Search PubMed⌕ Search

Biomedical subjects

D J Ruiter

Publications and source records attributed to D J Ruiter.

At least 199 records · Page 11Linked to original sources

Monoclonal antibody-defined human endothelial antigens as vascular markers.

A review is given of human endothelial antigens recognized by monoclonal antibodies and used as vascular markers. These antigens can be classified tentatively into two categories that partly overlap: 1) differentiation markers and 2) antigens involved in specific cellular functions. Monoclonal antibodies recognizing endothelial differentiation markers reacting with all types of human endothelium can be regarded as constitutive endothelial markers. Other differentiation markers have a restricted distribution that is associated with a subtype of endothelium. Although sensitivity of the markers is high in general, specificity for endothelium is not absolute, based on distribution studies in tissues or in cell lines. With the exception of PAL-E and EN-3/EN-4, it is not clear from the literature whether the antibodies also react with lymphatic endothelium. Immunohistochemical examination of other species indicate that only BW 200 is restricted to humans. Immunoelectron microscopy of microvascular cells in tissue specimens has revealed that the monoclonal antibodies recognizing differentiation antigens show different subcellular distribution patterns. PAL-E and BW 200 react with the luminal endothelial surface, in a local and diffuse pattern, respectively. Anti-Von Willebrand factor (i.e., Factor VIII-related ag) antibodies react with Weibel-Palade bodies but also with subendothelial structures. Applications of immunohistochemistry using monoclonal antibodies in diagnostic pathology include assessment of vascular invasion by cancer cells, and identification of endothelial neoplasms and related disorders. Because anti-Factor VIII-related antigen and BW 200 are applicable on formaldehyde-fixed and paraplast-embedded tissue, they are most suitable for histodiagnostic application. Immunohistochemistry using monoclonal antibodies recognizing endothelial antigens involved in specific cellular functions also may contribute to pathobiologic research on the characterization of blood-tissue barriers, e.g., in the tumor vascular bed.

Antibodies, Monoclonal↗

N-ras mutations in human cutaneous melanoma from sun-exposed body sites.

In 7 of 37 patients with cutaneous melanoma, mutations in the N-ras gene were found. The primary tumors of these seven patients were exclusively localized on body sites continuously exposed to sunlight. Moreover, the ras mutations were all at or near dipyrimidine sites known to be targets of UV damage. Two primary tumors were biclonal with respect to ras mutation. An active role for UV irradiation in induction of the mutations is suggested.

DNA, Neoplasm↗

Melanocytic atypia in dysplastic nevi. Immunohistochemical and cytophotometrical analysis.

In a double-blind study a correlation was found between the histologically assessed degree of nevomelanocytic atypia in 58 dysplastic nevi (DN) and the presence of two markers associated with malignant transformation. The markers included a marked expression of histocompatibility locus Class I antigens on nevomelanocytes (P less than 0.01) and abnormalities in the nuclear DNA content as measured by DNA cytophotometry (P = 0.01). Both markers were present in most of the markedly atypical DN, in about half of the moderately atypical DN, and in less than 30% of the mildly atypical DN. These findings suggest that a DN with marked or moderate melanocytic atypia indicates a premalignant condition and identifies a patient at risk for melanoma.

Antigens, Neoplasm↗

Diagnostic application of panels of antibodies in mucosal melanomas of the head and neck.

This article describes the use of panels of antibodies in the histopathologic diagnosis of ten malignant melanomas arising in the mucosa of the head and neck. The immunohistochemistry analysis was performed in a step-by-step manner. In the first step a panel of antibodies discriminating between carcinoma, malignant lymphoma, and melanoma was used. Staining with antivimentin and the melanoma-associated antigen, moAb NKI/C-3, was found to occur in all cases. The NKI/C-3 stained nine of 10 specimens from the first biopsy. Anti-S-100 protein, anti-HMW-MAA, and NKI-beteb was used as a panel in the second step. These stained ten of ten, five of six, and seven of seven cases, respectively. The diagnosis for melanin was confirmed by extensive sampling and a diligent search for melanin and (pre)melanosomes in different biopsy and surgical specimens. These results indicate that a step-wise application of immunohistochemistry is a very useful tool in the diagnosis of mucosal melanoma of the head and neck.

Aged↗

Level of HLA antigens in locoregional metastases and clinical course of the disease in patients with melanoma.

