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Biomedical subjects

N Khansari

Publications and source records attributed to N Khansari.

At least 19 recordsLinked to original sources
PubMed1989

Separation of bovine lymphocytes and granulocytes from blood by use of elutriation.

Bovine blood mononuclear cells were separated into 2 fractions by use of centrifugal elutriation. Total recovery, as well as recovery of each fraction, was greater than that obtained by use of Ficoll-sodium diatrizoate separation. The lymphocyte fraction contained less than 1% granulocytes, and the granulocyte fraction contained only 7% lymphocyte contamination. The technique was reproducible and results proved to be comparable with those of Ficoll-sodium diatrizoate density-gradient centrifugation; furthermore, the method is considerably cheaper and less time-consuming for processing large volumes of blood. Viability of cells separated by elutriation always was greater than 98%, whereas viability of cells separated by Ficoll-sodium diatrizaote was greater than 95%. Also, mitogen activation of lymphocytes separated by elutriation was superior to that of lymphocytes separated by Ficoll-sodium diatrizoate centrifugation.

Animals↗
PubMed1985

Human monocyte heterogeneity: interleukin 1 and prostaglandin E2 production by separate subsets.

Human peripheral blood monocytes were separated into four different subpopulations by means of a discontinuous bovine serum albumin gradient. Of the least dense population, 7% were present in fraction A, 11% in fraction B, 28% in fraction C and of the most dense, 34% were in fraction D. The rest (17%) of the recovered cells sedimented as a pellet, of which 95% were dead. The monocytes of fraction D (= greater than or equal to 1.075 kg/l) were major interleukin 1 (IL 1) producers and their presence enhanced immunoglobulin synthesis in vitro. Fraction C (= greater than or equal to 1.070 kg/l) were the major prostaglandin E2 (PGE2) producers and demonstrated suppressor activity on in vitro IgG and IgM synthesis. Fractions A and B had minimal production of either IL 1 or PGE2 and lesser effects on the IgG and IgM synthesis. These data demonstrate functional heterogeneity of peripheral blood monocytes with respect to production of both IL 1 and PGE2 as well as accessory cells for immunoglobulin synthesis.

Adult↗
PubMed1984

Effects of long-term treatment of mice with anti-I-J monoclonal antibody and dialyzable leukocyte extract on immune function and lifespan.

In 1969 Walford hypothesized that age-related dysfunctions of the immune system may be involved in the pathogenesis of the lesions and disease of aging. Studies were initiated to test whether immunologic interventions intended to maintain the integrity of the immune system would delay the onset of diseases of aging and prolong lifespan. Adult BC3F1 mice were treated with anti-I-J monoclonal antibody, with human dialyzable leukocyte extract, or with saline once a week for one year. Spleen cells from the mice were then assayed for suppressor, T-helper and B-cell activity. Treatment with dialyzable leukocyte extract decreased the elevated nonspecific suppressor activity. Mice treated with anti-I-J antibody had elevated T-helper cell activity. In another experiment, mice were treated weekly with anti-I-J antibody, dialyzable leukocyte extract, or saline from 18 months of age until natural death. The mice were immunized with avian gammaglobulin at 27 and again at 29 months of age. Both types of immunologic intervention resulted in a greater secondary antibody response than that of the saline-treated control mice. Mice treated with anti-I-J antibody survived longer than did mice of the other two groups. There was a correlation between the magnitude of the secondary response of individual mice and their lifespan. The results provide support for the immunologic theory of aging.

Aging↗
PubMed1984

Phencyclidine-induced immunodepression.

Phencyclidine ("PCP" or "angel dust") and some of its derivatives are psychotomimetic drugs that have been used in general anesthesia for some time. This drug blocks potassium ion channels in brain tissue, and there is a specific PCP binding to lymphocytes. In a study of the effects of this drug on immunocyte function, it was found that humoral and cellular immune responses in vitro were depressed when immunocytes were treated with PCP before biological assay. This finding has implications for PCP abuse and also for the use of its derivative in general anesthesia, where it may contribute to postoperative infection.

B-Lymphocytes↗
PubMed1984

The role of PNP enzyme in autologous rosette-forming cells.

Since purine nucleoside phosphorylase has been associated with suppressor function in lymphocytes, enzyme activities were studied in autologous rosette-forming cells, a subset showing suppressor properties. Levels of this enzyme were higher in these cells than in other T cells. Con A induction of autologous red cell receptors and suppressor activity of T cells were both inhibited in dose-dependent fashion by Formycin B, a well known inhibitor of purine nucleoside phosphorylase. Inhibition of autologous rosette-forming cells was obtained after pulse treatment of cells with Formycin B for as little as 1 hr, whereas cell proliferation was only inhibited when Formycin B was present throughout culture; this confirms the independence of cell proliferation, and development of red cell receptors and suppressor activity. This study indicates a crucial role for purine nucleoside phosphorylase enzyme in induction of T cell suppressor activity.

