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A S Krajewski

Publications and source records attributed to A S Krajewski.

At least 37 records · Page 2Linked to original sources
PubMed1992

Criteria for the definition of Epstein-Barr virus association in Hodgkin's disease.

There is a clear association between the Epstein-Barr virus (EBV) and Hodgkin's disease (HD). EBV is not, however, detectable within the affected tissues of all cases. The proportion of positive cases varies from 15-79% depending on the assay used to detect EBV. The techniques utilised vary not only in sensitivity but in their ability to detect viral DNA, RNA, or protein and in their ability to demonstrate the cellular localisation of the virus. Thus, the biological significance of a positive result will vary depending on the method of analysis. In the present study, four different methods of detecting EBV were compared. RNA in situ hybridization was found to be the most practical method of detecting EBV in tumour cells. Using this assay EBV was detected in the Reed-Sternberg cells of 33% and 45% of the two series of HD cases examined in this study. We believe that these cases should be considered EBV-associated.

Adolescent↗
PubMed1991

Immunohistological analysis of the immunoreactivity of normal lymphoid cells and lymphomas with the monoclonal antibody OPD4.

OPD4 is a recently described monoclonal antibody that recognizes a fixation-resistant 200 kD antigen restricted to a subset of T cells. Immunolabelling with OPD4 in paraffin sections of normal lymphoid tissues and cases of malignant lymphoma was compared with that of other antibodies in common use, including the T-cell restricted antibodies MT1 and UCHL1 and the B-cell restricted antibodies MB1, F8-11-13, and L26. OPD4 showed similar immunoreactivity to UCHL1 in normal tissues. OPD4 did not stain Reed-Sternberg cells in Hodgkin's disease. In non-Hodgkin's lymphomas, OPD4, like UCHL1, reacted with only 2/22 B-cell lymphomas. OPD4 was, however, less useful as a marker of T-cell lymphomas, staining only 11/32 cases, while UCHL1 stained 22/32 cases. We conclude that OPD4 is not a useful antibody for the routine diagnosis of T-cell lymphoma.

Adult↗
PubMed1991

Viral involvement in Hodgkin's disease: detection of clonal type A Epstein-Barr virus genomes in tumour samples.

Thirty-five cases of Hodgkin's disease (HD) were analysed for the presence of Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) DNA. EBV genomes were detected in 11/35 cases while none of the cases was positive for HHV-6. Ten of the EBV-positive cases were subsequently analysed using a probe for the terminal region of the virus; the results suggested that the EBV-infected cells were clonally expanded. EBV subtypes specific DNA amplification was used to demonstrate that EBV subtype A, and not subtype B was present in the EBV-positive cases. The age distribution of the EBV-positive cases indicated a statistically significant trend for an increase in positivity with increasing age. This is the first indication that EBV is significantly associated with any subset of HD patients.

Adolescent↗
PubMed1991

Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age.

An investigation as to whether any particular subgroup of patients with Hodgkin's disease was particularly likely to be Epstein-Barr virus (EBV) genome positive was made on samples from 95 patients. These were grouped according to age and Hodgkin's disease subtype, and analysed using Southern blot analysis. Most samples from children or adults aged 50 years or over contained detectable EBV genomes; samples from young adults were only rarely positive. The differences in EBV positivity by age were highly significant, but there was no significant association between EBV and histological subtype after allowing for the effect of age. The results support the hypothesis that Hodgkin's disease in different age groups may have different aetiologies, and suggest that EBV does have a pathogenetic role in Hodgkin's disease in children and older age groups.

Adolescent↗
PubMed1990

Analysis of T-cell receptor and immunoglobulin gene rearrangements in the diagnosis of Hodgkin's and non-Hodgkin's lymphoma.

The results of genotypic analysis of 29 cases of malignant lymphoma are reported and the application of this technique for differentiating between Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) is evaluated. Five cases with a differential diagnosis which included HD and NHL were analysed. These results are compared with those obtained for six B-cell NHLs, nine T-cell NHLs, and nine cases of HD. This report suggests that gene rearrangement analysis is useful in some cases in which the differential diagnoses includes HD and NHL as the absence of gene rearrangements is more consistent with a diagnosis of HD than of NHL. Two monoclonal antibodies reactive with the variable region of T-cell receptor beta-chain and molecular probes to the relevant variable region genes were used to assist in the diagnosis of T-cell lymphoma. This report confirms that genotypic analysis is useful diagnostically when the results are assessed in the context of the histopathological findings.

