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V P Butler

Publications and source records attributed to V P Butler.

82 records · Page 5Linked to original sources
PubMed1971

Radioimmunoassay of human fibrinopeptide A.

A radioimmunoassay capable of measuring 1 pmole of human fibrinopeptide A has been developed, and should prove useful to detect the release of this peptide from fibrinogen during the coagulation process. Antibodies to fibrinopeptide A were produced by injecting New Zealand white rabbits with a mixture of Freund's adjuvant and native fibrinopeptide coupled to human albumin. N-Tyrosyl fibrinopeptide A was synthesized by the solid-phase method, and was iodinated with (125)I by the Chloramine-T method. 48-73% of the radiolabeled peptide could be bound by the serum of a rabbit immunized with the fibrinopeptide-albumin preparation. Antibody-bound peptide was precipitated by dioxane and was thus separated from unbound peptide. The addition of excess native fibrinopeptide to the radiolabeled material prevented its binding to serum. Native fibrinopeptide A and synthetic fibrinopeptide A were identical in their ability to prevent binding, whereas fibrinogen was from 1/25,000 to 1/50,000 as effective on a weight basis. Plasma filtered through a membrane relatively impermeable to molecules larger than a molecular weight of 34,000 showed no fibrinopeptide reactivity, whereas a similar filtrate of serum gave quantitative recovery of fibrinopeptide reactivity.

Albumins↗
PubMed1971

Immunological protecion against dixin toxicity.

The lethal dose of digoxin was determined by administering 10 ml of a digoxin-saline solution to 26 nonimmunized rabbits through an ear vein over a 10 min period. Rabbits receiving less than 0.45 mg/kg digoxin showed no toxic effect, whereas all 15 rabbits that received 0.5 mg/kg developed an early arrhythmia and died within 1 hr. Moreover, eight rabbits which had been immunized with antigens unrelated to digoxin or injected with Freund's adjuvant mixture all died after receiving 0.6 mg/kg digoxin. Thus, it was concluded that 0.6 mg/kg digoxin was uniformly lethal in rabbits that had not been immunized or had received antigens unrelated to digoxin. By way of contrast, 17 rabbits immunized with a digoxin-albumin conjugate in complete Freund's adjuvant formed digoxin-specific antibodies and survived doses of digoxin varying between 0.6 and 0.9 mg/kg. In 10 rabbits immunized with digoxin-albumin conjugates, digoxin-specific antibody titers were determined following the administration of digoxin. There was a significant fall in antibody titer. This study indicates that rabbits protected by digoxin-specific antibodies suffer no acute adverse effects from an amount of digoxin which is uniformly lethal in nonimmunized rabbits and in rabbits immunized with other antigens.

Animals↗
PubMed1971

Reversal of digoxin toxicity with specific antibodies.

To determine whether digoxin-specific antibodies can reverse established digoxin toxicity in the dog, digoxin intoxication was produced by the intramuscular administration of digoxin, 0.09 mg/kg, on each of 3 consecutive days. All animals developed toxic arrhythmias (atrioventricular block, ventricular premature contractions and/or ventricular tachycardia). In control animals not receiving antidigoxin antibodies, the arrhythmias persisted throughout a 6 hr study period. Seven of the nine control dogs were dead within 24 hr and one moribund animal was sacrificed at that time; the last animal died within 48 hr.In contrast, in six of eight dogs given digoxin-specific antibodies in canine plasma and/or rabbit serum, the arrhythmias reverted to a sinus mechanism within 30-90 min after the start of the infusion. At the end of a 6 hr period of study, these six dogs were in normal sinus rhythm and all eight were alive and in normal sinus rhythm at the end of 72 hr. This study provides evidence that digoxin-specific antibodies can reverse severe established digoxin toxicity in the dog.

Animals↗
PubMedDate not supplied

Monoclonal antibodies to E92, an endothelial cell surface antigen.

Two hybridoma-derived monoclonal antibodies have been developed that react with an antigen of molecular weight 92,000 daltons on the surface of human endothelial cells. Cultured human umbilical vein endothelial cells were used for immunization, but the antigen is present on arterial, venous and capillary endothelium, as determined by biotin-avidin immunoperoxidase staining of tissue sections. With this technique, other cell types in the tissues which were examined were not reactive, except for scattered fibroblasts and histiomonocytic cells, trophoblastic cells of the placenta, and benign immature mesenchymal cells in a renal cystadenocarcinoma. By cytofluorography, the antibodies were found to be unreactive with granulocytes, T lymphocytes, B lymphocytes, and the majority of monocytes. Fibroblasts were reactive with the antibodies, but the fluorescence tracings indicated a lower density of antigen on these cells than on endothelial cells. Immunoreactivity of fibroblasts could be decreased by treatment of the cells with thrombin, trypsin, or neuraminidase, whereas these enzymes did not affect the immunoreactivity of endothelial cells. The reactive antigen (E92) does not appear to be any of several previously described endothelial cell proteins, because of its molecular weight and its absence on other cell types. The presence of E92 on trophoblastic cells of the placenta and immature mesenchymal cells, as well as fibroblasts and endothelial cells, may indicate that it is a primitive antigen of mesodermal tissue that is lost by most cell types during differentiation.

Adenocarcinoma↗