Biomedical subjects

D Y Mason

Publications and source records attributed to D Y Mason.

At least 73 records · Page 4Linked to original sources

PubMed1995

Discordant expression of immunoglobulin and its associated molecule mb-1/CD79a is frequently found in mediastinal large B cell lymphomas.

Mediastinal large B cell lymphomas are uncommon neoplasms that are thought to originate from thymic B cells. An unusual feature of these neoplasms is that they often lack surface immunoglobulin (Ig), a molecule ubiquitously expressed by most mature B cells. In the present study we have analyzed 12 cases of mediastinal large B cell lymphoma for the expression of the mb-1/CD79a polypeptide. This is a component, together with B29/CD79b, of a heterodimer that is associated with surface Ig on normal B cells. Our aim was to see whether loss of Ig in this type of lymphoma is associated with loss of the accompanying CD79a molecule. We have also evaluated 128 B cell lymphomas of other categories to see whether any of them show discordance between mb-1 and Ig expression and analyzed 30 T cell lymphomas as Ig-negative controls. We found that 5 of the 7 mediastinal large B cell lymphomas with interpretable staining results for both mb-1 and Ig, lack Ig but expressed CD79a (mb-1). This phenotype was very rare in other categories of B cell lymphoma, being found among 110 cases in only 5 cases that were all follicular lymphoma. The remaining 105 B cell lymphomas displayed mb-1+/Ig+ phenotype. All 30 T cell lymphomas were mb-1 negative. We conclude that discordant mb-1/Ig expression occurs commonly in mediastinal large B cell lymphomas. In addition, the finding that 11 of 12 of these neoplasms express a phenotype (CD10-, CD19+, CD20+, CD21-, CD22+, CD23-/+) that is very similar to that described for thymic medullary B cells reinforces the idea that most mediastinal large B cell lymphomas are of thymic B cell origin. The correlation between mb-1 and Ig staining patterns in B cell lymphomas of other categories reveals that in the majority (90%), expression of the antigen receptor complex parallels that of mature B cells. These data therefore confirm that the expression of the mb-1 protein provides independent strong evidence for the B lineage of lymphomas and may be used for their routine phenotypic characterization.

Antigens, CD↗

PubMed1994

Subcellular localization of the bcl-2 protein in malignant and normal lymphoid cells.

The bcl-2 oncogene is expressed in lymphoid and myeloid cells as well as in neurons and several types of epithelial cells and inhibits programmed cell death (apoptosis). Deregulation by the t(14;18) translocation in lymphoid malignancies induces inappropriate cell survival and serves as one of the steps toward a fully malignant behavior. Using pre- and postembedding immunoelectron microscopy in normal and neoplastic lymphocytes, we demonstrate bcl-2 immunoreactivity to the mitochondrial outer circumference and the nuclear envelope and to a lesser degree to the cell membrane. Mitochondrial staining was patchy, reminiscent of mitochondrial contact zones. Additionally, there was a suggestion of association with nuclear pores. In these regions, transmembrane transport is mediated. This may suggest that bcl-2 exerts its function in this process.

3,3'-Diaminobenzidine↗

PubMed1994

Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity.

This article reviews the evidence that the nodular form of lymphocyte predominance Hodgkin's disease ("nodular paragranuloma") should be recognised as a distinct clinico-pathological entity. The disease is characterised histologically by very large primary lymphoid follicles, containing polytypic small B lymphocytes and extensive meshworks of follicular dendritic cells. The "L and H" or "popcorn" cells scattered within the nodules show clear differences from classical Reed-Sternberg cells, both in their cytological appearance and in their marker profile, being frequently negative for CD15 and for the EBV genome, but often positive for B cell antigens, CD45 (leucocyte common antigen), CDw75 (LN1), epithelial membrane antigen (EMA) and J chain. These findings suggest that L and H cells may be Ig-synthesising monoclonal B cells. Nodular lymphocyte predominance Hodgkin's disease pursues a much more indolent courses that classical Hodgkin's disease, and long term survival is common. It has other distinctive clinical features, e.g. a unimodal age distribution, a predilection to involve single lymph nodes, and a very low incidence of thymic involvement. There is a tendency for diffuse large cell non-Hodgkin's lymphoma, usually of B cell type, to develop during the course of the disease. This type of Hodgkin's disease thus has many features that distinguish it from the nodular sclerosis and mixed cellularity varieties, and it is hoped that future studies will gather more information on its clinical behavior and on the nature of the putative neoplastic cells, as well as exploring different protocols for its treatment.