Adolescent↗
PubMed1990

Demonstration of clonality in T-cell lymphoma using an anti-T-cell receptor variable region antibody panel.

Frozen sections from 35 T-cell lymphomas were stained with the Diversi-T alpha beta T-Cell Receptor panel which includes seven antibodies to T-cell receptor variable region gene products. In five cases a monoclonal population of T-cells could be demonstrated (one case V beta 5+, three cases V beta 8+ and one case V beta 6+) and in a further case a biclonal population (V beta 5+ and V beta 8+). We conclude that this antibody panel is of limited usefulness for the demonstration of clonality in T-cell lymphoma.

Gene Rearrangement, beta-Chain T-Cell Antigen Rece↗
PubMed1989

Prognostic significance of activation and differentiation antigen expression in B-cell non-Hodgkin's lymphoma.

Immunophenotyping shows heterogeneity of expression of activation and differentiation antigens in B-cell non-Hodgkin's lymphoma (NHL). To investigate whether antigen expression correlates with clinical behaviour we have studied the clinical presentation and follow-up of a series of 111 B-cell lymphomas previously phenotyped for a panel of antigens including CD groups 5, 9, 10, 21, 23, 25, 30, 38, 4F2 antigen, and transferrin receptor. CD antigens 5, 10, and 23 were expressed significantly more often by low grade lymphomas whereas CD38, 4F2 antigen, and transferrin receptor were more often expressed by high grade lymphomas. There was a significant correlation with survival and age, stage at presentation, histological grade, and expression of 4F2 antigen and transferrin receptor but not with the other antigens studied. 4F2 antigen and transferrin receptor may identify a poor prognostic group of cases in low grade lymphoma but we conclude that phenotyping B-cell NHL for many of the antigens expressed at various stages of B-cell differentiation and activation does not provide clinically useful information in addition to that obtained from standard histological classifications.

Antigens, CD↗
PubMed1989

Distribution of a set of idiotopes detected by a monoclonal antibody panel in 42 cases of chronic lymphocytic leukaemia: definition of potential targets for immunotherapy.

Using a panel of 14 monoclonal V region reactive antibodies generated against a single IgG1 lambda paraprotein we have identified shared idiotopes in a group of 42 patients with chronic lymphocytic leukaemia (CLL). The specificity of cellular staining by indirect immunoperoxidase was confirmed in the majority of cases by an ELISA assay using secreted idiotypic immunoglobulin. In a few cases weak cellular binding by the panel antibodies could not be confirmed as specific for immunoglobulin. Four monoclonal antibodies specific for lambda chain determinants reacted with 5-29% of lambda expressing CLLs but the significance of this is uncertain as the antibodies may be recognizing one of the commoner V lambda subgroups. Two antibodies, which are only weakly reactive with normal serum immunoglobulin, detected heavy chain associated idiotopes which were expressed by 7% and 14% of CLL cases. One of these antibodies detects an idiotope which was expressed significantly more frequently by CLL associated immunoglobulin than by a panel of paraproteins. Such preferentially expressed idiotopes may be useful in investigating the biology of this disorder as well as providing attractive targets for immunotherapy.

Antibodies, Monoclonal↗
PubMed1989

Diagnosis of T-cell lymphoma using beta F1, anti-T-cell receptor beta chain antibody.

The reactivity of a new monoclonal antibody to the T-cell beta chain antigen receptor (beta F1) with routinely processed paraffin sections from patients with T-cell lymphoma is described. Staining of tumour cells was seen in 36/47 cases of T-cell lymphoma. No staining was seen in any cases of B-cell lymphoma (0/21 cases), nine of which had previously been shown to react with other T-cell antibodies (MT1/UCHL1). We conclude that beta F1 is a specific marker for demonstrating a T-cell histogenesis of lymphoma and with advantages over other currently available antibodies reactive with paraffin sections.

Antibodies, Monoclonal↗
PubMed1989

Suppression of malignancy in human lymphoid cell hybrids: the role of differentiation.

