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D H Wright

Publications and source records attributed to D H Wright.

At least 19 recordsLinked to original sources

Cytogenetic and molecular studies of t(14;18) and t(14;19) in nodal and extranodal B-cell lymphoma.

We have examined 107 cases of B-cell lymphoma for the t(14;18) translocation, characteristically described in follicular lymphoma. B-Cell lymphomas of extranodal origin, and in particular malignancies derived from mucosa-associated lymphoid tissue (MALT), were compared with node-based lymphomas of follicular and diffuse morphology. Cytogenetic techniques were supplemented by molecular analysis using probes which recognize both the major and the minor breakpoint regions of the bcl-2 gene located on chromosome 18 (q21). t(14;18) was detected in 55 per cent of follicular and 27 per cent of diffuse B-cell lymphomas thought to be of follicle centre cell origin. Cytogenetics and molecular analysis proved equally effective in demonstrating the translocation. t(14;18) was not observed in the 36 extranodal lymphomas examined, of which 20 were characterized histologically as lymphomas of MALT, using either technique. In addition, 30 cases demonstrated only a germline band when probed with a bcl-3 probe specific for t(14;19), a translocation observed in chronic lymphocytic leukaemia (CLL). Cytogenetic abnormalities were detected in all cases of extranodal lymphoma, although no consistent abnormality was observed. Numerical abnormalities of chromosomes 3, 6, 16, and 18; structural abnormalities of chromosomes 2, 6, 8, and 9; and small marker chromosomes were frequently seen. This study provides data which suggest that different genetic events are involved in the development of lymphoma of MALT from those giving rise to follicle centre cell lymphomas.

Autoradiography

Epstein-Barr virus latent membrane protein expression by Hodgkin and Reed-Sternberg-like cells in acute infectious mononucleosis.

In the light of reports of latent membrane protein (LMP) expression by Hodgkin and Reed-Sternberg (HRS) cells, paraffin sections of tonsil (two cases), lymph nodes (eight cases; three cervical, one axillary, and four inguinal) and spleen (four cases) from 14 patients with acute infectious mononucleosis (IM) have been examined for the presence of HRS-like cells and immunostained with an antibody to LMP. Sections of the tonsils and one lymph node were also stained with a panel of antibodies which characterize HRS cells of Hodgkin's disease. The tonsils contained abundant HRS-like cells, mainly adjacent to the crypts, which were highlighted by strong LMP expression. The immunophenotype of these cells closely, but not completely, resembled that of HRS cells of Hodgkin's disease. The lymph nodes and spleens showed the typical changes of acute IM but only few LMP-positive HRS-like cells were present in the cervical lymph nodes and hardly any were present in the inguinal nodes and spleen. These findings suggest that tonsillar crypt squamous epithelium may play a role in the formation of LMP-positive HRS-like cells; these cells could be progenitors of Hodgkin's disease HRS cells and, if so, this might explain the restricted sites of presentation of Hodgkin's disease.

Acute Disease

Alpha-1 anti-trypsin and CD30 expression occur in parallel in activated T cells.

We have performed an immunohistochemical study of immunoblastic T cell lymphoma and enteropathy-associated T cell lymphoma for alpha-1 anti-trypsin and CD30. Cytoplasmic staining for alpha 1 anti-trypsin is present in the malignant cells in both types of T cell neoplasm which also express CD30, a marker of lymphoid activation. Peripheral blood T lymphocytes on stimulation with mitogen also show granular cytoplasmic expression of alpha 1 anti-trypsin. Time course studies show that this parallels the expression of CD30. Alpha 1 anti-trypsin expression appears therefore to be associated with activation in T cells. Further studies of sub-fractionated T lymphocytes in vitro suggest that the expression of alpha 1 anti-trypsin on activation is not restricted to an individual lymphocyte subset.

Antigens, CD

The morphological spectrum of monocytoid B-cell lymphoma and its relationship to lymphomas of mucosa-associated lymphoid tissue.

We report 10 cases of monocytoid B-cell lymphoma, five of which had extranodal lymphomas of mucosa-associated lymphoid tissue (MALT) type. In one patient the MALT lymphoma in the salivary gland was microscopic. In another, the small bowel lymphoma, which preceded the monocytoid B-cell lymphoma by 11 years, showed different clonal immunoglobulin gene rearrangements. Attention is drawn to the extreme degree of plasmacytic differentiation and epithelioid cell infiltration that may occur in monocytoid B-cell lymphoma. In addition to the cytological and immunophenotypic likeness of monocytoid B-cells and centrocyte-like cells, monocytoid B-cell and MALT lymphomas share a number of micro-anatomical and behavioural characteristics. These include the sharp separation of the monocytoid B-cells and plasma cells, follicular colonization and progression to high-grade lymphoma. It is suggested that the frequent association of monocytoid B-cell lymphoma with Sjögren's syndrome may be due to the fact that the salivary glands drain to cervical lymph nodes that are part of the systemic, rather than the mucosal, lymphocyte circulation pathway.

