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E Haber

Publications and source records attributed to E Haber.

At least 199 records · Page 11Linked to original sources
PubMed1982

Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: experience in 26 cases.

Purified Fab fragments of digoxin-specific antibodies obtained from sheep were used to treat 26 patients with advanced, life-threatening digoxin (23 cases) or digitoxin (3 cases) toxicity. These patients had advanced cardiac arrhythmias, and in some cases hyperkalemia, which were resistant to conventional treatment. All patients had an initial favorable response to doses of Fab fragments calculated (in most cases) to be equivalent, on a molar basis, to the amount of cardiac glycoside in the patient's body. In four patients treated after prolonged hypotension and low cardiac output, death ensued from cerebral or myocardial hypoperfusion. In one case the available Fab fragment supply was inadequate to reverse a massive suicidal ingestion of digoxin, and the patient died after recurrent ventricular arrhythmias. In the remaining 21 patients, cardiac rhythm disturbances and hyperkalemia were rapidly reversed, and full recovery ensued. There were no adverse reactions to the treatment. We conclude that the use of purified digoxin-specific Fab fragments is a safe and effective means to reverse advanced, life-threatening digitalis intoxication.

Adolescent↗
PubMed1982

Myocardial injury: quantitation by cell sorting initiated with antimyosin fluorescent spheres.

Spheres coated with antibodies specific for myosin were used to detect myocardial cell membrane disruption by scanning electron microscopy. Injury in a population of cultured myocytes as then followed and measured by fluorescence-activated cell sorting. This approach provides a unique method for quantitating the evolution of myocardial injury and potentially for assessing the efficacy of interventions aimed at myocardial protection.

Animals↗
PubMed1982

Heart failure in outpatients: a randomized trial of digoxin versus placebo.

The view that digitalis clinically benefits patients with heart failure and sinus rhythm lacks support from a well-controlled study. Using a randomized, double-blind, crossover protocol, we compared the effects of oral digoxin and placebo on the clinical courses of 25 outpatients without atrial fibrillation. According to a clinicoradiographic scoring system, the severity of heart failure was reduced by digoxin in 14 patients; in nine of these 14, improvement was confirmed by repeated trials (five patients) or right-heart catheterization (four patients). The other 11 patients had no detectable improvement from digoxin. Patients who responded to digoxin had more chronic and more severe heart failure, greater left ventricular dilation and ejection-fraction depression, and a third heart sound. Multivariate analysis showed that the third heart sound was the strongest correlate of the response to digoxin (P less than 0.0001). These data suggest that long-term digoxin therapy is clinically beneficial in patients with heart failure unaccompanied by atrial fibrillation whose failure persists despite diuretic treatment and who have a third heart sound.

Adult↗
PubMed1982

Renin synthesis by canine aortic smooth muscle cells in culture.

Angiotensin-I generating activity has been detected in homogenates of arterial tissue but it remains unclear whether this enzymatic activity results from the presence of renin itself or from the action of other proteases such as cathepsin D. In an assay system employing anephric dog plasma as substrate and buffered to pH 7.4, we detected angiotensin-I generating activity in homogenates of canine aortic smooth muscle cells. This enzymatic activity was in large part inhibitable by renin-specific antisera raised to pure canine renal renin. Immunofluorescent study of cultured arterial smooth muscle cells was also performed using renin specific antiserum. Granular cytoplasmic immunofluorescence was detected when specific antirenin serum was used but not when preimmune serum was employed. The addition of pure canine renin to the renin antiserum during staining suppressed the granular immunofluorescence confirming the specificity of staining. Finally, biosynthetic radiolabelling studies were performed. Immunoprecipitation of newly synthesized proteins with antirenin serum and staphylococcal protein A followed by gel electrophoresis and autoradiography demonstrated the synthesis of an immunoreactive protein with the molecular weight of renin. Pretreatment of the antirenin serum with pure canine renin resulted in the disappearance of this immunoreactive protein band. Thus these studies provide multiple lines of evidence to indicate the in situ synthesis of renin by vascular smooth muscle cells.

Animals↗
PubMed1982

Increased specificity in human cardiac-myosin radioimmunoassay utilizing two monoclonal antibodies in a double sandwich assay.

