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Biomedical subjects

F Malavasi

Publications and source records attributed to F Malavasi.

At least 145 records · Page 8Linked to original sources
PubMed1986

Proliferation of human peripheral blood mononuclear cells induced by Candida albicans and its cell wall fractions.

Glutaraldehyde-inactivated cells and cell-wall fractions of Candida albicans were studied for their capacity to induce or inhibit the in-vitro proliferation of human peripheral blood mononuclear cells (PBMC), as measured by 3H-thymidine incorporation. Both the intact cells (CA) and a phosphorylated gluco-mannan-protein complex of the cell wall (GMP), in microgram doses, were strong inducers of PBMC proliferation, with a peak of activity at 6-9 days of culture and varying with the PBMC donor. A significant but much lower proliferation was observed on exposure of PBMC to a low-protein (less than 3% by weight) mannan component (M) of the cell wall. Both a hot-alkali extracted mannan-protein complex (M-alk), comparable to GMP in crude chemical composition, and an alkali-insoluble cell-wall glucan (GG) were inactive. None of the Candida fractions induced a lymphoproliferation of umbilical cord blood cells and all fractions, except GG, were equally effective in binding human anti-Candida antibodies as shown by a sensitive ELISA-inhibition assay. Moreover, a monoclonal antibody against the class II determinant of the HLA complex inhibited PBMC proliferation irrespective of the Candida antigen used. Taken together, the data shows that in inducing lymphoproliferation, Candida fractions act as specific antigens rather than as non-specific mitogens. Use of intact Candida cells and chemically-defined cell-wall components appears preferable to use of undefined antigenic mixtures as stimulators of PBMC proliferation.

Adult↗
PubMed1986

Reduced natural killer T-cells in B-cell chronic lymphocytic leukaemia identified by three monoclonal antibodies: Leu-11, A10, AB8.28.

The proportion of E-rosette positive T-lymphocytes capable of reacting with three monoclonal antibodies (MoAbs)--Leu-11, A10, AB8.28--which appear to recognize specifically natural killer (NK) cells, was assessed in a series of untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL). Irrespective of the clinical stage of the disease, the capacity of B-CLL T-lymphocytes to react with all three MoAbs was significantly reduced compared with that of normal circulating T-cells (Leu-11: 2.5% +/- 1.9 SD; A10: 2.3% +/- 1.3; AB8.28: 7% +/- 6.6 v Leu-11: 13.5% +/- 4.5; A10: 8.5% +/- 4.6; AB8.28: 12% +/- 5.5). Furthermore, a marked difference was demonstrated between the reactivity with the Leu-11, A10, AB8.28 MoAbs and the proportion of Leu-7 positive T-cells, which in B-CLL is significantly higher than in normal blood (23% +/- 12.1 v 11.9% +/- 5.9). These findings are in agreement with previous evidence of a discrepancy in B-CLL between the phenotypic expression, assessed by Leu-7 positivity, and the true functional activity of NK T-cells, and suggest that the Leu-11, A10 and AB8.28 MoAbs correlate well with the depressed NK function found in this disease.

Antibodies, Monoclonal↗
PubMed1986

3' c-myc rearrangement in a human leukemic T-cell line.

The human leukemic T-cell line Hut 78, derived from a patient suffering from Sézary syndrome and expressing a mature postthymic membrane phenotype, shows a c-myc rearrangement beginning within 500 base pairs immediately 3' to the c-myc exon 3. Chromosome analysis of the Hut 78 reveals the presence of a hyperdiploid karyotype with a large number of markers and rearrangements, though trisomy is the only cytogenetic anomaly involving chromosome 8. Moreover, as the abnormal c-myc appears to be duplicated, a duplication of the chromosome 8 carrying the abnormal c-myc probably occurred. Unlike four other human leukemic T-cell lines tested, the Hut 78 cells express a high amount of c-myc transcript, suggesting that the 3' c-myc anomaly may cause a deregulation of the expression of this gene.

Base Sequence↗
PubMed1986

Expression of HLA class II (DR, DQ) determinants by normal and chronic myeloid leukemia granulocyte/monocyte progenitors.

It has been suggested that the expression of certain HLA class II antigens stemming from three distinct loci (DR, DP, and DQ) is important not only in the regulation of the immune response but also on the response of hemopoietic precursors to factors inhibiting myelopoiesis. Changes in the expression of DR antigens may be involved in the pathogenesis of altered cell proliferation in chronic myeloid leukemia, since they result in decreased sensitivity of the colony forming units, granulocyte-macrophage to prostaglandin E and acidic isoferritins. In studies using monoclonal antibodies against monomorphic DR or DQ determinants, in a complement-dependent cytotoxic assay, it was found that nearly all normal and chronic myeloid leukemia bone marrow colony forming units, granulocyte-macrophage express DR antigens. The dose response curve was similar for both normal and leukemic precursors. Leukemic peripheral blood precursors were more sensitive than were normal peripheral blood precursors. Normal colony forming units, granulocyte-macrophage did not express DQ antigens, whereas these were expressed in varying quantities by leukemic cells. This study shows that, in the patients we studied, leukemic cells express DR antigens in amounts comparable to normal. In addition, varying amounts of DQ antigens may be observed on leukemic but not on normal progenitors, perhaps as a consequence of an increase in the number of antigens also expressed by normal cells, though in an amount below the detection threshold of cytotoxicity techniques.