Human somatic cell hybrids were generated from fusions between a tumorigenic B-cell line, and mononuclear cells from a patient with low-grade B-cell lymphoma in which the neoplastic cells largely corresponded to cells at an intermediate stage of differentiation. The resulting hybrids and the parent cells were immunophenotyped, karyotyped and genotyped in an effort to determine whether the stage of B-cell development of the fusion partners was important in the suppression of malignancy. The majority of hybrids demonstrated suppression of tumorigenicity as measured in immunodeprived mice. Chromosome markers and immunoglobulin gene rearrangements found in the patient's neoplastic cells were also present in several of the hybrids. One of the tumorigenic hybrids retained specific chromosomes also found in the non-tumorigenic hybrids, but demonstrated an immunophenotype and genotype possibly associated with a subset of early B-cells. In the non-tumorigenic hybrids that retained most of the chromosomes from both parents there was evidence of plasmacytoid differentiation. These results suggest that the ability of B-lymphocytes to suppress malignancy in human lymphoid hybrids may be dependent on the corresponding stage of normal B-cell ontogeny, and that suppression is associated with differentiation.

B-Lymphocytes↗
PubMed1989

Quantitation of expression of idiotopes recognized by a panel of monoclonal antibodies in normal serum immunoglobulin: use of a novel 4-stage ELISA assay.

This paper describes the application of a sensitive ELISA assay detecting as little as 10 ng/ml of a specific idiotope. Using this assay we were able to divide monoclonal anti-idiotypic antibodies generated using a single IgG1 lambda paraprotein as the immunogen into three distinct groups. Seven antibodies detected determinants which were expressed only by the immunogen. The remaining seven antibodies all reacted with normal serum immunoglobulin. Four antibodies reacted with "public" idiotopes which were strongly expressed by serum immunoglobulin, and three antibodies reacted with "restricted public" idiotopes which were only weakly expressed by serum immunoglobulin. This last group may be of significant interest as agents for the immunotherapy of B-cell malignancies. The conservation of expression of these idiotopes in many individual sera suggests that they have a physiological role in immune regulation and would therefore be excellent targets for immunotherapy of B-cell tumours while their quantitatively low expression by circulating immunoglobulin is unlikely to interfere with tumour cell specific binding in vivo.

Animals↗
PubMed1988

Activation and differentiation antigen expression in B-cell non-Hodgkin's lymphoma.

In an attempt to establish whether extended immuno-phenotyping allows more accurate definition of subgroups of B-cell non-Hodgkin's lymphoma (NHL) we have stained a series of 145 cases with a large panel of monoclonal antibodies that recognize B-cell differentiation and activation antigens. No antigen was expressed by all cases. The B-cell histogenesis in many cases could be confirmed only by using a panel of immunoglobulin and pan B-cell markers. There was marked phenotypic heterogeneity within and between major groups of B-cell NHL as delineated by the Kiel classification although the differentiation antigens CD5 (lymphocytic and centrocytic NHL) and OKT10 (plasma cell tumours) were more often expressed by certain morphological groups. The activation antigens 4F2 and transferrin receptor were expressed more strongly and more often by high grade NHL but other activation antigens (CD23 and CD25) were not more frequently associated with these tumours. Extended phenotyping may be of value in improving the understanding of biological abnormalities and processes involved in B-cell NHL, but we conclude that a limited panel of markers (CD3, CD5, CD22, CD45, IgM, kappa, and lambda) should be sufficient for routine diagnosis and classification of most cases.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

Paraffin section immunophenotyping of non-Hodgkin's lymphoma, using a panel of monoclonal antibodies.

The monoclonal antibodies F8-11-13, 4KB5, MB1, and MB2 recognize largely B-cell-restricted antigenic determinants that resist routine processing. Similarly, MT1, MT2, and UCHL1 react with fixation-resistant T-cell-restricted antigens. In order to evaluate the diagnostic potential of these antibodies, the authors have assessed their immunoreactivity with a series of 81 formalin-fixed and paraffin-embedded non-Hodgkin's lymphomas (48 B-cell, 33 T-cell) encompassing a wide variety of histologic subtypes, which had been fully characterized by frozen-section immunophenotyping. Ninety-six percent of B-cell lymphomas reacted with one or more of the B-cell-associated antibodies, whereas 100% of T-cell lymphomas reacted either with MT1, UCHL1, or both antibodies. MT2 was of no value in distinguishing between B- and T-cell lymphomas. None of the antibodies was entirely lineage specific; furthermore, a proportion of cases failed to react with one or more of the B- or T-cell-associated antibodies. Although these antibodies provide useful information in distinguishing between T- and B-cell lymphomas, the authors suggest that a panel of these antibodies is necessary for accurate determination of the histogenesis of these tumors. As with any immunohistochemical marker, interpretation of the immunostaining must be in the context of the morphologic features.

