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Biomedical subjects

D S Terman

Publications and source records attributed to D S Terman.

At least 19 recordsLinked to original sources

Extracorporeal immunoadsorption: initial experience in human systemic lupus erythematosus.

Extracorporeal immunoadsorption and filtration was used in treatment of a 29-year-old woman with severe lupus nephritis. For the previous 35 days single-stranded DNA (ssDNA) antibody and immune-complex levels had been continuously raised with only partial improvement on prednisone therapy. Levels of immune complexes and ssDNA antibodies were substantially reduced by extracorporeal plasma filtration and adsorption of DNA collodion charcoal. There were no major clinical complications. After perfusion, the reduction of ssDNA binding and immune complexes in serum was sustained, serum C'3 became normal, and serum creatinine and proteinuria improved. 28 days after perfusion, subendothelial glomerular deposits were much reduced compared with those in a pre-perfusion biopsy specimen. Selective immunoadsorption is a promising new approach to persistent lupus nephritis refractory to drug therapy alone.

Adult

Ex vivo removal of serum IgG in a patient with colon carcinoma: some biochemical, immunological and histological observations.

Plasma of a patient with metastatic colon carcinoma was perfused over Formalin and heat-killed S. aureus, in an extracorporeal filtration apparatus, in order to nonspecifically remove IgG and its complexes. Twenty ex vivo absorption procedures were done, over a five-month period, with a minimum of discomfort to the patient. Extracorporeal perfusion of plasma on S. aureus effectively reduced the levels of IgG and immune complexes in the perfused plasma. The nonspecific removal of IgG resulted in 1) slight biochemical alterations in the serum, 2) a transient reduction in the serum blocking activity and appearance of complement-dependent serum cytotoxicity, 3) an increase in the serum IgM levels, 4) a transient increase in the Ig surface-bearing lymphocytes and a decrease in "E" rosetting lymphocytes in the first 24-48 hours postperfusion, particularly during the early treatments, 5) an improvement in general condition of the patient and decrease in tumor size, and 6) histological changes in the tumor consistent with tumor destruction. The potential problems and clinical applications of procedures involving ex vivo specific or nonspecific immunoabsorbents are discussed.

Adenocarcinoma

Detection of porcine-specific canine antibodies by a radioimmunological technique.

A sensitive radioimmunological technique is described in which the primary interaction of 125I porcine membrane antigens with naturally occurring canine antibodies is measured by precipittion with 20% polyethylene glycol. Porcine membrane antigens were isolated, radiolabeled, and found to be maximally soluble in 20% polyethylene glycol solution. Binding of canine antisera to porcine antigens could be reduced by absorption with porcine lymphocytes. An eluate was obtained from a porcine kidney that was perfused in vivo for 330 min with oxygenated canine plasma and was identified as canine IgG by immunoelectrophoresis. When added to normal dog serum, the eluate markedly augmented the binding titer. Samples of dog serum taken after extracorporeal perfusion showed a significant decline in binding with no significant changes in lymphocytoxicity titer. These results suggest that this primary binding assay is a more sensitive indicator of the presence of graft-specific humoral antibodies and may be of value in evaluating prospective heterograft donors as well as in following the course of therapy.

Animals

Attenuation of canine nephrotoxic glomerulonephritis with an extracorporeal immunoadsorbent.

A novel immunoadsorbent is described in which soluble canine glomerular basement membrane (GBM) antigen was immobilized in collodion membranes adherent to small charcoal particles. As much as 80% of the added GBM antigen was retained in the collodion-charcoal. The binding of GBM antibody to immobilized GBM antigen in vitro and in vivo was demonstrated. For in vivo studies, an extracorporeal circulation system was established, and mongrel dogs were then injected intravenously with GBM collodion-charcoal for 4 h. Renal tissue was examined by fluorescence and light microscopy for the deposition of heterologous gamma globulin and glomerular inflammation before and after the extracorporeal procedure. Results showed less deposition of heterologous IgG and less inflammation in experimental dog kidneys than in control kidneys. There was no evidence of release of 131I-labeled GBM from the immunoadsorbent at the conclusion of perfusion experiments and no significant biochemical or hematologic alterations. Finally, extracorporeal immunoadsorbent treatment was capable of attenuating the early heterologous phase of passive canine nephrotoxic nephritis and may have a potential role in the therapy of anti-GBM-mediated nephropathy.

