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J A van Unnik

Publications and source records attributed to J A van Unnik.

At least 19 recordsLinked to original sources
PubMed1992

Islet amyloid polypeptide (IAPP) is synthesized in the islets of Langerhans. Detection of IAPP polypeptide and IAPP mRNA by combined in situ hybridization and immunohistochemistry in rat pancreas.

We investigated the localization of IAPP mRNA by means of in situ hybridization in tissue sections of rat pancreas. A 35S-labeled, IAPP-specific DNA probe--hybridized specifically in the islets of Langerhans. This localization was confirmed by immunohistochemical localization of insulin and IAPP polypeptides on adjacent tissue sections. Moreover, combined in situ hybridization of IAPP mRNA and immunohistochemistry of insulin and IAPP polypeptide on the same section, using insulin as specific marker shows the presence of IAPP mRNA in the islets of Langerhans.

Amyloid↗
PubMed1992

Malignant fibrous histiocytomas in dogs and cats: an immunohistochemical study.

Immunohistochemical staining was performed on seven canine and 10 feline soft tissue tumours histologically diagnosed as malignant fibrous histiocytomas (MFHs) or MFH-like tumours, and eight other histologically specified tumours (non-MFH). This was done to determine if commercially available antibodies that are used routinely in human diagnostic pathology for MFHs would express the same immunohistochemical patterns in canine and feline MFHs and MFH-like tumours. The antibodies were directed against human alpha 1-anti-trypsin (AT), human alpha 1-anti-chymotrypsin (ACT), human lysozyme, bovine S-100 protein and human desmin. AT did not show any immunoreactivity in the tissues investigated. Except for one MFH, all canine MFHs and other soft tissue tumours with a 'histiocytic' character stained for lysozyme and not for S-100. Six out of seven canine MFHs and MFH-like tumours stained positive for desmin as did most non-MFH sarcomas. Most of the canine and feline MFHs and MFH-like tumours were positive for ACT. These findings for ACT staining in canine and feline MFHs and MFH-like tumours are in agreement with the findings in human MFHs. The immunohistochemical results of canine MFHs and MFH-like tumours were different from those in cats. Feline MFHs differed from canine MFHs for both lysozyme and desmin staining.

Animals↗
PubMed1992

Expression of the first calcitonin/CGRP gene in spontaneous and transplanted rat medullary thyroid carcinoma: a comparison of dot-blot analysis, in situ hybridization, and immunohistochemistry.

Calcitonin (CT) and calcitonin gene-related peptide (CGRP) are encoded by a single gene, the CALC-I gene. They are expressed in the thyroid and in the nervous system by alternative splicing of the pre-messenger RNA derived from the CALC-I gene. In medullary thyroid carcinoma (MTC), a malignancy derived from the calcitonin-producing C-cells in the thyroid, production of calcitonin and CGRP is a common feature. We investigated the CT and CGRP production of four spontaneous MTCs transplanted three to four times and 14 MTC lines transplanted for several years in WAG/Rij rats, a strain with hereditary MTC. The expression of CT and CGRP in the spontaneous and in the transplanted tumors was studied by means of RNA in situ hybridization (RISH), dot-blot analysis, and immunohistochemistry. A down-regulation of CT production in transplanted compared with spontaneous tumors was observed, but an inverse relation between CT and CGRP mRNA content in both spontaneous and transplanted tumors was not observed. In this study, RISH proved to be as sensitive as dot-blot analysis to detect gene expression in tissue samples. The different approaches of analyzing the gene expression in tissue samples (the cellular localization of gene expression by ISH vs the analysis of an extract of a total tissue sample with dot-blot analysis) showed that each technique is equal in value and that they are complementary to each other.

Animals↗
PubMed1992

No constant relationship between islet amyloid polypeptide (IAPP) and insulin expression in insulinomas.

The relationship between insulin and islet amyloid polypeptide (IAPP) expression was studied at the level of RNA and peptide in 3 patients operated on for insulinoma. Two patients had a solitary tumour; one patient suffered from the MEN-I syndrome. In the 3 tumours, as in normal pancreas, the same 2 IAPP-specific mRNA species, approximately 1600 and 2100 nucleotides, respectively, were detected. In 2 patients, the IAPP mRNA concentration of the tumour was lower than the insulin mRNA concentration; in the third patient, however, the specific IAPP hybridization signal was at least equal to that for insulin. Amyloid deposits were found in one solitary tumour and in the tumour from the MEN-I patient, both staining strongly positive with anti-IAPP antibodies; cytoplasmatic IAPP was weak. In conclusion, at least in some insulinomas, no constant relationship exists between insulin and IAPP expression.