Antibodies, Monoclonal↗
PubMed1988

T-cell lymphoma: morphology, immunophenotype and clinical features.

The histology, immunophenotype and clinical presentation of 43 cases of T-cell lymphoma are described. Cases were classified into nine types; T-lymphocytic lymphoma (three), mycosis fungoides (six), Sézary syndrome (two), T-zone lymphoma (13), angioimmunoblastic lymphadenopathy (AIL)-like T-cell lymphoma (five), pleomorphic medium cell (one), large cell immunoblastic (four), large cell polylobated (five) and lymphoblastic (four). The patients comprised 26 males and 17 females aged between 15 and 86 years. The majority showed disseminated disease at the time of diagnosis (18 stage IV, nine stage III, five stage II, eight stage I and three cases not staged). Thirty-one patients showed lymph node involvement. Cutaneous involvement was a common finding (18 cases, 10 cases excluding mycosis fungoides and Sézary syndrome). Details of therapy and clinical follow-up were obtained in 37 cases. With simple chemotherapy only one complete response (7%, 1/16) was obtained. With aggressive therapy 48% (13/27) of patients showed complete responses. Twenty patients died during the follow-up period. Life table analysis showed a 58% probability of surviving 1 year and 36% probability of surviving 3 years. There was a significant difference in survival probability between low/intermediate-grade (lymphocytic, Sézary syndrome, mycosis fungoides and T-zone lymphoma including AIL-type) lymphomas and high-grade (large cell immunoblastic and polylobated and lymphoblastic) lymphomas (P less than 0.025). However, when survival of T-zone and AIL-like T-cell lymphoma was compared with survival of large cell immunoblastic and polylobated lymphomas no significant difference was detected. Age (less than 50 years) and stage I or II disease were associated with significantly better survival (P less than 0.005 and P less than 0.05).

Adolescent↗
PubMed1988

Characterization of a new non-Hodgkin's lymphoma cell line (NCEB-1) with a chromosomal (11:14) translocation [t(11:14)(q13;q32)].

A new cell line, NCEB-1, was established by Epstein-Barr virus (EBV) transformation of peripheral blood mononuclear cells from a patient with centroblastic-centrocytic diffuse lymphoma expressing IgM lambda. The transformed cells were lymphoblastoid, with many cells showing a plasmacytoid morphology. The NCEB-1 cells had cytoplasmic Ig (CyIg), with loss of the surface Ig (SIg) expression. Cytogenetic analysis of the cell line demonstrated two clones with variations: a hypodiploid clone, with a complex karyotype including a t(11;14)(q13;q32) similar to the original tumor cells, and a near tetraploid clone with the same markers. Southern blot analysis of DNA from the patient's neoplastic cells and NCEB-1 demonstrated identical Ig heavy chain gene rearrangement, confirming the origin of the cell line. The cell line was not tumorigenic when tested in an in vitro assay using immunosuppressed mice. NCEB-1 has been in continuous culture for 9 months and will be valuable for the in vivo study of non-Hodgkin's lymphoma and EBV transformation.

Cell Line↗
PubMed1988

Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes.

Enteropathy-associated T cell lymphoma (EATCL; malignant histiocytosis of the intestine) arises in patients with enteropathy, which in some cases is known to be a result of gluten sensitivity. The lymphoma arises in the intestine, where it may remain localized, although eventual dissemination is the rule. Intraepithelial tumour cells often are seen at the mucosal tumor margin. These features suggest that EATCL may be a tumor of intraepithelial lymphocytes. A monoclonal antibody (HML-1) has been produced recently that recognizes the entire intraepithelial lymphocyte population and 50% of lamina propria T cells but very few cells outside the mucosa. Immunocytochemistry has shown that all cases of enteropathy-associated T cell lymphoma studied are HML-1 positive and all peripheral T cell lymphomas and mucosal B cell lymphomas are HML-1 negative. This suggests strongly that EATCL is a tumor of mucosal T cells, possibly the intraepithelial T cell component.

Antibodies, Monoclonal↗