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A C Feller

Publications and source records attributed to A C Feller.

At least 19 recordsLinked to original sources
PubMed1992

Prevalence of Epstein-Barr virus DNA in different T-cell lymphoma entities in a European population.

The Epstein-Barr virus (EBV) has been classically associated with nasopharyngeal carcinoma and Burkitt's lymphoma, a monoclonal B-cell non-Hodgkin's lymphoma. Since the EBV genome has also been found in post-transplant lymphomas and lymphomas arising in individuals infected with the human immunodeficiency virus, evidence has now accumulated that EBV might be the initiator of a multi-step process leading from polyclonal B-cell hyperplasias to monoclonal lymphoma. In a retrospective study of 60 T-cell lymphomas of various types, we found EBV DNA in 21 (35%) using Southern- and/or dot-blot techniques. Eight of 14 nodal samples of angio-immunoblastic lymphadenopathy (57%) were shown to harbour detectable EBV DNA. The tumour with the next highest frequency, 47% (7/15 cases analyzed) was pleomorphic T-cell lymphoma, medium- and large-cell type; EBV was found both in nodal and in extranodal lymphomas of this type. Lymphoepitheloid (Lennert's) lymphoma and large-cell anaplastic lymphoma were positive in 2/5 and 3/8, respectively, of the cases analyzed. No viral DNA could be demonstrated in 3 T-immunoblastic and 5 T-lymphoblastic lymphomas. Clonotypic analysis revealed monoclonal as well as oligoclonal virus populations. Our data suggest that, at least in some of these entities, the presence of the EBV genome might be due to secondary mechanisms such as escape from immune surveillance.

DNA, Viral↗
PubMed1992

Activation of cytokines in Hodgkin's disease.

The complex histological pattern in Hodgkin's disease and in part in large cell anaplastic lymphomas (ALCL) suggests that close interactions exist between the tumor cells and reactive bystander cells. These interactions are most likely mediated by short ranged cytokines. The production of cytokines was analyzed in primary tissues and cell lines from Hodgkin's disease and ALCL by enzyme linked immunosorbent tests (ELISA), Northern blotting, immunohistological staining and in situ hybridization experiments. Our results indicate that Hodgkin's disease derived cell lines produce a variety of cytokines, such as IL1 alpha, IL4, IL5, IL6, IL8, IL9, TNF alpha and TNF beta but not IL1 beta, IL2, IL3 and G-CSF. In addition, the receptors for IL6 were detected in some of the cell lines. The expression of IL6 and IL6 receptors and IL9 has been confirmed for some primary tissues of Hodgkin's disease. From our data, we conclude that IL6, IL9 and additional cytokines are involved in the biology of Hodgkin's disease and ALCL.

Cell Line↗
PubMed1992

[Cytokines and malignant lymphomas].

Cytokines are potent modulators of the physiological immune response. A number of reactive processes are associated with a deregulation of this cytokine expression. Animal models with transgenic mice or transfection experiments have shown that an autocrine or paracrine pathway might be involved in tumor progression and/or tumorigenesis. The study of cytokine expression in malignant lymphomas showed a heterogeneous expression pattern with a number of cases which quantitatively show indications for a marked deregulation of the cytokine expression. The expression od IL-7 and IL-9 seem to be special features of Hodgkin's disease and large cell anaplastic lymphomas. Transfection experiment with IL-9 into mouse T cells results in an autocrine loop and tumorigenesis of the transfected cells. These tumors share a number of similarities to Hodgkin's disease and large cell anaplastic lymphomas in human.

Animals↗
PubMed1991

Expression of interleukin-6 and interleukin-6 receptor in Hodgkin's disease.

Interleukin-6 (IL-6) is a multipotent lymphokine that can mediate differentiation of B cells into Ig-secreting cells, stimulate the growth of plasmacytomas, hybridomas, and T cells, and induce acute-phase proteins in liver cells. It has been suggested that IL-6 is involved in the pathogenesis of several diseases by autocrine or paracrine pathways. To examine whether IL-6 is possibly involved in the pathophysiology of Hodgkin's disease (HD), we analyzed the expression of IL-6 and IL-6 receptor mRNA and protein in cell lines and primary specimens from patients with HD. IL-6-specific transcripts were detected in three of six HD-derived cell lines by Northern blot analysis. In the culture supernatants of four HD-derived cell lines, IL-6 was detected by radioimmunoassay. Biologic activity of IL-6 was confirmed by proliferation of an IL-6-dependent cell line. In situ hybridization experiments showed IL-6-specific transcripts in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues of two patients. In addition, mRNAs specific for the IL-6 receptor were detected in five HD-derived cell lines. Immunostaining experiments showed expression of IL-6 receptor molecules on H and RS cells in 8 of 16 cases with HD. Thus, our data suggest that IL-6 might be involved in the pathophysiology of HD.

