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M J Jager

Publications and source records attributed to M J Jager.

At least 55 records · Page 3Linked to original sources
PubMed1996

HLA expression and tumor-infiltrating immune cells in uveal melanoma.

BACKGROUND: In uveal melanoma, both the amount of tumor-infiltrating cells and the level of expression of HLA antigens are quite variable. We hypothesized that low levels of HLA expression lead to a lack of antigen presentation, which might prevent proper immunologic recognition of the tumor. This lack of recognition might subsequently lead to low levels of tumor-infiltrating cells. METHODS: To test this hypothesis, we determined the type and number of tumor-infiltrating cells in tumor sections from 24 uveal melanomas. We applied monoclonal antibodies directed against different types of immune cells and compared the results with the expression of HLA class I and class II antigens on the tumor cells. RESULTS: Infiltrating immune cells were observed in all uveal melanomas (although in small amounts), with a predominance of T lymphocytes. Significant positive correlations were observed between the number of CD3+ cells (T lymphocytes) and monomorphic HLA class I expression, allele-specific HLA-A2 and Bw4 expression, and HLA class II expression. Furthermore, the number of CD4+ cells (T helper cells, monocytes/ macrophages) and of CD11b+ cells (monocytes/macrophages) was significantly correlated with the level of monomorphic HLA class I expression. CONCLUSION: These data support our hypothesis that low levels of HLA expression (and therefore a lack of presentation of tumor-specific antigens) may lead to a low level of tumor infiltrate.

Adult↗
PubMed1996

Expression of CD44 and the pattern of CD44 alternative splicing in uveal melanoma.

In cutaneous melanoma, the standard CD44 molecule is abundantly expressed, whereas the expression of certain splice variants is related to tumour progression and to the metastatic potential of the cell line. In the present study we have investigated the expression of CD44 and the pattern of CD44 alternative splicing in uveal melanoma in relation to the cell type, diameter and invasiveness of the tumour. All uveal melanomas strongly stained with antibodies to the standard portion of CD44. No expression of the CD44 variant (v) exon CD44v7 was found, whereas v5, v6 and v10 were expressed (in 2/12, 5/12 and 8/12 cases, respectively). No correlation was observed between expression of particular splice variants and cell type, tumour diameter or invasion of the sclera or Bruch's membrane. All three uveal melanoma cell lines tested were strongly CD44 positive and expressed low levels of v6-containing isoforms at the cell surface, but v5, v7 and v10 were absent. Our results show that CD44 is strongly expressed in uveal melanoma and that the pattern of CD44 alternative splicing is similar to that observed in cutaneous melanoma. However, in uveal melanoma this alternative splicing does not appear to be related to prognostic parameters.

Alternative Splicing↗
PubMed1996

The role of macrophages in Acanthamoeba keratitis.

PURPOSE: Macrophages are thought to be the first line of defense in many infectious diseases and are present in high numbers in corneas with Acanthamoeba keratitis. Conjunctival macrophage depletion was performed in an animal model of Acanthamoeba infection to determine the importance of macrophages in this disease. METHODS: Selective elimination of macrophages was achieved by repeated subconjunctival injection of liposomes containing dichloromethylene diphosphonate in a Chinese hamster model of Acanthamoeba keratitis. RESULTS: Macrophage depletion affected the incidence, severity, and chronicity of keratitis. The incidence of infection in normal animals was approximately 60% but rose to 100% on day 4 in animals treated with liposomes containing dichloromethylene diphosphonate (C12MDP-LIP). Moreover, the clinical appearance of the keratitis in the C12MDP-LIP group was much more severe than in animals treated with liposomes containing phosphate-buffered saline at all time points. There was also a major change in the chronicity of keratitis, with an earlier onset and a prolonged and chronic course in the C12MDP-LIP treated hamsters. CONCLUSIONS: The profound exacerbation of Acanthamoeba keratitis in hamsters treated with C12MDP-LIP strongly suggests that macrophages play an important role in corneal infection with Acanthamoeba trophozoites, probably by acting as a first line of defense and eliminating significant numbers of Acanthamoeba trophozoites.

