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Biomedical subjects

J Ball

Publications and source records attributed to J Ball.

At least 73 records · Page 4Linked to original sources

Expression of adhesion molecules LFA-3 and N-CAM on normal and malignant human plasma cells.

Normal and malignant plasma cells were investigated for the expression of seven cellular adhesion molecules by immunofluorescence microscopy. The antigens investigated were CD2 and its ligand, LFA-3 (CD58). LFA-1 alpha (CD11a) and LFA-1 beta (CD18) and their ligand ICAM-1 (CD54), H-CAM (lymphocyte homing receptor; CD44) and N-CAM (CD56). Marrow from 18 patients with myeloma, two with plasma cell leukaemia (PCL), four with monoclonal gammopathy of uncertain significance (MGUS) and 10 normal allogeneic bone marrow donors was studied. All plasma cells from normals and multiple myeloma patients were negative for CD2, CD11a and CD18. All normal and myeloma marrow plasma cells were positive for ICAM-1. 16/18 myeloma cases tested, and all other samples (normal, MGUS and PCL), contained plasma cells positive for H-CAM. Only one normal, but 12/16 myelomas tested were positive for N-CAM (P less than 0.02). One of four MGUS cases was moderately positive and one other weakly positive for N-CAM. Both PCLs were N-CAM negative. 12/18 myelomas were positive for LFA-3, but only two normals (P less than 0.05). All MGUS cases were negative for LFA-3, as was one PCL, the other being weakly positive. Three cases were negative for both adhesion molecules, three cases expressed only N-CAM or LFA-3 and 10 cases expressed both. LFA-3 and N-CAM are expressed significantly in myeloma rather than normal plasma cells. Cases of MGUS may express N-CAM but not, in this small series, LFA-3. Plasma cells in the peripheral blood (PCL) and plasma cell lines express little or no LFA-3 or N-CAM.

Antigens, CD↗

A viral long terminal repeat expressed in CD4+CD8+ precursors is downregulated in mature peripheral CD4-CD8+ or CD4+CD8- T cells.

The long terminal repeat from a thymotropic mouse mammary tumor virus variant, DMBA-LV, was used to drive the expression of two reporter genes, murine c-myc and human CD4, in transgenic mice. Expression was observed specifically in thymic immature cells. Expression of c-myc in these cells induced oligoclonal CD4+ CD8+ T-cell thymomas. Expression of human CD4 was restricted to thymic progenitor CD4- CD8- and CD4+ CD8+ T cells and was shut off in mature CD4+ CD8- and CD4- CD8+ T cells, known to be derived from the progenitor double-positive T cells. These results suggest the existence of similar and common factors in CD4+ CD8- and CD4- CD8+ T cells and support a model of differentiation of CD4+ CD8+ T cells through common signal(s) involved in turning off the expression of the CD4 or CD8 gene.

Animals↗

The role of adhesion molecules in multiple myeloma.

Human myeloma plasma cells had been considered to express few surface antigens until recently. The past two International Workshops on Leucocyte Differentiation Antigens have shown that myeloma cells can express a range of surface molecules, and it has become clear that many of these have adhesive functions. The identification of ICAM-1 (CD54) and H-CAM (CD44) on human plasma cells was the initial observation, and other antigens such as N-CAM (CD56) and LFA-3 (CD58) have been confirmed as features of malignant plasma cells in particular. The degree of expression of LFA-1 (CD11a) remains to be characterised fully. It seems probable that the loss of some adhesion structures may be associated with increased malignancy and plasma cell leukaemia. At the present time there are few studies relating to the function of these molecules, although homotypic adhesion appears to occur, and it is likely that such studies will shed light on the pathogenesis of myeloma.

Antigens, CD↗

Characterisation of a series of human immunodeficiency virus isolates derived sequentially from a single patient.

Five HIV-1 isolates were obtained sequentially from a single seropositive individual during the later stages of AIDS. Four of these isolates were adapted to grow in a continuous human T-lymphocytic cell line. Comparative biological and biochemical studies of the virus isolates were made using persistently infected cultures or virus derived from these systems respectively. The data obtained clearly shows that viruses with different biological properties can be isolated from the same individual at different times during the course of clinical AIDS.

Acquired Immunodeficiency Syndrome↗

Surface antigen expression of human neoplastic plasma cells includes molecules associated with lymphocyte recirculation and adhesion.

The surface phenotype of neoplastic plasma cells from peripheral blood of plasma cell leukaemia patients and bone marrow of patients with myelomatosis was investigated with two monoclonal antibody panels including 50 selected from the B cell panel of the IVth International Workshop on Leucocyte Differentiation Antigens. The majority of myelomas expressed CD24 (HB8 epitope only), CD38, CD44, CD54, and the antigen recognized by the monoclonal antibody 8A. A range of other antigens may also be expressed including CD10, CD32 (FcR II), CD19, CD20 and MHC Class II. Antigens expressed by myeloma plasma cells can be considered in three groups: (a) antigens associated with lymphocyte and plasma cell differentiation: (b) antigens which are not lineage specific: and (c) molecules concerned with lymphocyte recirculation and intercellular adhesion (CD44 and CD54). The significance of CD44 and CD54 expression by plasma cells and the potential interaction of plasma cells with T lymphocytes and monocytes is discussed.

Antigens, Differentiation, B-Lymphocyte↗

A case of progressive encephalomyelitis with rigidity and positive antiglutamic acid decarboxylase antibodies [corrected].

A 50 year old woman developed progressive encephalomyelitis with rigidity over a three year period. Her CSF contained oligoclonal bands and both her serum and CSF contained antibodies directed against GABA-ergic synapses (antiglutamic acid decarboxylase [corrected] antibodies). These antibodies have recently been described in cases of stiff man syndrome. Both disorders may be part of a clinical spectrum that has an underlying autoimmune basis.