Immunohistochemical staining with monoclonal antibodies showed marked variations in the percentage of melanoma cells stained by anti-HLA Class I and anti-HLA Class II monoclonal antibodies among 48 locoregional metastases removed from 39 patients with malignant melanoma. On the other hand there was limited variation in the percentage of melanoma cells stained by anti-HLA antibodies in autologous locoregional metastases removed from 8 of 9 patients. In the remaining patient marked differences were found in the percentage of melanoma cells stained by anti-HLA Class I antibodies in the two parts of the lymph node metastasis analyzed. Therefore this patient was not included in additional analyses to correlate the level of expression of HLA antigens with the clinical course of the disease. In all the lesions tested the percentage of melanoma cells stained by anti-HLA Class II antibodies was lower than or equal to but never higher than that stained by anti-HLA Class I antibodies. According to the level of expression of HLA Class I and Class II antigens the 38 patients could be divided into three groups: Pattern A included lesions with more than 50% of tumor cells stained by anti-HLA Class I antibodies (mean, 86.1; median, 85) and 50% or less by anti-HLA Class II antibodies (mean, 10.5; median, 5); Pattern B included lesions with 50% or less tumor cells stained by anti-HLA Class I antibodies (mean, 14.9; median, 5) and by anti-HLA Class II antibodies (mean, 4.1; median, 1); Pattern C included lesions with more than 50% tumor cells stained by anti-HLA Class I antibodies (mean, 88.8; median, 92) and by anti-HLA Class II antibodies (mean, 70.0; median, 70). The survival of 21 patients with Pattern A was significantly longer than those of 13 and 4 patients with Patterns B and C, respectively. No difference in the survival of patients in the latter two groups was found. These results suggest that HLA antigens play a role in the biology of melanoma and that analysis of the level of HLA antigens in locoregional metastases of patients with melanoma may provide clinically useful information.

Adult↗

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↗

c-myc down-regulates class I HLA expression in human melanomas.

Expression of class I HLA antigen has been shown to be reduced in a number of human tumours. Here we show that in a panel of 11 melanoma cell lines with variable class I HLA expression an inverse correlation exists between the mRNA levels of c-myc and class I HLA. This suggests that high expression of the c-myc oncogene might inhibit the class I HLA expression. To test this hypothesis a melanoma cell line with a low c-myc and high class I HLA mRNA expression was transfected with a c-myc expression vector. All clones expressing the transfected c-myc gene show reduced class I HLA mRNA and beta 2-microglobulin mRNA expression. Reduced class I HLA mRNA levels result in a lowered class I protein expression on the cell surface. Treatment with gamma-interferon fully restores the class I HLA and beta 2-microglobulin expression in these cells. This effect is preceded by a transient decrease of the c-myc mRNA level. These results show that the class I HLA expression is modulated by the level of c-myc expression, thus opening up the possibility that high expression of this oncogene influences the interaction of melanoma cells with the immune system.

Gene Expression Regulation↗

Renal oncocytoma: a report of two cases with immunohistochemical evaluation.

Two cases of renal oncocytoma are characterized by histologic electron microscopic, and immunohistochemical evaluation. In one case there was a coexistent renal cell carcinoma. The immunophenotype of the oncocytes provide evidence for an origin from the distal nephron. The results indicate that immunohistochemical methods can be helpful in discriminating renal oncocytoma from (granular type) renal cell carcinoma.

Adenoma↗

Differential expression of HLA-DR, DQ, and DP antigens in primary and metastatic melanoma.

Fifty-five primary and 33 metastatic surgically removed melanoma lesions were stained in indirect immunoperoxidase with anti HLA-DR, DQ, and DP monoclonal antibodies and with the monoclonal antibody CL203.4 to a 96-K melanoma associated antigen (MAA). The latter antigen may represent a marker to monitor susceptibility of melanoma cells to modulation by IFN-gamma, because it is highly susceptible to induction by IFN-gamma. In primary melanomas 44%, 29%, 10%, and 55% of the lesions tested were evidently stained by anti HLA-DR, DQ, DP, and 96-K MAA monoclonal antibodies, respectively. A statistically significant association (P less than 0.01) was demonstrated between the degree of intratumoral lymphocytic infiltrate and the expression of HLA-DR and HLA-DQ antigens. In addition, a high degree of concordance in the reactivity pattern of individual lesions stained for HLA-DR antigens and for the 96-K MAA was found. In metastases 64%, 33%, 47%, and 100% of the lesions tested were evidently stained by anti HLA-DR, DQ, DP, and 96-K MAA monoclonal antibodies, respectively. This study indicates that HLA-DR and HLA-DP antigens are expressed in a higher percentage of metastatic than of primary melanomas and that there is no marked difference in the expression of HLA-DQ antigens between primary and metastatic melanomas. The data suggest that the regulatory mechanisms which control the expression of HLA-DR and DP antigens in primary and metastatic melanoma lesions are different. Locally produced IFN-gamma may play a role in the regulation of HLA Class II antigens in primary melanomas.