Hodgkin Disease↗

PubMed1994

The expression of the B-cell marker mb-1 (CD79a) in Hodgkin's disease.

Recent evidence indicates that membrane-bound immunoglobulin on B lymphocytes is associated with a molecule which comprises the products of the mb-1 and B29 genes. This molecule is a highly specific marker for B-cells, presumably because of its central functional role in antigen triggering, and has recently been clustered as CD79a at the 5th Leucocyte Workshop. Recently there has been controversy surrounding reports of B-cell antigen expression by Reed-Sternberg and related cells, and we have therefore studied 108 cases of Hodgkin's disease immunohistochemically using a novel antibody which detects mb-1 protein in paraffin sections. The results were compared with those achieved using antibody L26 to detect CD20. The mb-1 protein was present in the neoplastic cells in all 14 cases of lymphocyte predominance Hodgkin's disease studied, and CD20 immunoreactivity was also found in seven of the eight cases of this subtype studied. Of the non-lymphocyte predominance cases, 20% (19/94) expressed mb-1 and 30% (20/67) CD20 in the Reed-Sternberg cells, but the cells positive for either of these two markers usually constituted only a very small proportion of the neoplastic population. However, in occasional cases (one of 94 for mb-1 and five of 67 for CD20), more than 50% of the neoplastic cells expressed one or both B-cell antigens. These results confirm the B-cell origin of the neoplastic cells in lymphocyte predominance Hodgkin's disease, but they also indicate that, contrary to our previous study, mb-1 expression may occasionally be found in what appears, on histological grounds, to be other types of Hodgkin's disease.

Animals↗

PubMed1994

Cellular distribution of human leucocyte adhesion molecule ICAM-3.

AIMS: To describe the distribution of the recently cloned human leucocyte adhesion molecule ICAM-3 in normal and neoplastic tissues and cell lines. METHODS: A panel of four monoclonal antibodies to ICAM-3 were used to stain cell lines and sections of human lymphoid tissues using the alkaline phosphatase-anti-alkaline phosphatase immunocytochemical method (APAAP). RESULTS: In peripheral blood ICAM-3 was detected on monocytes, granulocytes, and most lymphocytes. In sections of human lymphoid tissue the antigen was also found on most lymphocytes, but many of the proliferating B cells found in the germinal centres of secondary lymphoid follicles were ICAM-3 negative. ICAM-3 was also found on neoplastic white cells (in chronic lymphocytic leukaemia, hairy cell leukaemia, acute and chronic myeloid leukaemia, and multiple myeloma) with the exception of Reed-Sternberg cells in Hodgkin's disease, many of which were negative. ICAM-3 was consistently absent from cells and tissues of non-haemopoietic origin. Endothelium (which expresses ICAM-1) was negative for ICAM-3, with the exception of vessels in some neoplastic lymphoid samples which showed variable staining for ICAM-3. CONCLUSIONS: These findings suggest that ICAM-3 is essentially restricted to the haemopoietic system and is reciprocal in its expression to ICAM-1, in that it is present on resting cells and its level falls as a result of cell activation.

Antibodies, Monoclonal↗

PubMed1994

A novel internal antigen which distinguishes germinal centre cells from other B-cell types.