Antibodies, Monoclonal↗
PubMed1991

[The diagnostic assessment of enlarged lymph nodes by the qualitative and semiquantitative evaluation of lymph node perfusion with color-coded duplex sonography].

Perfusion of enlarged lymph nodes by colour-coded sonography was studied prospectively in 105 benign and 115 malignant lymph nodes. The diagnosis was confirmed histologically in 158 and clinically in 62. Spectral analysis in the benign lymph nodes provided normal values for pulsatility and resistance indices. A pulsatility index greater than = 1.8, or a resistance greater than = 0.9 indicate lymph node metastases with positive prediction of 93% and specificity of 97%. In addition, subjective, semiquantitative classification of lymph node perfusion in relation to the surrounding fat or connective tissue improves the diagnosis of lymph node metastases and of malignant lymphomas.

Axilla↗
PubMed1991

Chromosomal translocation detected by bcl-1 and bcl-2 rearrangement in low-grade B-cell lymphomas in a European population.

Twenty-nine cases of non-Hodgkin's lymphoma of low-grade malignancy in a European population were investigated for the presence of bcl-2 and bcl-1 gene rearrangement. The cases were classified according to the Kiel classification. It was shown that bcl-2 gene rearrangements were exclusively confined to centroblastic-centrocytic lymphomas. bcl-1 rearrangements were found in two cases of chronic lymphocytic leukaemia. As the chromosomal translocation t(14;18) is reported to occur in up to 85% of follicular lymphomas, our results provide additional evidence that the differentiation of low-grade B-cell lymphomas according to the Kiel classification defines biologically distinct entities.

Chromosomes, Human, Pair 14↗
PubMed1991

Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue.

Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B-cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells.

Adult↗
PubMed1991

Expression of CD26 (dipeptidyl peptidase IV) on resting and activated human T-lymphocytes.

CD26 is an activation antigen which is expressed on the surface of human T-lymphocytes. It has been characterized to be the dipeptidyl peptidase IV (DPP IV). Considerable amounts of CD26 are already present on resting T-lymphocytes. The expression of CD26 is enhanced by T-cell mitogens or antigens. A correlation of CD26 expression and of enhanced enzymatic activity was observed after T-cell activation. Our data indicate that not only the immunoreactivity, but also the enzymatic activity of CD26 are detectable on the cell surface. In addition, de novo expression of CD26 was demonstrated on CD26-negative T-cells after mitogenic or antigenic stimulation. CD26 expression is initiated during the G1 phase of the cell cycle. The expression occurs nearly simultaneously with HLA-DR, but later than CD25. Similar to CD25 and HLA-DR, CD26 is not a permanent marker on the surface of T-lymphocytes, but is down-regulated after 7 days of culture. When testing the influence of interleukin 1, interleukin 2, tumour necrosis factor, and interferon-gamma on the expression of CD26, no effect was found on unstimulated or on mitogen-stimulated T-lymphocytes. The binding of two different monoclonal antibodies against CD26 (anti-DPP IV and anti-Tal) to resting and activated T-lymphocytes revealed a different pattern of immunoreactivity. Resting T-lymphocytes reacted stronger with anti-DPP IV than with anti-Tal. However, binding of the two monoclonal antibodies to T-cell blasts did not show significant differences. These data indicate that CD26 may be expressed in differently modulated configurations on the surface of T-cells, which may be associated with a distinct status of activation and/or function.

Amino Acid Sequence↗
PubMed1991

Cytokeratin expression and vimentin content in large cell anaplastic lymphomas and other non-Hodgkin's lymphomas.

The immunophenotypes of 74 malignant lymphomas (9 Hodgkin's disease, 19 low-grade B-cell, 20 high-grade B-cell, 8 T-cell, and 18 large cell anaplastic lymphomas [LCAL]) have been characterized with antibodies against leucocyte differentiation antigens, keratin, and vimentin. All the non-LCAL were CD45 positive and keratin negative. The LCALs had a more varied immunophenotype, with CD45 present only in 11 of 18 cases and keratin present in 5 of 18 of these rare lymphomas. The lymphoid origin of these latter cases was proven by gene rearrangement studies. All LCALs were CD30+, and, where tested, vimentin positive. Of four different vimentin monoclonal antibodies tested, V9 and MVI stained the highest number of lymphomas. Positive staining of tumor cells was seen in 61 of 71 cases. Vimentin-negative cases included Burkitt's as well as some follicular lymphomas.

DNA↗
PubMed1991

Cytokine expression in T-cell lymphomas and Hodgkin's disease. Its possible implication in autocrine or paracrine production as a potential basis for neoplastic growth.

