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Biomedical subjects

S C Jordan

Publications and source records attributed to S C Jordan.

At least 127 records · Page 7Linked to original sources

1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro.

The active form of vitamin D3, 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2-D3), suppresses in vitro immunoglobulin (Ig) production by activated peripheral blood mononuclear cells (PBM) from normal human subjects by inhibiting T helper/inducer TH cell activity. Normal PBM were fractionated into B, TH and T suppressor/cytotoxic (Ts) cells by fluorescence-activated cell sorting techniques. The resultant subsets were activated with mitogens and were cultured in the presence or absence of a receptor-saturating concentration of 1,25-(OH)2-D3. The sterol reduced [3H]thymidine incorporation in TH cells by 56%, with no effect on Ts or B cells. When 1,25-(OH)2-D3-treated TH cells were co-cultured with untreated B cells and culture supernatants assayed for Ig production, 1,25-(OH)2-D3 abrogated the inducing effect of TH cells on Ig synthesis by B cells. There was no inhibitory effect of the sterol on Ts or B cell activity. In addition, 1,25-(OH)2-D3 produced a dramatic inhibition of interleukin 2 (IL 2) production by activated PBM, but did not inhibit IL 2 receptor generation by these cells. Other vitamin D metabolites tested did not produce this effect. These results suggest that the TH lymphocyte is the specific cellular target for the immunoinhibitory effects of 1,25-(OH)2-D3.

Animals↗

False-negative anti-DNA antibody activity in infantile systemic lupus erythematosus (SLE).

A 2.5-month-old previously healthy female infant presented with serositis , nephrotic syndrome, progressive renal failure, anemia, and thrombocytopenia. Renal biopsy revealed a proliferative glomerulonephritis with glomerular and extraglomerular deposits of IgG, IgM, C3, and Clq by direct immunofluorescence (IF) techniques. Skin biopsy was positive for IgG and C3 deposits in the dermal-epidermal junction by IF. Despite strong clinical and pathological criteria for systemic lupus erythematosus (SLE), tests for antinuclear and anti-DNA antibodies were negative. Circulating immune complexes (CICs) were detected in three separate assay systems. Immunochemical analysis of isolated CICs showed that anti-DNA antibody was present. Analysis of kidney biopsy material by antigen-specific solubilization techniques showed antibodies reactive with ds-DNA in the kidney. These studies confirm that SLE may be a cause of the congenital nephrotic syndrome and that negative SLE serologies may be secondary to binding of available antibody by excess antigen. Analysis of CICs may be helpful in confirming the diagnosis of SLE in seronegative patients.

Adult↗

Prophylaxis against ventricular arrhythmias in suspected acute myocardial infarction: a comparison of tocainide and disopyramide.

Five hundred and seventy one patients admitted to a coronary care unit with suspected acute myocardial infarction were considered for entry into a double-blind study. Two hundred and eighty-three patients were excluded, mainly because of recent treatment with beta-adrenoceptor blocking agents, life threatening arrhythmias requiring specific treatment and left ventricular failure presenting with hypotension or pulmonary oedema. Two hundred and eighty-eight entered the trial of whom 202 were subsequently confirmed to have had myocardial infarction. The effects of tocainide and disopyramide on ventricular arrhythmias were compared with placebo over the first 48 h period. The three treatments were given by a combination of intravenous infusion and oral administration. The doses used were tocainide 500 mg intravenously over 30 min plus 2800 mg orally over 48 h and disopyramide 150 mg intravenously over 30 min plus 1050 mg orally over 48 h. As judged by counts of ventricular premature beats, tocainide and disopyramide exerted a similar and significant antiarrhythmic effect. The median number of ventricular premature beats over the first 24 h of treatment was 58 on placebo compared with 30 on tocainide (P less than 0.05) and 19 on disopyramide (P less than 0.05). The corresponding figures for the second 24 h were 9, 6 and 2, respectively. There were eight deaths and three episodes of ventricular fibrillation with no significant differences between the three treatment groups. Sustained ventricular tachycardia was observed in one patient in the tocainide group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

Acute bromate poisoning associated with renal failure and deafness presenting as hemolytic uremic syndrome.

A case of bromate-induced acute renal failure (ARF) in an infant associated with hemolysis, thrombocytopenia and deafness is presented. The initial clinical and laboratory features suggested the diagnosis of hemolytic uremic syndrome (HUS). The serum bromide level was in the nontoxic range (1.2 mg/dl). However, further investigation of the ingested material revealed the toxic agent to be bromate rather than bromide. The spectrum of bromate (BrO3-) toxicity is different from bromide (Br-) and includes the induction of ARF and deafness. This combined with clinical evidence of behavioral regression and speech loss led to detection of deafness in this patient and confirmed the diagnosis of bromate toxicity.

