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Biomedical subjects

C M Mooy

Publications and source records attributed to C M Mooy.

At least 37 records · Page 2Linked to original sources
PubMed1999

Late ophthalmological complications after total body irradiation in non-human primates.

PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

Age Factors↗
PubMed1998

Adhesion molecules in iris biopsy specimens from patients with uveitis.

BACKGROUND/AIMS: Earlier studies on intraocular tissue have demonstrated that T lymphocytes play a major role in the pathogenesis of uveitis. Adhesion molecules are immunoregulatory molecules for the interaction between T lymphocytes and vascular endothelium and they play an important role in the recruitment of specific T lymphocytes from the circulation into inflamed tissue. In uveitis an increased expression of some of these adhesion molecules may be expected. METHODS: The presence of adhesion molecules was investigated in iris biopsy specimens from 11 patients with uveitis and eight controls (patients with primary open angle glaucoma) immunohistochemically with a panel of monoclonal antibodies: LECAM (CD 62L), ICAM-1 (CD 54), LFA-1 (CD 11a/18), VCAM-1 (CD 106), VLA-4 (CD 49d), and HECA-452, a marker for high endothelial venules. RESULTS: Positive staining for ICAM-1, LFA-1 and VCAM-1 was found in the iris in a significantly higher number of uveitis patients than in controls. The remaining adhesion molecules were also found in a higher number of uveitis patients than in controls, but this difference did not reach statistical significance. CONCLUSION: An increased expression of adhesion molecules was found in the iris of patients with uveitis, indicating an immunoregulatory function for adhesion molecules in the pathogenesis of uveitis.

Adult↗
PubMed1997

Morphologic changes in age-related maculopathy.

Age-related maculopathy (ARM) is a degenerative disorder of the central part of the retina with a rising prevalence in patients 50 years of age and older, and comprises different histopathological changes. The morphologic changes in ARM are described and illustrated with light-microscopical, electron microscopical, and fundus pictures. Furthermore, the most important biochemical data are given. The most prominent aging changes in early stages of ARM are drusen and basal laminar deposit (BLD), both extracellular deposits, that are assumed to be important in the development of ARM. Drusen accumulate within Bruch's membrane, whereas BLD is present between Bruch's membrane and the retinal pigment epithelium. Although the histopathologic characteristics of the deposits are well documented, the chemical composition has only been partly resolved. Biochemical analysis of these deposits is necessary to determine the source of the deposits and to find possible ways to avoid or treat them. The late stages of ARM, geographic atrophy, and neovascular (disciform) degeneration, are called age-related macular degeneration (AMD), and result in severe and irreversible visual impairment. Since there is still no adequate therapy for the majority of people disabled by AMD, and because of the aging population resulting in even more patients with this disease, it is necessary to intensify the research on ARM in order to prevent AMD or find a therapy for it.

Basement Membrane↗
PubMed1997

Inverse correlation between expression of HLA-B and c-myc in uveal melanoma.

HLA class I is expressed in 75-85 per cent of uveal melanoma and cytoplasmic c-myc expression has been reported in 78 per cent of uveal melanoma. In skin melanoma, an inverse relationship has been observed between HLA class I expression and c-myc. The purpose of this study was to determine whether a similar correlation occurred between high expression of c-myc and low expression of HLA class I in uveal melanoma. The expression of c-myc, HLA-A, and HLA-B was determined by immunohistochemistry on formalin-fixed and paraffin-embedded sections of 30 uveal melanomas. Cell cultures from four primary uveal melanomas (lines 92-1, MEL 202, OCM-1, and EOM-3) and one uveal melanoma metastasis (line OMM-1) were tested for mRNA levels of c-myc and HLA-A and HLA-B in Northern blot assays. The high level of expression of cytoplasmic c-myc was significantly correlated with low expression of HLA-B (P = 0.03) and vice versa. High expression of HLA-B was significantly correlated with the presence of epithelioid cells (P = 0.004). The inverse correlation observed between c-myc and HLA-B expression is similar to previous observations in cutaneous melanoma. By downregulating HLA-B expression, c-myc may influence the immune response in uveal melanoma. Tumours containing epithelioid cells showed a significantly higher expression of HLA-B than tumours of the spindle cell type.

