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Biomedical subjects

A B Wilson

Publications and source records attributed to A B Wilson.

At least 37 records · Page 2Linked to original sources

Interleukin-2-induced production of interferon-gamma by resting human T cells and large granular lymphocytes: requirement for accessory cell factors, including interleukin-1.

Between 5 and 20% of normal human lymphocytes were found to synthesize interferon-gamma (IFN-gamma) in primary cultures with recombinant interleukin-2 (rIL-2). After 22 hr, IFN-gamma-producing cells included CD5+ T lymphocytes, CD16+ large granular lymphocytes (LGL), and a population of CD5-, CD16- blast cells. Only a small proportion (0-7%) of IFN-gamma-synthesizing cells expressed HLA-DR. The production of IFN-gamma by all rIL-2-responding lymphocyte subsets was shown to require the presence of DR+ accessory cells, probably including nonadherent, esterase-negative monocytes and/or dendritic cells. Accessory cell function in lymphocyte preparations depleted of DR+ cells, or in purified (greater than or equal to 95%) suspensions of LGL, was fully replaced either by addition of 2% autologous, adherent monocytes or by monocyte culture supernatant. The activity of monocyte supernatant was greatly reduced by treatment with antiserum specific for human interleukin-1 beta (IL-1 beta), although a combination of rIL-1 beta and rIL-2 failed to stimulate IFN-gamma production in DR- lymphocytes. These results indicate that rIL-2-induced IFN-gamma synthesis in both T cells and LGL requires the synergistic activity of IL-1, and possibly of one or more other monokines, as yet unidentified.

Antigen-Presenting Cells↗

Direct antibody rosette-forming reactions using monoclonal markers of lymphocyte subpopulations. Methodology and applications illustrated by investigations with rat pan-T antibodies of the CAMPATH series.

A sensitive direct antibody rosette assay has been developed for the detection of antigens on the lymphocyte cell membrane. Indicator cells for rosette tests were prepared by chromic chloride coupling of rat or mouse monoclonal IgG or IgM anti-lymphocyte antibodies to untreated or trypsinized bovine red blood cells. The monoclonal antibodies used were reactive with a range of cell surface markers which identify various lymphocyte subpopulations, including T cell antigens, HLA class II (Ia-like antigens), Leu-7 (HNK-1) and VEP 13, a determinant of Fc gamma receptors on large granular lymphocytes. Results obtained by direct rosette formation correlated well with those of parallel tests using indirect immunofluorescent antibodies staining. Several applications of the direct antibody rosetting procedure are described in further investigations with a series of pan-T monoclonal (CAMPATH) antibodies. These include the morphological examination of antibody-binding cells in cytocentrifuge smears, the separation of lymphocyte subsets by density gradient centrifugation, and the use of a rosette inhibition assay to identify monoclonal antibodies binding to the same (or closely associated) epitopes of the lymphocyte cell membrane.

Animals↗

An in vivo and in vitro study of selenium deficiency and infection in rats.

Selenium deficiency in rats impairs the ability of neutrophils and peritoneal macrophages to kill Candida albicans organisms in vitro. In contrast, killing of Salmonella typhimurium and Staphylococcus aureus organisms is unaffected by the deficiency. Survival of rats after intraperitoneal injection of 8 X 10(7) S. aureus organisms was not affected by Se deficiency, but a 5-fold increase in the dose (4 X 10(8) S. aureus organisms) led to a significantly greater mortality in the Se deficient rats.

Animals↗

Fc gamma-receptor-bearing, non-B lymphocytes in human peripheral blood: cytophilic immunoglobulin binds almost exclusively to large granular lymphocytes.

Cytophilic IgG (CYT-Ig) has previously been reported to bind to both the "TG" (E+, Fc gamma R+) and "L" (E-, Fc gamma R+) subsets of non-B lymphocytes in human peripheral blood. Present investigations show that IgG-binding cells, as detected by a sensitive antiglobulin rosetting reaction, are contained almost entirely within the large granular lymphocyte (LGL) subpopulation, and that fewer than 5% of other non-B lymphocytes acquire IgG from serum. Cell membrane-bound IgG sterically blocks the reaction of LGL with sheep red blood cells and therefore influences the proportions of these cells characterized as TG (E+) or L (E-) lymphocytes. Although the majority of TG lymphocytes are LGL, a further subpopulation of E+, Fc gamma R+ cells are detectable under particular test conditions. Unlike LGL, these lymphocytes do not react with rabbit IgG-coated ox RBC (EAG) in saline, but will form EAG rosettes when the reaction is enhanced in the presence of Ficoll. These Fc gamma R+ cells are mostly of typical small-lymphocyte morphology and do not bind detectable amounts of CYT-Ig, nor do they express the monoclonal antibody-defined VEP 13 determinant associated with Fc gamma R on LGL.

Antibody Affinity↗

Discrimination between innate and cytophilic immunoglobulin on human peripheral blood lymphocytes: analysis by the direct antiglobulin rosette-forming reaction.

Bovine red blood cells linked to polyclonal or monoclonal anti-immunoglobulin antibodies are used in the direct antiglobulin rosetting reaction to detect surface-Ig on human lymphocytes. The sensitivity of this test is markedly increased by pretreating the red cells with trypsin. Enzyme-treated red cells, coupled to anti-human Fab or anti-light chain antibodies, react not only with innate Ig on B lymphocytes but also with smaller amounts of passively adsorbed, cytophilic Ig on up to 25% of freshly prepared peripheral blood (non-B) lymphocytes. In contrast, trypsinized red cells carrying anti-Ig isotype-specific antibodies react exclusively with B cell surface-Ig. Cytophilic Ig is abnormally firmly bound to lymphocytes separated on Ficoll-Hypaque at 20 degrees C or below, and is released very slowly during 3 h or more at 37 degrees C in vitro. Lymphocytes are free of detectable cytophilic Ig when isolated on Ficoll-Hypaque at 37 degrees C, and very little Ig is retained by non-B cells in suspensions purified on Percoll which, unlike Ficoll, does not increase Ig binding affinity. These lymphocyte separation procedures are recommended as a preliminary to B cell assays by sensitive antiglobulin techniques.

