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Biomedical subjects

R Ahmad

Publications and source records attributed to R Ahmad.

At least 127 records · Page 7Linked to original sources
PubMed1987

Effect of polymeric IgG on human monocyte functions.

Fc and iC3b receptors are involved in various biological functions of phagocytic cells, such as immune adherence and phagocytosis of opsonized particles, degranulation and superoxide generation. In the present study we examined the expression of specific receptors for the Fc portion of IgG (FcR) and for iC3b (CR3), a cleavage product of the third complement component, on human monocytes following in vitro treatment with polymeric and monomeric IgG. Interaction of polymeric IgG (fluid phase) with the monocyte membrane led to a concomitant modulation of both Fc and iC3b receptors. Monomeric IgG, however, down modulated Fc receptor expression only if surface bound. Under these conditions, no concomitant modulation of the iC3b receptor could be observed. The down modulation of Fc and iC3b receptors induced by fluid-phase IgG polymers was also accompanied by a decrease in monocyte functions as expressed by reduced Fc receptor-mediated phagocytosis, decreased release of oxygen metabolites following stimulation by aggregated IgG and opsonized zymosan, as well as in impaired killing of bacteria. These data suggest that a down modulation of Fc and iC3b receptors might have important implications for host defense mechanisms, since interaction with these receptors is required for the proper elimination of many pathogens.

Blood Bactericidal Activity↗
PubMed1987

A component of factor VIII preparations which can be separated from factor VIII activity down modulates human monocyte functions.

In this study we investigated different aspects of monocyte functions following interaction of monocytes (Mo) with therapeutic concentrations of factor VIII (F VIII) concentrate. A short (one-hour) treatment of normal Mo with F VIII concentrates led to a significant (P less than 0.001) down modulation of Fc receptors expressed in the Mo plasma membrane. This down modulation was accompanied by a decrease of Mo effector functions that was expressed by a reduced capacity of F VIII-treated Mo to release O2 radicals (40% of controls) and to kill bacteria (% killing: control Mo, 65%; F VIII-treated Mo, 24% to 51%). Further studies showed that the modulating activity was due to a contaminant present in F VIII concentrates (immune complexes or IgG aggregates). Fractionation using molecular sieving revealed that the modulatory activity was confined to a high-molecular range fraction (Mr greater than 1,270,000 daltons), while the fraction containing monomeric IgG had no effect. Further fractionation by affinity chromatography on protein A-Sepharose separated the coagulation activity (effluent) from the Mo function-modulating activity (eluate). We conclude that treatment with F VIII concentrates might contribute to an immunocompromised state in some hemophiliacs and facilitate opportunistic infections in these patients.

Antigen-Antibody Complex↗
PubMed1987

Bupivacaine accentuates the cardiovascular depressant effects of verapamil in conscious dogs.

To investigate the potential risk of regional anaesthesia in a verapamil-treated patient, the cardiovascular effects of a combined intravenous infusion of bupivacaine and verapamil were studied in seven conscious and chronically instrumented dogs and were compared to those obtained when each drug was infused separately in the same animals. During verapamil infusion, the decrease in arterial pressure and myocardial contractile force, and the increase in heart rate were constant during the infusion. The lengthening of PR interval correlated with the plasma level of verapamil. During infusion of bupivacaine alone, there was an increase in heart rate and arterial pressure at the end of infusion, whereas the initial depression of myocardial contractile force was compensated. PR interval remained unchanged throughout the infusion of bupivacaine. During combined infusion of bupivacaine and verapamil, there was a time-dependent decrease in heart rate, arterial pressure and myocardial contractile force. A further increase in PR interval correlated with verapamil plasma concentrations which were higher than when verapamil was infused alone; bupivacaine plasma levels were in the same range as during bupivacaine infusion alone. Short periods of second-degree atrioventricular block developed in three out of the seven dogs but no relation was found between QT interval and heart rate in the whole group. Calcium chloride during bupivacaine-verapamil returned heart rate, arterial pressure and myocardial contractile force to their control values within 5 min. Atrioventricular block disappeared and PR interval was shortened following administration of calcium. Bupivacaine and verapamil have additive cardiovascular effects which lead to atrioventricular conduction dysfunction. The effects, at these doses, are reversed by calcium chloride.

Animals↗
PubMed1986

Effect of polymeric IgG on human accessory cell function.

Circulating immune complexes are considered to have a profound effect on host defense mechanisms against invading pathogens and to modulate cellular interactions required for an appropriate course of the immune response. In this study we have investigated the influence of polymeric IgG (used as a model system for immune complexes) on accessory functions of human monocytes. We show that a short (1 hr) incubation of human monocytes in the presence of polymeric IgG (16 hr prior to antigen pulsing) led to a significant decrease of these cells' antigen-presenting capacity while accessory functions in alloantigen- or mitogen-driven proliferation systems remained unimpaired. The polymeric IgG-induced impairment of antigen presentation, which was assessed by diminished proliferation of antigen-reactive T cells following stimulation by antigen-pulsed polymeric IgG-treated or Dulbecco's phosphate-buffered saline (PBS-D)-treated control monocytes, could not be attributed to the generation of suppressor mechanisms (no release of soluble suppressor factors, no induction of suppressive monocytes). The release of interleukin-1 by polymeric IgG-treated monocytes and PBS-D-treated monocytes was comparable and polymeric IgG did not down modulate major histocompatibility complex (MHC) class II molecules already expressed in the monocyte plasma membrane. Profound changes in the monocyte plasma membrane occurring subsequent to polymeric IgG treatment possibly accompanied by altered kinetics of MHC class II reexpression are likely to contribute to the observed decrease of antigen presentation.