Adolescent↗
PubMed1991

Cellular expression of K-type pyruvate kinase in normal and neoplastic human tissues.

The cellular expression of K-type pyruvate kinase was studied immunohistochemically in several normal and neoplastic tissues of human origin. The authors used the monoclonal antibody, designated as ES1, which was raised against human K-type pyruvate kinase. In contrast to the normal counterparts, a strong immunoreactivity was found in a rhabdomyosarcoma (n = 1), in a carcinoma of the pancreas (n = 1), and in neurofibromas (n = 2). Furthermore, the staining in leiomyosarcomas (n = 2) was shown to be more intense when compared with both normal smooth muscle cells and leiomyomas (n = 2). These findings show that knowledge about the cellular expression of the K-type pyruvate kinase identifies cell types for which its expression serves as oncodevelopmental marker. In addition, these immunohistochemical studies give information whether shifts toward K-type containing isozymes of pyruvate kinase, which are determined by electrophoresis in whole cytosolic extracts of various tumors, are due to an altered gene expression or due to proliferation of cells which normally express already the K-type pyruvate kinase. The first possibility probably occurs in rhabdomyosarcomas. The latter possibility seems to be valid for astrocytomas because astrocytes express the K-type pyruvate kinase in normal brain.

Antibodies, Monoclonal↗
PubMed1991

Pyruvate kinase activity and isozyme composition in normal fibrous tissue and fibroblastic proliferations.

Pyruvate kinase (PK) was studied in 57 fibroblastic and fibrohistiocytic proliferations and normal fibrous tissue (n = 10). The specific activity was significantly increased in malignant tumors (1.67 +/- 0.25) compared with normal tissue (0.26 +/- 0.04; P less than 0.001) and benign proliferations (0.52 +/- 0.05; P less than 0.005). Although an overlap exists between aggressive fibromatosis and the benign group, high values of PK activity are indicative of Grade 2 and 3 malignancy. Significant shifts in isozyme pattern, favoring the expression of K-type subunits were found in tumors with a metastasizing potential and aggressive fibromatosis. These changes in the isozyme pattern of PK in aggressive fibromatosis may act as another argument to place them in the category of malignant fibroblastic tumors.

Adult↗
PubMed1990

Distribution of actin isoforms in sarcomas: an immunohistochemical study.

The actin immunophenotype of eight benign mesenchymal tumors, 14 nonsarcomatoid tumors, and 46 sarcomatoid tumors was studied, using monoclonal antibodies (MoAb) specific for alpha-smooth muscle actin (clone 1A4), alpha- and gamma-smooth muscle actin (designated CGA7), and muscle actin (designated HHF35) on frozen sections. Tumor cells of nonsarcomatoid tissues were not reactive, but all leiomyomas and five of the seven leiomyosarcomas reacted with the three MoAbs. One leiomyosarcoma was immunoreactive for the MoAb 1A4 only. One of the six malignant schwannomas showed staining for muscle actin (HHF35). The 22 malignant fibrous histocytomas (MFH) expressed these actin isoforms in various degrees. One case immunoreacted with all three MoAbs, three reacted with 1A4 only, seven reacted with CGA7 and HHF35, and two reacted with HHF35 only. Nine MFHs were not immunoreactive for any of the MoAbs specific for (smooth) muscle and actin. In addition, the expression of desmin and collagen type IV was investigated for the group of leiomyosarcomas and MFHs. Desmin was found in five leiomyosarcomas and in two MFHs. Collagen type IV was seen in all leiomyosarcomas, and was seen weakly in a few small areas in four MFHs. When we take into account the expression of all markers tested [( smooth] muscle actin, desmin, and collagen type IV), then six of the 22 MFHs were unreactive for all these markers. Five of these six tumors were located intramuscularly, whereas only half of the total number of MFH cases had an intramuscular location. The fact that 15 of 22 MFHs displayed one or more markers linked with (smooth) muscle differentiation suggests that some of the MFHs may be classified as poorly differentiated leiomyosarcomas, and that MFH is not a unique entity.

