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Biomedical subjects

M J Jager

Publications and source records attributed to M J Jager.

At least 73 records · Page 4Linked to original sources

Genetic and clinical determinants for the T cell mediated immune response against the cornea specific protein BCP 54.

T cell mediated immune responses against the cornea specific protein BCP 54 have been observed in patients with uveitis, Fuchs' heterochromic cyclitis, and corneal disease. The pathophysiological role of this anti-BCP 54 response in corneal disease is not known. In order to ascertain whether the presence of such an immune response is related to the corneal disease itself or related to genetic influences, the anti-BCP 54 response was determined in 104 patients with severe corneal disease, using a monocyte migration inhibition assay. The results were compared with the presence of a variety of ocular parameters as well as with the distribution of HLA antigens in these patients. While only 7% of healthy controls responded to BCP 54, 37% of the patients showed a positive response (p = 0.002); in particular, patients with previous graft rejection, non-herpetic keratitis, and bullous keratopathy reacted against BCP 54. No relation with known risk factors for corneal transplantation, such as corneal neovascularisation, was observed. No significant association with the presence of any of the HLA antigens was observed. It was concluded that the main inducer of an anti-BCP 54 response is corneal disease itself, and that the presence of corneal disease is able to break the immunological privilege typical of normal corneas.

Adolescent↗

Immunohistology of eye muscle in idiopathic orbital inflammatory disease (pseudotumor), Graves' ophthalmopathy and healthy controls.

Inflammatory orbital disease can be triggered by a variety of causes. Two such diseases are pseudotumor orbitae and Graves' ophthalmopathy, and both involve extraocular muscles. Biopsies were obtained from ocular muscles during a quiet phase in these two diseases. Biopsies obtained from a previous pseudotumor orbitae showed complement deposits and increased expression of HLA class-I antigens in the intermuscular tissue. The biopsies from two out of four pseudotumor cases and two out of four Graves' ophthalmopathy cases contained increased numbers of intermuscular HLA class-II-expressing cells. In spite of clinical remission, the local condition in all four pseudotumor cases and in two out of four cases of Graves' ophthalmopathy still suggests active inflammatory disease.

Adult↗

Changes in the immune response against BCP 54 following corneal transplantation in man.

Bovine corneal protein (BCP) 54 is the major soluble protein of the cornea. Immune responses against this protein can be observed in patients with corneal disease or inflammatory disease of the anterior chamber of the eye. We wanted to determine whether an immune response against this corneal protein plays a role in corneal transplantation. A cell-mediated immune response against BCP 54 was therefore determined in 46 patients prior to and on several occasions during the first year following corneal transplantation. The presence of an anti-BCP 54 response before transplantation was not associated with any clinical parameters or with rejection following transplantation. The highest frequency of positive responses was observed three months after transplantation. Transplantation may have stimulated a temporary immune response against a previously sequestered antigen, but this tissue-specific immune response did not necessarily lead to rejection. Therefore, no prognostic value can be attributed to the anti-BCP 54 response.

Adult↗

Integrin expression in uveal melanoma differs from cutaneous melanoma.

PURPOSE: During the process of metastasis, changes in cell-cell and cell-matrix contacts occur; therefore, expression of integrins, a superfamily of adhesion molecules, may be important. Expression of integrins has been studied extensively in cutaneous melanoma. Because it is known that uveal melanoma has a metastatic behavior different from cutaneous melanoma, the authors investigated integrin expression in uveal melanoma. METHODS: The authors used monoclonal antibodies recognizing integrin subunits alpha 1-6, alpha v, beta 1, and beta 4 and integrins alpha v beta 3 and alpha v beta 5 on frozen sections of 32 human primary uveal melanomas and 4 metastases, followed by an avidin-biotin-peroxidase complex-immunoperoxidase technique. RESULTS: As in cutaneous melanoma, alpha 4 expression was rare, but most lesions expressed alpha 3 and alpha 6. In contrast to cutaneous melanoma, in which alpha 2 is well expressed in most lesions and alpha 5 is expressed only in a small percentage of lesions, alpha 2 expression was rare in uveal melanoma and alpha 5 expression was found in all lesions. A major difference was observed with regard to the alpha v beta 3 vitronectin receptor. In contrast to cutaneous melanoma, in which alpha v beta 3 is expressed in advanced primary melanomas and metastases, alpha v beta 3 was not detected in any of the primary uveal melanomas, but all lesions strongly expressed alpha v beta 5. CONCLUSIONS: Integrin expression in uveal melanoma cannot be correlated with cell type or invasiveness. In contrast to cutaneous melanoma, it seems that determination of the integrin expression profile is not suitable for categorizing uveal melanomas as less malignant and highly malignant lesions.

