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Biomedical subjects

D J Ruiter

Publications and source records attributed to D J Ruiter.

At least 217 records · Page 12Linked to original sources

Monoclonal antibody G 250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney.

This report describes a monoclonal antibody designated G 250, subclass IgGl, that recognizes an antigen preferentially expressed on cell membranes of renal-cell carcinoma cells (RCC) and not expressed in normal proximal tubular epithelium. G 250 antibody reacted with 46 of 47 primary RCC, with 7 of 8 RCC metastases and with a few other malignant tumors. The staining pattern of G 250 differs from that of other RCC-related antibodies described. Preliminary experiments show that this antibody can be used to visualize RCC xenografts in nude mice by immunoscintigraphy.

Animals↗

Prognoses and surgical treatment of patients with stage I melanomas of the skin: a retrospective analysis of 211 patients.

From 1960 to 1982, a total number of 216 patients with Stage I melanoma underwent local excision as the single treatment. Life-table analysis was performed on 211 evaluable patients to investigate the prognostic value of several factors on survival as well as disease-free survival. The influence of sex, age, localization of the tumor, and margin of the excision on prognosis was not statistically significant. The Clark level and Breslow thickness were important factors to predict the prognosis. Local recurrence occurred in only one patient; in most cases tumor growth close to the original site of excision indicates early manifestation of hematogenic spread. Lymph node metastases developed in 31 patients; ten of them remained free of disease after node dissection. Six patients died from hematogenic metastases without nodal involvement. Tumors with thickness less than 1.5 mm have excellent prognosis regardless of the location of the melanoma or the margin of the excision. With increasing thickness of the tumor, prognosis is proportionally worse. By performing wide excisions the final outcome can not be improved.

Adolescent↗

Cell type heterogeneity of cytokeratin expression in complex epithelia and carcinomas as demonstrated by monoclonal antibodies specific for cytokeratins nos. 4 and 13.

Three monoclonal antibodies, 1C7, 2D7 and 6B10, directed against cytokeratins of human esophagus were isolated and characterized by one- and two-dimensional gel electrophoresis and by immunohistochemical staining on sections of human epithelial tissues. In immunoblot experiments, antibodies of clones 1C7 (IgG2a) and 2D7 (IgG2b) react only with cytokeratin no. 13 of the acidic (type I) subfamily of cytokeratin polypeptides (Mr 54000; pI 5.1); antibodies of clone 6B10 (IgG1) detect only cytokeratin no. 4 (Mr 59000; pI 7.3) of the basic (type II) cytokeratin subfamily and allows the detection of this protein and possible degradation products at high sensitivity. In immunohistochemical staining all three antibodies stain non-cornifying squamous epithelium (e.g., tongue, esophagus, anus) and transitional epithelium of the bladder. Antibodies of clone 6B10 also stain cells in certain ciliated pseudostratified epithelia and ductal epithelia of various exocrine glands. These monoclonal antibodies are the first examples of antibodies specific for individual cytokeratin polypeptides characteristic of certain complex epithelia. They allow the identification of distinct minor populations of cells present in certain complex and glandular epithelia and in tumors derived therefrom which hitherto have not been distinguished. The possible reasons for the occurrence of cell type heterogeneity of cytokeratin expression in complex epithelia and in some carcinomas are discussed.

Antibodies, Monoclonal↗

Correlation of histopathological characteristics with staining patterns in human melanoma assessed by (monoclonal) antibodies reactive on paraffin sections.

In order to investigate their possible role as prognostic markers, staining with the antibodies NKI/C-3 and anti-S100, that are applicable on paraffin sections, was examined using a group of primary cutaneous melanomas and autologous metastases using the immunoperoxidase procedure. All melanoma lesions stained with anti-S100, and the large majority with NKI/C-3. In primary melanomas showing a moderate or dense associated lymphocytic infiltrate, significantly more tumour cells stained with anti-S100 than in primary melanomas with a slight or absent infiltrate. In markedly pigmented metastases, significantly more tumour cells stained with NKI/C-3 than in less pigmented lesions; in primary melanomas this phenomenon just failed to be significant. In metastases with a high mitotic index a significantly lower proportion of tumour cells stained with NKI/C-3 than in lesions with a low mitotic index. No significant differences in staining were found between a group of primary melanomas with metastases and a group without metastases within a follow-up period of 5 years. Therefore, although staining with NKI/C-3 and anti-S100 appears to be associated with certain histopathological characteristics, it has no direct contribution to the assessment of prognosis in primary melanoma.

Antibodies↗

Primary melanoma in the female distal urethra.