Acanthamoeba Keratitis↗
PubMed1996

Membrane-bound regulators of complement activation in uveal melanomas. CD46, CD55, and CD59 in uveal melanomas.

PURPOSE: To identify the presence of membrane-bound regulators of complement activation (m-RCA) on uveal melanomas and uveal melanoma cell lines and to examine their role in the inhibition of complement-mediated lysis in vitro. METHODS: Immunohistochemistry and flow cytometric analysis with monoclonal antibodies directed against m-RCA CD46, CD55, and CD59 were applied to tissue sections of 10 uveal melanomas, three primary uveal melanoma cell lines, and one uveal melanoma metastatic cell line. A microcytotoxicity test was used for measuring antibody-dependent complement-mediated lysis. RESULTS: The tissue sections and all four uveal melanoma cell lines expressed CD46, CD55, and CD59. Complement-mediated lysis in the presence of human complement was increased after partial removal of the m-RCA CD55 and CD59 with phosphatidylinositol-specific phospholipase C from the uveal melanoma cell line 92-1. CONCLUSIONS: These results demonstrate that CD46, CD55, and CD59 are expressed in uveal melanomas and that CD55 or CD59, or both, plays a role in resistance to complement-mediated cytotoxicity. The finding that m-RCA are expressed in uveal melanomas may have implications for the effectiveness of the anti-tumor response and in the therapeutic application of monoclonal antibodies directed against tumor-associated antigens.

Aged↗
PubMed1996

Association between NM23-H1 gene expression and metastasis of human uveal melanoma in an animal model.

PURPOSE: To evaluate the role of nm23 gene expression in the development of metastases of human uveal melanomas in an animal model. METHODS: Seven human uveal melanoma cell lines and two murine skin melanoma cell lines were subjected to Northern blot analysis for the detection of nm23-H1 mRNA and to immuno-histochemistry to detect nm23 antigen. Each tumor cell line was transplanted intracamerally into nude mice, and the metastatic behavior was evaluated by histopathologic analysis of the livers and by determining host survival times. RESULTS: There was a strong inverse correlation between the levels of nm23 mRNA expression and nm23 antigen expression and the development of metastases of all seven human uveal melanomas and both murine skin melanomas transplanted intracamerally. Host survival time also was correlated with the degree of nm23 gene expression. CONCLUSIONS: The expression of nm23 mRNA and nm23 antigen in human uveal melanomas is correlated closely with reduced metastatic behavior in experimental animals and may serve as a sensitive prognostic indicator of malignancy and survival in patients with uveal melanomas.

Animals↗
PubMed1995

Establishment and characterization of an uveal-melanoma cell line.

A human uveal melanoma cell line (92-1) was established from a primary uveal melanoma, and has now been maintained in culture for over 2 1/2 years. Light microscopy of the cultured cells demonstrated extremely pleiomorphic cells with large prominent nucleoli. Cell proliferation was determined with a non-radioactive propidium-iodide assay and indicated an in vitro doubling time of approximately 58 hr. Furthermore, the cell line was characterized by cytogenetic analysis, electron microscopy, immunocytochemistry and Northern blotting for HLA and c-myc-mRNA analysis. Cytogenetic analysis revealed numerical abnormalities of chromosome 8 and structural abnormalities of chromosome 6. By electron microscopy, different stages of melanosome development were observed. Immunocytochemical analysis demonstrated expression of the melanoma-associated antigen gp 100. Expression analysis of HLA antigens revealed a very low level of, in particular, the HLA-B locus products, which could be induced by interferon-alpha or -gamma treatment. Likewise, Northern-blot experiments revealed decreased levels of HLA-B mRNA as compared with HLA-A. In addition, high levels of c-myc expression were observed. The phenotypic characteristics of the cultured cells indicate that we have established an uveal melanoma cell line. This now well-characterized uveal melanoma cell line can be used in future studies.

