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Biomedical subjects

D S Terman

Publications and source records attributed to D S Terman.

At least 37 records · Page 2Linked to original sources

Tumoricidal responses in spontaneous canine neoplasms after extracorporeal perfusion over immobilized protein A.

I describe morphologic, histologic, immunohistochemical, and serologic changes in dogs with spontaneous breast adenocarcinoma, squamous cell carcinoma, hemangiopericytoma, and fibrosarcoma after extracorporeal perfusion of plasma over heat-killed and formalin-stabilized Staphylococcus aureus Cowans I (SAC), which was embedded in a membrane filtration system. In 12 dogs with breast adenocarcinoma, tumor necrosis was observed within 12 hours after perfusion; 24 hours after perfusion, multiple visible lesions in 6 of 6 dogs exhibited necrosis, but there was no reaction in uninvolved normal mammary tissue. In 8 dogs, healing of large ulcerated areas of cutaneous tumor was observed within 8 to 18 days after perfusion. Similar tumoricidal responses were observed in dogs with other neoplasms after SAC perfusion. Tumor cell necrosis oserved within 4 hours after extracorporeal perfusion was associated with immunohistochemical deposits of IgG and C'3 and ultrastructural evidence of lytic lesions on tumor cell membranes. No tumoricidal effects were observed after perfusion over Staphylococcus aureus Woods (SAW) (non-protein A bearing) in 3 dogs that previously or subsequently responded to SAC perfusion. No tumoricidal reactions were noted after phlebotomy of up to 50% of plasma volume in 6 tumor-bearing dogs that subsequently responded to SAC perfusion. SAC but not SAW perfusion was followed by increases in circulating tumor associated antibodies (TAA) for up to 48 hours after perfusion. Immune complexes increased after perfusion and remained elevated fo 72 hours. Findings suggest that the acute tumoricial responses are not due to mere removal of circulating immune reactants and may be initiated by TAA that are rendered operational after extracorporeal perfusion over SAC. The rapidity, specificity, and magnitude of the observed tumoricidal effects in various canine neoplastic diseases suggests that this may have potentially broad-based therapeutic and biologic implications for canine neoplasia.

Adenocarcinoma↗

Tumoricidal response induced by cytosine arabinoside after plasma perfusion over protein A.

In dogs with spontaneous mammary adenocarcinomas, a single nontoxic infusion of cytosine arabinoside after extracorporeal perfusion of plasms over immobilized protein A resulted in a necrotizing response rapid in onset and specific for tumorous tissue. Gross tumoricidal reactions 12 hours after this combined treatment exceeded the algebraic sum of responses to cytosine arabinoside and protein A perfusion treatments alone in the same dogs, implying a synergistic effect between the two. The magnitude, rapidity, and specificity of the tumoricidal response after the combined treatment suggests that it may be an effective chemimmunotherapeutic approach to breast adenocarcinoma.

Adenocarcinoma↗

Antibodies to human glomerular basement membrane: modified methodology for detection in human serum.

A new radioimmunoassay for detection of circulating antibodies to human glomerular basement membrane (GBM) is described. GBM was isolated, purified, and an antigenic component extracted by 8 M urea incubation. The 8 M urea extract was radiolabelled, separated on Sephadex G-150, and employed as GBM antigen for detection of binding in a double antibody radioimmunoassay (RIA). Three groups of sera were studied: (a) 40 normal subjects bound a mean of 0.5% +/- 3.4% (s.d.), (b) 12 patients with glomerulonephritis with non-linear immune deposits in direct immunofluorescent staining of kidneys bound a mean of 0.2% +/- 4.4% (s.d.), (c) 14 patients with Goodpasture's syndrome or glomerulonephritis with linear deposits in direct immunofluorescent staining of kidneys bound a mean of 23% +/- 9.1% (s.d.). Serial dilutions of sera from patients with Goodpasture's syndrome showed a progressive reduction in binding while binding of positive sera was inhibited by increasing quantities of unlabelled GBM. The GBM antigen extracted with 8 M urea is convenient to prepare and conditions for performance of the RIA are reproducible. Hence, this may represent a valuable on-site aid for diagnosis and management of patients with anti-GBM mediated glomerulonephritis.

Adult↗

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↗