The detection of an increasing number of cytokines and the demonstration of autocrine and paracrine mechanisms perpetuating tumor growth prompted the investigation of the expression of the cytokines IL-2, IL-3, IL-4, IL-5, IL-6, IFN gamma, Tac, and GMCSF in primary lymph-node biopsies of patients with peripheral T-cell lymphoma (n = 11), Hodgkin's disease (n = 13), and large-cell anaplastic lymphoma (n = 6) by means of Northern blot analysis and in situ hybridization (ISH); 15 of 28 cases had IL-6 message, predominantly in cases of Hodgkin's disease (HD) and large-cell anaplastic lymphomas (LCAL). Interferon gamma was found in about 50% of the cases among all entities. Other cytokine expression was rare except two cases of HD with high amounts of IL-4 mRNA. These results indicate that large amounts of growth factor transcripts are present in a variety of malignant lymphomas. The meaning of this expression is still unclear. It may be a loss of physiologic regulation within the cytokine network which may thus influence neoplastic cell growth as some cases have a quantity of cytokine expression which is similar or even above that of stimulated T cells. ISH demonstrates in individual cases that the expression is at least in part due to malignant cells.

Antibodies, Monoclonal↗
PubMed1990

Induction of antigen expression of follicular dendritic cells in a monoblastic cell line. A contribution to its cellular origin.

Experiments were carried out to elucidate the cellular origin of the dendritic reticulum cell (DRC). The monoblastic cell line THP-1, the histiocytic cell line U-937, and the mononuclear cell fraction from peripheral blood (PMC) were stimulated with supernatants from lectin-stimulated peripheral blood lymphocytes and from stimulated T- and B-cell lines. Differentiation towards DRC was assessed by immunocytochemical demonstration of the DRC-specific antigen Ki-M4. Supernatants from isolated peripheral T lymphocytes and from T- and B-cell lines were capable of stimulating THP-1 to Ki-M4 antigen expression, whereas U-937 and the PMC fraction remained negative for this antigen throughout the experiments. These results provide further evidence for a relationship of DRCs with the mononuclear-phagocytic cell system and hence for their bone marrow origin. Furthermore, the data suggest that soluble factors of T and/or B cells are involved in mediating the differentiation process of precursor cells to DRC.

Antigens, Surface↗
PubMed1990

Inv(14) with distal breakpoint in 14q32.1 in three cases of T cell lymphoma.

The distal breakpoint of inv(14) in T cell clones, established from patients with ataxia telangiectasia, lies outside the immunoglobulin heavy chain gene locus on 14q32.3, and more proximal to the centromere than the distal breakpoint of inv(14) in the T cell lymphoma cell line SUP-T1. We report 3 cases of T cell lymphoma cytogenetically showing the same type of inv(14) as the AT T cell clones. All 3 cases express a similar immunophenotype, which is that of peripheral T lymphocytes with phenotypic remnants of thymic or postthymic lymphoblasts. This finding provides evidence that this type of inv(14) is involved in the malignant transformation of mature T lymphocytes.

Adult↗
PubMed1990

Epstein-Barr virus infection rapidly progressing to monoclonal lymphoproliferative disease in a child with selective immunodeficiency.

We report on a 30-month-old previously healthy Turkish boy who presented with fever, hepatosplenomegaly and generalized lymphadenopathy. He died 4 months after admission in spite of treatment with steroids, acycloguanosine and cyclophosphamide. Epstein-Barr virus (EBV) DNA was detected in the patient's bone marrow and in a lymph node biopsy. Cells from the lymph node biopsy showed monoclonal rearrangements of immunoglobulin heavy chain genes but no rearrangements of T-cell receptor beta-chain genes or immunoglobulin kappa chain genes. Serological data indicated chronic active EBV infection. There was a slight increase of CD8 positive cells in peripheral blood and a normal response to T-cell mitogens. However, T-cell lines established with interleukin 2 from lymph node biopsy completely failed to kill autologous EBV-transformed B-cells and K 562 target cells. Moreover, in regression tests the patient's peripheral blood mononuclear cells completely failed to limit outgrowth of autologous EBV infected B-cells. We conclude that the patient's selective immuno-deficiency had led to the rapid development of EBV-associated monoclonal lymphoproliferation.

Antibodies, Viral↗
PubMed1990

Genomic analysis of T-cell receptor and immunoglobulin antigen receptor genes and breakpoint cluster regions in gastrointestinal lymphomas.

Sixteen cases of gastrointestinal B- and T-cell lymphoma were investigated for clonal rearrangements of immunoglobulin and T-cell receptor genes. In all cases the immunogenotype data corresponded well with the immunohistochemical findings, thus confirming the biologic heterogeneity of these lymphomas. Some cases could be distinguished by additional heterogeneity in their genotype which could not be detected by immunohistochemical methods. Moreover, the B-cell lymphomas were studied for the presence of the chromosomal translocations t(11;14) and t(14;18) using probes for bcl-1 and bcl-2 genes, respectively. While bcl-1 rearrangement was not present in these gastrointestinal lymphomas, one case of diffuse low-grade lymphoma of mucosa-associated lymphoid tissue and three cases of centroblastic lymphoma (diffuse large cell) could be shown to have detectable bcl-2 rearrangement.