Biomarkers, Tumor↗

Possible relation between HLA and ABO type and prognosis of uveal melanoma.

Not only local parameters but also genetic determinants like the HLA genes may play a role in the development and clinical behavior of malignant tumors. In skin melanoma the presence of HLA-B40 is associated with a poor prognosis. We tested the hypothesis that the clinical behavior of uveal melanoma is influenced by the HLA type of the patient. The HLA types of 44 patients with uveal melanoma had been determined before operation with a view to using the cornea of the enucleated eye for an HLA-matched corneal transplantation. We compared the ABO and HLA types of the patients with the development of metastases and with the ten-year patient survival. An association was observed between the presence of HLA-B40 and death due to metastasis of uveal melanoma. We conclude that the HLA type of the patient may influence the clinical behavior not only of skin melanoma but also of uveal melanoma.

ABO Blood-Group System↗

Iris nevi and melanomas: a clinical follow-up study.

A follow-up study of 113 patients with suspicious iris nevi who were referred to our clinic between 1973 and 1991 was carried out by: reviewing their clinical records, fluorescein angiography, obtaining recent data with cooperation of their own or the referring ophthalmologist and contacting patients for reexamination. After examination the diagnoses were: 64 suspicious nevi, 23 melanomas, 15 ciliary body tumors with iris involvement and 11 other pseudomelanomas. In the group of suspicious nevi 86% was localized in the inferior part and 66% in the temporal part of the iris; for the melanoma group these figures were 78% and 75% respectively. The chamber angle was more often involved in the melanoma group, 40% against 17% in the suspicious nevi group. In this group 11 cases (21.6%) showed growth during the follow-up (mean 10.6 years). In three cases the tumor was surgically removed, with as histopathologic diagnosis: 1 xanthogranuloma, 1 neurolemmoma and 1 possible melanoma. In the melanoma group 16 lesions (76%) showed growth during the follow-up (mean 7.2 years), in most cases within 5 years of the initial diagnosis. The lesion was surgically removed in 11 cases. The histopathologic diagnoses were: 8 melanomas, 1 xanthogranuloma, 1 possible melanoma and 1 metastasis of a skin melanoma. Our study shows that periodic ophthalmic check-ups are of great importance in the management of iris lesions suspect for melanoma.

Adult↗

Presence of Langerhans cells in the central cornea linked to the development of ocular herpes in mice.

Recurrences of herpetic stromal keratitis are believed to be initiated by reactivation of herpes simplex virus infection, probably in the trigeminal ganglion. Genetic features of the virus and the host as well as the immune status of the host influence the outcome of infection. Following infection on the snout with HSV-1, mice with normal corneas usually develop mild anterior segment disease. We studied the induction of herpetic infection in mice that had abnormal corneas, containing center due to trauma or a spontaneous dystrophy. The corneal abnormality led to more frequent herpetic stromal keratitis and more severe anterior chamber reaction. In addition, we found that snout-infected mice with dystrophic corneas had an increased risk of dying from viral infection. Our data suggest that not only the strain of virus and the genetic background of the mouse, but also the state of the cornea itself, can contribute to susceptibility to ocular herpes infection.

Animals↗

Hamster Greene melanoma implanted in the anterior chamber of a rabbit eye: a reliable tumor model?