Actins↗
PubMed1990

Activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase in smooth muscle proliferation.

The specific activity of hexokinase, phosphofructokinase, aldolase, enolase, pyruvate kinase and glucose-6-phosphate dehydrogenase was measured in 41 smooth muscle cell tumors: 20 leiomyomas and 21 cases of leiomyosarcoma. Statistical analysis revealed no significant differences in specific activity between normal smooth muscle tissue and the benign and malignant tumors originating from it. Quantification of the isozyme composition of pyruvate kinase showed a significant shift in isozyme pattern towards K-type subunits in leiomyosarcomas as compared to leiomyomas.

Fructose-Bisphosphate Aldolase↗
PubMed1990

Activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase in lipoblastic and neurogenic proliferations.

The alterations in specific activity and/or isozyme pattern of hexokinase, phosphofructokinase, aldolase, enolase, pyruvate kinase and glucose-6-phosphate dehydrogenase were studied in the tissue specimens of 26 patients with lipoblastic tumors and 28 patients with tumors of neurogenic origin. Although the biochemical data demonstrated that the activities of most enzymes studied were elevated in the specimens of the malignant tumors, only the differences in activity of hexokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase measured between benign and malignant neurogenic tumors were significant. In malignant tumors, especially those of neurogenic origin, the isozyme pattern of pyruvate kinase showed a shift towards K-type subunits.

Adolescent↗
PubMed1988

Multilobated non-Hodgkin's lymphoma. A clinicopathologic entity.

Multilobated non-Hodgkin's lymphomas (NHL) have recently been recognized as an NHL variant. During a period of 10 years we observed 30 individuals with NHL in which more than 30% of the malignant cells had a characteristic multilobation. The immunologic phenotype was determined in 14 of these cases. One was of T-cell lineage, and the others exhibited B-lymphoid markers. Sixty-eight percent of the patients presented with extranodal localizations. In the clinical follow-up a complete remission was observed in 78% of patients with a mean duration of 37 months (range, 5 to 120 months). The actuarial survival after 5 years was 45%. From these data we conclude that multilobated NHL are comparable to diffuse, large cleaved-cell NHL of an intermediate grade malignancy according to the Working Formulation or are comparable to the diffuse centrocytic-centroblastic NHL according to the Kiel classification. The neoplastic cells are to be considered as variants of follicle center cells, but the clinicopathologic correlation indicates that multilobated NHL represent a distinct nosologic entity.

Adolescent↗
PubMed1988

Aberrant immunophenotypes in mycosis fungoides.

Skin biopsy specimens from 40 patients with mycosis fungoides (MF) were examined by a selective procedure for the assessment of immunophenotypic deviation. In 19 cases (48%), aberrant phenotypes were detected. Type and degree of aberration differed greatly without apparent clinicopathologic correlation. Different phenotypes in the same patient occurring either simultaneously or during the course of the diseases were observed. Phenotypic aberration showed a statistically significant correlation with tumor stage MF, the large cerebriform tumor cell type, blast cell transformation, and diffuse dermal infiltration. In combination with longer-existing disease, more lymph node and visceral involvement and a higher mortality rate of MF in the aberrant group indicated an association with advanced disease. Its prognostic relevance for the individual patient, however, seemed limited because of the association of aberration and a long-lasting indolent course in many other patients. The assessment of phenotypic aberration formed a valuable contribution to the diagnosis of MF, especially in cases with little cellular atypia.

Adult↗
PubMed1988

The expression of the Hodgkin's disease-associated antigen Ki-1 in cutaneous infiltrates.

Reactivity for Ki-1 antibody was studied in 145 patients with a large variety of cutaneous disorders. The antigen was consistently expressed and by a high proportion of tumour cells in infiltrates in which atypical cells revealed a 'histiocytic' appearance, i.e. lymphomatoid papulosis (LP), T-immunoblastic lymphoma with the characteristic of true histiocytic lymphoma, Hodgkin's disease, T-blast cell proliferation with giant multivesicular bodies, concurrent LP and mycosis fungoides (MF), and two cases of MF. Ki-1+ cells with the usual morphology of atypical T-cells formed a major component in 2 other cases of MF, and a minor component in 7 other cases of MF. A possible non-neoplastic counterpart was found in small to medium-sized Ki-1+ cells, including blast cells, which occurred occasionally in the T-cell infiltrates of eczema, actinic reticuloid, lichen planus and pityriasis lichenoides. Small Ki-1+ cells which were observed in the reactive B/T cell component of lymphocytoma cutis but also in similar components occurring occasionally in non-epidermotropic cutaneous T-cell lymphoma, and malignant B-cell lymphomas, might be analogous to the Ki-1+ cells in normal lymphoid tissue.