Adolescent↗
PubMed1997

Increased expression of angiogenic growth factors in age-related maculopathy.

AIMS/BACKGROUND: The late stages of age-related maculopathy (ARM), especially neovascular macular degeneration (ARMD), can severely affect central vision and are the main cause of blindness in the elderly in the Western world. It has been shown that angiogenic growth factors are present in neovascular membranes in ARMD. However, it is not known if angiogenic growth factors play a role in the onset of neovascularisation. METHODS: In order to elucidate the involvement of angiogenic growth factors in the initiation of neovascularisation in early stages of ARM, the expression patterns of VEGF, TGF-beta, b-FGF, and PDGF-AA on 18 human maculae with ARM, and on 11 control specimens were investigated immunohistochemically. RESULTS: A significantly increased expression of VEGF (p = 0.00001) and TGF-beta (p = 0.019) was found in the retinal pigment epithelium (RPE) of maculae with ARM compared with control maculae. Furthermore, an increased expression of VEGF and PDGF was found in the outer nuclear layer of maculae with ARM. CONCLUSION: These results demonstrate an increased expression of VEGF in the RPE, and in the outer nuclear layer in maculae with ARM, that could be involved in the pathogenesis of neovascular macular degeneration. Furthermore, enhanced TGF-beta expression in the RPE cells of maculae with early stages of ARM was shown.

Adult↗
PubMed1997

Syringomatous carcinoma of the eyelid and orbit: a clinical and histopathological challenge.

AIMS: To present three patients with a syringomatous carcinoma (SC). SC is a rare cutaneous neoplasm, most frequently situated on the face and scalp and histologically characterised by an infiltrative pattern of basaloid or squamous cells, a desmoplastic stromal reaction, keratin filled cysts, and granular structures. METHODS: The clinical histories of the patients with a SC were investigated retrospectively. RESULTS: Patient 1 had a benign appearing tumour of the lower eyelid. Five tumour excisions were necessary to remove the SC completely. Patient 2 had a tumour on the lateral part of the lower eyelid and in the medial canthal area. The histopathological findings revealed a squamous cell carcinoma, later revised as a SC. In spite of two excisions and one microscopically controlled excision, a recurrence occurred. An exenteration orbitae was recommended. Patient 3, known to have a history of multiple malignant skin tumours after kidney transplantation and use of cyclosporin, presented with a firm mass in the eyebrow region and in the nasal area of the orbit. The pathological diagnosis of this adnexal tumour was difficult. An exenteration was recommended. CONCLUSIONS: SC is a benign appearing but extremely invasive, locally destructive, slowly growing adnexal tumour, derived from eccrine sweat glands. It is often mistaken, both clinically and microscopically, for other benign and malignant entities. The tumour recurrence is high due to extensive perineural invasion, but regional or distant metastases are rare. The local aggressive nature of the tumour and the high recurrence rate may necessitate mutilating procedures. Optimal treatment consists of a complete microscopically controlled surgical excision with clear surgical margins.

Aged↗
PubMed1996

Metastatic uveal melanoma. A morphologic and immunohistochemical analysis.