In some instances, even the increased resolution that may be afforded in immunoassays by the use of monoclonal antibodies fails to effect resolution among molecules that share many epitopes. An immunoradiometric assay that simultaneously measured two different epitopes on the same molecule was devised to overcome this difficulty in the differentiation between cardiac- and skeletal-myosin light chains. Three monoclonal antibodies were examined that were 100% (1C5), 25% (2B9) and 17% (4F10) cross reactive, respectively, between the two antigens. One antibody of the pair to be studied was immobilized to cyanogen bromide-activated Sepharose 4B while the other was iodinated with 125I using the lactoperoxidase method. The antigen was mixed with the immobilized antibody, the labeled antibody was added and the precipitate then washed and counted in a gamma counter. When both antibodies of the pair to be studied (immobilized and labeled) were the same (2B9), no radioactivity above background was bound to the precipitate, indicating that the second antibody could not bind to an already occupied epitope. When two different antibodies were employed, the specificity of the assay increased over that of a single antibody. The cross reactivity of a pair approximated the product of the cross reactivities of the individual antibodies. Thus, 1C5 and 2B9 were 25% cross reactive together, 1C5 and 4F10 17% cross reactive, and 2B9 and 4F10 4.3% cross reactive.

Antibodies, Monoclonal↗
PubMed1982

Classification of mouse VK groups based on the partial amino acid sequence to the first invariant tryptophan: impact of 14 new sequences from IgG myeloma proteins.

Fourteen new VK sequences derived from BALB/c IgG myeloma proteins were determined to the first invariant tryptophan (Trp 35). These partial sequences were compared with 65 other published VK sequences using a computer program. The 79 sequences were organized according to the length of the sequence from the amino terminus to the first invariant tryptophan (Trp 35), into seven groups (33, 34, 35, 36, 39, 40 and 41aa). A distance matrix of all 79 sequences was then computed, i.e. the number of amino acid substitutions necessary to convert one sequence to another was determined. From these data a dendrogram was constructed. Most of the VK sequences fell into clusters or closely related groups. The definition of a sequence group is arbitrary but facilitates the classification of VK proteins. We used 12 substitutions as the basis for defining a sequence group based on the known number of substitutions that are found in the VK21 proteins. By this criterion there were 18 groups in the Trp 35 dendrogram. Twelve of the 14 new sequences fell into one of these sequence groups; two formed new sequence groups. Collective amino acid sequencing is still encountering new VK structures indicating more sequences will be required to attain an accurate estimate of the total number of VK groups. Updated dendrograms can be quickly generated to include newly generated sequences.

Amino Acid Sequence↗
PubMed1982

Sulfur protection with the 3-nitro-2-pyridine sulfenyl group in solid-phase peptide synthesis.

The 3-nitro-2-pyridinesulfenyl (Npys) group has been used successfully for side chain protection of cysteine during the stepwise solid-phase synthesis of Lys8-vasopressin (LVP) on benzhydrylamine resin. The versatility and limitations of this group have been evaluated by comparison of this synthesis with a parallel control synthesis using the 3,4-dimethylbenzyl (DMB) group and with a synthesis utilizing a combination of both groups. The Npys group was found to be stable to TFA as reported and, in addition, was found to be stable to HF: anisole (9:1) for 45 min at 0 degree, but not when thiol was present in either reagent. Furthermore, compatibility of the Npys group with the Boc-benzyl synthetic tactic in solid-phase peptide synthesis was demonstrated. LVP with full biological activity was obtained after purification by gel filtration and reverse-phase HPLC.

Amino Acid Sequence↗
PubMed1982

Immunological probes in cardiovascular disease.

The immune system has long been recognised as playing a central role in the organism's defence against infectious diseases and possibly the development of neoplasia. The active stimulation of the immune system by immunisation and the passive administration of antitoxins have a venerable history in medicine. Yet the concept that antibodies may be used to modify physiological or pharmacological effects or may act as diagnostic agents in the living organisms has only recently come to be recognised. Advances, both in an understanding of the structural chemistry of the antibody molecule and in the ability to culture antibody-producing cells, now permit the selection and production of homogeneous antibodies and their smaller fragments in quantity by means other than conventional immunisation. These innovations will allow the development of a new pharmacology based on the remarkable resolving power of the antibody combining site. Antibodies or their fragments are shown to inhibit the pressor action of renin, to neutralise the pharmacological actions of digitalis, to block the beta-adrenergic receptor, and to detect and image myocardial infarcts.

