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Biomedical subjects

D M Salter

Publications and source records attributed to D M Salter.

At least 19 recordsLinked to original sources

Tenascin immunoreactivity in cryptogenic fibrosing alveolitis.

Tenascin is a hexameric extracellular matrix (ECM) glycoprotein which has been demonstrated to have a temporal relationship with active scar formation in adult tissues. We hypothesized that this ECM protein might therefore serve to identify areas of active scarring in lung biopsies from patients with cryptogenic fibrosing alveolitis (CFA). The distribution of tenascin was examined in open lung biopsies from ten patients with CFA, six patients with sarcoidosis, and six pulmonary resection specimens from patients with no evidence of interstitial lung disease, using an immunohistochemical technique. Immunoreactive tenascin was not identified in histologically normal control lung parenchyma and was only focally found around large aggregates of granulomas in sarcoidosis. In the CFA, tenascin production was demonstrated in minimally damaged alveolar walls and areas of active disease but not in end-stage scarred lung. There was considerable local heterogeneity of staining within cases, which did not appear to relate to the density of the local inflammatory infiltrate. Large plaques of tenascin were noted to be particularly associated with hyperplastic type II alveolar epithelial lining cells, which are recognized to produce fibrogenic cytokines. The examination of tenascin expression in open lung biopsies from patients with CFA may be useful in assessing fibrogenic activity and may thus provide additional prognostic information.

Biomarkers

Angioleiomyomas of the hand. A report of 14 cases.

We have reviewed a series of 14 angioleiomyomas of the hand. Unlike angioleiomyomas elsewhere, those occurring on the hand are less commonly painful, have an equal sex distribution and are not predominantly of the solid type as seen in the lower limb. We were unable to find a strong association between histological appearance and clinical presentation. We were able to demonstrate nerve fibres within angioleiomyomas, which have not been reported previously.

Adolescent

CD44 expression in human bone: a novel marker of osteocytic differentiation.

CD44 is a transmembrane glycoprotein with cell-cell and cell-matrix adhesion functions that is expressed by a wide variety of cell types and has a number of known biologic functions. Because of its ability to bind matrix macromolecules, such as fibronectin, collagen, and hyaluronate, we investigated the possibility that it is expressed by the cells of bone, the matrix receptors of which are largely unknown. Immunohistochemical study of a variety of sources of human bone was carried out using a panel of six well-characterized anti-CD44 monoclonal antibodies. Osteocytes strongly expressed CD44, whereas osteoblasts and lining cells were negative. Osteoclasts and periosteal cells also expressed CD44, although not as strongly as osteocytes. These patterns of staining were observed with all six antibodies. These results demonstrate that acquisition of CD44 immunoreactivity is a sensitive marker of osteocytic differentiation and raise the possibility that CD44 acts as a cell matrix receptor in bone.

Bone Diseases

Tenascin is increased in cartilage and synovium from arthritic knees.

Tenascin is a major extracellular glycoprotein known to have important functions in processes such as wound repair and embryogenesis including bone and cartilage formation. The expression of this molecule in articular cartilage and synovium from normal and abnormal (OA and inflammatory joint disease including RA) human knee joints was studied by an immunohistological technique using paraffin embedded tissue and a specific anti-human tenascin monoclonal antibody (BC4). The results show that in normal articular cartilage tenascin is expressed in small amounts in the surface zone and in synovium is present in significant levels in the walls of blood vessels only. In diseased joints expression is greatly increased both in articular cartilage and synovium. Increased production of tenascin is likely to be part of a reparative response in injured joints the understanding of which may suggest novel mechanisms to modify disease progression in degenerative and inflammatory joint disease.

Adolescent

Lymphocytes in pseudomembranes of late prosthetic joint failure.

