ABSTRACT
Humoral and cellular immune responses were followed in multiple sclerosis patients treated with Copolymer 1 (Cop1, glatiramer acetate, Copaxone) who participated in three different clinical trials. All patients (130) developed Cop1 reactive antibodies, which peaked at 3 months after initiation of treatment, decreasing at 6 months and remaining low. IgG1 antibody levels were 2-3-fold higher than those of IgG2. The proliferative response of Peripheral Blood Mononuclear Cells (PBMC) to Cop1 was initially high and gradually decreased during treatment. Antibodies and T cell responses to MBP were low and did not change significantly during the treatment. The humoral and cellular immunological responses to Cop1 do not correlate with the side effects and do not affect its therapeutic activity. The preferential production of IgG1 over IgG2 antibodies may indicate that Th2 responses are involved in mediating the clinical effect of Cop1.
Subject(s)
Multiple Sclerosis/drug therapy , Peptides/therapeutic use , Adult , Antibody Affinity/immunology , Cell Division/drug effects , Double-Blind Method , Female , Glatiramer Acetate , Humans , Immunoglobulin G/blood , Leukocytes, Mononuclear/drug effects , Male , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Myelin Basic Protein/immunology , Myelin Basic Protein/pharmacology , Peptides/adverse effects , Peptides/immunology , Recurrence , Severity of Illness Index , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Treatment OutcomeABSTRACT
Here we report that atrial natriuretic peptide (ANP), a known activator of particulate guanylate cyclase, induces attraction and swimming speed enhancement of human spermatozoa in vitro. Using capillary assays under a variety of experimental conditions (ascending or descending gradients of ANP, or no gradient at all) and microscopic assays in which individual spermatozoa could be followed, we found that spermatozoa followed the gradient of ANP and accumulated in it. Speed enhancement was detected in the presence of ANP without a gradient. These observations suggest either that an ANP-like substance is the physiological attractant for human spermatozoa, or, more likely, that ANP directly affects guanylate cyclase in a manner similar to that caused by the physiological attractant.
Subject(s)
Atrial Natriuretic Factor/pharmacology , Chemotaxis/drug effects , Spermatozoa/drug effects , Glycopeptides/pharmacology , Humans , Male , Neprilysin/antagonists & inhibitorsABSTRACT
The ability to deform is an important feature of red blood cells (RBCs) for performing their function of oxygen delivery. Little is known about the hormonal regulation of RBC deformability. Here we report that human atrial natriuretic peptide (ANP) acts directly on human RBCs leading to the elevation of local bending fluctuations of the cell membrane. These changes are accompanied by an increase in the filterability of RBCs. These ANP effects were mimicked by cyclic GMP analogues, suggesting modulation of local membrane bending fluctuations and RBC filterability via a cyclic GMP-dependent pathway. The effect of ANP on the mechanical properties of RBCs suggests that ANP may increase the passage red blood cells through capillaries resulting in an improved oxygen delivery to the tissues.
Subject(s)
Atrial Natriuretic Factor/pharmacology , Erythrocyte Deformability/drug effects , Erythrocytes/drug effects , Dibutyryl Cyclic GMP/pharmacology , Dose-Response Relationship, Drug , Humans , MovementABSTRACT
Thymocytes from SJL/J mice exhibit a periodicity in their response to hormonal stimulation with isoproterenol. This periodicity (5-9 days) is expressed in large changes in the intensity of the response (peak levels of intracellular cAMP which vary approximately 6-fold), and in the response pattern, i.e., in the occurrence or non-occurrence of an immediate hormone-induced desensitization. In contrast, C57BL/6 thymocytes have a homogeneous response pattern (in all cases there was an immediate desensitization). Their response does change with the same periodicity, but these changes are restricted to the intensity of response (the peak of cAMP levels varies only approximately 2-fold). Using T, B and pre-B shown that these periodic changes may be due to fluctuations in T cell subpopulations in the thymus and possibly also the infiltration of B cells into it. These observations provide a useful system for studying at the cellular and molecular level the known correlation between endocrine disorders and neoplasia in mice. On the other hand, the set of cell lines with such different response patterns to a single hormone may be used for the identification and isolation of additional cellular constituents involved in the cellular response to hormones and its immediate desensitization.
Subject(s)
Endocrine System Diseases/pathology , Isoproterenol/pharmacology , Mice, Inbred Strains/physiology , Thymus Gland/drug effects , Animals , B-Lymphocytes/drug effects , Cell Line , Cell Movement , Cells, Cultured , Cyclic AMP/metabolism , Disease Susceptibility , Endocrine System Diseases/metabolism , Female , Leukemia, Experimental/genetics , Male , Mice , Mice, Inbred C57BL , Periodicity , Stimulation, Chemical , T-Lymphocytes/drug effects , Thymus Gland/pathologyABSTRACT
Preparations of the catalytic subunit of cAMP-dependent protein kinase from rabbit skeletal muscle, which appear to be homogeneous by SDS-polyacrylamide gel electrophoresis, were often found to contain a hormone-like factor (HLF) which causes an immediate rise, then a decline of intracellular cAMP in a B-lymphoma cell line. Active HLF is released when the fractions that contain it in an inactive form are incubated with cAMP prior to chromatography, or passed through an immobilized cAMP column. HLF seems to be a peptide: it loses its cell-stimulating capability after proteolysis and has an apparent molecular mass of 2.2-2.5 kDa.
