positive for S-100 protein. Neuron-specific enolase-positive melanoma cells were few in number and occurred in small clusters, and were somewhat more common in irradiated cases. A few lymphocytes and macrophages, which were preferentially found near the choroid, infiltrated every melanoma, but only single cells were associated with radiation necrosis. A mild scleritis near the tumour was present irrespective of irradiation. Although the melanomas were quite large for irradiation, the lack of necrosis in optimally irradiated basal parts of the tumour additionally indicates substantial radioresistance.

Adult↗
PubMed1988

Expression of intermediate filaments and synaptophysin show neuronal properties and lack of glial characteristics in Y79 retinoblastoma cells.

The expression of intermediate filaments and synaptophysin in Y79 retinoblastoma cells was studied. The cells grew normally in suspension as floating aggregates. Sodium butyrate and dibutyryl cyclic AMP induced adherence and rapid spreading of Y79 cells on laminin-coated substratum and many of the cells presented long cellular extensions. As judged by immunostaining with monoclonal and polyclonal antibodies, most untreated Y79 cells expressed synaptophysin, whereas only vimentin intermediate filaments were detected in a few cells. A more bright fibrillar vimentin-positivity, which responded by coiling to disruption of microtubules, could be seen in the spread cells. Furthermore, especially when exposed to butyrate, a distinct fibrillar positivity could be revealed in some of the spread cells with antibodies recognizing a phosphorylated epitope in neurofilaments. Western blotting results showed the presence of the molecular weight 57,000 vimentin polypeptide and the molecular weight 38,000 synaptophysin polypeptide in both undifferentiated and spread Y79 cells, and a phosphorylated molecular weight 200,000 neurofilament polypeptide in spread cells only. In contrast, both immunostaining and Western blotting results with several antibodies indicated lack of glial fibrillary acidic protein in Y79 cells suggesting hence, a lack of glial differentiation. The present results do not support the hypothesis that retinoblastomas would originate from a common precursor cell of neurons and glia, and show the presence of mainly neuronal features in Y79 retinoblastoma cells.

Blotting, Western↗
PubMed1987

A lectin cytochemical study of glycoconjugates in the human retina.

The binding to morphologically normal human retina of eleven biotin- or peroxidase-coupled lectins with different carbohydrate specificities was studied. Eight formalin-fixed and paraffin-embedded eyes were examined. Photoreceptor cells bound Lens culinaris (LCA), wheat germ (WGA), peanut (PNA) and Ricinus communis (RCAI) agglutinins, and concanavalin A (ConA). The outer segment region was labeled more strongly that the inner segment region, and PNA labeled only cones. All these lectins except PNA bound to both plexiform layers, and all but PNA and RCAI to the nuclear layers. Pretreatment with neuraminidase to remove sialic acid resulted in increased binding of RCAI and PNA, which now labeled both rods and cones, and in decreased binding of WGA. Bandeiraea simplicifolia (BSAI), Dolichos biflorus (DBA), soybean (SBA), Ulex europaeus (UEAI), and Lotus tetragonolobus (LTA) agglutinins, as well as pokeweek mitogen (PWM) reacted only with retinal vascular endothelial cells, which were also labeled with the other lectins. The results indicate that alpha-mannose, alpha-glucose, beta-galactose, N-acetyl-D-glucosamine and N-acetylneuraminic acid are present in glycoconjugates of human neuroretina.

Acetylglucosamine↗
PubMed1987

Glycoconjugates in retinoblastoma. A lectin histochemical study of ten formalin-fixed and paraffin-embedded tumours.

