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Biomedical subjects

L J Murray

Publications and source records attributed to L J Murray.

At least 55 records · Page 3Linked to original sources
PubMed1995

Helicobacter pylori infection: relation with cardiovascular risk factors, ischaemic heart disease, and social class.

OBJECTIVE: To determine whether Helicobacter pylori infection is associated with the development of ischaemic heart disease and whether such infection can explain the social class inequality in ischaemic heart disease. DESIGN: Cardiovascular risk factor levels, prevalence of ischaemic heart disease (Rose questionnaire angina, and/or a history of myocardial infarction), and serum antibodies to H pylori (enzyme linked immunosorbent assay) were assessed in a cross sectional population based survey. SETTING: Belfast and surrounding districts, Northern Ireland. PARTICIPANTS: 1182 men and 1198 women aged 25-64 years randomly selected from the Central Services Agency's general practitioner lists. MAIN OUTCOME MEASURES: The relation of H pylori infection with cardiovascular risk factors and ischaemic heart disease. The association of social class with ischaemic heart disease. RESULTS: Systolic and diastolic blood pressure, plasma viscosity, and total cholesterol were not associated with H pylori infection. A weak negative association existed between H pylori infection and fibrinogen (mean (SE) difference in fibrinogen between infected and uninfected individuals -0.09 (0.04) g/l, P = 0.02) and between infection in women and high density lipoprotein (HDL) cholesterol (mean (SE) difference in HDL cholesterol between infected and uninfected individuals -0.06 (0.02) mmol/l, P = 0.006). A potentially important association was demonstrated between H pylori infection and ischaemic heart disease but this did not reach statistical significance (odds ratio (95% confidence interval (CI) 1.51 (0.93 to 2.45), P = 0.1). Social class was associated with ischaemic heart disease independently of cardiovascular risk factors and H pylori infection (odds ratio, manual v non-manual (95% CI) 1.82 (1.14 to 2.91), P = 0.01). CONCLUSION: H pylori may be independently associated with the development of ischaemic heart disease but if this is so the mechanism by which this effect is exerted is not through increased concentration of plasma fibrinogen. H pylori infection does not explain the social class inequality in ischaemic heart disease which exists independently of known cardiovascular risk factors.

Adult↗
PubMed1994

Generation of T cells from cytokine-mobilized peripheral blood and adult bone marrow CD34+ cells.

The present study compared the T-cell progenitor content of CD34+ lineage (Lin)- cells isolated from normal adult bone marrow (ABM) and mobilized peripheral blood (MPB). Both cell populations were found to differentiate into T cells when injected into human fetal thymi implanted into severe combined immunodeficient mice. Cytokine-MPB cells were less efficient than ABM cells in engrafting in the fetal human thymus, although both gave rise to thymocytes with identical phenotypes based on the analysis of CD1a, CD3, CD4, and CD8 expression. Thymocytes derived from adult CD34+ Lin- cells were capable of fully differentiating into mature CD3+ T cells expressing either the T-cell receptor (TCR) gamma delta or the TCR alpha beta (the later associated with CD4 or CD8), showing that the T-cell progenies of adult CD34+ cells were polyclonal and functional. Our data indicate that human MPB CD34+ cells are qualitatively identical to their BM counterparts, and demonstrate the existence of T-lymphoid progenitor cell activity in MPB.

Adult↗
PubMed1994

The Plasmodium falciparum protein RESA interacts with the erythrocyte cytoskeleton and modifies erythrocyte thermal stability.

The ring-infected erythrocyte surface antigen (RESA) associates with spectrin in the erythrocyte membrane (Foley, M., Tilley, L., Sawyer, W. H. and Anders, R. F. (1991) Mol. Biochem. Parasitol., 46, 137-148). A fragment of the RESA protein, which was expressed in Escherichia coli, was found to bind to inside-out vesicles of erythrocyte membranes in an apparently saturable manner. Upon extraction of inside-out vesicles with Triton X-100, the RESA fragment remained associated with the erythrocyte cytoskeleton. Using the technique of steady-state fluorescence polarisation, we have studied the thermal denaturation of fluorescein-labelled spectrin in the presence of recombinant RESA. We found that the RESA fragment partially protected spectrin against heat-induced conformational changes. Furthermore, erythrocytes infected with a RESA (-) laboratory strain (FCR3) were shown to be more susceptible to heat-induced fragmentation than erythrocytes infected with a RESA (+) strain of the parasite. RESA does not, however, appear to play an essential role in the invasion process per se as erythrocytes resealed to contain anti-RESA antibodies were efficiently invaded.