Concanavalin A↗
PubMed1984

Role of autorosette forming cells in antibody synthesis in vitro: suppressive activity of ARFC in humoral immune response.

The role of autologous rosette forming cells (ARFC) in humoral immune responses was studied using an in vitro system. While depletion of ARFCs from PBL resulted in a significant increase of either total IgG or anti-TT IgG, addition of these cells to the system decreased the production of immunoglobulin to a level comparable to that of unfractionated PBL. The majority of the ARFCs reacted with anti-Leu2a and anti-Leu8. In contrast, the majority of non-ARFCs reacted with Leu3a and only 10% with Leu8 monoclonal antibodies. Stimulation of unfractionated PBL with concanavalin A (ConA) resulted in an increase of the ARFC population. ConA stimulation also increased the number of cells reactive with anti-Leu2 and/or anti-Leu8. The autorosette population had a higher purine nucleoside phosphorylase (PNP) content than the non-ARFC population. Although the ARFC suppressed synthesis of antibody by B cell in vitro when they were mixed with either autologous or allogeneic B cells, a marked proliferation of non-B cells was evident. We conclude that at least two different subpopulations of T cells are capable of forming rosettes with autologous red blood cells.

Antibodies, Monoclonal↗
PubMed1984

Functional heterogeneity of human cord blood monocytes.

Human cord blood monocytes were separated into four different subpopulations by means of a discontinuous bovine serum albumin (BSA) gradient. Of the least dense, 31% were present in fraction A, 17% in fraction B and 13% in fraction C and of the most dense, 20% were in fraction D. The rest (17%) sedimented as a pellet, of which 93% were dead cells. The monocytes of fraction C (density greater than or equal to 1.070) demonstrated suppressor activity on in vitro antibody synthesis of maternal B cells. Fraction D (density greater than or equal to 1.075) monocytes enhanced antibody synthesis of maternal B cells compared with synthesis produced in a similar experiment with unfractionated monocytes. Addition of either fraction A or B monocytes to the mixed culture of T and B cells resulted in antibody production comparable to that produced by addition of unfractionated monocytes. The functional heterogeneity of the cord monocytes was assayed also by 2-deoxyglucose (2-DOG) uptake, a marker for immunological macrophage activation. Fractions A and D showed significantly higher 2-DOG transport than that of unfractionated monocytes; in contrast, fraction C showed a 50% reduction of 2-DOG uptake. Furthermore, in contrast to fraction D, fraction C possessed only minimal phagocytic activity (for antibody-coated sheep erythrocytes) and minimal hemoxygenase enzyme activity. These data demonstrate functional heterogeneity of cord blood monocytes.

Antibody Formation↗
PubMed1984

Specificity of antigen induced helper factor for antibody synthesis in vitro and its relation to lymphocytes interaction.

Human peripheral blood B-cells can be stimulated with PWM and antigen to produce specific antibody in vitro. This stimulation depends on the presence of T-cells and antigen. T cells, however, can be replaced by a soluble factor derived from a 48-hr culture of T-cells with either PWM and/or antigen. The helper factor, in the absence of antigen, acts as a polyclonal activator causing minimal proliferation of B-cells. When antigen is present, production of specific antibody is not dependent on the source of helper factor. Removal of monocytes abolished synthesis of both Ig and specific antibody although antigen and/or helper factor were present. While production of total IgG required autologous monocytes, the origin of the helper factor was not crucial. Production of specific antibody required that both monocytes and helper factor be derived from the same donor; therefore it seems that cooperation of B-, T-cells and monocytes for production of specific antibody is probably Ia restricted. In contrast, for production of polyclonal Ig (in the absence of antigen), cooperation of B-cells and monocytes with T-cells is not.

Antibody Formation↗
PubMed1984

Immune diagnosis of a subset of Alzheimer's disease with preliminary implications for immunotherapy.

Based on remarkable similarities between the central nervous system and the immune system [e. g., both systems have memory cells, both appear to have identical receptors for dopamine, acetylcholine, enkephalins, endorphins, sharing of antigenic determinants on one or another CNS cell and one or another type of immunocyte cell, both systems communicate by soluble substances (e.g., neurotransmitters and lymphokines, respectively)], we have postulated that some forms of Alzheimer's disease are due not to CNS cell death but rather to excess suppression of the brain "B-cell equivalent". We found a pyrrolidone analog useful in stimulating lymphocyte B-cell mitogenesis and function in vitro; this agent subsequently proved dramatically effective in several patients with severe T cell dysfunction and severe recurrent viral infection due to excess T cell suppression. Its use (3-6 months) proved remarkedly effective in certain patients with Alzheimer's disease (frontal lobe cerebral atrophy on CAT scan, duration at least 2 years). A subset with certain immunological dysfunction responded dramatically both immunologically and clinically. In responders in in vitro studies, the defect was corrected in vitro in the presence of the pyrrolidone analog but not by various neuroleptics. Patients without the defect or with the defect but no in vitro correction by pyrrolidone analog agent did not respond clinically. A switch from pyrrolidone to placebo resulted in immunologic and clinical relapse in 2-4 months.