BACKGROUND: Uveal melanoma often metastasizes late and preferentially to the liver, in contrast to cutaneous melanoma. The objective of the current study was to evaluate the histopathologic and immunohistochemical changes in primary uveal melanomas and their corresponding metastases. METHODS: The morphology and immunohistochemical reactivity for the melanoma-associated antibodies HMB-45, S-100 protein, and NKI-C3 were assessed for 29 primary uveal melanomas and their corresponding metastatses. RESULTS: A significant difference in cell type of the primary and the metastatic uveal melanoma was found (P = 0.0001). The metastases derived from the 29 patient's revealed 82.5% epithelioid or nonclassifiable cells. Positive staining of the primary uvea melanomas and their metastases was found to be 93% and 91%, respectively, for HMB-45, 80% and 66%, respectively, for S-100, and 56% and 71%, respectively, for NKI-C3. CONCLUSIONS: Metastases of uveal melanomas are comprised of a higher grade of malignant cell types. Nonclassifiable cells can be observed in 40% of metastatic lesions. In the current study, HMB-45 proved to be the most sensitive immunohistochemical marker in the analysis of metastatic uveal melanoma and should be used as part of a panel of monoclonal antibodies in the analysis of any metastatic tumor of unknown origin.

Antigens, Neoplasm↗
PubMed1996

Establishment and characterization of primary and metastatic uveal melanoma cell lines.

We report on the establishment and characterization of 2 primary (EOM-3, EOM-29) and 3 metastatic uveal melanoma cell lines (OMM-1, OMM-2, OMM-3) and further cytogenetic characterization of a previously described primary uveal melanoma cell line (OCM-1). Only a few long-term growing primary uveal melanoma cell lines have as yet been established, while of metastatic uveal melanoma cell lines we have found no descriptions. The morphology of the in vitro cultured cells varied from spindle to epithelioid. The cell lines were characterized by immunocytochemistry, electron microscopy and cytogenetical analysis. The relative growth rate was determined by bromodeoxyuridine (BUdR) incorporation. The melanocytic origin of the cell lines was determined by positive staining with antibodies identifying melanoma-associated antigens. Melanosomes and pre-melanosomes were indeed observed by electron microscopy in all cell lines. The stem-cell karyotype was found to be normal in 3 cell lines (EOM-29, OMM-2, OMM-3) and abnormal in 3 others (EOM-3, OCM-1, OMM-1) showing a net loss of chromosome 6. The OCM-1 and the OMM-1 cell lines even demonstrated a large amount of structural chromosomal aberrations, the former being near-tetraploid and the latter triploid. The EOM-29 cell line, cultured from a ciliary body melanoma, did not show the previously described chromosome 3 and 8 abnormalities.

Aged↗
PubMed1996

Identification of glycosaminoglycans in age-related macular deposits.

We investigated the presence and localization of glycosaminoglycans in basal laminar deposit and drusen in age-related maculopathy. Conventional histological staining techniques and monoclonal antibodies specific for several glycosaminoglycans were used on paraffin-embedded human maculae. Furthermore, macular homogenates were analyzed with two-dimensional electrophoresis. Quantitative analysis of glycosaminoglycans was done spectrophotometrically using dimethylmethylene blue. Immunohistochemically, all basal laminar deposit stained positive for chondroitin 4-sulfate and focally positive for heparan sulfate proteoglycan. Drusen were not stained with any of the monoclonal antibodies. With two-dimensional electrophoresis, it was demonstrated that macular extracts with and without age-related maculopathy contained chondroitin sulfate. Heparan sulfate was only expressed in maculae with age-related maculopathy. The total amount of glycosaminoglycans was significantly higher in maculae with basal laminar deposit than in maculae without basal laminar deposit (P = .001). There were significant differences in the amount and composition of glycosaminoglycans between maculae with and without age-related maculopathy.

Aged↗
PubMed1996

HNK-1 antigens on uveal and cutaneous melanoma cell lines.

