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D H Wright

Publications and source records attributed to D H Wright.

At least 109 records · Page 6Linked to original sources

Phenotypic and genotypic heterogeneity of peripheral T-cell lymphoma.

A series of 21 phenotypically characterised T-cell lymphomas histologically defined as lymphocytic, lymphoblastic, immunoblastic, AILD type, pleomorphic, T-zone and Lennert's T-cell lymphoma, were investigated for T-cell receptor (TcR) and immunoglobulin (Ig) gene rearrangements. Phenotypic analyses of frozen sections and cell suspensions were heterogeneous and in many cases no single T-cell marker recognised all of the malignant cells. Data derived by staining with antibodies reactive with antigens in paraffin embedded tissue were consistent with T NHL in all cases except lymphoblastic lymphoma. TcR gene rearrangements were observed in lymphocytic, lymphoblastic and immunoblastic lymphoma, however, in the remaining 14 phenotypically and histologically defined peripheral T-cell lymphomas, 2 showed rearrangement of TcR gamma and beta genes consistent with T NHL and 2 showed Ig JH rearrangements only, suggestive of either reactive T-cell populations masking cryptic disease or presence of tumour populations with aberrant gene rearrangement and expression of T lineage antigens. No Ig or TcR gene rearrangements were found in the remaining 10 cases, in which morphologically identifiable tumour cells comprised 10-90% of the cell population. In 3/6 cases tested some CD3 positive cells failed to stain with WT31 or beta F1, monoclonal antibodies that recognise determinants on combined TcR gamma beta or TcR beta chains respectively. Whether these cases represent tumours arising from an undetermined cell of origin or polyclonal expansions of T-cells remains to be determined. Our results confirm the phenotypic heterogeneity of histologically defined peripheral T-cell lymphoma and indicate that in these particular histological subtypes gene rearrangement analysis can also yield heterogeneous results which may be unhelpful in determining cell lineage and clonality.

DNA Probes↗

The immunoglobulin E- and calcium-dependent release of histamine and eicosanoids from human dispersed mastocytosis spleen cells.

The clinical features of systemic mastocytosis have been ascribed to mast cell-dependent mediators, but there have been no studies of their release from isolated cells. We have investigated the release of histamine and eicosanoids from isolated spleen cells obtained from tissue of a mastocytosis patient undergoing therapeutic splenectomy. Dispersed cell preparations contained lymphocytes 65.9%, monocytes/macrophages 22.3%, neutrophils 9.9%, mast cells 1.1%, and eosinophils 0.8%; upon challenge with 0.1-3.0 microM A23187 they released histamine much greater than PGD2 greater than TXB2 greater than LTB4 greater than LTC4 approximately equal to LTD4 greater than LTE4. With immunological activation of passively sensitized cells, histamine and PGD2 release had similar dose-response characteristics, but TXB2, LTC4, LTD4, and LTE4 release differed in reaching maximum at 50 micrograms/ml and declining at 125 micrograms/ml anti-human IgE. Percoll centrifugation separated most of the histamine-containing cells to the middle of the gradient, but they were refractory to release with 0.3 microM A23187 or 50 micrograms/ml anti-IgE. Spontaneous release of histamine from these cells was not abnormally high (1.3%-4.5%). Electron microscopy of tissue sections revealed large numbers of mast cells with empty granules. It is possible that the refractory cells observed are such mast cells where intracellular histamine is no longer granule-associated. Most net histamine and PGD2 release was confined to cells at the bottom of the gradients (1.078-1.09 g/ml), although some release of PGD2 occurred near the top (1.05-1.058 g/ml). There was a significant correlation between the net release of histamine and PGD2 with both immunological (r = 0.92; n = 16) and A23187 (r = 0.97, n = 14) activation. These studies provide evidence for a link between PGD2 and histamine release in mastocytosis spleen cells.

Adult↗

Immunohistochemical study of 22 cases of thymoma.

The histological and clinical features of 22 thymomas were reviewed. Immunohistochemical studies were performed using antibodies to cytokeratins (CAM 5.2 and S29) and to desmosomal protein. The heterogeneity of staining patterns seen in the epithelial cells supported the concept of separating thymomas into cortical, medullary, or mixed groups. Interdigitating cells were identified by antibody to S100 protein, and these varied in number between different tumours. Clustering of interdigitating reticulum cells occurred in association with foci of mature lymphocytes which were shown by staining of the leucocyte common antigen (CD45). The extent to which this occurred was used to assess the degree of medullary differentiation within the thymomas and this was correlated with the histological and clinical features. The lymphocyte population of six of the thymomas was studied using a range of antibodies to T and B cells; this showed the presence of B lymphocytes in thymomas.