The binding of eleven biotin- or peroxidase-coupled lectins with different carbohydrate specificities to tumour tissue and remaining morphologically normal retina was studied in ten formalin-fixed and paraffin-embedded human eyes with retinoblastoma. In undetached retinas, outer and inner segments of photoreceptors bound concanavalin A (ConA) as well as Lens culinaris (LCA), wheat germ (WGA) Ricinus communis (RCAI) and peanut (PNA) agglutinins. Both nuclear and plexiform layers bound ConA, LCA and, in some specimens, WGA and RCAI. These results agree with those obtained with normal adult human retina, the main difference being that PNA labelled some rods in addition to cones in the retinoblastoma eyes. Flexner-Wintersteiner rosettes reacted with ConA and LCA, and often with WGA, PNA and RCAI. Undifferentiated retino-blastoma cells always bound ConA and LCA, and in some tumours WGA, PNA and RCAI. Pretreatment with neuraminidase increased the number of cells that bound PNA and RCAI, but diminished binding of WGA. Pokeweed mitogen and Bandeiraea simplicifolia I, Dolichos biflorus, soybean, Ulex europaeus I and Lotus tetragonolobus agglutinins labelled only vascular endothelial cells. Retinoblastoma cells most closely resembled photoreceptor cells in their lectin-binding patterns.

Carbohydrates↗
PubMed1986

Expression of the HNK-1 carbohydrate epitope in human retina and retinoblastoma. An immunohistochemical study with the anti-Leu-7 monoclonal antibody.

Fifty formalin-fixed and paraffin-embedded retinoblastoma specimens and five normal human eyes were studied with the monoclonal anti-Leu-7 antibody, directed against the HNK-1 carbohydrate epitope that is shared by human natural killer cells and many neuronal, glial and neuroectodermal cells. The laboratory method was a sensitive immunohistochemical staining procedure, and neuroectodermal tumours that usually express this epitope were used as positive controls. In the human retina, Müller cell membranes were positively stained, but additional staining of neuronal cells was not excluded at the light microscopical level. A positive cytoplasmic reaction was also seen in ciliary and retinal pigment epithelial cells. All but one intraocular retinoblastomata studied contained cells staining positively for the HNK-1 epitope, but these cells were probably not neoplastic. Although positive reaction has previously been reported in three retinoblastomata, the present results suggest that positive cells are derived from entrapped and infiltrated retina. Staining of adjacent sections against leukocyte common antigen suggested that the positively staining cells were not natural killer cells.

Antibodies, Monoclonal↗
PubMed1986

S-100 protein in retinoblastoma revisited. An immunohistochemical study.

Fifty formalin-fixed and paraffin-embedded retinoblastoma specimens were studied for the presence of S-100 protein in malignant tumour cells and in reactive glial cells. Its distribution in four normal human eyeglobes enucleated because of an orbital tumour was also studied. The laboratory method was a sensitive immunohistochemical staining procedure, and sections from human brain served as controls. Three anti-S-100 protein antisera were used to determine whether previously reported discrepancies could be related to differences in antibody specificity, but all gave identical results. In morphologically normal human retina, a strong reaction for S-100 protein was seen in astrocytes, and a faint, inconsistent positivity was detected in Müller's cells. All intraocular retinoblastomata studied contained cells positive for S-100 protein, which seemed to be reactive glial cells derived from infiltrated retina. Undifferentiated malignant retinoblastoma cells, as well as differentiated tumour cells in Flexner-Wintersteiner rosettes were negative for S-100 protein. Differentiated tumours appeared to contain more S-100 protein-positive glial cells than undifferentiated tumours, but this may be related to their different growth rates. The results do not support the theory that retinoblastoma cells express glial properties.

Eye Neoplasms↗
PubMed1986

Neuron-specific enolase in retinoblastoma. An immunohistochemical study.

Forty-six retinoblastoma specimens were studied for the presence of neuron-specific enolase (NSE) in the tumour cells and in the remaining morphologically normal retina. The laboratory method was a sensitive immunohistochemical peroxidase staining procedure, and normal ocular nerves were used as positive controls. Neuron-specific enolase was found in perikarya and cell processes in all layers of morphologically normal appearing neuroretina, but not in Müller's cells. All but two of the retinoblastomata studied contained positively staining tumour cells, whereas stromal cells remained constantly negative. Many Flexner-Wintersteiner rosettes stained positively as well. The proportion of retinoblastoma cells expressing neuron-specific enolase seemed to be greater in small tumours, in bilateral cases, and in tumours that contained rosettes. The presence of neuron-specific enolase in tumour cells seems to favour a neuronal or neuroectodermal origin for retinoblastoma, but it should be noted that this marker has recently been found in several non-neuronal and non-neuroectodermal malignant neoplasms.