Autoantibodies↗

Normal and neoplastic human plasma cells express bcl-2 antigen.

The bcl-2 (B-cell leukaemia/lymphoma 2) proto-oncogene is associated with the 14;18 translocation in follicular lymphoma juxtaposing bcl-2 with the immunoglobulin heavy chain region. bcl-2 has been cloned and sequenced and a monoclonal antibody to amino acids 41 to 54 of the bcl-2 protein has been raised. The expression of bcl-2 in follicular lymphoma has been demonstrated by immunohistological staining and also in normal lymphocytes. The presence of the bcl-2 onco-protein has been demonstrated by immunofluorescence using conventional and confocal microscopy in normal and malignant plasma cells from myeloma patients and myeloma cell lines. Plasma cells from 8/8 normal donors were positive, although the proportion of positive cells and the intensity of staining varied. Eight of 10 patients with myeloma or plasma cell leukaemia had positive plasma cells, and 6/11 plasma cell lines and one lymphoma cell line also expressed the onco-protein. bcl-2 expression is a feature of normal plasma cells and data from the cell lines confirm that expression is not dependent on the presence of the 14;18 translocation.

Chromosomes, Human, Pair 14↗

Sign for the times.

Explore the source record for details and available documents.

Management Information Systems↗

Characterization of new IgG lambda myeloma plasma cell line (EJM): a further tool in the investigation of the biology of multiple myeloma.

A new IgG lambda myeloma plasma cell line known as EJM was established from a peritoneal effusion from a patient with extramedullary myeloma. The EJM cells have a plasmablastic morphology with abundant rough endoplasmic reticulum and grow in liquid culture with a doubling time of 72 h and a labelling index of 36%. In addition to cytoplasmic IgG lambda, the cells are positive for CD9, 20, 32, 38, 44, 54, 71, 78, MHC Class II DR, DP and DQ. Studies on the control of the cell line proliferation by cytokines have demonstrated stimulation with interleukin 6. In contrast interferon alpha produces marked inhibition of proliferation in doses of greater than 100 units/ml. The culture conditions and the importance of accessory cells and cytokines in supporting myeloma plasma cell growth in vitro are discussed.

Ascitic Fluid↗

Rapid assessment of haemophilia A carrier state by non-invasive techniques using the polymerase chain reaction.

The polymerase chain reaction (PCR) was used to amplify two polymorphic regions in the factor VIII gene. In vitro synthesis of DNA was achieved using samples obtained from buccal cells, urine, and hair follicles in addition to purified genomic and crude DNA samples prepared from whole blood. Female members of two kindreds affected with haemophilia A were assessed for carrier state using direct restriction fragment length polymorphism analysis of amplified gene products in the Bc1I and XbaI regions. It is concluded that this is a non-invasive, rapid, and inexpensive technique for carrier detection.

Carrier State↗

The expert system approach to predicting protein structure.

Prediction of protein structure is an open-ended problem. Since an approach from first principles cannot be taken in reasonable computer time, short-cuts using further data are necessary. Such data include information about the specific protein in question, and information in databases which are about proteins in general. Is it possible to write a general, flexible 'superalgorithm' which would suit most circumstances? If so, it would seem likely to overcome one of the most understated but nonetheless greatest difficulties associated with molecular modelling and computer-aided drug design--reproducibility. To this end, a 'polymorphic programming environment' has been developed which represents both an expert system and a high-level language for theoretical chemists and molecular biologists. This language is GLOBAL (Ball et al., 1990). In a series of earlier studies, and more recently by means of GLOBAL itself, the nature of reproducibility and its rather surprising limits have been explored, and in general the current status and future potential of protein modelling have been examined.

Expert Systems↗

DN 9693: a phosphodiesterase inhibitor with a platelet membrane effect.

We have examined the in vitro effects of DN 9693 (piperidinylimidazo-quinazolinone) on various aspects of platelet reactivity. Our results are consistent with its known function as a phosphodiesterase inhibitor in that it increased platelet cyclic AMP, particularly in conjunction with an adenylate cyclase stimulator, and exerted a profound inhibitory effect on platelet aggregation responses to a variety of agonists. DN 9693 also inhibited ristocetin-induced platelet agglutination (RIPA). We therefore examined its effect on ristocetin co-factor assays and on the binding of a monoclonal antibody (McAb) to platelet membrane glycoprotein Ib (GPIb). The drug inhibited the binding of the monoclonal antibody in a dose-dependent manner. This suggests an effect of the drug on the platelet surface membrane with reduced expression of GPIb. Our results indicate that in addition to its anticipated inhibitory effect on platelet aggregation, DN 9693 may also inhibit platelet adhesion.

3',5'-Cyclic-AMP Phosphodiesterases↗

Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease.

Schizophrenia is associated with structural changes (eg, a mild degree of ventricular enlargement) in the brain, although whether these precede onset of illness or progress with episodes is not established. In a postmortem study, we find that ventricular enlargement affects the posterior and particularly the temporal horn of the lateral cerebral ventricle. By comparison with controls and with patients suffering from Alzheimer-type dementia (in which there is also temporal horn enlargement), the change is highly significantly selective to the left hemisphere. This deviation was not accompanied by an increase in glial cell number (examined chemically by assay of diazepam-binding inhibitor immunoreactivity and microscopically by density of staining with the Holzer technique). The findings are consistent with the view that schizophrenia is a disorder of the genetic mechanisms that control the development of cerebral asymmetry.

Alzheimer Disease↗