Adult↗

Clinical features and management of malignant histiocytosis of the intestine.

This article documents the clinical course of nine patients diagnosed as having malignant histiocytosis of the intestine (MHI). Five patients had a history of gluten-sensitive enteropathy. This tumor commonly affects the small bowel in a widespread, patchy fashion causing ulceration, stricture formation, and perforation. Metastases to mesenteric nodes, liver, and the bone marrow were common. Although the diagnosis of MHI was often made at laparotomy, surgical resection, even when extensive, was not curative in any case. All nine patients were treated with a variety of chemotherapeutic regimes. This tumor proved chemosensitive, although response was usually brief and difficult to accurately evaluate. Chemotherapy was poorly tolerated because these patients were malnourished. In two cases small bowel perforation occurred, and in one gastrointestinal bleeding occurred after chemotherapy. Eight patients have died of disease from 0 to 16 months after the diagnosis was made, and a single patient is apparently cured 5+ years after completing chemotherapy. Malignant histiocytosis of the intestine has a characteristic clinical course. It is hoped that increased clinical awareness and early diagnosis will improve the outcome.

Adult↗

Monoclonal antibody to desmosomal glycoprotein 1--a new epithelial marker for diagnostic pathology.

Desmosomes are intercellular adhesive junctions that occur in almost all epithelia and should therefore be useful as epithelial markers in tumour diagnosis. Here, we describe a monoclonal antibody, 32-2B, to a major desmosomal glycoprotein (dgl) which reacts with human tissues in paraffin sections. This antibody was tested for its ability to stain epithelia and tumours. It reacted with all epithelia tested and with every specimen of a wide range of carcinomas. It also stained meningiomas, another desmosome-containing tumour. It did not stain other types of tumours including lymphomas, melanomas, and various sarcomas, or normal tissues which lack desmosomes. These characteristics demonstrate that 32-2B is a reliable epithelial marker that may have a useful role in diagnostic histopathology.

Animals↗

A comparison of three methods for the determination of the growth fraction in non-Hodgkin's lymphoma.

The proliferation rate of non-Hodgkin's lymphomas (NHL) was estimated by using 3 different methods. In cell suspension we determined the proportion of cells in cycle with the monoclonal antibody (Mab) Ki-67 and also in S-phase after the incorporation of bromo-deoxyuridine (BrdU) utilizing Mab anti-BrdU. In low grade lymphomas 3.5 +/- 1.6% of the cells were in cycle and 1.2 +/- 0.9% in S-phase, the corresponding values for high grade lymphomas were 22.5 +/- 18.7% and 8.9 +/- 7.8% respectively. Frozen sections of NHL were reacted with an antibody to the transferrin receptor (TR) and Ki67 as markers for proliferative activity. A high number of TR positive cells was found in low grade lymphomas of all histological types, whereas Ki67 positivity correlated closely with grading. With a few exceptions, low grade lymphomas contained less than 25% Ki67 positive cells within the tumour cell population. This observation is relevant to treatment strategies for low grade NHL.

Adult↗

Identification of tissue histiocytes on paraffin sections by a new monoclonal antibody.

A mouse monoclonal antibody (MAC 387) with specificity for monocytes and tissue histiocytes was produced by immunization of a BALB/c mouse with peripheral blood monocyte components derived by affinity chromatography of detergent-solubilized monocyte material on Sepharose 4B coupled to rabbit anti-monocyte antibodies. MAC 387 strongly stained the cytoplasm of cells of the monocyte/macrophage series on paraffin sections after controlled trypsinization of sections. The antibody showed broad reactivity for a variety of tissue histiocytes, including infiltrating and reactive histiocytes, alveolar macrophages, Kupffer cells, follicle-center macrophages, splenic red pulp macrophages, tumor-infiltrating macrophages, sinus histiocytes, epithelioid giant cells (variably), and cases of histiocytosis X and dermatopathic lymphadenopathy. Molecular weight data obtained by Western blotting, immunoprecipitation, and immunoaffinity-purification revealed that the antigen was present in different forms in the monocyte and granulocyte. In the granulocyte, free alpha (Mr 12 KD) and beta (Mr 14 KD) chains expressing the MAC 387 epitope were found together with associations of one alpha and one beta chain linked by disulfide bonds to yield a heterodimer of Mr 26 KD. In the monocyte, free alpha and beta chains are not found, but instead the heterodimer and associations of two (Mr 56 KD) and four (Mr 112 KD) heterodimers are disulfide-linked together. This new monoclonal reagent should have particular value for identification of tissue histiocytes in routine paraffin sections and particularly for demonstration of histiocytes in malignant lymphomas.