A new monoclonal antibody, 4KB51, is described which labels the majority of B cells in blood and in mantle and marginal zones but not germinal centre lymphocytes or plasma cells. Antibody 4KB51 also stains monocytes, neutrophils and the majority of T cells. It recognizes an intracellular antigen of 160,000 MW (unreduced) and 68,000 MW (reduced). Antibody 4KB51 labels the tumour cells in all cases of hairy cell leukaemia and in four of the 16 cases of centrocytic B-cell lymphoma studied. No labelling of the other lymphomas (114 cases) or lymphoid leukaemias (13 cases) tested was seen. Antibody 4KB51 may be of value in defining B-cell subsets and in the differential diagnosis of hairy cell leukaemia and centrocytic lymphomas. The pattern of reactivity of 4KB51 suggests that its target antigen may play a functional role, possibly involved in lymphocyte homing.

Antibodies, Monoclonal↗

PubMed1993

Induction of tyrosine phosphorylation in human B lineage cells by crosslinking MB-1 molecule of B cell receptor-related heterodimer complex.

B cell antigen receptor is composed of immunoglobulin and associated MB-1 and B29. Here, we found that anti-human MB-1 stimulation induced tyrosine phosphorylation in immature B cells (FL4.4 and Nalm-6) but not in mature B cells (Daudi). Coprecipitated complex with the heterodimer component in Daudi and Nalm-6 contained the kinase molecule(s) which act on the heterodimer protein, while the complex in early lymphoid cell with germ line antigen receptor genes (FL4.4) did not. Candidate Fyn and Lyn are expressed in Nalm-6 and Daudi but are not expressed in FL4.4. These results suggested that src-type tyrosine kinases as Fyn and Lyn are responsible for the phosphorylation of MB-1 and B29 heterodimer, but anti-MB-1 stimulation can induce tyrosine phosphorylation reaction mediated by other kinase molecule(s) in the progenitor type cells.

Amino Acid Sequence↗

PubMed1993

bcl-2 protein in non-small-cell lung carcinoma.

BACKGROUND: The proto-oncogene bcl-2 encodes a protein that inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but no data are available on the frequency or clinical importance of its expression in carcinoma. We studied bcl-2 expression in patients with non-small-cell lung carcinoma and correlated this phenomenon with survival. METHODS: Immunochemical analysis with a monoclonal antibody specific for bcl-2 was used to detect the protein in tumor samples from 122 patients undergoing surgery for squamous-cell carcinoma (80 patients) or adenocarcinoma (42 patients). The possibility that bcl-2 expression correlated with survival was investigated with use of the log-rank test, hazard ratios, and their confidence intervals. RESULTS: We detected bcl-2 protein in 25 percent of squamous-cell carcinomas (20 of 80) and 12 percent of adenocarcinomas (5 of 42). In adjacent normal respiratory epithelium, bcl-2 was expressed only in basal cells. Survival at five years was higher among patients with bcl-2-positive tumors, both in the group as a whole (P < 0.1) and in the group with squamous-cell carcinoma (P < 0.02). Patients 60 years of age or older who had bcl-2-positive tumors had the best prognoses, both in the group as a whole (P < 0.02) and in the group with squamous-cell carcinoma (P < 0.01). CONCLUSIONS: The proto-oncogene bcl-2 is abnormally expressed in some lung carcinomas, and its expression may have prognostic importance.

Adenocarcinoma↗

PubMed1993

mb-1: a new marker for B-lineage lymphoblastic leukemia.

