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Biomedical subjects

B R Gordon

Publications and source records attributed to B R Gordon.

At least 55 records · Page 3Linked to original sources

Plasma high density lipoprotein is increased in man when low density lipoprotein (LDL) is lowered by LDL-pheresis.

Plasma high density lipoprotein (HDL) concentrations were increased in five hypercholesterolemic normoglyceridemic patients after removal of plasma low density lipoprotein (LDL) by LDL-pheresis. In each patient up to 80% of circulating LDL was removed by passing plasma through immunoadsorption columns containing antibody to apolipoprotein B immobilized to Sepharose. Rebound of LDL was slow after the procedure: 5-7 days in four non-familial hypercholesterolemic patients and greater than 14 days in one patient with homozygous familial hypercholesterolemia. Plasma HDL rose above the pretreatment baseline during the interval between treatments in four of the five patients. When treatments were repeated weekly, time-averaged plasma LDL was lowered by 40-70%, while plasma HDL cholesterol and apolipoprotein AI were increased up to 2-fold, depending on the degree of LDL lowering. Plasma HDL concentrations fell back to their baseline values when LDL-pheresis was stopped and rose again when treatment was restarted. Thus, LDL-pheresis may augment the therapeutic effectiveness of LDL lowering by raising plasma HDL levels and the concentration of HDL relative to LDL.

Adult↗

Plasmapheresis in five dogs with systemic immune-mediated disease.

Five dogs with signs referable to systemic immune-mediated disease, four with systemic lupus erythematosus, and one with probable lupus myopathy were treated with plasmapheresis in combination with low-dose immunosuppressive drug therapy. Previous treatment with conventional dosages of prednisone was not satisfactory and was associated with adverse side effects. Two dogs had short-term responses to combined therapy, and 3 dogs had sustained responses. Clinical remission was associated with normalization of serum complement levels and decreases in antinuclear antibody titers. Toxicosis potentially related to plasma component depletion was observed in 2 dogs. Acute clinical illness and disease states refractory to conventional immunosuppressive therapy should be considered indications for plasmapheresis.

Adrenal Cortex Hormones↗

Plasmapheresis as adjuvant therapy for autoimmune hemolytic anemia in two dogs.

Severe, acute, autoimmune hemolytic anemia in 2 dogs was treated, using prednisone, cyclophosphamide, plasmapheresis, and blood transfusion. In 1 case, splenectomy was performed successfully after plasmapheresis and blood transfusion. Antibody removal by means of plasmapheresis effected short-term stabilization to severe hemolysis in both dogs, but was suspected to have contributed to the death of 1 dog.

Anemia, Hemolytic, Autoimmune↗

Plasmapheresis in a patient with angioimmunoblastic lymphadenopathy. Improvement in clinical and immunologic abnormalities.

A patient with steroid resistant, allergen related angioimmunoblastic lymphadenopathy underwent a course of six plasmaphereses during a three-week period. A 75% reduction in lymph node size along with the disappearance of her night sweats occurred. Immunologic abnormalities prior to plasmapheresis included the presence of elevated levels of circulating immune complexes, high levels of spontaneous mononuclear cell blastogenesis and abnormal mitogen responses to Conconavalin A and phytohemagglutinin. Following plasmapheresis there was a marked reduction in immune complex levels, and return of spontaneous blastogenesis and mitogen responses to normal levels. Mechanisms for the beneficial effect seen in this patient include removal of: (1) the antigenic stimulus; (2) antigen antibody complexes; and (3) other humoral factors which may modulate lymphocyte or macrophage function. Additional studies of plasmapheresis are warranted in selected patients with allergen related AIL.

Aged↗

Plasmapheresis-immunoadsorption for treatment of systemic lupus erythematosus in a dog.

Systemic lupus erythematosus was diagnosed in a 3-year-old, male German Shepherd Dog. Clinical signs included lethargy, partial anorexia, fever, joint swelling, and skin and oral ulceration. The diagnosis was confirmed on the basis of an antinuclear antibody titer of 1:640 and immunofluorescence for immunoglobulin G at the dermal-epidermal junction in skin biopsy specimens. Treatment with prednisone and cyclophosphamide failed to induce remission. Intensive plasmapheresis-immunoadsorption, using purified Staphylococcus protein A in combination with low-dose prednisone therapy, resulted in sustained remission.

Animals↗

Post-partum hemolytic uremic syndrome: treatment with plasma exchange.