A case of primary urethral oligomelanotic melanoma is presented. Melanoma of the female distal urethra is a rare tumor with a poor prognosis. Imprint cytology was used for detection. Electron microscopy and immunohistochemistry were used to confirm the histologic diagnosis.

Aged↗

TCA: a polymorphic genetic marker in leukemias and melanoma cell lines.

TCA (T Cell system A) is a di-allelic system of HLA-like antigens encoded by genes located about 15 cM telomeric to HLA-A. In normal individuals, TCA antigens are only expressed on a subpopulation of T cells, the TG lymphocytes. We now report on the expression of TCA on leukemias and other malignancies. An increased proportion of cells carrying the TCA phenotype was encountered in testing peripheral blood lymphocytes from patients with acute lymphoblastic T-cell leukemia (T-ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). In contrast, patients with B-cell malignancies such as chronic lymphatic leukemia (CLL) and hairy cell leukemia (HCL) or non-T/non-B common acute lymphoblastic leukemia (common ALL) had normal proportions of TCA-positive lymphocytes. Quantitatively different levels of TCA expression are found on some melanoma cell lines and others are TCA negative. These variations are independent of the expression of HLA Class I antigens by the same cells. The expression of TCA antigens by malignant nonlymphoid cells suggests that this system may code for differentiation markers, important in the biology of neoplastic transformation.

Antigens, Neoplasm↗

Immunohistochemical analysis of monoclonal antibodies to renal antigens. Application in the diagnosis of renal cell carcinoma.

Four mouse monoclonal antibodies reacting with renal proximal epithelium were characterized on normal adult tissues, fetal kidneys, and various malignancies. These four antibodies were found to react with renal cell carcinomas (RCCs) but not with a variety of other tumors. Three antibodies react only with some primary RCCs and not with metastatic RCCs. The fourth antibody, RC 38, reacts with 46 of 47 primary RCCs tested and with 8 of 13 RCC metastases. No reaction was seen with 179 tumors of various origin, which indicates that this antibody is very useful in diagnosing RCC.

Adenoma↗

Phenotypic dynamics of tumor progression in human malignant melanoma.

The phenotypic changes in human melanoma cells during the course of tumor progression were studied with monoclonal antibodies (MAbs) against the melanoma-associated antigens (MAA) M.2.2.4, H.2.8.10, K.1.2, A.1.43, and A.10.33, and HLA-(A,B,C and D). Cryostat sections of 172 primary melanomas of the skin, 157 melanoma metastases and 56 nevi were investigated with an indirect immunoperoxidase method. Phenotypic heterogeneity was observed within lesions at all stages, and also within different tumors of the same patients. Despite this heterogeneity, principles of antigen expression were found. From the reaction pattern of MAbs, the following classifications of antigens were derived: "constitutive" markers of nevomelanocytic cells (M.2.2.4 and H.2.8.10) were found expressed over a wide range of local and systemic tumors. One MAA, K.1.2 (Suter et al., 1985), that declines with progression of melanoma, was classified as an "early" antigen, whereas MAA that appear in primary melanoma in proportion to invasiveness, and which are expressed in metastases of lymph nodes and visceral organs (A.1.43, and A.10.33), were classified as "late" markers of tumor progression. HLA-antigens were classified as "intermediate" markers, HLA-A,B,C, as an "early-intermediate", and HLA-DR as a "late-intermediate" marker. The occurrence of class II HLA, A.1.43-, and A.10.33-positive tumor cells in primary melanoma indicates a high metastatic potential of tumors, independent of tumor thickness. The data show that local and systemic progression of melanoma is associated with qualitative changes in tumor cells which can be recognized by MAbs.

Antibodies, Monoclonal↗

Intermediate filaments in Merkel cell tumors.

A series of ten Merkel cell tumors is described, with special emphasis on intermediate filament expression. The presence of cytoskeletal proteins was studied with a polyclonal antiserum directed against cytokeratin and with monoclonal antibodies against cytokeratin, neurofilament, and vimentin by the immunoperoxidase technique. Cytokeratin was demonstrated in nine of ten tumors. Neurofilament was observed in the two snap-frozen tissues tested and in three of the eight formalin-fixed, paraffin-embedded tissues. No reactivity for vimentin was found. By electron microscopy desmosomes were found to be present in all cases, while tonofilaments were found in only a few cases. neurosecretory granules, although seen in all tumors, were generally present in low numbers. The results of this study indicate that the Merkel cell tumor is a poorly differentiated small cell carcinoma that has the ability to express some neuroendocrine features.