Antibodies, Monoclonal↗

The efficacy of histopathological criteria required for diagnosing dysplastic naevi.

The efficacy of specific histopathological features for diagnosing dysplastic naevi was established by comparing their frequency in 62 dysplastic naevi, from 36 patients with the dysplastic naevus syndrome, with those in 326 ostensibly benign naevocellular naevi derived from a group of 67 autopsy cases. Individual diagnostic features had a low sensitivity, a low specificity or low predictive values. Discriminant analysis showed that the presence of dust-like melanin, irregular naevoid nests, markedly increased junctional activity and melanocytic nuclei equal or larger in size than overlying keratinocyte nuclei were the most discriminating features. Using two or more of these criteria plus a lymphocytic infiltrate as an obligatory diagnostic criterion, a reasonable efficacy could be reached for dysplastic naevi. Based on these combinations of criteria the prevalence of histologically proven dysplastic naevi in the autopsy group would be 10%. Lesions with all these four discriminating features were found in half of the patients from the dysplastic naevus syndrome group, but were absent in the autopsy group. We suggest that such severely atypical dysplastic naevi may be indicative of patients at high risk for developing malignant melanoma.

Adolescent↗

Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives.

Peliosis hepatis, a condition characterized by the presence of blood-filled lacunar spaces in the liver, has been described primarily in patients on androgenic steroid medication and patients with tuberculosis. It has never been reported as a complication of the use of oral contraceptives, except in association with and localized in contraceptive-induced hepatic tumors. The present report concerns a 43-yr-old woman with generalized peliosis hepatis that developed during long-term use of oral contraceptives. Extensive examination did not reveal a hepatic tumor. Liver cirrhosis and portal hypertension developed, although the oral contraceptives had been withdrawn. She finally underwent successfully an orthotopic liver transplantation.

Adult↗

A monoclonal antibody specific for cells of the melanocyte lineage.

A monoclonal antibody, NKI/beteb, was prepared against membranes from a human melanoma metastasis, and in immunoprecipitates of melanoma cell lysates specific 100- and 7-kd glycoproteins were found. The large glycoproteins were also present in conditioned medium of melanoma cell lines. The antigen is located on the inner side of membranes of (pre)melanosomes and premelanosomelike vesicles. The antibody reacted in the immunoperoxidase test on frozen tissue sections with 27 of 28 nevocellular nevi (15/16 common, 12/12 dysplastic), 39/39 primary melanomas (3 intraepidermal, 24 cutaneous, 12 choroidal), 56/63 melanoma metastases, and 4/4 clear-cell sarcomas (melanoma of soft tissue). With sections of formalin-fixed paraffin-embedded tissues, the reaction was less sensitive. No reactivity was detected with frozen sections of 185 other tumors, except for 1 case of non-Hodgkin's lymphoma in which macrophages were positive. With the exception of melanocytes, all frozen sections of adult tissues that were tested were negative with NKI/beteb. On the basis of its tissue distribution so far, the antigen recognized by NKI/beteb seems to be a specific and sensitive diagnostic marker for cells of the melanocyte lineage.

Animals↗

Tumor progression in human malignant melanoma: five stages defined by their antigenic phenotypes.

The antigenic profile of melanocytic cells in the course of local and systemic tumor progression of human malignant melanoma was investigated by the reactivity of a panel of monoclonal antibodies (MAbs) in frozen sections of histologically defined melanocytic lesions. Specific antigenic phenotypes made it possible to distinguish 5 groups of lesions which could be ranked in relation to each other due to the sequential acquisition or loss of progression markers. On this basis, a scheme of antigenic changes which accompany the stepwise transformation of normal skin melanocytes into highly malignant metastatic melanoma cells is proposed. The steps of tumor progression identified solely by phenotyping with MAbs were in complete concordance with the concept of melanoma progression derived from histological, statistical and clinical analyses. Furthermore, our finding that the expression of gp89 as well as HLA-DR antigens can be induced by interferon-gamma in vitro provides evidence that immune interferon may play a role in the regulation of genes leading to phenotypic changes in progressing melanoma cells.

Animals↗

HLA antigens in colorectal tumours--low expression of HLA class I antigens in mucinous colorectal carcinomas.