Aged

CD43 expression in B cell lymphoma.

AIMS: To determine the expression of CD43 in frozen sections in a range of B cell lymphomas. METHODS: The monoclonal antibody WR14, clustered provisionally in the Fourth Leucocyte Typing Workshop as a CD43 reagent, was investigated by epitope blocking studies on formalin fixed reactive lymph node tissue, using the established CD43 antibody MT1, to validate its use as a CD43 reagent. CD43 expression was studied in 131 immunophenotypically defined B cell lymphomas, including lymphocytic lymphoma (Lc, n = 13), centrocytic lymphoma (Cc, n = 14), and a range of follicle centre cell lymphomas (FCC) including centroblastic/centrocytic follicular (CbCcF, n = 48), centroblastic diffuse (CbD, n = 39), centroblastic/centrocytic diffuse (CbCcD, n = 4), centroblastic follicular and diffuse (Cb FD, n = 3) and centroblastic/centrocytic follicular and diffuse (CbCc FD, n = 1). Nine lymphomas of mucosa associated lymphoid tissue (MALT) were also examined. RESULTS: Epitope blocking studies showed that WR14 is a CD43 reagent that binds to an epitope identical with or close to that recognised by MT1. Eleven of 13 (84%) cases of Lc and 11 of 14 (78%) cases of Cc expressed CD43; 87 of 95 (91%) cases of FCC did not. All eight low grade lymphomas of MALT were negative. One high grade lymphoma, transformed from a low grade MALT lymphoma, was positive for CD43. The expression of CD43 by tumours of B cell lineage was associated with the expression of CD5 (p < 0.001) although either antigen could occasionally be found in the absence of the other. CONCLUSION: CD43 reagents can be used in conjunction with CD5 antibodies for the immunophenotypic discrimination of follicle centre cell lymphomas from non-follicle centre cell lymphomas.

Antibodies, Monoclonal

Alpha-1 antitrypsin gene exon use in stimulated lymphocytes.

AIMS: To investigate the expression of mRNA transcripts containing exon A or B in lymphocyte cultures. METHODS: An in situ hybridisation technique, using synthetic, biotinylated oligonucleotide probes was deployed to allow the demonstration of exon A, exon B, or the normal hepatocyte message containing exon C. RESULTS: Lymphocytes used the same alternative splicing technique as monocytes in the generation of their alpha-1 antitrypsin message. They also provided data on the frequency of exon A and B expression in cells from different subjects. Most circulating granulocytes failed to show the alpha-1 antitrypsin message, suggesting that this protein is synthesised in the marrow and represents a stored protein component in polymorph and circulating nuclear lymphocytes. CONCLUSIONS: In situ hybridisation is a sensitive technique for the detection of individual gene exon use in cell populations. Lymphocytes show the same promoter use as that described for monocytes.

Antisense Elements (Genetics)

Follicular colonization in thyroid lymphoma.

The presence of neoplastic (light chain restricted) B-cell follicles in low-grade B-cell gastrointestinal (GI) lymphoma of mucosa-associated lymphoid tissue (MALT) has been explained on the basis of specific colonization of reactive follicles by centrocyte-like (CCL) cells. Low-grade B-cell thyroid lymphomas have been included in the category of MALT lymphoma, but the frequent presence of a follicular pattern in these tumors has contributed to the view that they are follicle center cell (FCC) tumors. We have reviewed the histology and investigated the phenotype and genotype of nine cases of primary low-grade B-cell lymphoma of the thyroid, all of which were distinguished by a predominantly follicular pattern. All cases also demonstrated features of MALT lymphoma, including CCL cells and lymphoepithelial lesions. The appearances and immunohistology of the follicles were those of follicular colonization as described in GI MALT lymphoma rather than FCC follicular lymphoma. The predominant pattern of follicular colonization was replacement of the follicle center by slightly enlarged CCL cells that showed a strikingly high proliferation rate. No evidence of the t(14;18) translocation was found in any case, using the polymerase chain reaction (PCR) on DNA extracted from fresh (n = 1) or paraffin-embedded (n = 9) tissue. These findings argue against a FCC lineage for primary thyroid lymphomas and support their inclusion in the MALT category.

Base Sequence

Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial T lymphocytes?