The expression of the Ig-linked mb-1 polypeptide was analyzed by immunocytochemistry (alkaline phosphatase anti-alkaline phosphatase technique) using a specific monoclonal antibody in 165 cases of acute leukemia, with 88 being lymphoblastic (ALL) and 77 myeloid (AML). The purpose of the study was to investigate the specificity of this reagent for B-lineage cases and its reactivity on leukemias that coexpress myeloid and B-cell antigens (biphenotypic). The majority (89%) of 72 B-cell precursor ALL patients were positive. Of these, mb-1 was expressed in all 9 patients with early-B-ALL (CD10-, c mu-), in all 11 patients with pre-B-ALL (c mu+) and in the single case of B-ALL (smIgM+). Forty-three of 51 patients with common-ALL (CD10+, c mu+) were also positive. All 16 T-lineage ALL patients and 72 (93.5%) of the AML patients examined were mb-1 negative. Four of the 5 mb-1-positive AML patients were considered biphenotypic and expressed other B-cell antigens such as CD10, CD19, and/or cCD22 and all showed rearrangement of the Ig heavy chain genes. Within the AML cases, mb-1 and cCD22 were more useful than other B-cell antigens in detecting biphenotypic cases, and mb-1 showed the highest correlation with the clonal rearrangement of Ig heavy chain genes. These results indicate that mb-1 is a sensitive and specific reagent for B-lineage blasts that will aid in the classification of B-cell precursor ALL and in the identification of biphenotypic leukemia presenting as AML.

Antibodies, Monoclonal↗

PubMed1993

Detection of T and B cells in many animal species using cross-reactive anti-peptide antibodies.

A wide range of lineage-specific Ag are detectable in the human lymphoid system using mAb, but only a few such markers are detectable in animal species. In this paper, we have investigated the interspecies reactivity of antibodies raised against intracytoplasmic peptide sequences from two T cell Ag (CD3 and CD5) and two B cell markers (the Ig-associated polypeptides encoded by the mb-1 and B29 genes). Immunocytochemical labeling of tissue sections showed that these antibodies cross-react widely between different species (including ungulates, rodents, and marsupials), staining B or T cell areas selectively in lymphoid tissue. The specificity of these antibodies for the animal homologues of the human T and B cell markers was confirmed for the rat by Western blotting analysis. The broad cross-reactivity of these antibodies appears to be due to the fact that they were raised against intracytoplasmic peptide sequences that are highly conserved between humans and rodents, i.e., 80% for mb-1, 85% for CD5, and 100% for CD3 and B29. This strategy should, in the future, widen the range of lineage-associated markers detectable in experimental animals.

Amino Acid Sequence↗

PubMed1993

The structure of the mu/pseudo light chain complex on human pre-B cells is consistent with a function in signal transduction.

Prior to immunoglobulin (Ig) light (L) chain rearrangement, pre-B cells can express mu heavy (H) chains at the cell surface in association with pseudo (psi) L chains. This complex may be essential for B cell development. We have investigated the composition of the mu/psi L chain complex of a human pre-B cell line, in view of its potential role in transmembrane signal transduction. The mu/lambda receptor of a mature B cell line was analyzed in comparison. The mu/psi L chain complex is associated with disulfide-linked molecules that are homologous or identical to the mb-1 and B29 proteins, known to be integral components of membrane Ig receptors on mature B cells. Both receptors contain tyrosine (Tyr) kinase activity. In the mu/lambda receptor, the lyn and lck Tyr kinases could clearly be identified. The mb-1 and B29 proteins in both mu/lambda and mu/psi L chain receptors are substrates for in vitro phosphorylation on Tyr, but also on serine (Ser) and threonine (Thr) residues. The undefined mu-associated Ser/Thr kinase also phosphorylates the src-related kinases in the mu/lambda receptor and a 43-kDa mu-associated protein that is present in both complexes. The 43-kDa protein may be an integral part of both receptor types, or a transiently associated molecule instrumental in the signaling process. We conclude that the mu/psi L receptor on human pre-B cells fulfills the presently known criteria to function as a signal transduction unit.

Amino Acid Sequence↗

PubMed1993

A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily.