Animals↗
PubMed1993

Preclinical analysis of cytokine therapy in the SCID-hu mouse.

A severe combined immunodeficient (SCID)-hu mouse model implanted with human fetal bone was used to assess the effects of various recombinant human (rh) hematopoietic growth factors, administered either alone or in combination, on human hematopoiesis in vivo. Treatment with rh granulocyte colony-stimulating factor (G-CSF) elicited the expansion of mature neutrophilic granulocyte populations in human marrow. Administration of rh interleukin-3 (IL-3) induced significant increases of eosinophilic granulocyte and burst-forming unit, erythrocyte (BFU-E) activity. The rhIL-6 did not cause significant changes in the subpopulations of human hematopoietic cells within the grafts, but did increase the number of colony-forming unit, granulocyte-macrophage and BFU-E. Pretreatment with rhIL-3 followed by rh erythropoietin (Epo) administration enhanced Epo-induced human erythropoiesis significantly. No synergistic effects on myelopoiesis were observed using sequential treatment with rhIL-3 followed by rhG-CSF. Instead, these factors seemed to work independently, with rhG-CSF increasing the percentage of neutrophils and rhIL-3 increasing the percentage of eosinophils. When administered simultaneously with rhEpo, rhIL-6 showed dose-dependent inhibitory effects on in vivo Epo-induced human erythropoiesis. The rhIL-6 also caused a reduction in the percentage of human neutrophils induced by rhG-CSF. These results suggest that the SCID-hu mouse provides a useful small animal model to assess the in vivo effects of hematopoietic growth factors on human hematopoiesis.

Animals↗
PubMed1990

The ring-infected erythrocyte surface antigen protein of Plasmodium falciparum is phosphorylated upon association with the host cell membrane.

The ring-infected erythrocyte surface antigen (RESA) is a 155-kDa malarial polypeptide which is released from merozoites and becomes associated with the erythrocyte membrane at the time of invasion. Inside-out vesicles (IOVs) prepared from Plasmodium falciparum-infected erythrocytes contain RESA, presumably bound to the membrane skeleton, as it is largely insoluble in Triton X-100. When these IOVs were incubated with [gamma-32P]ATP, a 155-kDa polypeptide was labeled in IOVs from infected, but not from uninfected erythrocytes. Immunoprecipitation using specific rabbit antisera confirmed that RESA is indeed a phosphoprotein. Phosphoamino acid analysis revealed phosphoserine and a small amount of phosphothreonine, but no phosphotyrosine. Labeling of intact parasitized erythrocytes with inorganic [32P]phosphate for several hours in culture resulted in RESA in Triton-insoluble extracts being phosphorylated. Labeling of synchronized parasites showed that RESA was phosphorylated only when it became associated with the erythrocyte membrane, and although RESA was abundant in mature parasites, it was not phosphorylated. RESA, released into the culture supernatants during the growth of P. falciparum, bound to IOVs prepared from normal uninfected erythrocytes, and subsequent labeling with [gamma-32P]ATP resulted in the phosphorylation of RESA. The evidence suggests that RESA is phosphorylated by an erythrocyte membrane kinase and probably not by a parasite-encoded enzyme.

Adenosine Triphosphate↗
PubMed1990

In vivo cytokine gene expression in T cell subsets of the autoimmune MRL/Mp-lpr/lpr mouse.

Expression of cytokine genes in freshly isolated T cell subsets in the autoimmune lpr mouse has been studied to determine what factors may be produced by these cells in vivo. RNA prepared from T cell subsets from diseased lpr mice and from the normal congenic strain, MRL/n, was tested for the presence of cytokine-specific message using the polymerase chain reaction. Cells of the expanded abnormal T cell subset were shown to express genes encoding interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, TNF-alpha and interleukin (IL)6, cytokines which are associated with inflammatory immune responses. These cells may thus play an important role in exacerbation of the pathological symptoms of the systemic autoimmune disease. These cells expressed no detectable IL1, IL2, IL3, IL4 or IL5. Phenotypically normal CD4+ and CD8+ T cells from both lpr and MRL/n also contained transcripts for IFN-gamma, TNF-alpha, TNF-beta and IL6. IL2 mRNA was found almost exclusively in the CD4+ subset, indicating that the CD8+ T cells in the lpr mouse are not highly activated through their class I major histocompatibility complex molecules to produce IL2, as could occur if a virus infection was inducing autoimmunity in these mice. Similar levels of IL2 mRNA were present in the CD4+ T cells of lpr and MRL/n mice, demonstrating that these cells are not defective in IL2 production in vivo.