Animals

Specific removal of antibody by extracorporeal circulation over antigen immobilized in collodion-charcoal.

Studies were undertaken to determine whether BSA immobilized in collodion membranes adherent to activated charcoal particles, would be capable of specifically removing circulating BSA antibody in vitro and in vivo in an extracorporeal system in dogs. Up to 59-8 mg of BSA were retained in collodion membranes adherent to small particles. In vitro studies demonstrated that immobilized BSA could specifically reduce BSA binding activity from circulating antisera. For in vivo studies, an extracorporeal circulation system was established and arterial blood was circualted through a continuous flow celltrifuge in which plasma was separated from formed elements of the blood. Only plasma was circulated over the BSA collodion-charcoal immunoadsorbent. Anti-BSA and anti-HSA atibodies were passively infused into dogs and, after an equlibration period of 12 or 15 min, plasma was passed over the BSA collodion-charcoal immunoadsorben. Plasma exhibited a sharp reduction in BSA binding over the next 30-60 min with only slight reduction in anti-HSA binding the same period. Dogs, actively immunized to BSA and HSA, were also treated by extracorporeal plasma perfusion over BSA collodion-charcoal. A specific decline in BSA binding of sera, was again observed with minimal changes in HSA binding. A post-perfusion rebound of BSA binding was observed which reached pre-perfusion levels after 6-8 days. A second treatment during the rebound period also resulted in a specific decline in BSA binding with a similar pattern of antibody rebound. There were no significant changes in I-labelled BSA recorded on the charcoal before and after in vivo procedures and no signifcant alterations in haematocrit, serum sodium, potassium, calcium, magnesium or creatinine levels before and after the procedures. These data suggests that antigen-coated charcoal may specifically withdraw circulating antibodies in vivo with minimal release of the entrapped antigen and little alteration in the host's haematological and biochemical status.

Animals

Renal failure following gentamicin in combination with clindamycin.

Acute renal failure (ARF) occurred concomitantly with the administration of gentamicin in combination with clindamycin in three patients in whom no other known predisposing cause of ARF could be demonstrated. The evidence for combined nephrotoxicity consisted of the temporal relationship between administration of the antibiotics and the development of ARF, and the prompt improvement in renal function upon cessation of therapy. Complete or partial recovery of renal function occured in all patients. Renal function should be carefully monitored in patients receiving this antibiotic combination.

Acute Kidney Injury

Degradation of circulating DNA by extracorporeal circulation over nuclease immobilized on nylon microcapsules.

Studies were undertaken to determine whether deoxyribonuclease I, (DNase I) once immobilized on activated nylon microspheres, would be capable of degrading circulating DNA in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 4.73 mg of Dnase I. In vitro studies showed that DNase I immobilized on microspheres degreded a significant percentage of 125I-native DNA (nDNA) within 15 min. Mongrel dogs were injected with 125I-nDNA and a variation in initial t 1/2 in individual animals was observed. Therefore, for experimental studies, 125I-nDNA was injected and decay was recorded during a control period in which untreated microcapsules were utilized in the extracorporeal system. DNase I microspheres were then introduced into the extracorporeal circuit which resulted in an acceleration of degradation of acid precipitable 125I-nDNA. When 200 mug of unlabeled DNA with 125I-nDNA was injected, a similar augmentation of DNA degradation was noted after extracorporeal circulation over DNase I microcapsules. This effect could not be attributed to release of DNase I from the microspheres since no 131I-DNase was detected in the serum or organs of the dogs at the conclusion of the experiments. 125I-nDNA:anti-DNA complexes were passively injected into dogs and after a similar control period of circulation over untreated microcapsules. DNase I microspheres were introduced. Results showed a rapid acceleration in the degradation rate of 125I-nDNA:anti-DNA complexes precipitable with (NH4)2SO4. Extracorporeal circulation over nylon microspheres resulted in no significant alteration of the host's hematocrit or platelet count, and little residual cellular debris on the microcapsules. These data suggest that DNAase immobilized on nylon microspheres may have a potential role in the specific therapy of systemic lupus erythematosus, when it is desirable to hydrolyze DNA circulating free or in combination with antibody.