The antibodies Ki-M8, Ber-Mac3, GHI/61 and SM4 define a human macrophage-associated antigen with a relative molecular mass of 130,000 which we designate M130. The protein was purified by immunoaffinity chromatography and an N-terminal and three internal amino acid sequences were obtained. A cDNA fragment was initially obtained by polymerase chain reaction (PCR) using reverse-translated primers. Several variant cDNA clones, derived from alternative spliced messages, were obtained from a lipopolysaccharide-stimulated human monocyte library and were sequenced. The relative abundance of these variants was evaluated by a series of overlapping PCR reactions. The size of the most representative cDNA is 3.7 kb and closely agrees with the mRNA size of 3.8 kb determined by Northern blot analysis. The membrane protein encoded contains a leader peptide of 40 residues, a putative extracellular domain of 1003 residues, followed by a hydrophobic segment of 24 residues and a cytoplasmic domain of 49 residues. The extracellular domain was found to contain nine repeating elements, of about 110 residues, which are similar to those of the scavenger receptor superfamily.

Amino Acid Sequence↗

PubMed1993

An immunocytochemical study of p53 and bcl-2 protein expression in Hodgkin's disease.

In view of their reported reciprocal effects on apoptosis, the expression of p53 and bcl-2 proteins was studied in 46 cases of Hodgkin's disease by immunocytochemical labeling. We found p53 protein in Reed-Sternberg cells and their mononuclear variants in 16 of the 46 cases (34.7%) of Hodgkin's disease, mainly in a nuclear pattern. This restricted expression on Reed-Sternberg cells and variants supports their neoplastic nature. This overexpression of p53 protein in one third of Hodgkin's disease cases is similar to that seen in many other human malignancies. bcl-2 protein was present in mantle zone B cells and scattered T cells in all cases, and in 17 cases (37.7%) of Hodgkin's disease in Reed-Sternberg cells and their mononuclear variants. Six cases coexpressed both proteins, whereas in 18 cases neither was identified. There is no apparent relationship between p53 and bcl-2 protein expression, and on the basis of the present results there is no reason to suppose that they have any particular complementary effects on the neoplastic transformation in Hodgkin's disease.

Antibodies↗

PubMed1993

ZB51: a monoclonal antibody reactive with human plasma cells.

Several monoclonal antibodies have been raised in the past which react with human plasma cells but they have all shown additional reactions with other cell types. In this paper we describe a new monoclonal antibody, ZB51, which recognizes an intracellular antigen in normal plasma cells in cryostat tissue sections and cell smears, and which also reacts with neoplastic cells in most cases of myeloma and with plasma cell lines. The antibody shows minimal reactivity with a few eosinophils and myelocytes in bone marrow and stains a myeloid cell line. Whilst normal epithelium is not labelled, antibody ZB51 stains two carcinoma cell lines. Although it was not possible to characterize the target antigen in terms of molecular weight, the reactivity of antibody ZB51 with normal and neoplastic plasma cells makes it a useful new immunocytochemical reagent.

Antibodies, Monoclonal↗

PubMed1993

Antibody By114 is selective for the 90 kD PI-linked component of the CD66 antigen: a new reagent for the study of paroxysmal nocturnal haemoglobinuria.

This paper describes a monoclonal antibody which reacts with transfected cells carrying a gene (NCA-50/90) which has been shown to encode the human CD66 antigen. However, antibody By114 recognizes only a single 90 kD polypeptide from human neutrophils, whereas the antibodies which originally defined the CD66 antigen also recognize a larger 180-200 kD protein. We conclude that antibody By114 is selective for the smaller of the two CD66 gene products, which is a surface membrane phosphatidyl-inositol (PI)-linked molecule. The reactivity of antibody By114 on peripheral blood cells (positive on neutrophils, weak or negative on eosinophils, and negative on basophils, monocytes and lymphocytes) and myeloid precursor cells was identical to those of a reference CD66 antibody, as was the staining of leukaemic cells. However, the reactions of the two antibodies differed on kidney, liver and pancreas, and in cases of myeloma, Waldenström's macroglobulinaemia and lymphoma, indicating that By114 represents a new CD66 sub-specificity. Granulocytes from a case of paroxysmal nocturnal haemoglobinuria (PNH) were negative with antibody By114, indicating that it may be of value in detecting the defect in PI-linked surface molecules characteristic of this condition. Antibody By114 also stained formalin fixed paraffin embedded tissues and may therefore be of use in routine diagnostic histopathology.