Aged↗
PubMed1995

Corneal neovascularization in rats as a model for photothrombotic therapy using bacteriochlorin a and an argon laser.

BACKGROUND: The presence of vessels has a negative influence on corneal transplant survival. Closure of such vessels prior to transplantation may improve the transplant results, and this might be achieved by irradiating the vessels with argon laser light after intravenous administration of a photosensitizer, e.g. bacteriochlorin a (BCA). A suture-induced corneal neovascularization model in rats was set up to test this hypothesis. METHODS: Suture-induced vessels in the cornea of male Wistar rats were irradiated with argon laser light after intravenous administration of BCA. We applied irradiation of varying energy levels and duration and assessed the changes in the vessels by slit-lamp examination, fluorescein angiography and histology. RESULTS: Suture-induced corneal vessels in the rat could be used effectively to study photothrombosis therapy. Intravenous administration of BCA prior to irradiation (lambda = 514.5 nm) of the corneal vessels led to vessel closure at lower energy levels and of longer duration than occurred with laser treatment alone. CONCLUSIONS: Suture-induced corneal neovascularization in the rat can be used as a model to study the efficacy of photothrombosis therapy. BCA can be used to enhance the rate and duration of vessel closure.

Animals↗
PubMed1995

Recurrent herpetic keratitis in penetrating keratoplasty.

In a retrospective study we evaluated 49 consecutive penetrating keratoplasties for herpes simplex keratitis. Mean follow-up was 44.2 months. Survival analysis with Kaplan-Meier curve showed an overall survival rate (clear graft) of 88% at one year, 76% at two years and 72% at four years postoperatively. Survival analysis showed a recurrence-free survival rate of 72% at one year, 59% at two years and 51% at four years postoperatively. Of the 13 non-primary graft failures, 9 happened in eyes with an HSV recurrence. Recurrence of HSV infection occurred in 18 (39%) eyes at an average of 12.6 months after surgery (range 0.3-46). Five (28%) of the recurrences occurred within two months after the start of steroid treatment for rejection. Nine (50%) of the recurrences cases resulted in a clouded graft at the end of follow-up. 73% of the eyes with a clear graft had a VA of 0.25 or better. We conclude from these data that a recurrence of a herpetic infection following corneal transplantation is the main reason for graft failure in this group.

Adolescent↗
PubMed1995

HLA antigen expression on uveal melanoma cells in vivo and in vitro.

Immunotherapy with cytokines may be an additional option in the treatment of primary uveal melanoma or melanoma metastases. A study of the effect of cytokines on cultured uveal melanoma cells may predict the effect that cytokines may have in vivo. Knowledge about the influence of cytokines on HLA expression may be especially beneficial, as HLA expression is essential for immune recognition. However, little is known about the normal expression of the HLA antigens on uveal melanoma cells in tissue culture. We therefore determined the HLA expression on short-term cultures of uveal melanoma cells and compared the results to the expression on tissue sections of the original tumors. In vivo and in vitro expression of the monomorphic HLA class I determinants and of HLA-A (R = 0.77) correlated well. A slightly lower agreement was observed for expression of HLA-B (R = 0.68). In vitro growth was associated with a decrease in expression of the class II determinant HLA-DR. We conclude that expression of HLA class I on cultured melanoma cells corresponds to the expression on the original tumor, allowing the applicability of cultured cells as predictors of responsiveness to cytokines in vivo.

Adult↗
PubMed1995

Immunosuppressive properties of cultured human cornea and ciliary body in normal and pathological conditions.