Animals

Specific removal of DNA antibodies in vivo with an extracorporeal immuno-adsorbent.

The selective removal of circulating antibody specific for DNA was affected with an immuno-absorbent consisting of DNA-cellulose incorporated into agar gel. Antisera to DNA obtained from patient with systemic lupus erythematosus was circulated in vitro through experimental and control columns by a dual channel haemodialysis pump and serial aliquots were withdrawn and assayed for antibody. A 65% reduction in DNA binding of serum was achieved at a flow rate of 210 ml/min over a 4-hr period with no release of 125I-labelled DNA from the column into the serum. For in vivo studies, 2-6-3-8 kg rabbits were actively immunized with methylated bovine serum albumin conjugated to single-stranded DNA (MBSA-ssDNA). Whole blood was pumped from the femoral artery through an immuno-adsorbent composed of ssDNA-cellulose in an agar matrix. Results showed significant reductions in ssDNA binding activity over various periods after connection of the rabbit's circulation to the immuno-adsorbent with only minimal changes in BSA binding during the same period. Little release of incorporated 125I-labelled DNA from the column as assayed in the blood and tissues of the experimental animals occurred during the procedure. The immuno-adsorbent columns showed no residual cellular debris or thrombotic material. These results suggest that this immuno-adsorbent system may be used to specifically withdraw circulating DNA antibodies in vivo. Such a system may have clinical potential for specific therapy of systemic lupus erythematosus.

Adsorption

Specific extraction of antigen in vivo by extracorporeal circulation over antibody immobilized in collodion-charcoal.

A novel extracorporeal immunoadsorbent is described in which anti-bovine serum albumin (anti-BSA) was entrapped in collodion membranes adherent to activated charcoal particles. This immunoadsorbent was capable of specifically removing circulating BSA in vitro and in vivo in an extracorporeal system in dogs. In preparation of the immunoadsorbent, up to 81.2% of added anti-BSA was retained on collodion-charcoal. In vitro circulation studies demonstrated that anti-BSA collodion-charcoal removed 812% more 125I-BSA than control colloidon-charcoal. For in vivo studies, an extracorporeal circulation system was established and arterial blood was passaged through a continuous flow celltrifuge wherein plasma which was separated from formed elements of the blood was circulated over anti-BSA and control rabbit gamma-globulin collodion-charcoal. 125I-BSA was passively infused into mongrel dogs, and plasma was then circulated over extracorpeal immunoadsorbents for 2 hr. Results showed up to 896% greater uptake of circulating 125I-BSA on the charcoal containing immobilized anti-BSA compared to control charcoal. There was no evidence of release of anti-BSA from the immunoadsorbent since 125I-anti-BSA cpm on the charcoal before and after the experiments were unchanged. In addition, there were no significant alterations in hematocrit, leukocyte counts, serum sodium, potassium, calcium, magnesium, or creatinine levels before and after in vivo procedures. These data suggest that this immunoadsorbent consisting of anti-BSA immobilized in collodion membranes adherent to charcoal particles may specifically withdraw circulating antigens in vivo with minimal release of entrapped antibodies and no significant alteration in the host hematologic and biochemical status.

Animals