Antibodies, Monoclonal↗

PubMed1993

Immunohistological patterns of myeloid antigens: tissue distribution of CD13, CD14, CD16, CD31, CD36, CD65, CD66 and CD67.

A number of differentiation antigens on myeloid cells have been defined on the CD classification system by the four International Workshops on Human Leucocyte Differentiation Antigens. The distribution of eight of these antigens (CD13, CD14, CD16, CD31, CD36, CD65, CD66, CD67) have been studied in human tissues, with the aim of documenting their immunohistological patterns and their degree of myeloid restriction. CD13, the most widely distributed antigen, was found in skin, bile canaliculi, kidney and pancreas. CD14 was not restricted to monocytes and tissue macrophages, being also strongly expressed on dendritic reticulum cells. CD16 was expressed on granulocytes and tissue macrophages (alveolar and Kupffer cells) and in the red pulp of the spleen. CD31 and CD36 gave a characteristic staining of vascular endothelium, corresponding to their identification as the platelet glycoproteins gp IIa and gp IV. Antibodies against the most recently defined myeloid antigens (CD65, CD66 and CD67) appeared to be more specific for myeloid differentiation than previously described 'myeloid antigens'.

Antibodies, Monoclonal↗

PubMed1993

Immunohistochemical detection of p53 and bcl-2 proteins in non-Hodgkin's lymphoma.

We have investigated the immunohistochemical expression of p53 protein in 96 cases of non-Hodgkin's lymphoma using a panel of five antibodies. Positive neoplastic cells were found in 30 (31.2%) cases, which could be divided into two groups according to their patterns of reactivity with the different antibodies; i.e. those positive with both polyclonal and monoclonal antibodies, and those which were stained only by monoclonal antibodies PAb1801 and/or PAb240. Positivity was nuclear in all but six cases in which cytoplasmic staining was found. In view of the hypothesis recently raised that p53 protein induces apoptosis we have compared our results with parallel staining for bcl-2 protein since bcl-2 is believed to be important, at least in lymphomas, in suppression of apoptosis. Staining for bcl-2 protein was performed on 83 cases and it was shown that p53-positive cases accounted for 10 out of 17 (59%) of the bcl-2-negative lymphomas but only for 15 out of the 66 (23%) bcl-2-positive cases, suggesting a possible relationship between the expression of these two proteins. Thus, our data show that p53 protein is abnormally expressed in a substantial proportion of non-Hodgkin's lymphomas and bears a significant inverse relationship to bcl-2 protein expression. However the molecular basis of this expression remains to be elucidated.

Humans↗

PubMed1993

Expression of the Ig-associated heterodimer (mb-1 and B29) in Hodgkin's disease.

Eighty-three cases of Hodgkin's disease were studied immunocytochemically for the presence of the Ig associated heterodimer (mb-1 and B29) which is believed to be a specific pan B-cell marker. These results were compared with those achieved using other B-cell markers against CD19, CD20 and CD22. Although a small number of cases of nodular sclerosis and mixed cellularity subtype showed positivity for CD19, CD20 or CD22, no case showed any reactivity with antibodies against mb-1 or B29. This contrasted markedly with the cases of lymphocyte predominance where all seven cases expressed one or more of the B-cell antigens, with six cases being positive for mb-1. These results confirm previous studies that have suggested lymphocyte-predominance Hodgkin's disease is of B-cell origin and different from the other subtypes. However, they do not provide support for the thesis that these other subtypes may also have a B-cell origin, albeit with a different phenotype to lymphocyte predominance.

Antigens, CD↗