Expression of HLA antigens and beta 2-microglobulin was studied by immunoperoxidase staining of frozen sections of 9 mucinous and 10 nonmucinous colorectal adenocarcinomas, 1 cloacogenic carcinoma, 12 colorectal adenomas and 4 samples of normal colorectal mucosa using monoclonal antibodies (MAbs). Staining results were related to histopathological features. HLA Class I antigens were strongly expressed in morphologically normal colorectal epithelium, in all adenomas tested and in all non-mucinous carcinomas. In contrast, expression of HLA class I antigens by the majority of tumour cells was present in only 2 of the 9 mucinous carcinomas, whereas 2 of these mucinous carcinomas were completely negative. In the mucinous carcinomas a striking scarcity of mononuclear inflammatory infiltrate, especially around the mucus accumulations, was observed. HLA class II antigen expression was not detected in normal epithelium and was only focally present in 1 of the 12 adenomas. In 6 out of the 20 carcinomas tested between 20% and 90% of the tumour cells were stained by MAbs against HLA class II antigens. Apart from the low expression of HLA class I antigens in mucinous carcinomas no relationship was found between expression of HLA antigens and histological features of the tumours. The relative poor prognosis of mucinous colorectal carcinoma as reported in the literature may be associated with low expression of HLA class I antigens and scant mononuclear inflammatory infiltrate, which may be a reflection of a weak immune response to the tumour cells.

Adenocarcinoma↗

Heterogeneous expression of melanoma-associated antigens in uveal melanomas.

Twenty-five uveal melanomas were stained with seven monoclonal antibodies (MoAbs) recognizing different antigens on cutaneous melanomas. A two step immuno-peroxidase procedure was used. Phenotypic heterogeneity was observed for four MoAbs (M.2.2.4, AMF-7, 225.28S, PAL-M1) while two MoAbs (NKI-beteb, CL203.4) reacted strongly with most (85%) uveal melanomas, and one MoAb (R-24) showed very low reactivity. Despite heterogeneity, co-expression of some antigens was observed. Expression of the antigen recognized by MoAb M.2.2.4. was significantly lowered by pre-enucleation irradiation while the other antigens remained unchanged. Expression of antigens on uveal melanomas differed markedly from primary cutaneous melanomas. The clinical relevance of these findings awaits further study.

Antibodies, Monoclonal↗

Coexpression of intermediate filament polypeptides in human fetal and adult tissues.

Tissues from human fetuses (12 to 14 weeks) were studied by using immunohistochemical methods, with special emphasis on coexpression of intermediate filaments. Well-characterized antibodies, monoclonal as well as polyclonal were used. Indirect immunoperoxidase staining disclosed simultaneous expression of cytokeratin and vimentin, or vimentin and desmin in several tissues, whereas some other tissues coexpressed three classes of intermediate filaments, i.e., cytokeratin, vimentin, and desmin. Coexpression of cytokeratin and vimentin was seen in immature tubules of the kidney localized in the blastema and in one case in a small area of the epithelium of the tongue. Coexpression of vimentin and desmin was found in stromal cells of the medulla of the kidney, in stromal cells of the decidua (maternal tissue) and in muscle cells in blood vessels of small intestine, kidney and decidua. Coexpression of cytokeratin, vimentin, and desmin was present in mesothelial cells of serosa, pleura and pericardium, in stroma of umbilical cord and placental villi, in muscle cells of small intestine, tongue, and heart, and in muscle cells of blood vessels of lung, heart, umbilical cord, and placental villi. Mesothelium and reactive submesothelial stroma cells also coexpressed three classes of intermediate filament polypeptides. In some cases, immunoperoxidase results were confirmed by double labeling immunofluorescence microscopy or by immunoblotting experiments. The results of this study indicate that coexpression of different types of intermediate filaments is a more general phenomenon in fetal tissues than previously realized and it also occurs in some reactive proliferative lesions in the adult.

Antibodies, Monoclonal↗

Expression of HLA antigens in paraffin sections of uveal melanomas.

Expression of histocompatibility (HLA) antigens on tumor cells may influence the recognition of these tumor cells by the immune system. Immunological recognition may influence tumor growth and patient survival. Although HLA class I and II antigens are known to be present on several tissues in the eye, their presence on ocular tumors had not yet been demonstrated. We studied the expression of these antigens on paraffin preparations of uveal melanomas. Most tumors carried class I and beta 2m antigens on most of their cells while class II antigens were less often expressed. No association with tumor cell type or tumor size was observed. Further studies will be necessary to determine the relevance of different levels of antigen expression with regard to patient survival.

HLA Antigens↗