Animals↗
PubMed1987

Structure and function of candidate vaccine antigens in Plasmodium falciparum.

Analysis of Plasmodium falciparum antigens expressed in Escherichia coli has identified several different proteins as potential vaccine components. Fragments of one of these antigens, the ring-infected erythrocyte surface antigen (RESA) have been used to protect Aotus monkeys against overwhelming infection with P. falciparum. In this vaccine, trial protection correlated with antibody responses to two of three repetitive sequences in RESA. RESA is released from merozoites and becomes associated with the erythrocyte membrane at the time of merozoite invasion. The 3' repeat structure of RESA encodes a polyacidic sequence that has homology with the N-terminal sequence (cytoplasmic domain) of band 3, the erythrocyte anion transporter. These homologous sequences both include a recognition sequence for a protein tyrosine kinase. It is postulated that RESA disrupts the normal intermolecular interactions of the cytoplasmic domain of band 3 and that phosphorylation of RESA by an erythrocyte membrane kinase in some way regulates this function of RESA.

Amino Acid Sequence↗
PubMed1985

Expression of Burkitt lymphoma-associated antigen (defined by the monoclonal antibody 38.13) on both normal and malignant germinal-centre B cells.

Monoclonal antibody 38.13 was raised against the Burkitt lymphoma cell line Daudi and has been previously shown to recognize a globotriaosylceramide (Pk) determinant expressed selectively on Burkitt and a few other B-cell lymphomas. We report here that 38.13 binds to a subset of normal B lymphocytes in germinal centres of secondary lymphoid follicles as well as to blood vessels. In malignant populations equivalent to various developmental compartments of the B-cell lineage, only those with a follicular phenotype express the Pk determinant at detectable levels. The expression of this tumour-associated antigen, in common with many others, is therefore regulated in concert with cell lineage and maturation status.

Animals↗
PubMed1985

Chromosome mapping of cell membrane antigens expressed on activated B cells.

Hybrids formed by fusion of either human acute lymphoblastic or chronic lymphocytic leukemia cells and the mouse myeloma P3.X63.Ag8/653 have been used to show that the expression of two cell surface antigens, Bp37 and p76, associated with B cell activation and detected by the monoclonal antibodies BB1 and BB2, respectively, segregate with human chromosomes 12 and 19, respectively. Another antigen expressed on activated B cells (p24) also maps to chromosome 12 (Katz et al., Eur. J. Immunol. 1984. 13: 1008) which is of interest in the light of the frequent involvement of this chromosome in certain B cell leukemias and lymphomas.

Animals↗
PubMed1985

T lymphoblastic lymphoma with LEU-7 positive phenotype and unusual clinical course: a multiparameter study.

Immunologic phenotype studies were performed on cells and on frozen sections of involved tissue from a 20 year old female with typical T-cell lymphoblastic (convoluted) lymphoma. The cells demonstrated a thymic phenotype but in addition marked with Leu-7 (HNK-1)--an antibody reported to identify human natural killer/killer (NK/K) cells. Normal or neoplastic cells with this phenotype have not been previously reported. These findings support the existence of a thymic precursor for a T-cell subset of Leu-7 + cells. The unusual clinical response to therapy is another feature of this unique case.

Adult↗
PubMed1985

B- and T-cell subsets in follicular centroblastic/centrocytic (cleaved follicular center cell) lymphoma: an immunohistologic analysis of 26 lymph nodes and three spleens.

Follicular centroblastic/centrocytic (CB/cc/F), or cleaved follicular center cell, lymphomas are known to contain admixtures of B cells and, often, numerous T cells. To analyze the presence and distribution of B and T cells and their subsets in CB/cc/F lymphomas, 26 lymph nodes and three spleens (from 24 patients) were studied with a panel of monoclonal antibodies and peanut lectin by the avidin-biotin immunoperoxidase technique on frozen sections. Immunoglobulin studies revealed monoclonal neoplastic follicles in most cases, although cells of the nondominant light chain were occasionally present. Rarely, the follicles showed both kappa and lambda light chains or were immunoglobulin-negative. Although monoclonal mantles were observed in only one case, more than half of the nodes demonstrated monoclonal interfollicular infiltrates. In most cases the phenotype of the follicular cells was similar to that of the predominant cells in the normal follicles. Interfollicular lymphomatous cells had variable phenotypes that, unlike the normal situation, sometimes resembled those in the follicles. Phenotypic variation was present within single neoplastic clones and sometimes suggested more mantle-like differentiation. Phenotypic changes were also observed in repeat biopsies. T cells, usually predominantly of the T-helper phenotype, were present in variable numbers in all cases. Although present in the neoplastic follicles, they were usually more common in the interfollicular areas. Six nodes and two spleens had definite rims composed predominantly of T cells around neoplastic follicles. Apparently "activated" (Tac-positive) T cells were often present and showed accentuation around the follicles in some cases. Thus, CB/cc/F lymphoma is a malignant lymphoma that closely resembles follicular hyperplasia but that also has distinctive features.