Animals↗
PubMed1985

Functional and molecular characterization by the CB04 monoclonal antibody of a cell surface structure exerting C3-complement receptor activity.

CB04 monoclonal antibody which reacts with an epitope of a surface molecule expressed on human monocytes has been elicited using peripheral blood lymphocytes as immunizer. The characterization of the monoclonal antibody examined at the phenotypic, molecular, and functional levels indicates that the CB04 antibody defines a structure present on monocytes, tissue macrophages, B cells, polymorphonucleates, and erythrocytes. The molecular weight (220 kD), the tissue distribution in health and disease conditions, and the involvement in relevant biological processes indicate that the CB04 structure is the receptor for the C3b fragment of the complement. The binding of the antibody to the cell surface induces inhibition of the C3bi receptorial function.

Animals↗
PubMed1985

Murine monoclonal antibodies as probes for the phenotypical, functional, and molecular analysis of a discrete peripheral blood lymphocyte population exerting natural killer activity in vitro.

Two monoclonal antibodies (AB8.28 and A10) reacting with large granular lymphocytes were extensively studied and characterized. The two peripheral blood lymphocyte subsets positive for the expression of AB8.28 and A10 determinants were isolated by cell sorting and the phenotype analyzed using a panel of anti-lymphocyte reagents. Both subsets displayed the characteristics of "null cells." Moreover, these subsets encompassed a significant amount of the natural killer activity, since preparations of peripheral blood lymphocytes deprived of AB8.28+ and A10+ cells showed a remarkable reduction of such activity. The analysis of the distribution of the AB8.28 and A10 epitopes has been carried out using a variety of cells, i.e., normal tissues, tumor cells, established cell lines, and preparations obtained from patients with different leukemic disorders. The structure bearing the epitopes recognized by the two monoclonal antibodies was characterized immunologically (immunoprecipitation, SDS-PAGE analysis, immunomodulation, and competition with other antibodies) and by various functional assays. On the basis of inhibition tests, the AB8.28 molecule seems to be related functionally and/or structurally with the IgG Fc receptor. By contrast, the A10 structure does not share this activity and so far has eluded any precise biological characterization.

Antibodies, Monoclonal↗
PubMed1985

Further antigenic determinants on HLA-A molecules.

Monoclonal antibodies detect a new polymorphic antigenic determinant shared by HLA-A2, 3, 28, 29, 30, 31 and w33. This was demonstrated by population and family studies, including an HLA-A,B recombinant family, and by lysostrip experiments. Competition experiments, measuring the binding of 125I labelled MoAbs to B lymphoblastoid cell lines coated with anti-HLA conventional alloantisera and MoAbs showed that this new epitope is spatially distant from other known epitopes of A3 molecules and from monomorphic and polymorphic determinants of A2 molecules detected by monoclonal antibodies. On the other hand, anti-HLA-A2 polyclonal alloantisera are able to inhibit binding.

Antibodies, Monoclonal↗
PubMed1985

The monoclonal antibody AC1.59 defines a new polymorphic determinant on HLA-DR molecules.

2-dimensional gel electrophoresis analysis and sequential immunoprecipitation studies have shown that the monoclonal antibody (MoAb) AC1.59 recognizes a gene product of the HLA-DR locus. The determinant defined by the MoAb AC-1.59 has an unusual distribution on HLA-DR allospecificities, since it is expressed by HLA-DR1, DRw8, DRw9 antigens and by subtypes of HLA-DRw6 and HLA-DR4 antigens. In the latter allospecificity the expression of the MoAb AC1.59 defined determinant correlates with the cellularly defined HLA-Dw4 alloantigen. The present investigation provides evidence of serological heterogeneity within HLA-DR alloantigens. Furthermore these results suggest that monoclonal antibodies can sharpen the discriminatory power of serological assays to dissect the heterogeneity and complexity of HLA-DR alloantigens.

Antibodies, Monoclonal↗
PubMed1985

Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma.

Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells.

Adult↗
PubMed1985

Antibody-induced redistribution of Heymann antigen on the surface of cultured glomerular visceral epithelial cells: possible role in the pathogenesis of Heymann glomerulonephritis.