Corneal transplantations may survive when transplanted orthotopically even in the presence of massive corneal neovascularization, while such grafts would be rejected in heterotopic locations. Experiments with murine tissues have shown that cultured corneal tissue as well as iris/ciliary body (I/CB) tissue produce immunosuppressive factors. This was not the case when traumatized corneas were tested. We therefore wondered whether the same difference could be observed when explants of normal or pathological human corneas or I/CB tissues were tested. Supernatant of cultured cornea and I/CB tissue was added to a mixed lymphocyte reaction (BALB/c responder and C57B1/6 stimulator cells) and thymidine incorporation was measured. Culture supernatants from normal corneas and corneas with bullous keratopathy achieved similar levels of MLR inhibition, which could not be blocked by addition of anti-transforming-growth factor-beta 2 antibody or indomethacin. The supernatant from cultured I/CB cells from normal eyes and from eyes containing a posterior segment melanoma did not differ in their immunosuppressive effect. The MLR inhibitory effect of supernatant from I/CB cells was partly blocked by addition of indomethacin. We conclude that MLR inhibiting factors are produced by normal and pathological corneas and by I/CB cells, but the supernatants from these tissues achieve their effect by different means. It is likely that the ability of cornea and I/CB tissues to produce immunosuppressive factors contributes to the success of orthotopic corneal transplants in man.

Aged↗
PubMed1995

Regulators of immunological responses in the cornea and the anterior chamber of the eye.

Although the eye is considered to be immunologically privileged, this privilege is not absolute. This is well demonstrated by, for example, the fate of corneal transplantations. Clinical studies in man and experimental studies in animals have shown that survival of a corneal transplant depends on the local condition of the cornea and the anterior chamber of the eye. The presence of neovascularisation or Langerhans cells in the recipient cornea endangers the graft, while the intracorneal production of immunosuppressive factors may inhibit the development of rejection. The balance between suppressive and stimulatory factors determines whether a local immune response will develop.

Animals↗
PubMed1995

Cytokine-mediated modulation of integrin, ICAM-1 and CD44 expression on human uveal melanoma cells in vitro.

Adhesion molecules are likely to play a role in the process of tumour progression. We investigated the expression of integrins, ICAM-1, and CD44 and the influence of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha) on expression of these molecules on four uveal melanoma cell lines. The in vitro integrin expression was quite variable. The alpha V and beta 1 subunits were expressed on all cell lines, and none of the cell lines showed any alpha 3, beta 2, or beta 4 expression. Other integrin subunits showed a more variable pattern. ICAM-1 and CD44 were strongly expressed on all cell lines. IFN-alpha, IFN-gamma, and TNF-alpha upregulated alpha 1, alpha 2, and alpha 3 expression, and did not alter alpha 4, alpha 5, alpha 6, beta 2, alpha v beta 3, and beta 4 expression. The effects on alpha V and alpha V beta 5 were variable. ICAM-1 was upregulated by IFN-gamma and TNF-alpha, but not by IFN-alpha. Cytokine treatment hardly changed CD44 expression. In one case a comparison was made between expression on cultured cells and on tissue sections of the tumour of origin. Differences in expression were observed for the integrin subunits alpha 2, alpha 3, and alpha 5. This study shows that integrins and ICAM-1 expression on uveal melanoma cells in vitro are susceptible to cytokine treatment, but that the effects on integrin expression are cytokine and cell line dependent. Furthermore, some differences in integrin expression between cells in vivo and in vitro exist.

Cryoultramicrotomy↗
PubMed1995

Effects of interferon alfa and gamma on human uveal melanoma cells in vitro.

BACKGROUND: Uveal melanoma is a tumour with a high incidence of metastasis and a high mortality rate. Additional therapies to obtain a better local control or an effective treatment of metastases are necessary. Interferons may be applied. METHODS: The effects of human interferon alfa and gamma on proliferation and expression of immunologically important molecules of human uveal melanoma cells in vitro were studied. A propidium iodide assay was used to determine proliferation and immunostaining with monoclonal antibodies was applied to detect changes in antigen expression on two primary uveal melanoma cell lines, Mel 202 and 92-1. RESULTS: Interferon alfa inhibited proliferation of cell line 92-1 at a concentration of 50 IU/ml, but had no effect on cell line Mel 202, while interferon gamma inhibited growth of both cell lines. Only interferon gamma had a visible effect on cell morphology. With respect to the immunomodulatory effects, interferon alfa increased monomorphic HLA class I expression, but did not affect HLA class II expression. Interferon gamma induced not only HLA class I but also class II expression. The effects on HLA expression were locus-specific with the strongest effects observed for HLA-B and DR products. Small differences were observed with respect to the susceptibility of two different melanoma cell lines to antiproliferative effects and to modulation of antigen expression. CONCLUSION: The effects of interferon alfa and gamma on human uveal melanoma cells in vitro suggest a potential role of these cytokines in the treatment of patients with uveal melanoma. In particular, the immunomodulatory effects of these cytokines in vitro imply that treatment of patients with these cytokines might stimulate a beneficial antimelanoma immune response in vivo.