Enteropathy-associated T-cell lymphoma commonly presents with malabsorption, and debate continues as to whether adult-onset coeliac disease (CD) is itself a form of low-grade lymphoma. A 59-year-old man with adult-onset CD required resection of a segment of oedematous jejunum. Histological examination of this tissue revealed an intense intraepithelial lymphocytosis. Immunophenotypic (CD3-, CD4-, CD8-, CD34-, and CD45 RO-) and cytogenetic (deletion of the Y chromosome and chromosome 9) abnormalities were found, together with monoclonal T-cell-receptor gene rearrangements. Some patients with adult-onset CD may have low-grade lymphoma from the outset of their illness.

Biopsy

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

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

The distribution of non-Burkitt, non-Hodgkin's lymphomas in Uganda in relation to malarial endemicity.

Biopsies of malignant lymphomas collected from all districts of Uganda, filed in the Kampala Cancer Registry for the 8-year period 1966-1973, were reviewed. This review confirmed a relatively low frequency of follicle-centre-cell lymphomas with a follicular growth pattern and the geographical co-distribution between malaria and Burkitt's lymphoma (BL). It also showed a similar, though less marked, association between non-Burkitt, non-Hodgkin's lymphoma (NBNHL) and malarial endemicity, and a correlation in the regional incidence between BL and NBNHL. In both comparisons, these associations were strong for high-grade lymphomas and weak for low-grade neoplasms. BL and other NHL may therefore share, to a varying degree, some common pathogenesis. The excess in frequency of NBNHL of high-grade malignancy in malarial endemic areas appears to be in contrast to Western countries where most non-Hodgkin's lymphomas are of low-grade malignancy.

Humans

Lymphocyte predominance Hodgkin's disease--an immunohistochemical study.

Lymph node biopsies from 57 local and referred cases, previously diagnosed at Southampton between 1978 and 1987 as lymphocyte predominance Hodgkin's disease were examined using the monoclonal antibodies MT1, UCHL1, L26, LN-1, E29/68 (EMA), Leu-M1 (CD15) and Ber-H2 (CD30). Of the 34 cases with a nodular architecture, 21 (19 male, two female) contained polylobated Reed-Sternberg cell variants with a B-cell phenotype, which lacked expression of CD15. In all cases, the polylobated cells showed positive staining with L26 and LN-1. Six cases expressed EMA and three showed positive staining with Ber-H2. Two cases lacking polylobated cells were reclassified as reactive follicular hyperplasia with progressive transformation of germinal centres. The remaining 11 cases had an atypical immunophenotype and were reclassified, mainly as mixed cellularity Hodgkin's disease. In six cases, the lymph node architecture showed a mixture of nodular and diffuse growth patterns. Five of these cases contained polylobated cells with the typical morphology and immunophenotype of those seen in nodular lymphocyte predominance Hodgkin's disease. The sixth case contained cells expressing CD15, and was reclassified as nodular sclerosing Hodgkin's disease. Of the fifteen biopsies with a diffuse architecture, four contained polylobated B-cells lacking expression of CD15. These were considered to be diffuse lymphocyte predominance Hodgkin's disease. The remaining 11 cases were reclassified as either Hodgkin's disease, mixed cellularity or as T-cell lymphomas.

Adult

Differential expression of MHC- and macrophage-associated antigens in human fetal and postnatal small intestine.

A panel of monoclonal antibodies against major histocompatibility complex (MHC)- and monocyte/macrophage-associated antigens was used to compare human fetal and postnatal small intestinal macrophage subpopulations. Cryostat sections were stained using an indirect immunoperoxidase technique. Within the human fetal intestine from 12 weeks gestation, the antibody KiM8 identified a widespread population of type I accessory cells, which showed variable expression of HLA-DR. In contrast, the antibody 3.9 identified small clusters of HLA-DR- and HLA-DQ-positive lamina propria macrophages, presumably type II accessory cells. Comparison of fetal with postnatal small intestine revealed mainly quantitative changes, with an absolute increase in 3.9-, KiM8-, KiM6-, 10.1- and UCHMI-positive accessory cells in the postnatal intestine. The proportions of both UCHM1- and KiM6-positive cells relative to the KiM8-positive population was also increased postnatally. The villous population of 3.9- and KiM6-positive interdigitating type II macrophages characteristic of the postnatal lamina propria was largely absent from fetal small intestine. The monoclonal antibody 3.9 further reacted with the cytoplasm of ganglion cells and nerve fibres within the nerve plexuses of fetal and postnatal small intestine. The significance of this cross-reactivity remains unclear.

Antigens, Differentiation