Animals↗

Evaluation of PAS-diastase and carcinoembryonic antigen staining in the differential diagnosis of malignant mesothelioma and papillary serous carcinoma of the ovary.

A series of malignant mesotheliomas and papillary serous carcinomas of the ovary were stained using the periodic acid Schiff reaction with diastase digestion (PAS-D) and an immunoperoxidase technique for carcinoembryonic antigen (CEA). The methods were evaluated in terms of repeatability and validity. Staining reactions were classed as positive or negative by three 'blinded' observers. Within-observer repeatability was greater for PAS-D than for CEA but there was no statistically significant difference for between-observer repeatability. The validity of the methods clearly differed, however, since the sensitivity and specificity of CEA were consistently less than that of PAS-D. Our most consistent estimates of sensitivity and specificity were compared with those of other studies and the reasons for this difference were analysed. Positive PAS-D and CEA staining were uncorrelated but a combination of the two did not appear significantly superior to PAS-D alone. We believe that PAS-D remains the method of choice for differentiating peritoneal mesotheliomas and disseminated papillary serous carcinoma of the ovary in the absence of reliable evidence of an ovarian primary because the significance of CEA positivity in occasional mesothelial tumours remains to be determined.

Amylases↗

The distribution of iron and iron binding proteins in spleen with reference to Hodgkin's disease.

The distribution of iron and iron binding proteins (IBP) have been compared with control spleen tissue in an attempt to establish a pattern of staining restricted to Hodgkin's disease (HD). All but one of the HD spleens examined stained for ferritin, which was largely present in red pulp dendritic macrophages (DM). In spleens histologically involved with HD heavy deposits of ferritin were seen around tumour nodules. Staining for ferritin increased with involvement of the spleen in HD but DM still represented the bulk of positive cells. However, ferritin positive DM were frequently seen in control spleens, and often in large numbers. Staining of ferric iron by Perls technique was less prominent than ferritin but this observation was also true of the non-HD spleens studied. Patterns of staining with transferrin were equivalent in both groups of spleens with DM being the most frequently positive cell type. Polymorphous macrophages showing erythrophagocytosis were present in the red pulp sinuses of all groups of spleens and although these cells have been considered as precursors of the Reed-Sternberg cell their presence seemed related to total splenic ferritin regardless of the disease process. These cells marked as macrophages and their presence was not restricted to HD. The results show that there is no particular appearance of iron or IBP distribution which is restricted to HD spleens. However, staining for ferritin and iron increased in HD spleens with tumour involvement and could contribute to circulatory abnormalities in this disease.

Ferritins↗

T-cell lymphomas.

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Antigens, Neoplasm↗

Competition and efficiency in closed freshwater algal systems: tests of ecosystem design principles.

Seven species of freshwater algae were grown in defined media in monoalgal and mixed cultures, to test whether species interactions and community efficiency were predictable on the basis of ecological theory. Results supported the prediction of competitive interactions, although no differences were detectable in the strength of competition in two and three species mixed cultures, nor was the severity of competitive effects predictable on the basis of relatedness at the level of phyla. On a community level, cultures with two and three species fixed a greater proportion of available carbon than cultures with only one species, implying a more efficient overall use of available resources. Implications for the design of artificial closed ecosystems are discussed.

Ecology↗

Primary malignant lymphoma of the thyroid--a tumour of mucosa-associated lymphoid tissue: review of seventy-six cases.

Seventy-six cases of primary thyroid lymphoma have been reviewed employing the Kiel classification. These lymphomas are almost entirely of follicle centre cell origin, occur predominantly in elderly females, and are frequently associated with lymphocytic thyroiditis or Hashimoto's disease. The overall prognosis is variable, with long-term survival in a substantial number of cases following thyroidectomy and radiotherapy. Results of histological examination including immunoperoxidase studies are described. It is proposed that thyroid lymphoma represents a neoplasm of mucosa-associated lymphoid tissue (MALT), and the implications of this are discussed.

Adult↗

The use of an image processing system in radiotherapy simulation.

Image quality produced in radiotherapy simulation is often so poor in certain anatomical sites (e.g. the pelvis) that it can adversely affect clinical judgement with regard to treatment set-up. In treatment planning both the field arrangement and the availability of accurate anatomical information are important, and should ideally be provided at the time of simulation by methods based on the principle of computerised tomography. In this work an image processing system has been used as a link between the video output from the simulator and the treatment planning computer in order to implement a CT facility on the simulator, as well as allowing real-time image enhancement to be investigated as a method of improving picture quality. This approach also enables a new method of simulation to be considered which reduces patient dose and prolongs the useful working life of the X-ray tube.

Humans↗