In this study we analyze the ability of antibodies that produce passive Heymann glomerulonephritis to induce antigen redistribution on the surface of cultured glomerular visceral epithelial cells (GEC). Polyclonal antibodies produced by immunization with membrane vesicles prepared from proximal tubule brush borders (BB) and polyclonal (rabbit) and monoclonal (mouse) antibodies to a membrane glycoprotein (gp 330) purified from epithelial cells of rat proximal tubule were used. The study by immunofluorescence of GEC kept at 4 degrees C or fixed with paraformaldehyde showed that the three antibody preparations reacted with the plasma membrane in a punctate pattern known to be due to staining of coated pits or coated vesicles on the cell surface. At 37 degrees C and, at a slower rate, at 22 degrees C, the two polyclonal antibodies induced a rapid clustering of antigen-antibody complexes on the nonadherent surface of living cultured GEC with subsequent formation of patches and caps and, after prolonged incubation, with temporary disappearance of Heymann antigen from the cell surface, so-called antigenic modulation. Antigen redistribution and modulation were inhibited by sodium azide, indicating that these processes are energy dependent. Monovalent Fab fragments of antibodies to BB vesicles did not alter the distribution of Heymann antigen unless they were subsequently cross-linked. Monoclonal anti-gp330 induced a modest degree of antigen redistribution, which was increased by subsequent cross-linking. Exposure of glomerular epithelial cells to cytochalasin B, colchicine, or ionophore A23187 prevented or altered antigen redistribution at 37 degrees C. Furthermore, the antibody-induced antigen redistribution was associated with changes in distribution of cytoplasmic actin, myosin, and tubulin, indicating that it is related to the contractile activity GEC. LEW rats, given i.v. injection of IgG directed against BB membrane vesicles, developed passive Heymann glomerulonephritis (i.e., immune deposits in the lamina rara externa of the glomerular basement membrane). In contrast, the glomeruli of rats exposed for longer periods to larger amounts of Fab fragments of the same antibodies failed to develop immune deposits. These studies show that the antibodies to the nephritogenic antigen of Heymann glomerulonephritis may induce a redistribution of immune complexes (IC) in the membrane of glomerular epithelial cells that is similar to that produced by other plasma membrane antigen-ligand interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Phorbol ester induces abnormal chronic lymphocytic leukemia cells to express features of hairy cell leukemia.

We have investigated the relationship between chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and different normal B cell subsets: Mrbc+, T1+ and slgM+ tonsil cells; germinal center; mantle zone; and peripheral blood B lymphocytes. Both malignant and normal cells were incubated in vitro with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 72 hours and the morphology, cytochemical profile, and surface markers were evaluated. The results show that CLL cells TPA-induced become indistinguishable from HCL by four independent criteria: the morphology; the cytoplasmic tartrate resistant acid phosphatase (TRAP) enzyme activity; the membrane positivity with anti-Leu M5 (SHCL3); and anti-Tac monoclonal antibodies which, in the uninduced state, react only with HCL. The features of TRAP and Tac positivity are also expressed (though in variable degree) by different normal B cell populations activated with TPA or pokeweed mitogen (PWM). It is concluded that HCL might represent an aberrantly activated variant of CLL (or of a CLL-related disorder).

Acid Phosphatase↗
PubMed1984

Characterization of a murine monoclonal antibody specific for human early lymphohemopoietic cells.

This paper summarizes the results of the characterization of A10, a murine monoclonal antibody which recognizes an epitope not restricted to cells of a definite lineage, but which seems to be specific for an early differentiation antigen present on precursors of circulating T and B cells. The structure recognized by the A10 monoclonal antibody, although strikingly structurally similar to the HLA-A,B,C complex, is immunologically different both from histocompatibility antigens and from beta 2 microglobulin. Furthermore, the distribution of the A10 antigen is analyzed in different cell and tissue samples, both in health and disease conditions.

Animals↗
PubMed1984

Generation and characterization of murine monoclonal antibodies against HLA Class II molecules.

HLA Class II antigens (human la) are coded by Major Histocompatibility Complex and play important biological roles in health and disease. In this report we describe the generation and characterization of nine murine monoclonal antibodies (MoAbs) specific for determinants localized on the human la molecules. The reactivity of these MoAbs inferred from serological analysis along with the data obtained from biochemical characterization of the target structures allowed a classification of these reagents as monomorphic and polymorphic. Two monomorphic MoAbs, identifying different subsets of human la molecules, were studied in detail.

Animals↗
PubMed1984

Release of platelet-activating factor (PAF)-like material from human lymphoid cell lines.

The release of platelet-activating factor (PAF)-like material was evaluated from eight B and T human leukemic cell lines and from three lymphoblastoid cell lines obtained after Epstein-Barr virus (EBV) transformation. All cell lines were stimulated with ionophore A23187, phytohemagglutinin (PHA), or both either in the presence of or without acetyl coenzyme A (AcCoA). After appropriate stimuli, all cell lines tested released PAF-like material, irrespective of the surface phenotype and of the level of differentiation. Some cell lines released PAF-like material after stimulation with A23187 (Molt-4, Jurkat, 1301, Raji, FM007), others only if AcCoA was added to A23187 (CCRF/CEM, HUT 78, Daudi, Nalm-1). In some cases, PHA was capable of enhancing the effect of A23187 (Molt-4, HUT 78, Daudi, IBW4) and finally, in a lymphoblastoid cell line (WT20), the release of PAF-like material was achieved only in the presence of both A23187 and PHA. These findings demonstrate for the first time that human lymphoid cells both of B- and of T-cell origin can release a PAF-like material after appropriate stimuli.

B-Lymphocytes↗