Antigen-Presenting Cells↗
PubMed1986

A functional defect in the early phase of the immune response observed in patients with hemophilia A.

In search of a functional immunological defect in patients with hemophilia A, we investigated the early phase of the immune response and found a deficiency in the monocyte-T cell interaction after in vitro exposure to a bacterial antigen. T-cell proliferation in response to Escherichia coli-pulsed autologous monocytes was significantly (P less than 0.025) reduced in hemophiliacs [mean dpm +/- SEM (n = 25): 9036 +/- 2600] as compared to healthy controls [mean dpm +/- SEM (n = 24): 17,812 +/- 2985]. This functional defect was expressed in a severe form (antigen-induced monocyte-T cell interaction less than or equal to 2000 dpm) in both HTLV III antibody-positive and -negative patient populations. Significantly decreased T-helper/T-suppressor-cell ratios (mean dpm +/- SEM: patients 1.47 +/- 0.13; controls 2.04 +/- 0.11; P less than 0.001)--but without a concomitant reduction in the absolute number of T-helper cells--could also be observed.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Reduced antigen-induced proliferation and surface Ia expression of peripheral blood T cells following tetanus booster immunization.

Immune regulatory changes after tetanus booster immunization were studied by measuring T-cell proliferation and surface Ia expression after cocultivation of T cells with autologous tetanus toxoid pulsed macrophages. Both soluble and aluminium-absorbed tetanus toxoid was used as antigen. T cells proliferated readily prior to immunization, if TTAl was used as an antigen (when proliferation was measured by the uptake of [3H]thymidine: mean +/- SEM 64.5 +/- 11.5 X 10(3) dpm). The proliferative response of the peripheral blood T cells studied decreased significantly to 29.3 +/- 9.3 X 10(3) dpm (P less than 0.01) 1 week postimmunization, returned to preimmunization values after 2 to 4 weeks, and increased further thereafter. Surface Ia expression paralleled the proliferative response at every point pre- and postimmunization. Serum antibody levels increased steadily during the first weeks. These results demonstrate a functional parallel to the previously described changes in T-cell phenotypes (M. M. Eibl, J. W. Mannhalter, and G. Zlabinger, N. Engl. J. Med 310, 198, 1984) after tetanus booster immunization.

Adult↗
PubMed1985

Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation.

The regulatory effects of an adjuvant (aluminium hydroxide) on the early phase of the immune response have been investigated. Adsorbing a soluble antigen (tetanus toxoid) to aluminium hydroxide led to a significant increase (P less than 0.001) in antigen-induced T-cell proliferation (macrophage-T-cell interaction, MTI) making aluminium hydroxide-adsorbed antigens especially suitable to study immunoregulatory changes in the early phase of the immune response. First studies revealed that this increase was due to an enhancement of antigen uptake by the antigen-presenting cell. However, under conditions allowing for the uptake of comparable amounts of soluble (TTs) or aluminium hydroxide-absorbed (TTAL) antigen, T-cell proliferation in response to TTAL was still higher than in response to TTS. This difference was especially pronounced if suboptimal antigen concentrations were used and could be explained by differences in the TTS-versus TTAL-induced release of interleukin-1 (IL-1). Pulsing with TTAL led to a substantial increase in IL-1 release by monocytes (MO) which then subsequently augmented antigen-induced T-cell proliferation. This was further supported by addition of exogenous IL-1 to cultures of T cells and TTS-pulsed MOs, which also significantly increased the T cells' proliferative response. These findings demonstrate that in the early phase of the immune response, aluminium hydroxide exerts its regulatory effect at the level of the antigen-presenting and mediator-releasing accessory cell.

Adjuvants, Immunologic↗
PubMed1984

Recurrent pyoderma in a family with a defect in leucocyte locomotion.

Granulocyte functions including leucocyte locomotion and chemoluminescence were studied in three generations of a family in which all male members had presented with recurrent pyoderma. While parameters of humoral immunity including serum concentrations of IgG, IgA, IgM, and IgE and of complement components C3 and C4 as well as the response of mononuclear leucocytes to mitogens proved to be within the normal range, leucocyte locomotion was found to be severely impaired in all affected subjects. Moreover, granulocyte dysfunction in male members was associated with the occurrence of a single haplotype (HLA-A2, B13, DR7). These findings suggest that the defect in leucocyte locomotion and the pyoderma might not only have been inherited in an X linked manner but might also have been linked to a gene within the inherited HLA haplotype.

Antibody Formation↗
PubMed1984

Peripheral blood mononuclear cells of splenectomized patients are unable to differentiate into immunoglobulin-secreting cells after pokeweed mitogen stimulation.

The function of B cells from the peripheral blood of splenectomized patients has been investigated at the cellular level. The peripheral blood of these patients contained normal numbers of mononuclear cells (MNC) spontaneously secreting IgG and IgM, but an increased amount of IgA-secreting cells. In contrast to MNC isolated from healthy controls, the patients' peripheral blood MNC were unable to differentiate into immunoglobulin-secreting cells in a pokeweed mitogen-driven culture system. Proliferation in response to pokeweed mitogen, however, was significantly higher with patient MNC as compared to control MNC.

Adolescent↗