The hamster Greene melanoma (HGM), implanted into the anterior chamber (AC) of a rabbit eye, has previously been used as a model for testing experimental therapies against human uveal melanomas. Even without therapy, the tumor showed necrosis and hemorrhages 8-10 days after inoculation. These changes could interfere with the interpretation of the results of experimental therapies. In 8 rabbits, a piece of HGM was implanted subcutaneously, and after 4 weeks, HGM was also implanted in the AC of the eye. In these eyes, tumor growth in the AC slowed down, and more necrosis and hemorrhages were found clinically and histologically as compared to 8 rabbits without previous subcutaneous implantation of HGM. In spite of the long use of this tumor and frequent transfer, the tumor cells did not lose their antigenic potential.

Animals↗

Cellular and humoral anticorneal immune response in corneal transplantation.

Immunologic responses play a role in the rejection process of corneal transplants. Both histocompatibility antigens and tissue-specific antigens may be potential targets for such an immune response. To identify relevant responses, the humoral immune response against corneal tissue and the cellular immune response against one specific corneal protein were determined in patients before and after corneal transplantation. The results were compared with known risk factors for corneal transplantation, but no correlations were observed. A conversion from negative to positive in cellular immune response against the cornea-specific protein was seen in patients who had experienced an inflammatory episode during the time interval between measurements. The anticorneal protein response may therefore be the result of an intraocular inflammatory response, but not a prognostic factor to help predict the patients at risk for rejection.

Adolescent↗

Herpetic stromal keratitis in mice: less reversibility in the presence of Langerhans cells in the central cornea.

Infection on the snout with HSV-1 in mice with normal corneas produced a mild ocular disease, characterized by a zosteriform skin lesion around the eye, enlargement of the pupil, hyperemia of the iris and, sporadically, transient keratitis. By contrast, snout infection after prior cauterization of the cornea induced significantly more frequent and more severe corneal disease, in which keratitis was usually permanent. Corneal cauterization also produced increased numbers of Langerhans cells in the central cornea. We speculate that the combination of virus and increased numbers of Langerhans cells within the cornea may lead to an exaggerated ocular immune response that is destructive to the cornea.

Animals↗

Ki-67 immunostaining in uveal melanoma. The effect of pre-enucleation radiotherapy.

The reactivity of 33 choroidal and ciliary body melanomas with monoclonal antibody Ki-67, which recognizes a proliferation associated nuclear antigen, has been assessed and compared with clinicopathologic parameters. In 23 cases, 8 Gy irradiation was given 2 days before enucleation. Nonirradiated melanomas had a significantly higher proliferation rate as defined by staining with monoclonal antibody Ki-67 as compared with irradiated tumors (P = 0.007). Similarly, a strong relationship was found between pre-enucleation irradiation and low mitotic activity (P = 0.001). There was no significant correlation between the presence of Ki-67-positive nuclei and histologic classification, largest tumor diameter, localization of the tumor, age, sex, scleral invasion, pigmentation, and lymphocytic infiltration. The relevance of Ki-67 immunohistochemistry for the assessment of the life prognosis of patients with uveal melanoma has to be studied prospectively.

Antibodies, Monoclonal↗

Radioimmunoscintigraphy and immunohistochemistry with melanoma-associated monoclonal antibodies in choroidal melanoma: a comparison of the clinical and immunohistochemical results.

