ABSTRACT
Peripheral blood mononuclear cells (PBMC) of 29 patients with systemic lupus erythematosus (SLE) and 14 normal individuals were investigated for the in vitro production of anti-nuclear antibodies (ANA). Twenty-eight of 29 SLE patients but only one control spontaneously produced ANA in unstimulated PBMC. Pokeweed mitogen induced ANA synthesis in six controls. No detectable ANA was observed in B cell enriched fraction except in two cases of SLE. Recombination of B + T cell enriched fractions and PBMC supernatants from SLE patients could induce B cells to synthesize ANA. These results indicate that: (1) SLE patients spontaneously produced ANA in vitro whereas controls rarely did; (2) autoreactive clones exist in normal individuals but are kept under control and (3) T cell help is required for ANA triggering.
Subject(s)
Antibodies, Antinuclear , Lupus Erythematosus, Systemic/immunology , Lymphocytes/immunology , Antibodies, Antinuclear/analysis , B-Lymphocytes/immunology , Cells, Cultured , Humans , In Vitro Techniques , Lymphocyte Cooperation , T-Lymphocytes, Helper-Inducer/immunologyABSTRACT
The in vitro production of anti-double stranded DNA antibodies (anti-DNA) by peripheral blood mononuclear cells (PBMC) was investigated in 19 patients with systemic lupus erythematosus (SLE) and in 12 normal individuals, using a micro solid phase enzyme immunoassay. PBMC from SLE patients spontaneously produced anti-DNA with a higher frequency (16 of 19) than did PBMC of controls (three of 12). In addition SLE patients produced predominantly IgG antibodies. PWM and DNA enhanced anti-DNA synthesis is spontaneously low and non-producers, but acted as inhibitors in spontaneously high producers. The partial removal of T cells decreased or abolished anti-DNA synthesis in four of nine SLE patients. In contrast the B cell enriched fractions of five of nine SLE and five of seven normal patients produced the same or higher anti-DNA levels than did the corresponding unseparated PBMC. These results suggest evidence for autoreactive B cells in SLE as well as in normals, and therefore the combination of these autoreactive B cells with helper and/or suppressor T cell disorders could lead to the over production of anti-DNA seen in different patients with SLE.
Subject(s)
Antibodies, Antinuclear/analysis , DNA/immunology , Lupus Erythematosus, Systemic/immunology , Lymphocytes/immunology , Adult , B-Lymphocytes/immunology , Cells, Cultured , Humans , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Lymphocytes/drug effects , Pokeweed Mitogens/pharmacologyABSTRACT
The substitution of aminochlorambucil by a methyl group increased the chemical reactivity in IV b (n = 1) and IV b (n = 2) but their cytotoxicity remained low. The immunosuppressive effect (adjuvant arthritis in Rats and tuberculin related skin reaction) was observed with IV b (n = 2). Aminochlorambucil was effective on adjuvant arthritis only and IV b (n = 1) had no activity. Aminochlorambucil, IV b (n = 1) and IV b (n = 2) were devoid of any non-specific anti-inflammatory activity.
Subject(s)
Chlorambucil/analogs & derivatives , Animals , Anti-Inflammatory Agents , Antineoplastic Agents , Arthritis, Experimental/drug therapy , Chlorambucil/pharmacology , Immunosuppressive Agents , Male , Rats , Tuberculin TestABSTRACT
The separation of 5-cholestene-3 beta, 25 (RS), 25-triol 3,26-diacetate into the diastereoisomers 25R and 25S by means of high pressure liquid chromatography (HPLC) is described. Their absolute configuration cannot be yet established. The less polar diastereoisomer is arbitrarily called 25 zeta1 and the more polar one 25 zeta2. Bromination, dehydrobromination and ultraviolet irradiation conducted to 25 zeta1, 26(OH2D3 and 25 zeta2, 26(OH)2D3 respectively. Their biological activity is described.
Subject(s)
Dihydroxycholecalciferols , Dihydroxycholecalciferols/isolation & purification , Hydroxycholecalciferols , Animals , Bone and Bones/drug effects , Bone and Bones/metabolism , Calcium/metabolism , Dihydroxycholecalciferols/pharmacology , Hydroxycholecalciferols/isolation & purification , Magnetic Resonance Spectroscopy , Male , Rats , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The resolution of 5-cholestene-3 beta, 24 RS,25 triol 3,24-diacetate into the diastereoisomers 24 R and 24 S by means of liquid chromatography is described. Bromination, dehydrobromination and ultraviolet irradiation of both diastereoisomers led to 24 R,25 (OH)2D3 and 24 S,25 (OH)2D3 respectively. Their structure was further confirmed by thin layer chromatography, ultraviolet and mass spectroscopy.