Antibodies, Monoclonal↗
PubMed1988

Leiomyosarcomas: three cases with desmin positive tumour cells, lacking ultrastructural features of smooth muscle cells.

A combined study of light and electron microscopy and of immunolabelling of three pleomorphic spindle cell sarcomas is presented. The light and electron microscopic features of these sarcomas were most compatible with those described for malignant fibrous histiocytoma (MFH, pleomorphic-storiform subtype). Electronmicroscopically undifferentiated and fibroblast-like cells, fibrohistiocytes and multinucleated histiocytes were observed. Characteristics belonging to smooth muscle cells were absent. By immunostaining, vimentin and desmin could be observed in tumour cells of all three cases, at least on frozen sections. Other markers such as alpha 1-antichymotrypsin, S-100 proteins, laminin, collagen IV and markers specific for skeletal muscle cells (myoglobin, actin and myosin specific for skeletal muscle) could not be demonstrated. These findings indicate that three MFH's are, in fact, poorly differentiated variants of smooth muscle tumours. It is concluded that immunophenotyping is very useful for this type of neoplasm.

Adult↗
PubMed1987

T-cell signet-ring cell proliferation in the skin simulating true histiocytic lymphoma.

We report the case of a solitary ulcerating lesion on the elbow of a 32-year-old man. Routine histopathological examination strongly suggested a histiocytic malignancy. However, electron-microscopical, enzyme-cytochemical, and immunological studies revealed that the "tumor" cells were T lymphocytes with an unusual (Leu 1+, Leu 3a+, Leu 4+, Leu 5b+, OKT4+, HLA-DR+, Ki-1+, Leu MI+) immunological phenotype and an even more uncommon morphology characterized by the development of giant multivesicular bodies giving some cells a signet-ring cell appearance, and autophagocytosis. The lesion healed spontaneously, notwithstanding its malignant histology.

Adult↗
PubMed1987

Low-grade lymphoma of immature T-cell phenotype in a case of lymphocytic interstitial pneumonia and Sjögren's syndrome.

A 19-year-old male patient presented with lymphocytic interstitial pneumonia and Sjögren's syndrome, confirmed by histopathology. He was treated with prednisone; 4 months later, cyclophosphamide was added. A lymph node taken at presentation revealed no histological signs of malignancy. Lymph nodes obtained 1 and 2 years later exhibited an effaced structure and a diffuse infiltration of small-sized lymphocytic cells compatible with a low-grade non-Hodgkin's lymphoma. The immunological phenotype of the lymphoma resembled that of immature T-cells present in the normal thymus cortex--positivity for CD1, CD2, CD4, CD7, CD38 and terminal deoxynucleotidyl transferase; faint positivity for CD5 and in the second specimen for CD3; negativity for CD6 and MHC class 1 antigen. The occurrence of such a peculiar lymphoma in Sjögren's syndrome has not been reported thus far. Small numbers of putative malignant cells were found on immunohistochemistry in a lymph node and a lung biopsy obtained at presentation. This is suggestive of one underlying pathogenetic event in the development of lymphocytic interstitial pneumonia, Sjögren's syndrome and non-Hodgkin's lymphoma.

Adult↗
PubMed1987

Abnormal T-lymphocytes in lymphomatoid papulosis. A cytomorphological study with a reconstruction of a major part of the cell differentiation cycle.

The abnormal cell population in lymphomatoid papulosis was studied by immunohistochemistry, light and electron microscopy in five cases. It resulted in a comprehensive description of all the main variants within the abnormal cell population. In one of the cases an irreversible intracytoplasmic process in the abnormal lymphocytes made it possible to demonstrate the derivation of lymphomatoid cells with cerebriform nuclei resembling the mycosis cells in mycosis fungoides from large histiocyte-like cells resembling the Reed-Sternberg cells in Hodgkin's disease. Variable numbers of the abnormal cells expressed Ki-1 reactivity in all four cases tested and T-cell associated antigens in two cases.

Adult↗