Antigens, CD↗
PubMed1990

T-cell receptor and immunoglobulin gene rearrangements in cutaneous T-cell-rich pseudolymphomas.

T-cell rich, small lymphoid infiltrates of the skin may cause considerable problems in the differential diagnosis of reactive versus neoplastic lymphoproliferations, particularly when they lack the morphologic and immunophenotypical criteria for a malignant lymphoma. We did histologic, immunohistologic, and gene rearrangement studies on 10 biopsies from patients with persistent nodular T-cell-rich skin lesions refractory to topical therapy. Based on clinical and immunohistochemical findings, no discrimination was possible between reactive lesions and malignant lymphoproliferations. Histologically, most of the cases contained T-lymphocytic infiltrations that were assumed to be reactive; however, in four biopsies a neoplastic infiltration could not be excluded. Although the T-cell receptor (TCR) beta chain and the immunoglobulin heavy chain (IgH) genes were in germ-line configuration in nine of 10 cases, indicating a predominantly polyclonal lymphocellular infiltrate, in one patient without clinical evidence of malignant lymphoma at presentation a clonally rearranged TCR beta chain gene with the IgH gene in germ-line configuration was detected. One year later, the patient developed a cutaneous pleomorphic T-cell lymphoma and subsequently a large cell anaplastic (CD30+) T-cell lymphoma in an inguinal lymph node. We conclude that clonal T-cell proliferations can be detected by molecular genetic analysis of T-cell-rich, small lymphoid infiltrates of the skin. This finding may precede development of an overt malignant T-cell lymphoma.

Adult↗
PubMed1990

Increased serum levels of soluble IL-2 receptor, CD30 and CD8 molecules, and gamma-interferon in angioimmunoblastic lymphadenopathy: possible pathogenetic role of immunoactivation mechanisms.

Abnormal immunoreaction associated with increased cell activation phenomena might play a role in the pathogenetic events leading to the development of angioimmunoblastic lymphadenopathy (AILD). In the present study we investigated the serum levels of some soluble molecules related to cell activation in 24 patients with AILD at presentation. In particular, we measured by immunoenzymatic or immunoradiometric techniques the levels of the Tac peptide (sIL-2R), soluble CD30 (sCD30) and CD8 (sCD8) antigens, and gamma-IFN (gIFN). The results show that all the above molecules are increased as compared to normal controls, with a different pattern of increase for the different molecules. The sIL-2R levels were very high in all cases with no overlap between AILD and control samples (mean 6315 +/- 3374 U/ml, controls 271 +/- 112 U/ml, P less than 0.001). Very high values of the sCD30 antigen (722 +/- 895 U/ml) were detected in all cases but five, as opposed to the lack of detectable levels in controls. A significant increase of sCD8 (978 +/- 646 U/ml, controls 334 +/- 95 U/ml, P less than 0.01) and gIFN (329 +/- 236 U/ml, controls 97 +/- 43 U/ml, P less than 0.01) was also observed with some overlap between AILD samples and controls. The above findings further support the view that a condition of abnormally enhanced cell activation is likely to play a central role in the pathogenetic events leading to the composite clinicopathological picture of AILD.

Antigens, CD↗
PubMed1990

CD26 antigen is a surface dipeptidyl peptidase IV (DPPIV) as characterized by monoclonal antibodies clone TII-19-4-7 and 4EL1C7.

In this study we investigated the binding of three different monoclonal antibodies (MoAb), TII 19-4-7, 4EL1C7, and B1.19.2, which are clustered in CD26 to the ectoenzyme dipeptidyl peptidase IV (DPP IV) and to T lymphocytes. We found that all three MoAb bind to both unstimulated and mitogen-stimulated T lymphocytes. Further results indicated an inconsistency within the CD26-clustered MoAb: TII 19-4-7 and 4EL1C7, but not B1.19.2, recognized DPP IV on the surface o T lymphocytes and immobilized on solid-phase ELISA or Western blot. There was competition of binding to DPP IV between TII 19-4-7 and 4EL1C7. From these results we conclude that CD26 antigen is represented by the ectoenzyme DPP IV. TII 19-4-7 and 4EL1C7 recognize the same or partly identical epitopes on DPP IV, whereas B1.19.2 recognizes a different antigen. TII 19-4-7 and 4EL1C7, but not B1.19.2, should be clustered in CD26.

Antibodies, Monoclonal↗