Agglutination↗

Mitochondrial abnormalities in muscle from vitamin B12-deficient sheep.

Skeletal and cardiac muscles from vitamin B12-deficient sheep were examined. Histochemical studies did not reveal any gross pathological changes in the muscle structure, but there was an abnormal distribution of the product of the NADH-diaphorase reaction. Electron microscopy revealed an abnormal distribution of mitochondria, changes in the number and arrangement of cristae within the mitochondria and the presence of inclusions. The possibility that alterations in mitochondrial morphology are early lesions attributable to metabolic changes in vitamin B12 deficiency is discussed.

Animals↗

Effect of zinc deficiency on muscle fibre type frequencies in the post-weanling rat.

Male weanling rats were maintained on diets either deficient or adequate in zinc for a period of 4 weeks. The rats on the deficient diet showed a reduction in food intakes and growth. After 4 weeks both soleus muscles and the lateral portion of the diaphragm were studied histochemically to examine the relative frequencies of the fibre types. The soleus muscles of the deficient animals showed a significant change in the proportion of slow and fast fibres. The diaphragm muscles of the deficient animals had a significant increase in the proportion of fast-twitch oxidative glycolytic fibres and a significant decrease in fast-twitch glycolytic fibres compared with the controls. Stainable lipid increased in the diaphragm muscle of the deficient animals with respect to their pair-fed controls.

Animals↗

Evidence that the fourth component of complement (C4) is carried on a high proportion of normal guinea-pig B lymphocytes.

The fourth component of complement (C4) has been demonstrated on the cell membrane of guinea-pig B lymphocytes isolated from blood, lymph nodes and spleen. In lymph nodes, at least, the C4-positive cells also carry receptors for C3 and most bind IgG-Fc. Few, if any, T lymphocytes have detectable C4. Resynthesis of cell-surface C4 could not be shown following in vitro culture of lymphocytes stripped of C4 by proteolytic enzymes, and it is likely that the C4 is passively acquired in vitro from tissue fluids, possibly by a mechanism similar to that involved in the binding of C4 (Chido and Rodgers determinants) to human erythrocytes.

Animals↗

Interaction of antibody-aggregated C4 and guinea-pig red cells: coagglutination phenomenon of Bordet and Gengou.

The component of bovine serum (coagglutinogen) responsible for coagglutination of guinea-pig red cells has been shown to be c4, as anticipated from our previously reported findings on human serum. To effect coagglutination, the C4 needs to be aggregated by antibody; thereby probably increasing the avidity of the C4 for the receptors on guinea-pig red cells. The coagglutinating activity is lost if univalent Fab anti-C4 is used, but it can be restored by adding IgG antibody to the Fab. A procedure is described for producing antibody reagents to human or bovine C4 by injecting guinea-pigs with well-washed coagglutinated guinea-pig red cells.

Animals↗

The coagglutination phenomenon of Bordet and Gengou involves a reaction between antibody-aggregated fourth component of complement and a receptor on guniea pig red cells.

The coagglutination phenomenon of Bordet and Gengou has been re-investigated. Many of the original observations have been confirmed. However, the explanation of the phenomenon has been found to be more special than that offered by Bordet and Gengou, who envisaged 'entrainment; or enmeshment of guinea pig red cells by lattices formed by antibodies reacting with serum proteins. We found that, so far as human serum is concerned, coagglutination of guinea pig red cells is confined to an activity of the fourth component of complement following its reaction with antibody. The nature of the association between antibody-reacted or antibody-aggregated C4 and the receptor on the guinea pig red cells is still to be elucidated.

Agglutination↗

Receptors on guinea-pig erythrocytes specific for cell-bound fourth component of human complement (C4).

Guinea-pig erythrocytes have receptors for heterologous (human and rabbit) complement activated by the classical pathway on cell surfaces. This was shown in the present study by rosette-forming reactions of guinea-pig erythrocytes and human lymphocytes or sheep erythrocytes pre-treated with antibody and human R3 complement. The binding is temperature-dependent and is enhanced by treating the guinea-pig erythrocytes with neuraminidase. The receptors were shown to be specific for C4 by inhibition tests employing a range of anti-human complement antibodies (including anti-Clq, -Cl inhibitor, -C4, -C2, -C3 and -C3b inactivator). Of these reagents, only anti-C4 inhibited the receptor activity, indicating that the guinea-pig erythrocyte C4-receptors differ from those on lymphocytes, monocytes, polymorphonuclear leucocytes and human erythrocytes which are reported to react with both C3b and C4b. In contrast to the strong affinity observed for heterologous C4, guinea-pig erythrocytes appear to react very weakly, if at all, with homologous C4.

Animals↗

The Primary Mental Health Project (PMHP): evaluation of current program effectiveness.

This study evaluated the effectiveness of the Primary Mental Project (PMHP), a program for early detection and prevention of school adjustment problems. Pre- and postprogram assessments were done with 215 primary-grade children seen in PMHP, usig teacher ratings of problem behaviors and competencies, and child-aide ratings of problems. School mental health professionals judged educational and behavioral changes in project children during the year. Significant across-the board improvements were found on all criterion measures. Modest intercorrelations among criterion change estimates suggested that the observed changes were due to program, rather than halo, effects. PMHP children also improved significantly more than matched, retrospective controls.

Child↗