Adult↗
PubMed1984

Effect of polyvinyl pyrrolidone derivative compound on production of interleukin-1 by monocytes.

We studied the effect of 1-acetamide, 2-pyrrolidone (PVP-A), a B-cell mitogen derivative, on interleukin-1 (IL-1) production by peripheral blood monocytes. The compound was capable of inducing monocytes to produce IL-1 to an extent significantly lower than that induced by lipopolysaccharide (LPS). However, addition of PVP-A in conjunction with LPS resulted in IL-1 superinduction. Furthermore, PVP-A addition to monocytes of patients with Alzheimer's disease (AD) restored diminished IL-1 production by these cells to levels comparable with monocytes from age-matched healthy individuals. We also examined the effect of PVP-A on immunoglobulin (Ig) synthesis in vitro. PVP-A increased the production of both IgM and IgG by peripheral blood lymphocytes (PBL) in response to pokeweed mitogen (PWM). We conclude, since Ig synthesis of B-cells requires monocytes, that perhaps PVP-A activated monocytes can boost B-cells resulting in augmented Ig production.

Adult↗
PubMed1983

Immune elimination of aging platelets by autologous monocytes: role of membrane-specific autoantibody.

Membrane-bound IgG was found only on old populations of platelets from normal individuals. This IgG could be dissociated from senescent cells by repeatedly heating the cells. Heat-eluted IgG (He-IgG) prepared from senescent red blood cells was capable of binding to either heat-treated old platelets or Vibrio cholerae neuraminidase (VCN)-treated young platelets, suggesting expression of a common age-dependent antigen on the senescent red blood cells and old platelets. We analyzed the role of membrane-bound IgG in the immune elimination of aging platelets by direct phagocytosis of different platelet subpopulations by autologous monocytes in vitro. While removal of He-IgG from old platelets inhibited their phagocytosis, preincubation of either heat-treated old or VCN-treated young platelets promoted phagocytosis of these cells by autologous monocytes. The phagocytosis of senescent cells required intact IgG on these cells. Either removal of Fc fragments from He-IgG or treatment of autologous monocytes with Fc fragments prior to the phagocytosis assay resulted in a marked reduction of phagocytosis (greater than 75%). We conclude that Fc receptors on the monocytes and the presence of membrane-specific IgG are crucial elements for immune elimination of senescent platelets.

Antigens, Surface↗
PubMed1983

Immune elimination of autologous senescent erythrocytes by Kupffer cells in vivo.

It has been shown previously that autologous monocytes recognize and phagocytose aging self-erythrocytes in vitro. The recognition requires the presence of an autoantibody present in all normal serum. Herein a similar mechanism of recognition and immune elimination of senescent erythrocytes in vivo is reported. When autologous rabbit red blood cells (RBCs), aged either in vivo or neuraminidase-treated young, were reinjected into the animal, most of the old RBCs were trapped in the liver while the majority of the young cells lodged in the spleen. Following reinjection of aging RBCs, the activity of microsomal heme oxygenase enzyme of the liver tissue increased greater than fourfold, suggesting erythrophagocytosis activity of Kupffer cells.

Animals↗
PubMed1983

Phagocytosis of senescent erythrocytes by autologous monocytes: requirement of membrane-specific autologous IgG for immune elimination of aging red blood cells.

The role of membrane-bound IgG present on the membrane of senescent erythrocytes in immune eliminations of aging red cells was investigated. Phagocytosis of populations of red blood cells (RBC) of different ages by autologous monocytes was assessed both by direct phagocytosis and by induction of microsomal heme oxygenase. Removal of IgG from older RBCs inhibited their phagocytosis; in contrast, preincubation of neuraminidase-treated young or in vitro aged RBCs with IgG eluted from old cells led to phagocytosis of RBCs treated by autologous monocytes. It was also found that the Fc portion of membrane-bound IgG is essential for the elimination of senescent cells; less than 15% of old heat-inactivated RBCs coated with F(ab)2 fragment of membrane-bound IgG were phagocytosed. In contrast, more than 50% of old heat-inactivated RBCs coated with heat-eluted IgG were phagocytosed by autologous monocytes. A possible mechanism of elimination of aged cells is discussed.

Adult↗