Radioimmunoscintigraphy with monoclonal antibodies (MoAbs) to melanoma associated antigens is a new technique that can be used as an additional test to detect ocular melanomas in clinically difficult cases. Immunoscintigraphy with 99mtechnetium-labelled monoclonal antibody fragments of MoAb 225.28S in 14 patients with melanoma yielded a positive image in only six cases (43%). The expression of high molecular weight melanoma-associated antigen (HMW-MAA) was immunohistochemically assessed in melanoma tissue obtained from these 14 patients to find a possible correlation between the results of immunoscintigraphy and expression of the HMW-MAA. The melanoma tissues were immunohistochemically stained by a sensitive immunoperoxidase procedure with three different monoclonal antibodies to the HMW-MAA: 225.28S, Mel-14, and AMF-6. Expression of the antigen detected by MoAb 225.28S was found in 13 of 14 melanomas; the MoAbMel-14 reacted positively with all 14 melanomas; staining with MoAb AMF-6 was achieved in 10 melanomas. No correlation was found between the immunohistochemical staining results, the conventional histopathological findings, and the immunoscintigraphic results. The immunohistochemical staining results suggest that anti-HMW-MAA MoAbs bind to the melanoma tissue and are therefore potentially suitable for immunoscintigraphy.

Aged↗

Visual results after corneal transplantation.

The results of corneal transplantation can be measured by the percentage of clear grafts and by the subsequent visual acuity. In this study we summarized the visual results in five corneal diseases with a low rate of graft failure. Keratoconus patients achieved an average visual acuity of 0.5 one year after transplantation, while patients with corneal decompensation after previous cataract operation only reached an average of 0.2. Sometimes visual results were hampered by clouding of the graft and the reason for clouding was analysed in such cases. Reversible and irreversible rejections occurred with the highest frequency immediately after transplantation, and while in primary grafts 60% of rejections was reversible, only two out of ten repeat transplants could be saved. This indicates that more measures are necessary to prevent failure of secondary transplants in order to obtain the goal of useful vision.

Corneal Transplantation↗

Decreased expression of HLA class II antigens on human uveal melanoma cells after in vivo X-ray irradiation.

In order to determine the presence of HLA antigens on human uveal melanomas, we tested anti-HLA monoclonal antibodies on tissue sections of these tumors. A great variety in expression of HLA class I and II antigens was present. A significantly lower expression of HLA class II antigens was present on uveal melanomas that had been irradiated before enucleation. These tumors lacked a lymphocytic infiltrate in comparison with nonirradiated tumors. These data suggest that radiotherapy affects expression of histocompatibility antigens on tumors.

Adult↗

Genetics of two human monocyte antigens.

HMA-1 and HMA-2 are two serologically defined alloantigens that are present on human monocytes and granulocytes. Previous panel studies suggested that these two antigens comprise a diallelic system. We therefore performed segregation studies on 10 randomly chosen families and on 22 nucleus families belonging to one large pedigree. All individuals were either positive for HMA-1, HMA-2, or both. Segregation of HMA-1 showed autosomal inheritance with complete penetrance. The cytotoxicity negative, absorption positive (CYNAP) phenomenon sometimes occurred for HMA-2, and because absorptions for HMA-2 could not be performed on all cells, linkage studies were only performed for HMA-1. No linkage of HMA-1 with HLA, immunoglobulin allotypes, granulocyte antigens, or any of the erythrocyte blood groups tested was observed.

Alleles↗

9a: risk factor in bone marrow transplantation?

Graft-versus-host disease is a severe complication which may occur even after bone marrow transplantation between HLA identical siblings. Minor transplantation antigens have been implicated as a causal factor. Therefore the influence of the monocyte/granulocyte antigen 9a on GvHD was studied. No influence on GvHD was observed, but absence of the 9a antigen in the donor was associated with an early death of the recipient.

Bone Marrow Transplantation↗

Two alloantigens on human monocytes: a diallelic system?

A positive monocyte crossmatch and therefore anti-monocyte antibodies are negative factors in bone marrow and renal transplantation. When the monocyte antigens themselves can be recognized, matching for the antigens involved here may become a possibility. In order to find useful anti-monocyte sera as typing reagents, human sera were screened against panel cells. Several monocyte specific sera were obtained. These sera recognized two monocyte antigens, HMA-1 and HMA-2. No similarity with any of the HLA antigens was observed. Every individual tested was positive for at least one of these two monocyte antigens, suggesting that HMA-1 and HMA-2 constitute a diallelic system.

Fluorescent Antibody Technique↗