Four patients with post-partum hemolytic uremic syndrome were treated with plasma exchange using fresh frozen plasma as replacement. Each patient had microangiopathic hemolysis, thrombocytopenia, and progressive renal and hepatic failure. Disseminated intravascular coagulation was a major feature in each case. The microangiopathy and thrombocytopenia resolved in each patient following plasma exchange. Normalization of renal and hepatic function occurred in three patients, including one patient who died as a result of coronary artery dissection. One patient died as a result of an intracerebral bleed. Plasma exchange with fresh frozen plasma replacement appears to be of benefit if used early in the course of post-partum hemolytic uremic syndrome.

Acute Disease↗

Protein A-independent tumoricidal responses in dogs after extracorporeal perfusion of plasma over Staphylococcus aureus.

Protein A-positive or -negative Staphylococcus aureus preparations were used in an extracorporeal system to treat dogs with spontaneously occurring cancers. Tumor regression was seen in 4 of 7 dogs treated by reinfusion of plasma that had been incubated with protein A-positive S. aureus Cowan I strain (SAC). Therapy was associated with fever, liver enzyme abnormalities, and hypocomplementemia. Tumor response and toxicity could be diminished by more extensive washing of the SAC preparation. Tumor regression was also seen in 2 of 2 animals treated with protein A-negative S. aureus Wood strain 46. In addition, tumors regressed in 3 of 4 dogs treated with infusions of protein A-free saline extracts from S. aureus. These results suggest that the release of a non-protein A bacterial product contributes to tumor regression following incubation of plasma with S. aureus.

Alanine Transaminase↗

Immunologic abnormalities in myelofibrosis with activation of the complement system.

Eighteen patients with agnogenic myeloid metaplasia with myelofibrosis were studied for clinical and laboratory evidence of immunologic dysfunction. Clinical findings included the presence of arthritis, vasculitis, and erythema nodosum. Laboratory abnormalities included the presence of circulating immune complexes, antinuclear antibodies, positive direct Coombs tests, elevated latex fixations, and a circulating lupus type anticoagulant. Total hemolytic complement was markedly depressed in four patients. Analysis of complement (C) components C1-C9 and factor B demonstrated significant reduction of only C3 and factor B. By crossed-immunoelectrophoresis, both C3 and factor B, but not C4, were cleaved, indicating that C activation was occurring predominantly via the alternative pathway. The control proteins beta 1H and C3b inactivator were decreased in three of four patients with hypocomplementemia. These data suggest that immunologic mechanisms associated with activation of the complement system play an important role in the disease process of some patients with agnogenic myeloid metaplasia with myelofibrosis.

Aged↗

Glucocorticoid suppression of human lymphocyte DNA synthesis: influence of phytohemagglutinin concentration.

Glucocorticoids have been shown to suppress lectin-stimulated lymphocyte DNA synthesis in some studies, whereas in other studies, the hormones have had little effect. We have found that the position on the PHA dose-response curve that is studied is the most important determinant of whether cortisol inhibits 3H-thymidine incorporation into lymphocyte DNA. The proportion of monocytes in culture also influenced the cortisol effect, but it was quantitatively less important than PHA concentration. Cortisol (5 nM to 100 microM) had little effect on blastogenesis or thymidine incorporation into DNA in cultures that contained both a high concentration (14% +/- 2 (S.E.)) of monocytes and a concentration of PHA (0.6 to 1.2 microgram/ml) that produced maximal stimulation of mitogenesis. When monocytes were reduced from 14% to 1.4%, cortisol (5 microM) caused a 30% reduction in thymidine incorporation in cultures stimulated by 0.6 to 1.2 microgram/ml PHA. Much greater cortisol suppression of thymidine incorporation occurred if the concentration of PHA was reduced. For example, reduction of the PHA concentration from 1.2 to 0.075 microgram/ml resulted in an increase in suppression by 5 microM cortisol from 5% to 90% even in the presence of 14% monocytes. These data indicate that the suppressive effects of glucocorticoids on blastogenesis and thymidine incorporation in vitro depend principally on the concentration of PHA used to stimulate blastogenesis and secondarily on the proportion of monocytes in the culture system.

Binding Sites↗

Circulating immune complexes in sera of dogs with benign and malignant breast disease.

