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Biomedical subjects

D H Wright

Publications and source records attributed to D H Wright.

At least 91 records · Page 5Linked to original sources

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↗

Pathology of Hodgkin's disease: anything new?

This presentation deals with the gross and microscopic pathology of HD. Recent advances in immunohistochemistry, gene rearrangement studies and cell culture are not discussed, except where they shed light on the pathology. Clinical and pathological experience, over the past 2 decades, suggests that HD should be divided into six subtypes, as originally proposed by Lukes et al. (1966b), rather than the four subtypes included in the Rye classification. Nodular lymphocyte/histiocyte predominant HD forms a clinicopathological entity separate from the other subtypes. It most frequently presents at a single nodal site and, even without therapy, progresses only slowly over a period of many years. A proportion of the patients (in the region of 10%) develop large cell NHL and a smaller number develop other types of Hodgkin's disease. This progression is not due to therapy since it most frequently occurs in untreated patients. Characteristic polylobated RS cell variants are seen in NLPHD. These differ from classic RS cells in that they have a B-cell phenotype, they do not show light chain restriction and, therefore, they do not appear to be a clonal proliferation. Although current dogma states that classic RS cells must be identified before a diagnosis of HD, including NLPHD, is made, it is the author's contention, supported by immunohistochemistry, that this type of RS cell does not occur in NLPHD. Polylobated RS cell variants in the appropriate cellular setting are, in themselves, diagnostic of NLPHD. They also serve to differentiate NLPHD from progressive transformation of germinal centres, an unusual proliferative expansion that may occur in association with HD but which, in itself, appears to be an entirely benign, reactive process. Diffuse lymphocyte/histiocyte predominant HD (DLPHD) differs from NLPHD in its diffuse growth pattern and the frequent presence of larger numbers of histiocytes. Polylobated RS cells are characteristic of both diseases. In some biopsies nodular and diffuse areas are seen in the same lymph node. Despite these similarities, the two diseases differ clinically (NLPHD is usually stage 1, DLPHD is frequently of a higher stage) and in their immunohistochemistry (fewer RS cell variants in DLPHD contain J-chain than in NLPHD). The reasons for these differences are not apparent and require further investigation. It may be due, at least in part, to the inclusion of cases of MCHD and NHL in the DLPHD category. Nodular sclerosis is the commonest category of HD in most reported series.(ABSTRACT TRUNCATED AT 400 WORDS)

Hodgkin Disease↗

Involvement of the ileocaecal region by non-Hodgkin's lymphoma in adults: clinical features and results of treatment.

Between January 1977 and January 1988, 19 patients with non-Hodgkin's lymphoma (NHL) involving the ileocaecal region were cared for by the CRC Wessex Medical Oncology Unit. Fifteen of these patients had primary ileocaecal NHL (stages IE or IIE) and four had secondary involvement of this region (stage IV). The commonest clinical presentation was with abdominal pain and a palpable mass in the right iliac fossa. Bulky (greater than 10 cm) disease was a particularly common feature, and complete surgical removal was possible in only seven patients. All patients had intermediate (18) or high grade (one) NHL using the Working Formulation. The commonest histological subtype was diffuse large cell. Seventeen patients received postoperative therapy, comprising local radiotherapy in one and combination chemotherapy in the remaining 16. Eleven of the 19 patients remain disease-free 6-60 months from diagnosis. Because of the high incidence of bulky disease at this site, postoperative therapy may be indicated, even for patients with apparently completely excised stage I disease.

Adult↗

The Reed-Sternberg cell/lymphocyte rosette. I. Properties of rosettes formed between Hodgkin's cell lines and allogeneic lymphocytes.

The properties of rosettes formed between the Hodgkin's cell lines, L428 and L591, and allogeneic peripheral blood mononuclear cell populations have been investigated. Immunocytochemical analysis showed that the majority of adherent cells were T-cells of both the CD4 and CD8 subsets. Only relatively few B-cells and monocytes were seen to adhere. However, when peripheral blood mononuclear cell populations were fractionated, it was found that monocytes were as good as T-cells at forming rosettes with both L428 and L591, though B-cells were shown to be poor at forming such associations. Treatment of both L428 and L591 with neuraminidase resulted in a significant reduction (P less than 0.01) in the mean number of adherent lymphocytes and in the numbers of Hodgkin's tumour cells which formed rosettes. Smaller, less significant effects were observed for Cytochalasin B and trypsin. EDTA (10(-2) M) at pH 7.2 had no significant effect on rosetting for L428 or L591. Adherence of allogeneic lymphocytes to L428 or L591 was pH dependent but did not appear to correlate with cell surface charge. Treatment of L428 cells with Fab fragments prepared from the IgG fraction of a hyperimmune rabbit anti-L428 antiserum, significantly (P less than 0.05) inhibited the adherence of allogeneic lymphocytes, but only when used at high concentration. The binding requirements of the Hodgkin's cell lines with allogeneic peripheral blood lymphocytes, as described in this study, appear to be quite different from those described for freshly isolated Hodgkin's tumour cells with autologous intratumoral lymphocytes. This suggests that the two phenomena may be unrelated. There would appear to be an absolute requirement for cell surface sialic acid for allogeneic lymphocyte attachment to the HD cell lines. This might suggest that the receptor-ligand system involved contains sialic acid as an integral part of the cell surface receptor structure involved in recognition of the appropriate ligand.

Cell Adhesion↗

Leucocyte common antigen expression on T cells in normal and inflamed human gut.

The expression of the 220,000 MW (p220) glycoprotein component of the leucocyte common antigen (LCA) family by intestinal mucosal lymphocytes was studied using the CD45R monoclonal antibody WR16. In normal intestine, a proportion of CD3+ mucosal T cells were WR16+ and this population resided predominantly in the mid-villus and crypt region of lamina propria. In the inflammatory infiltrates of both coeliac disease and Crohn's disease the CD3+, WR16+ population was markedly reduced. The monoclonal antibody UCHL1 identifies the 180,000 MW member of the LCA family and is expressed on T cells and in macrophages. CD3+ lymphocytes expressing this marker were widespread in normal lamina propria and epithelium. In contrast with WR16, UCHL1+ cells remained at a high level in coeliac disease and Crohn's disease. Our results support the view that loss of the p220 molecule occurs upon T-cell activation in inflammation.

Antigens, Differentiation↗