Eye Neoplasms↗
PubMed1986

Intermediate filaments in the human retina and retinoblastoma. An immunohistochemical study of vimentin, glial fibrillary acidic protein, and neurofilaments.

Fifty-five retinoblastoma specimens were studied by a sensitive immunoperoxidase method to determine the intermediate filament types present in human retina and retinoblastoma. Polyclonal antiserum against vimentin and monoclonal antibodies to glial fibrillary acidic protein (GFAP) and to the 200 kD neurofilament triplet protein were used. In the human retina, Müller's cells coexpressed vimentin and GFAP in most instances, probably as a reactive phenomenon. Surprisingly, the horizontal cells did not stain with any of the antibodies used, and may thus lack intermediate filaments. Also, the meshwork of neural fibers in the inner plexiform layer was unusually sparse. Retinoblastoma cells were found to be devoid of all intermediate filament types studied. The tumors contained, however, vimentin and GFAP in the stromal cells. All neurofilament-positive cells in retinoblastoma apparently derived from infiltrated retina. One retinoblastoma eye was also studied by indirect immunofluorescence microscopy of frozen sections with identical results.

Animals↗
PubMed1983

Carcinoembryonic antigen in retinoblastoma. An immunohistochemical study.

Pathological amounts of carcinoembryonic antigen (CEA) have earlier been reported in the plasma of patients with retinoblastoma, and it has been suggested that CEA determinations be used in the follow-up of treatment of these patients. In the present study, 47 retinoblastoma specimens from the years 1962-1982 were examined. These specimens represented different clinical and pathological tumour types. Colon adenocarcinomata positive for CEA were used as controls. The laboratory method was a highly sensitive immunohistochemical peroxidase-staining procedure. By this method, CEA was not found in any of the retinoblastomata examined. It is probable that retinoblastoma does not produce CEA, but in theory it may indirectly increase the CEA titre or, on the other hand, be fully independent of CEA. Only after this relationship has been thoroughly clarified can determinations of plasma CEA in patients with retinoblastoma be used in clinical work.

Adult↗
PubMedDate not supplied

The Merkel cell and associated neoplasms in the eyelids and periocular region.

Merkel cells are clear oval cells in the epidermis and outer root sheaths of hair follicles, which are probably of epithelial origin, share ultrastructural features with neuroendocrine cells, and are found in association with touch receptors. In the eyelid, they occur singly in the epidermis and external root sheaths of hairs and eyelashes, and in specialized touch spots alternating with eyelashes. Their typical electron microscopical and antigenic features include dense-core granules, intranuclear rodlets, spinous processes, and a positive reaction for specific cytokeratins, epithelial membrane antigen, neuron-specific enolase, chromogranin and synaptophysin. Merkel cell carcinoma probably develops from precursor cells which give rise to keratinocytes and Merkel cells, and nearly one out of ten Merkel cell carcinomas occur in the eyelid and periocular region. They tend to be bulging lesions near the lid margin of elderly patients, reddish in color, and erythematous with telangiectatic vessels. The diagnosis is based on the frequent presence of neurofilaments and paranuclear aggregates of intermediate filaments in addition to features typical of normal Merkel cells. The tumor often mimics lymphoma or undifferentiated carcinoma and frequently invades lymphatic vessels. One third of Merkel cell carcinomas recur, almost two thirds give rise to regional node metastases, and up to one half metastasize widely and result in death. Initial treatment should be prompt and aggressive, with wide resection and routine postoperative irradiation. Although metastatic lesions often respond to radiation therapy and cytostatic drugs, these treatments are mainly of palliative value.

Carcinoma, Merkel Cell↗