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Biomedical subjects

C Bode

Publications and source records attributed to C Bode.

At least 199 records · Page 11Linked to original sources
PubMed1989

[Antibody mediated thrombolysis. A new therapeutic principle].

Thrombosis of a coronary artery is the most common cause of myocardial infarction. Thrombolytic therapy, when instituted timely, has been shown capable of reducing morbidity and mortality. However, the use of presently available thrombolytic agents is associated with a bleeding tendency and efficacy is not optimal. This article reviews one of several lines of investigation that are presently being pursued in order to improve efficacy and specificity of thrombolytic therapy. The chemical conjugation of a fibrin specific monoclonal antibody and urokinase or tissue plasminogen activator results in markedly enhanced thrombolytic potency, both in vitro and in vivo. Specificity of the conjugates is greater than that of the parent plasminogen activators as reflected by conservation of fibrinogen, plasminogen and alpha-2 antiplasmin. A bispecific antibody, with specificity for both, fibrin and tissue plasminogen activator, has the potential of concentrating endogenous tissue plasminogen activator at the site of a thrombus. In the presence of the bispecific antibody, efficacy and specificity of tissue plasminogen activator are markedly enhanced in vitro and in vivo. The tools of molecular biology are presently being applied in order to translate these findings into better thrombolytic therapy.

Antibodies, Monoclonal↗
PubMed1989

Antibody-directed fibrinolysis. An antibody specific for both fibrin and tissue plasminogen activator.

An investigation was made to determine whether it is possible to attract tissue plasminogen activator (tPA) to the site of a thrombus by means of an antibody with affinites for both tPA and fibrin. A bispecific antibody conjugate was constructed by cross-linking two monoclonal antibodies: one specific for tPA, the other specific for fibrin. The bispecific antibody enhanced fibrinolysis by capturing tPA at the site of a fibrin deposit. In an in vitro quantitative fibrinolysis assay, the relative fibrinolytic potency of tPA bound to the bispecific antibody was 13 times greater than that of tPA and 200 times greater than that of urokinase. When fibrin was treated with the bispecific antibody before being mixed with tPA, the relative fibrinolytic potency of tPA was enhanced 14-fold. This capture also occurred when the concentration of tPA present in the assay was less than the concentration of tPA present in normal human plasma. In a human plasma clot assay, samples containing both the bispecific antibody and tPA exhibited significantly more lysis than did samples containing tPA alone. In spite of the increased clot lysis effected by the presence of bispecific antibody, there was no significant increase in fibrinogen or alpha 2-antiplasmin degradation at equal tPA concentrations. The ability of the bispecific antibody to concentrate exogenous tPA in vivo was then examined in the rabbit jugular vein model. Systemic infusion of a small amount of tPA (10,000 units) produced no significant increment in thrombolysis over the level of spontaneous lysis (14 +/- 8%). However, the simultaneous infusion of 10,000 units of tPA and 2 mg of bispecific antibody resulted in 42 +/- 14% (p less than 0.01) lysis. These results suggest that a molecule capable of binding both fibrin and tPA with high affinity could enhance thrombolysis in the circulation by capturing endogenous tPA.

Animals↗
PubMed1989

Chromogenic endotoxin assay in plasma. Selection of plasma pretreatment and production of standard curves.

The aim of this study was to define the optimal conditions for the plasma pretreatment and to improve the production of standard curves for plasma endotoxin determination by a chromogenic substrate assay. Endotoxin standard from E. coli O 111:B 4 (0-50 ng/l) was added to pyrogen-free water or to plasma samples from 12 healthy subjects and 24 alcoholics, before pretreatment by heating (75 degrees C, 5 minutes) or with perchloric acid (0.32 mol/l). When endotoxin standard curves were determined using a microprocessor-controlled reader, the slopes of the curves obtained with plasma differed from those with pyrogen-free water. The slope of the standard curve prepared with plasma samples from different patients exhibited marked interindividual variations. Compared with the heating method, the perchloric acid method gave more variable results and a lower recovery of added endotoxin, especially in plasma from alcoholics. The results permit the following conclusion: 1. For plasma endotoxin determination, a standard curve should be prepared for each individual plasma sample. 2. The endotoxin standard should be added before pretreatment of the plasma. 3. Pretreatment of the plasma by heating at 75 degrees C for 5 minutes provides more reliable results than pretreatment with perchloric acid.

Adult↗
PubMed1989

Effect of acute ethanol ingestion on human gastric luminal prostaglandin E2, prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha.