The HNK-1 epitope has been associated with the metastatic behaviour of uveal melanomas. We characterized HNK-1 antigens on four human uveal (primary and metastatic) and two primary cutaneous melanoma cell lines by immunocytochemistry and Western blot analysis. We also determined the involvement of the HNK-1 epitope in cell-cell interactions on a matrigel layer. Three uveal melanoma cell lines (one primary and two metastatic) and one cutaneous melanoma cell line showed HNK-1 expression by immunocytochemistry. On matrigel, only the HNK-1-positive cutaneous melanoma cell line Bowes grew in a honeycomb-like structure which disappeared after adding HNK-1 antibodies to the culture medium. Immunoblot analysis of the primary uveal melanoma cell line EOM-3 revealed five HNK-1-positive protein bands with apparent molecular weights of 200, 160, 115, 95 and 75 kDa. The cutaneous melanoma cell line Bowes showed three HNK-1-positive protein bands with apparent molecular weights of 150, 135 and 90 kDa. This study shows that two uveal (primary and metastatic) and one primary cutaneous melanoma cell lines express HNK-1 antigens on immunoblot. Only in the HNK-1-positive cutaneous melanoma cell line Bowes did the HNK-1 epitope have a function in intercellular adhesion. Although the primary uveal melanoma cell line EOM-3 showed a similar HNK-1 immunoreactivity, we could not demonstrate HNK-1-mediated cell adhesion. On immunoblot, the two cell lines displayed different HNK-1 antigens, which may explain the difference in cell adhesion.

Blotting, Western↗
PubMed1995

Components of the plasminogen activation system in uveal melanoma--a clinico-pathological study.

In tumour development, proteases such as plasminogen activators (PAs) play a role in degradation of the extracellular matrix and other tissue barriers. Recently, we demonstrated that plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of cutaneous melanocytic tumour progression. In this study we investigated the expression and distribution of the various components of the PA system and the presence of PA enzyme activity in 45 freshly frozen primary uveal melanoma with known follow-up (14 spindle and 31 non-spindle type) and in metastases (n = 5). Tissue-type PA (t-PA) was found in endothelium of blood vessels and in tumour cells in almost all lesions, and was markedly present at the invasive front (towards the sclera and Bruch's membrane), but no correlation with tumour-related death could be established. Urokinase PA (u-PA) was expressed focally, by only five non-spindle cell melanomas but in all metastases. u-PA expression correlated with occurrence of metastasis. u-PA receptor (u-PAR) was present in one-third of all the tumours examined. Plasminogen activator inhibitors (PAI-1 and PAI-2) were found only focally in approximately 10 per cent of the lesions. Staining of t-PA, u-PA, and PAI was observed in all the metastases. We conclude that in uveal melanoma, u-PA expression may be associated with metastatic disease and accordingly with a poor prognosis. Further research on a larger group of tumours with known follow-up is needed to establish whether u-PA positivity is of additional prognostic value in uveal melanoma.

Biomarkers, Tumor↗
PubMed1995

Neural cell adhesion molecule distribution in primary and metastatic uveal melanoma.

Tumor cell adhesion, detachment, and aggregation play an important part in tumor invasion and metastasis, and a variety of cell adhesion molecules have been found on tumor cells. Cell adhesion molecules, including those of the immunoglobulin superfamily, are associated with the development of metastatic behavior in cutaneous melanomas. The neural cell adhesion molecule (NCAM) belongs to this family. To investigate its possible role in the development metastatic behavior of uveal melanomas, the authors studied immunohistochemically the expression of NCAM by using an antibody that recognizes all three major isoforms of NCAM and an antibody that recognizes the HNK-1 epitope present on some isoforms of NCAM. The authors studied 32 primary uveal melanomas from 32 patients (among these, 12 were rapidly metastasizing and 16 slowly metastasizing) and 29 metastases from 19 patients. From 13 patients the primary, as well as the metastatic, tumors were available. With one exception, all HNK-1 positive primary and metastatic tumors were also positive for NCAM. NCAM was significantly more expressed in aggressive, rapidly metastasizing primary tumors (P = .02 and .04, respectively) and in metastases. HNK-1 was significantly (P = .04) more expressed in larger tumors. In liver metastases HNK-1 immunoreactivity was significantly (P = .005) less frequently expressed than NCAM. Therefore, NCAM isoforms that lack the HNK-1 epitope might play a role in the organ specific metastatic behavior of uveal melanomas.

Antibodies, Monoclonal↗
PubMed1995

No demonstrated effect of pre-enucleation irradiation on survival of patients with uveal melanoma.