Acute Kidney Injury↗

1 alpha,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells.

Activated B and T lymphocytes from normal human subjects are known to have the specific high-affinity receptor for 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3). In an attempt to determine a functional role for the sterol in such cells, we studied the effect of 1,25-(OH)2-D3 on DNA synthesis and Ig production by normal human peripheral blood mononuclear (PBM) cells activated in vitro by the polyclonal lymphocyte activators pokeweed mitogen and phytohemagglutinin, and the specific antigen dermatophyton O. A dose-dependent inhibition of [3H]thymidine incorporation was observed in cells incubated with 1,25-(OH)2-D3 in concentrations ranging from 10(-10) to 10(-7) M. Production of IgG and IgM, determined by enzyme-linked immunosorbent assay, was similarly inhibited by increasing concentrations of 1,25-(OH)2-D3. Half-maximal inhibition of DNA and Ig synthesis was found at 10(-10) to 10(-9) M 1,25-(OH)2-D3. This suppressive effect was specific for 1,25-(OH)2-D3; of the other vitamin D metabolites examined, only 10(-7) M 24R,25 dihydroxyvitamin D3 (24,25-(OH)2-D3) had a similar inhibitory effect. 1,25-(OH)2-D3 was not cytotoxic and did not affect unactivated PBMs. These data demonstrate that 1,25-(OH)2-D3 is a potent inhibitor of human PBM Ig production in vitro and suggest that this action is mediated through the hormone's antiproliferative effect on Ig-producing B cells and/or helper T cells.

24,25-Dihydroxyvitamin D 3↗

Continuous ambulatory peritoneal dialysis catheters in children.

Based on clinical experience with 35 subjects younger than 21 years of age who underwent continuous ambulatory peritoneal dialysis (CAPD) during a two-year period at our institution, this procedure was found to be superior to hemodialysis in children because it allowed great freedom of activity and produced fewer complications requiring hospitalization. Moreover, CAPD appeared to be less expensive than hemodialysis, and no mortality or significant morbidity occurred during the 386 patient-months of catheter usage. Exit site infections, peritonitis, and abdominal hernias were the most common complications, often requiring minor surgical repairs. Using a specific operative technique for catheter placement and smaller volumes of dialysate during the first week after placement, these complications were minimized. Thus, CAPD is an effective, advantageous method for treatment of end-stage renal disease in children.

Adolescent↗

Characterization of soluble circulating immune complexes by antigen-specific dissociation: detection in the Raji cell radioimmune assay.

The Raji cell radioimmune assay (RC-RIA) was used to demonstrate antigen-mediated dissociation of soluble circulating immune complexes (CICs). The dissociation resulted in a reduction in size and number of CICs which was reflected in diminished RC-RIA activity. Two sets of experiments were performed to examine the effect of preincubating excess antigen with immune complexes. First, bovine serum albumin (BSA) was preincubated with preformed BSA-anti-BSA immune complexes and RC-RIA activity was examined before and after incubating. Second, CIC-positive sera from two patients with human thyroglobulin (HuTg)-mediated immune complex glomerulonephritis were preincubated with HuTg and RC-RIA activity was examined. Significant reductions in RC-RIA activity were seen in both situations. The validity of these observations was confirmed by immunofluorescence and electrophoretic techniques. Sucrose density gradient ultracentrifugation studies confirmed the antigen-mediated diminution in size and number of soluble immune complexes as the mechanism responsible for diminished RC-RIA activity.

Animals↗

Cadaver renal transplant outcome in recipients with autolymphocytotoxic antibodies.

The major impact of autolymphocytotoxic antibodies (ALCA) on renal transplantation has been in the interpretation of the pretransplant crossmatch as a cause of false-positive results. Less attention has been paid to the direct affects of ALCA on renal allografts. We have examined the sera of 38 recipients of 41 cadaver renal allografts for the presence of ALCA. There were 9 patients with ALCA who received 10 allografts. In these allografts with ALCA, actuarial graft survival was significantly improved (P less than 0.05) over that of 31 transplants without ALCA. In recipients with ALCA, graft survival was 90% at six months and 60% at one and two years; in recipients without ALCA, graft survival was 48% at six months, 35% at one year and 24% at two years. ALCA may be exerting graft-enhancing properties by means of an autoregulatory effect upon the recipient's immunologic system.

Autoantibodies↗

Peritonitis in children undergoing continuous ambulatory peritoneal dialysis.