The Raji cell radioimmunoassay was adapted to measure circulating immune complexes (CIC's) in the sera of 74 dogs with benign and malignant breast disease. In dogs with recently diagnosed spontaneous breast cancer, 57% (29 of 51) had elevated CIC's, with some levels as high as those found in the sera of dogs with systemic lupus erythematosus. The sera of 10 of 23 dogs with benign breast disease also demonstrated elevated levels of CIC's. Two weeks following mastectomy, repeat CIC levels were obtained in 30 dogs. Elevated CIC levels returned to normal in all dogs with benign breast disease but in only 33% of dogs with breast cancer. Dogs with persistent elevation of CIC's were at greater risk of developing metastatic breast cancer. Serum total hemolytic complement was significantly higher (p < 0.05) in dogs with untreated breast cancer than in healthy dogs but did not correlate with the level of CIC's found. Two weeks after mastectomy, total hemolytic complement levels had returned to normal. By sucrose density gradient ultracentrifugation, the complexes were shown to sediment at 19 S. These studies indicate that the dog may be a good model for elucidating the significance of elevated CIC's in breast cancer.

Adenocarcinoma↗

Exodus of 42K+ and 86Rb+ from rat thymic and human blood lymphocytes exposed to phytohemagglutinin.

We have found that PHA produces an alteration in the lymphocyte membrane which allows 86Rb+ or 42K+ in prelabeled lymphocytes to exchange for cations present in washing solutions. These observations suggested that PHA might induce an increase in the exodus of intracellular potassium during incubation in physiologic media. We, therefore, examined 86Rb+ and 42K+ efflux from rat and human lymphocytes during incubation in tissue culture medium. The rate constant for efflux, Ke, was significantly increased by PHA. 86Rb+ efflux was increased by 27% in rat thymic lymphocytes and by 78% in human blood lymphocytes following PHA treatment.

Animals↗

Human lymphocyte potassium content during the initiation of phytohemagglutinin-induced mitogenesis.

The K+ content of human lymphocytes has been examined during the initial 24 hours after exposure of cells to phytohemagglutinin (PHA). We have reconfirmed that lymphocyte K+ exchanges rapidly for extracellular counterions during preparative washing if cells are exposed to PHA. By using a technique to measure cation content which does not require removal of cells from their culture medium, we have shown that K+ does not change for 24 hours following PHA treatment. Previous reports have demonstrated that an enhanced uptake of K+ occurs in lymphocytes treated with PHA. This increased uptake may be a compensatory change for an increased exodus, explaining the failure of K+ to change following lectin treatment.

Biological Transport↗

A rapid phytohemagglutinin induced alteration in lymphocyte potassium permeability.

The exposure of rat and human lymphoid cells to mitogenic concentrations of phytohemagglutinin resulted in an apparent decrease in cellular K+ without a significant change in cellular Na+ when the cells were washed with isotonic Hepes buffered choline chloride prior to cation determination. The apparent reduction in total cellular Na+ plus K+ concentration, however, was not accompanied by a change in cell volume. We inferred that the constant cell volume could occur only if the lost intracellular K+ was exchanged for an external cation during the washing procedure used to prepare cells for Na+ and K+ measurement. This inference was supported by the quantitative recovery of lost cellular K+ in the choline chloride washing solution and the demonstration that a comparable proportion of 86Rb+ (K+ analogue) 42K+ was lost from prelabelled cells during choline chloride washing. Use of medium 199 with Hanks salts, 150 mM NaCl, or 100 mM MgCl2 as the washing solution did not prevent K+ exchange although exchange was less in the presence of MgCl2. These findings indicate that phytohemagglutinin produces a rapid alteration in lymphocyte plasma membranes so as to allow abnormal K+ exchange. This observation is of importance because investigators who measure intracellular solutes in phytohemagglutinin-treated lymphocytes must consider the possibility of lossduring preparative washes. Also, changes in membrane permeability following phytohemagglutinin treatment may modulate mitogenesis and/or permit the transmission of chemical messages between cells.

Animals↗

Plateletpheresis residues: a source of large quantities of human blood lymphocytes.

The residue from single-donor plateletpheresis contains a large number of human mononuclear cells. We have been able to harvest more than 1 X 10(9) viable lymphocytes for laboratory study from the leukocyte-rich sediment that previously had been discarded. Prior to removal by adherence 5 X 10(8) monocytes were also available for future purification, if desired. The physical properties and response to phytohemagglutinin were very similar when lymphocytes isolated from plateletpheresis residues were compared with those obtained directly from veneous blood.

Blood Platelets↗