Adenocarcinoma↗

Monoclonal antibodies selected to discriminate between malignant melanomas and nevocellular nevi.

Two monoclonal antibodies (MoAbs), PAL-M1 and PAL-M2, are described that were selected to discriminate between melanomas and nevocellular nevi (NN) in frozen sections. MoAb PAL-M1 reacted with all 15 melanoma metastases (MM), with 14 of 19 primary cutaneous melanomas (PCM), 9 of 35 dysplastic nevi (DN), and 2 of 26 NN. The 2 NN stained were removed from patients with the dysplastic nevus syndrome. MoAb PAL-M2 reacted with 9 of 15 MM, 5 of 19 PCM, 3 of 35 DN, and did not react with 26 NN after usual staining conditions. The proportion of melanocytic cells stained was low in DN and much higher in PCM and especially in MM. Staining in DN was restricted to intraepidermal or subepidermal nests of atypical melanocytes. In PCM, staining with PAL-M2 was observed only in tumors with a Breslow thickness of 0.76 mm or higher. PAL-M1 and PAL-M2 may be immunohistochemical markers for tumor progression in melanocytic proliferations.

Adolescent↗

Analysis of major histocompatibility antigens and the mononuclear cell infiltrate in halo nevi.

A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other cases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA-A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic neiv. These findings also indicate the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T-cell immune response and not necessarily related to the presence of nevomelanocytic atypia.

Adolescent↗

Variations in histopathological evaluation of non-neoplastic colonic mucosal abnormalities; assessment and clinical significance.

The variation between three pathologists examining histological features seen in non-neoplastic colonic mucosa from 40 biopsies was analysed. Several procedures to express observer variation were used and compared, with emphasis on kappa statistics. Only five features, the presence of ulceration, villous surface, epithelioid granulomas, severe mucus depletion and crypt abscesses were sufficiently reproducible by the three pairs of pathologists. These findings suggest that other criteria used for the classification of inflammatory bowel disease are potentially unsatisfactory. When results from different studies on biopsies are being compared, influence of observer variation should be identified. Comparison of statistical techniques showed overall variation to be less useful than other statistical procedures. There was little difference between results from kappa statistics and other measures of agreement (overall agreement excluded).

Biopsy↗

Monoclonal antibody PAL-E specific for endothelium.

A monoclonal antibody, PAL-E, is described that is specific for endothelial cells. The monoclonal antibody, an IgG2a, markedly stains endothelium of capillaries, medium-sized and small veins, and venules in frozen sections of human and some animal tissues tested. It reacts not at all or only weakly with endothelium of large, medium-sized, and small arteries, arterioles, and large veins and does not stain the endothelial lining of lymphatic vessels and sinus histiocytes. The cellular staining pattern and tissue staining were different from those obtained with antifactor VIII R:AG antiserum and Ulex europaeus I lectin. Blocking experiments indicated that these three reagents recognize different endothelial binding sites. Therefore, PAL-E is a new staining reagent for endothelium in frozen sections. Based on immunoelectronmicroscopic observations, the antigenic determinant recognized by PAL-E is associated with endothelial vesicles.

Animals↗

Immunohistochemical and histochemical tools in the diagnosis of amelanotic melanoma.

The histologic diagnosis of (metastatic) oligomelanotic or amelanotic melanoma may be difficult. In most cases this diagnosis can be established with conventional light and electron microscopic examination, supplemented with staining for melanin on ultrathin sections, but in other cases it remains equivocal. Therefore, the melanoma-associated monoclonal antibody NKI/C-3, effective on paraffin sections, was tested with an indirect immunoperoxidase technique. All 19 metastatic melanomas, used as positive controls, were stained. Seventeen of 23 primary melanomas and 8 of 9 initially equivocal eventually unequivocal melanomas (Group I) were stained with a diffuse cytoplasmic and in some cases locally peripheral pattern. Only two large cell undifferentiated carcinomas of 58 histogenetically unrelated but differential diagnostically relevant tumors showed localized staining in few tumor cells. Furthermore, 10 of 20 histogenetically related tumors (neuroendocrine tumors and clear cell sarcomas) were positive. These tumors however, can easily be differentiated from melanomas by other means. Of 15 equivocal melanomas (Group II) 9 cases reacted with NKI/C-3, suggesting that it may be a useful marker for difficult metastatic tumors suspect for amelanotic melanoma. Although sensitivity of NKI/C-3 for metastatic melanomas is high, its specificity is not sufficient. It therefore can be applied most properly in a selected panel of different tumor-associated antibodies that are reactive in formaldehyde fixed, paraffin-embedded tissue.

Adolescent↗