Antibodies, Monoclonal↗
PubMed1985

Two monoclonal antibodies raised against a Burkitt lymphoma cell line recognise different cell types within lymphoid follicles.

Monoclonal antibodies were raised against a laboratory derived variant of the Raji Burkitt lymphoma cell line. We have characterized two of these antibodies by screening on haematopoietic cell lines, and frozen sections of both reactive and neoplastic lymphoid tissue, and found reactivity with separate cellular components of lymphoid follicles. Monoclonal FW37.4.D5 reacts in section specifically with follicular dendritic reticular cells. Monoclonal 35.1C5 reacts with a subpopulation of splenic marginal zone, and lymph node mantle zone, B lymphocytes, but stains only rare cells within germinal centres. This monoclonal is operationally B lymphocyte specific, distinguishing an 'intermediate' B cell subset, represented in lymphoma by B chronic lymphocytic leukaemia, B hairy cell leukaemia and centrocytic lymphoma.

Animals↗
PubMed1984

Lymphocytic lymphoma/B-chronic lymphocytic leukaemia--an immunohistopathological study of peripheral B lymphocyte neoplasia.

Twenty seven patients with malignant lymphoma of lymphocytic type/B-chronic lymphocytic leukaemia (ML, L/B-CLL, Kiel classification) diagnosed from lymph node and splenectomy specimens were studied histologically and immunologically. Lymph node biopsies showed a diffuse effacement of normal architecture by small round lymphocytes usually with scattered proliferation centres (PC). A1 spleens showed white pulp with or without red pulp involvement, sometimes with tumour nodules present. PC-like cells or PC were only found in the white pulp or tumour nodules. Studies of 13 specimens using the ABC immunoperoxidase technique on frozen sections with a large panel of monoclonal antibodies showed that although a part of the monoclonal B cell neoplasm, the proliferation centres or splenic white pulp have a different phenotype from the surrounding cells. Some of these phenotypic changes are similar to those reported with in vitro induction of "maturation" of ML, L/B-CLL cells. The implications for normal B-cell development are discussed. In contrast to reported peripheral blood findings, T cells, predominantly of T helper phenotype in lymph nodes, were present but usually not numerous.

Antibodies, Neoplasm↗
PubMed1984

Natural killer (Leu 7+) cells in reactive lymphoid tissues and malignant lymphomas.

Leu 7 (HNK-1) is a monoclonal antibody reported to identify human natural killer/killer cells. The frequency and distribution of Leu 7+ cells in 14 reactive lymphoid tissues and 47 malignant lymphomas were studied using the frozen section immunoperoxidase technic. In reactive lymphoid tissues, Leu 7+ cells were concentrated in the pale zone of germinal centers and usually were relatively scarce in the interfollicular areas. Of the malignant lymphomas, follicular lymphomas most consistently had numerous admixed Leu 7+ cells and lymphoblastic lymphomas the least. The authors' findings suggest that Leu 7+ cell accumulation in normal and neoplastic lymphoid tissue is associated at least in part with something shared by the pale zone of the normal germinal centers and the presence of neoplastic germinal centers. This association does not appear to be a simple response to lymphoid proliferation.

Antibodies, Monoclonal↗
PubMed1984

Distribution of B lymphocyte subsets in normal lymphoid tissue.

Using the ABC avidin-biotin peroxidase techniques and a series of monoclonal antibodies against B cell associated antigens, the anatomical distribution of B lymphocyte subsets was studied in reactive lymph node, tonsil and spleen. Evidence is presented for at least five major phenotypically distinct B cell subsets, each localized to specific compartments of peripheral lymphoid tissue. The possible relationship of these subsets of B lymphocytes to activation, maturation and function in the B cell lineage is discussed.

Antibodies, Monoclonal↗