PURPOSE: To evaluate the hypothetical effect of pre-enucleation irradiation on survival of patients with uveal melanoma. METHODS: In a prospective study between 1978 and 1990, 145 patients with uveal melanoma were treated by irradiation in two fractions of 4 Gy before enucleation. A historical control group of 89 patients with uveal melanoma treated by enucleation alone was operated on between 1971 and 1990. Patients were followed up until December 1992 or until death. The mean follow-up period was 65 months in the irradiated group and 88 months in the control group. RESULTS: The preoperatively irradiated group of patients showed no significant improvement of the survival rate after 7 1/2 years (75.9%) compared with the control group (72.1%). Preoperative irradiation was not associated with survival (P = .93), as assessed by Cox proportional hazard analysis, adjusted for age, gender, tumor location, tumor size, cell type, and year of enucleation. Women in both the irradiated and control groups had a better prognosis than men (P = .002). CONCLUSION: Preoperative irradiation in this nonrandomized study had no effect on survival of patients with uveal melanoma.

Eye Enucleation↗
PubMed1995

Immunohistochemical and prognostic analysis of apoptosis and proliferation in uveal melanoma.

Neoplasia can be defined as deregulated tissue homeostasis caused by an imbalance between proliferation and apoptosis. Many genes are involved in the maintenance of tissue homeostasis, eg, the c-myc oncoprotein, which is an important regulator of cell proliferation and Bcl-2 protein, which is involved in the regulation of apoptosis. We studied retrospectively indices of proliferation, such as mitotic count and the Mib-1 index, on 51 uveal melanomas and compared their prognostic significance with established indicators of prognosis such as cell type and tumor size. Along the same line we investigated the expression of the regulating proteins c-myc and Bcl-2. Of all parameters tested, the largest tumor diameter and mitotic count were most strongly associated with tumor-related death (P < 0.001 and P = 0.005, respectively). In addition, cell type, the presence of epithelioid cells, the Mib-1 index, and the percentage of cytoplasmic c-myc-positive cells were significant predictive factors. Multivariate analysis showed that the Mib-1 index, largest tumor diameter, and the percentage of cytoplasmic c-myc-positive cells were independent prognostic parameters. Bcl-2 expression did not correlate with clinical outcome. The Mib-1 index correlated with the presence of epithelioid cells (P < 0.03) and the presence of apoptotic bodies (P < 0.001) and c-myc. A strong inverse relationship was found between (nuclear and cytoplasmic) c-myc and Bcl-2 (P < 0.00004 and P < 0.006, respectively), suggesting that Bcl-2 cooperates with c-myc to immortalize uveal melanoma cells.

Apoptosis↗
PubMed1994

Immunohistochemical light and electron microscopy of basal laminar deposit.

The formation of basal laminar deposit (BLD) is one of the histopathologic changes in the aging human macula. BLD is assumed to be an early stage of age-related macular degeneration. The location of BLD, between the RPE plasma membrane and its basement membrane and in the outer collagenous zone of Bruch's membrane, and its ultrastructure suggest that it is composed of excessive amounts of basement membrane material. The main components of basement membranes are type IV collagen, heparan sulfate proteoglycans (HSPG) and laminin. Labeled antibodies against these components can therefore be used for the identification and localization of basement membrane material by means of immunohistochemical techniques. In this study the presence of type IV collagen, laminin and HSPG was determined in aged human maculae by immunohistochemistry and immunoelectron microscopy. Tests for the presence of type VI collagen and fibronectin were also performed. We obtained 76 eyes from 68 human subjects at autopsy or after surgical enucleation for anteriorly located choroidal melanomas. The finely granular component of BLD stained positive with antibodies against type IV collagen, HSPG and laminin, but the long-spacing collagen component of BLD did not. Neither component of BLD was stained with antibodies against type VI collagen or fibronectin. We conclude that BLD consists partly of excess basement membrane material.

Adult↗