The incidence of peritonitis in 29 children undergoing continuous ambulatory peritoneal dialysis during a 20-month period was one episode every 12.5 patient-months. Of the 20 episodes of peritonitis, seven (35%) were treated on an ambulatory basis, and 13 required patient hospitalization. The annualized hospitalization rate for the 29 patients during 252 patient-months was 3.8 days per patient. All patients recovered from peritonitis; the only complication was the need to replace two peritoneal catheters. These data would seem to indicate that the potential threat of peritonitis should not curtail continued utilization of continuous ambulatory peritoneal dialysis in children.

Adolescent↗

Plasma inhibition of lymphocyte proliferation in nephrotic syndrome: correlation with hyperlipidemia.

Plasma-mediated inhibition of normal lymphoproliferation is an unexplained immunologic abnormality frequently observed in nephrotic syndrome. Since hyperlipidemia, also common in nephrotic syndrome, has been linked with in vitro and in vivo immunodeficiency in other diseases, we have quantitated plasma-mediated inhibition of lymphoproliferation and related it to the degree of hyperlipidemia in 19 patients with nephrotic syndrome. Fifteen patients were hyperlipidemic; the plasma of 9 of these 15 caused greater than 60% inhibition of antigen-specific proliferative responses of normal lymphocytes. None of the four normolipidemic plasmas, nor a hyperlipidemic plasma depleted of lipoproteins by ultracentrifugation, was inhibitory. A highly significant correlation between the degree of inhibition and the plasma triglyceride levels in patients with nephrotic syndrome was observed (P less than 0.001). The results suggest that elevated plasma lipids may be the cause of the plasma-mediated inhibition of lymphoproliferation in nephrotic syndrome.

Adolescent↗

Circulating immune complexes during various forms of renal allograft rejection episodes.

Previous reports on the nephritogenic and immunological enhancing capacity of posttransplant circulating immune complexes (CICs) are conflicting and have been confined to the study of acute rejection episode (AR). This study was undertaken to assess the nephritogenicity of CICs in patients undergoing accelerated acute rejection (AAR) and chronic rejection (CR) episodes. We also assessed the possible role of CICs as mediators of immunological enhancement by assessing CIC levels in long-term-stable allograft recipients. To asses the nephritiogenic role of CICs, 98 CIC determinations were performed on 49 serum samples from 41 pediatric renal transplant recipients using the C1q solid-phase assay (C1q-SPA) and the Raji cell radioimmunoassay (Raji-RIA). Serum samples from normal subjects served as controls. No recipient undergoing AAR had evidence of CICs by eigher assay. 5 of 21 (23.8%) recipients undergoing CR had positive CIC levels in the Raji-RIA, while 4 of 21 (19%) recipients had positive CICs inthe C1q-SPA. There was no statistically significant correlation of CIC levels with long-term allograft function. In addition, there was no evidence supporting antithymocyte globulin as an immunogen in patients demonstrating posttransplant CICs. In summary, CICs do not appear to be an important mediator of AAR or CR episodes, and CICs were not routinely detected in patients with good long-term allograft function.

Antigen-Antibody Complex↗

Circulating immune complexes in pediatric renal allograft rejection.

Previous reports on the generation and nephritogenic capacity of post-transplant circulating immune complexes (CICs) are conflicting. To assess the pathogenicity of CICs in acute rejection (AR), 784 CIC determinations were performed on 392 serum samples from 27 pediatric renal allograft recipients using the C1q-solid phase assay (C1q-SPA) and the Raji cell radioimmunoassay (Raji-RIA). Serum samples from transplant recipients not undergoing rejection episodes and from normal subjects served as controls. Of the 784 CIC determinations, 723 (92.3%) were negative in both assays. CICs were present at some point post-transplant in eight (19.6%) recipients. Correlation of CIC levels with allograft rejection was found in only two patients with CIC levels responding to antirejection therapy; however, statistical analysis of data by chi 2 analysis failed to reveal a significant correlation of CICs with AR episodes. Allograft histology in three recipients demonstrated characteristic signs of AR. Immunofluorescent studies did not reveal significant deposition of immunoglobulin or complement. Sucrose density gradient ultracentrifugation studies confirmed the immune complex nature of materials reactive with the CIC assays. There was no immunological evidence supporting antithymocyte globulin (ATG) as an immunogen in patients demonstrating CICs post-transplant. CICs do not appear to be an important mediator of AR. Statistical analysis of data using the chi 2 test failed to reveal a positive correlation of CIC levels with AR or ultimate allograft outcome.

Antigen-Antibody Complex↗