The pseudomembrane formed in association with late aseptic prosthesis failure contains a mixed giant cell and histiocytic infiltrate with variable numbers of lymphocytes. Immunolabelling with a panel of antibodies on paraffin sections was undertaken to define the nature of the lymphoid infiltrate in 19 cases. In all cases, the predominant lymphoid cell was a memory (CD45RO+, CD45RA-) T-cell. B-cells were rare. Tissue from patients with rheumatoid arthritis (RA) contained greater numbers of T-cells when compared with patients with osteoarthritis (OA), suggesting that the intensity of the lymphoid infiltrates reflects the underlying joint disease rather than necessarily being part of a hypersensitivity response to wear debris.

Aged

Changing prevalence of osteomalacia in hip fractures in southeast Scotland over a 20-year period.

In a randomized study of 81 patients with fresh hip fractures who underwent bone biopsy at the time of surgery there was no histologically detectable osteomalacia. This represented a fall in prevalence since a similar study 20 years previously had shown a 12 per cent incidence in the same population. The implications for routine histological screening and measurement of serum bone biochemistry in patients with hip fractures is discussed. The majority of patients in the study group had histologically detectable osteoporosis suggesting that this was an important factor in the aetiology of femoral neck fractures.

Aged

Integrin expression by human articular chondrocytes.

Expression of integrins, a family of cell adhesion proteins, by human articular cartilage chondrocytes in vivo has been studied by immunohistological techniques using cryostat sections and a panel of anti-integrin monoclonal antibodies. Chondrocytes strongly expressed beta 1 and alpha 5 integrin subunits, known to form the classical fibronectin receptor, VLA-5, strongly. alpha 1 was expressed more weakly and variably; alpha 3 was expressed by occasional cells only. Chondrocytes did not express beta 2, beta 3 or other integrin alpha subunits tested.

Antigens, CD

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

Composition and organization of cell-substratum contacts in normal and neoplastic renal epithelium.

We have investigated the molecular basis of the organization of cell-substratum contact in normal and neoplastic renal epithelium. The several components of focal contacts and non-collagenous basement membrane glycoproteins have been identified by antibodies, detected by immunofluorescence and viewed by laser scanning microscopy. Tubular epithelial cells grown on glass coverslips expressed laminin at the cell periphery. Co-localized with laminin were receptors of the beta 1 integrin class, and the cytoplasmic plaque proteins vinculin and talin. When basement membrane glycoproteins laminin or fibronectin were exogenously supplied by growing cells on coated coverslips, the vinculin-, talin- and integrin-containing contacts became organized into linear arrays with intervening free cell membranes. Under these conditions the actin cytoskeleton became highly organized. By contrast some tumour cells showed a reduction in focal contact molecules and a failure to organize these structures in response to laminin or fibronectin. This loss of cell matrix interaction may be important during the progression of renal tumours.

Basement Membrane

An investigation into the role of human papillomavirus in endobronchial papillary squamous tumours.

Tissue specimens from 15 patients with endobronchial papillary squamous tumours were probed for the presence of human papillomavirus DNA using the technique of in situ hybridization with probes to human papillomavirus genotypes 4, 5, 6b, 8, 11, 16 and 18. Despite the histological similarity of these lesions to known human papillomavirus-associated tumours no evidence of hybridization was detected in any of the cases analysed. It is thus unlikely that human papillomavirus has a significant role in the genesis of these tumours.

Aged

A comparison of methods for nasal mast cell demonstration.

Nasal turbinates were studied from 14 rhinitis patients following surgical turbinectomy, and from five subjects at autopsy. Mast cell counts on turbinectomy specimens were compared following staining with toluidine blue or Alcian blue and safranin after fixation in either paraformaldehyde or neutral buffered formalin. Mast cell numbers were significantly greater in the superficial submucosa than in the epithelium or deep submucosa in both the rhinitis group and the autopsy subjects. The combination of PFA fixation and ABS staining gave maximum mast cell counts, revealed two morphological mast cell sub-types and gave optimal demonstration of nasal tissue. Nasal mast cells are thus not uniformly distributed, appear heterogeneous under light microscopy, are present in large numbers even in the elderly, and are best demonstrated using PFA fixation and ABS staining.

Adolescent

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

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

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

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

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