In healthy human volunteers we evaluated the effect of a single oral dose of 1 g/kg of alcohol (12.5%, v/v) on the output of prostaglandin E2, prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha in the gastric juice. In control experiments performed at intervals of 5-8 days, the subjects received the identical volume of water. Ninety minutes after the ingestion of alcohol, or water, first the basal secretion and subsequently the secretion after injection of pentagastrin (6 micrograms/kg, i.m.) were collected over periods of 60 min. The concentrations of the three prostaglandins were determined by radio-immunoassay. After ingestion of alcohol, the volume of gastric juice in response to pentagastrin stimulation was reduced by 24.6%, as compared with the control period. Ingestion of alcohol led to a significant reduction in the concentration of prostaglandin E2 (-42.7%) after stimulation with pentagastrin. The prostaglandin E2 output per hour was markedly inhibited by the ingestion of alcohol, both in the basal period (-47%) and after stimulation with pentagastrin (-55%). While stimulation with pentagastrin did not influence the secretion of PGE2 or PGF2 alpha, the output of 6-keto-PGF1 alpha increased appreciably (+88%) after the administration of pentagastrin. Alcohol also significantly (-28%) inhibited the secretion of 6-keto-PGF1 alpha in the period following the administration of pentagastrin. It is supposed that the inhibition of the secretion of prostaglandin E2 and 6-keto-prostaglandin F1 alpha by acute alcohol ingestion, might be of significance for the development of alcohol-induced mucosal damage in the stomach.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Efficacy of intravenous prourokinase and a combination of prourokinase and urokinase in acute myocardial infarction.

Fifty-four patients with Q-wave acute myocardial infarction (AMI) were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (prourokinase). To determine the optimal treatment regimen, prourokinase was applied in 3 different ways: group I received a bolus of 7.5 mg and a subsequent infusion of 40.5 mg over 60 minutes. Patency of the infarct artery was observed in 7 patients (50%) at the end of the infusion time. One hour after the end of the infusion the fibrinogen level had decreased to 87 +/- 12% of the preinfusion level; the plasminogen and alpha-2 antiplasmin levels to 61 +/- 13% and 59 +/- 34%, respectively. In group II prourokinase was administered as a 7.5 mg bolus followed by 66.5 mg over 60 minutes. Eleven patients (55%) had patent infarct-related coronary arteries and fibrinogen, plasminogen and alpha-2 antiplasmin levels had decreased to 58 +/- 29%, 38 +/- 18% and 21 +/- 14%, respectively. Group III was treated with a bolus of 3.7 mg prourokinase and 250,000 IU urokinase followed by 44.3 mg prourokinase, resulting in a patency rate of 65% (13 patients). Fibrinogen, plasminogen and alpha-2 antiplasmin levels decreased to 76 +/- 15%, 67 +/- 15% and 47 +/- 29%, respectively. Fibrin-specific thrombolysis can be achieved with glycosylated prourokinase. At higher dosages considerable systemic activation of the fibrinolytic system with little enhancement of the observed therapeutic effect occurred. The combination of prourokinase and urokinase yielded a higher patency rate than either dosage of prourokinase alone, although the difference was not statistically significant in this pilot trial.

Clinical Trials as Topic↗
PubMed1988

Conjugation to an antifibrin monoclonal antibody enhances the fibrinolytic potency of tissue plasminogen activator in vitro.

Tissue plasminogen activator (tPA) was covalently linked by disulfide bonds to a monoclonal antibody specific for the amino terminus of the beta chain of fibrin (antibody 59D8). The activity of the tPA-59D8 conjugate was compared with that of tPA, urokinase (UK), and a UK-59D8 conjugate. For lysis of fibrin monomer, tPA was 10 times as potent as UK, whereas both UK-59D8 and tPA-59D8 conjugates were 100 times as potent as UK and 10 times as potent as tPA. Conjugation of tPA or UK to antibody 59D8 produced a 3.2-4.5-fold enhancement in clot lysis in human plasma over that of the respective unconjugated plasminogen activator. However, the UK-59D8 conjugate was only as potent as tPA alone. Antibody-conjugated tPA or UK consumed less fibrinogen, alpha 2-antiplasmin, and plasminogen than did the unconjugated activators, at equipotent fibrinolytic concentrations. Antibody targeting thus appears to increase the concentration of tPA in the vicinity of a fibrin deposit, which thereby leads to enhanced fibrinolysis.

Antibodies, Monoclonal↗
PubMed1988

What is established in thrombolytic therapy of acute myocardial infarction? Pharmacological approaches.

Thrombolytic therapy by early reopening of an occluded coronary vessel, and hence re-establishing oxygen delivery, can significantly reduce infarct size. The result depends both on the duration of ischemia and the presence of collaterals. By early initiation of intravenous thrombolytic therapy and shortening the ischemic period, the functional results may be improved. PTCA has to be considered in order to avoid reocclusion of the infarct vessel, mainly in patients with high-grade residual stenosis and viable myocardium in the poststenotic area. The benefit of early thrombolytic therapy in acute myocardial infarction has been proven in randomized trials. However, to achieve statistical significance, a large number of patients had to be included. It is mainly the patients with previous myocardial infarction with a large area at infarct risk and/or anterior myocardial infarction that derive most benefit from this intervention.