Cell Division↗
PubMed1994

Circulating cornea-specific antibodies in corneal disease and cornea transplantation.

In order to establish the significance of circulating cornea-specific antibodies, we determined the presence of anti-corneal antibodies in the serum of 100 patients with corneal disease and in 50 healthy controls, and subsequently followed the pattern of antibody reactivity in 46 patients who underwent corneal transplantation. An indirect immunofluorescence test on cryostat sections of rabbit corneas was used for screening. The reactivity against two known bovine corneal epithelial proteins was also tested: a 54-kD protein (BCP 54) and an 11-kD protein (BCP 11/24). No significant difference in the presence and specificity of anti-corneal antibodies was observed between the group of patients with corneal disease, taken as a whole, and the healthy controls. Patients with keratoconus or non-immunological graft failure, however, were significantly more often positive for anti-corneal antibodies. Neither the presence of antibodies prior to corneal transplantation nor their appearance post-transplantation had a predictive value for corneal graft survival.

Aldehyde Dehydrogenase↗
PubMed1994

Are atypical nevi a risk factor for uveal melanoma? A case-control study.

Atypical nevi and other potential risk factors for uveal melanoma were studied in 109 uveal melanoma patients and 149 controls. Information concerning employment, medical history, drug use, family history of cancer, excess sun exposure, and blistering sunburn before and after the age of 15 was obtained. A total skin examination was performed and skin type, hair color, eye color, freckles, actinic damage, the total number of common acquired nevi, and the number of clinically atypical nevi were noted. More atypical nevi were found in uveal melanoma patients than in controls (age- and sex-adjusted odds ratio of 2.9 [95% confidence interval 1.2-6.3] for one or two atypical nevi versus none; odds ratio of 5.1 [95% CI 1.3-20.0] for three or more atypical nevi versus none). Light skin types and freckling also prevailed in uveal melanoma cases. In our study, atypical nevi are more common in uveal melanoma patients than in controls. Further studies will have to indicate whether risk factors comparable to those for cutaneous melanoma really exist for uveal melanoma.

Adult↗
PubMed1994

Possibilities and limitations of radioimmunoscintigraphy and conventional diagnostic modalities in choroidal melanoma.

A prospective clinical study to assess the value of immunoscintigraphy with a monoclonal antibody (MoAb) against high molecular weight melanoma associated antigen (225.28S) was performed in 43 patients with choroidal melanoma; in six patients with a lesion suspected of being choroidal melanoma, and in seven patients with a benign lesion simulating a choroidal melanoma. The results of immunoscintigraphy in choroidal melanoma were compared with results of conventional diagnostic modalities like ultrasonography and fluorescein angiography. Planar scintigraphy showed a detection rate of 49% which is comparable with other studies. The detection with scintigraphy was correlated to the size of the choroidal melanoma. The use of single photon computed tomography did not increase the sensitivity of immunoscintigraphy. Ultrasonography yielded a correct diagnosis in 37 of 42 melanomas (88%). With fluorescein angiography a correct diagnosis was obtained in 11 of 30 melanomas (36.6%). The value of immunoscintigraphy with MoAb 225.28S in small choroidal melanomas is limited; its reliability increases in large tumours. Immunohistochemistry with MoAb 225.28S showed antigen expression in 95% of the stained tissue specimens of choroidal melanoma.

Adult↗