Adolescent↗
PubMed1982

An antiidiotypic antibody that recognizes the beta-adrenergic receptor.

Antialprenolol rabbit antibodies were fractionated on an acebutolol affinity resin, followed by L-propranolol elution so as to separate a class of binding sites that mimic the beta-adrenergic receptor. Allotype-identicaL rabbits were immunized with this fraction. After 6 mo, antisera exhibited antiidiotypic activity inhibiting [3H]alprenolol binding to the original antibody and to rabbit antiacebutolol antibodies, which had a spectrum of ligand-binding properties identical to the original idiotype. Those antisera demonstrating the original idiotype. Those antisera demonstrating the most potent antiidiotypic activity also blocked [3H]alprenolol binding to the beta-adrenergic receptor of turkey membrane, canine pulmonary membrane, and rat reticulocyte. An idiotype affinity-purified fraction showed similar activity, inhibiting beta-receptor binding with a calculated dissociation constant (KD) of 53 nM. Isoproterenol-mediated adenylate cyclase activity was also inhibited in a competitive manner. The universality of recognition of these antiidiotypic antisera indicate that the three-dimensional structure of a receptor's binding site can be modeled by a subset of an elicited antibody population.

Acebutolol↗
PubMed1982

Studies on two novel angiotensin II actions.

Animal data suggest that angiotensin II may directly affect renal sodium retention independent of aldosterone (4,6). Additionally there is evidence to suggest that the hormone can stimulate protein synthesis in a variety of tissues and that indeed it may be a vasculotoxin (5,7). We describe here experiments designed to elucidate the role of angiotensin II in renal sodium retention in normal man. Additionally we present preliminary evidence suggesting that unlike the rapid sodium retaining effect, some delayed (trophic) actions of the hormone may be generated by a hitherto unappreciated mechanism.

Adult↗
PubMed1982

Are inactive renins in plasma and kidney related to prorenin?

The availability of elegant studies examining in vitro RNA translation of renin's message, the cDNA sequence of mouse-renin messenger RNA, and the complete amino acid sequence of active renin reveals the biosynthetic pathway of this enzyme. This pathway proceeds in a series of steps that correspond to the common mode of synthesis of secreted proteins. This information must now be correlated with a profusion of observations concerning inactive forms of renin that are found in kidney and other tissues in far higher concentration than the active enzyme in human plasma. At this time, in spite of great efforts on the part of many laboratories, the connection between the inactive renins of tissue or plasma and renin's biosynthetic precursors is unknown. Furthermore, the physiologic and pathophysiologic roles that inactive renins play, if any, have not been defined.

Amino Acid Sequence↗
PubMed1982

Antibodies in vivo.

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Adrenergic beta-Antagonists↗
PubMed1982

Fab fragments of digoxin-specific antibodies used to reverse ventricular fibrillation induced by digoxin ingestion in a child.

Digitalis poisoning is a rare problem in children, but it may be life threatening. A case of massive overdose of digoxin in a 2 1/2-year-old boy that produced prolonged ventricular fibrillation refractory to conventional therapy is reported. After two hours the boy was given digoxin-specific Fab fragments of antibody in sufficient quantity to bind his estimated dose of 10 mg. By completion of the treatment minutes later, normal rhythm and circulation were restored. The serum free digoxin level before antibody administration was greater than 100 ng/ml, and it rapidly fell to undetectable levels after antibody was given. Digoxin bound to the antibody had a clearance half-life of approximately 48 hours. The child had no apparent neurologic damage and his intellectual function was normal on discharge. He had a transient hematuria and a residual incomplete right bundle branch block. Administration of purified Fab fragments of digoxin-specific antibodies can be life saving in children with digitalis poisoning, and prolonged cardiopulmonary resuscitation in children is justified when the cause of cardiac arrest is potentially reversible.

Animals↗