Acute Disease↗
PubMed1988

Effect of acute and chronic alcohol feeding on prostaglandin E2 biosynthesis in rat stomach.

The effect of acute and chronic alcohol ingestion on gastric prostaglandin E2 synthesis and the PGE2 content in the stomach was studied in rats. Up to 8 hr following a single oral load of 20% alcohol (v/v; 4 g/kg body weight), the PGE2 synthesis in isolated microsomes from rat stomach remained unchanged as compared with control values. Feeding a liquid alcohol-containing diet (37% of total Joules) for 1, 6, or 12 weeks significantly decreased the rate of PGE2 synthesis (percentage inhibition as compared with control values 39, 27, and 57, respectively). In addition, chronic alcohol feeding led to a drop in the tissue content of PGE2, the decrease being more pronounced after 6 (-49%) and 12 (-58%) weeks than after 1 week (-24%). The results suggest that the inhibition of endogenous PGE2 synthesis in the stomach following ingestion of appreciable quantities of alcohol might play a role in the pathogenesis of alcohol-induced injury of the gastric mucosa.

Animals↗
PubMed1987

Characterization of an antibody-urokinase conjugate. A plasminogen activator targeted to fibrin.

The plasminogen activator urokinase was linked covalently to a monoclonal antibody specific for the amino terminus of the beta chain of human fibrin by means of the unidirectional cross-linking reagent N-succinimidyl-3-(2-pyridyldithio)propionate. N-Succinimidyl-3-(2-pyridyldithio)propionate allowed the amino groups on urokinase to be coupled to the sulfhydryl groups on iminothiolane (which had been introduced into the antibody before the coupling reaction). The inter-heavy chain sulfhydryl of the Fab' of this antibody was also linked to N-succinimidyl-3-(2-pyridyldithio)propionate-substituted urokinase. The antibody- or Fab'-urokinase complexes were purified by two affinity chromatography steps. In the first, benzamidine was used as ligand for urokinase, in the second, a heptapeptide consisting of the 7 amino-terminal residues of the beta chain of fibrin (beta peptide) was used as ligand for the antibody. The activity of the purified conjugates was compared with that of urokinase alone in an assay measuring lysis of 125I-fibrin monomer covalently linked to Sepharose CL-4B. For any concentration of either urokinase alone or urokinase-antifibrin antibody conjugate, an equivalent amount of lysis (release of labeled peptide from fibrin monomer-Sepharose) was obtained with 1/250 the concentration (with respect to urokinase content) of antifibrin antibody-urokinase conjugate. The antifibrin Fab'-urokinase conjugate exhibited a similar enhancement of activity in comparison with urokinase. Enhanced fibrinolysis was fully inhibited by beta peptide. These results suggest that antibody targeting enhances the concentration of urokinase in the vicinity of immobilized fibrin monomer, thereby also increasing the local conversion of plasminogen to plasmin, which in turn degrades its substrate, fibrin. Univalent antigen-antibody binding is sufficient for optimal efficiency.

Antibodies, Monoclonal↗
PubMed1987

Percutaneous endoscopic duodenostomy (PED). Case report.

Surgeons are increasingly using endoscopy to place transabdominal feeding tubes for enteral nutrition or gastric decompression. A possible extension for the application of this new technique is the direct placement of the feeding tube into the duodenal bulb. Two patients are presented in whom percutaneous endoscopic duodenostomy was successfully performed, although percutaneous endoscopic gastrostomy was not possible. It shows that this new method is technically possible. In both patients the positive influence of this technique on the patient's quality of life could be shown using the Spitzer Quality of Life Index and the Karnofsky Performance Status. Enteral nutrition was maintained for more than 6 weeks.

Aged↗
PubMed1987

Palmitate uptake in calcium tolerant, adult rat myocardial single cells--evidence for an albumin mediated transport across sarcolemma.

The dependence of (1-14C)-palmitate uptake in adult rat heart single cells on albumin was investigated. The apparent initial rate of palmitate uptake vs total palmitate concentration exhibited saturation kinetics, provided the concentration ratio of palmitate vs albumin was kept constant. However, if total palmitate was increased at constant albumin concentrations, the dependence of the initial rate on palmitate concentration was linear. Within the concentration range of total palmitate investigated in this study, the concentration of free palmitate remained almost constant. These results favour the hypothesis, that palmitate uptake in rat myocardium may be mediated by an albumin dependent sarcolemmal transport system.

Albumins↗