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Biomedical subjects

K Stocker

Publications and source records attributed to K Stocker.

At least 19 recordsLinked to original sources
PubMed1999

[Use of snake venom proteins in medicine].

Snakes feed exclusively on freshly killed prey animals which, following their immobilization, have to be swallowed whole. Venomous snakes effect prey immobilization by injection of their venom. Snake venoms are highly concentrated, complex mixtures of individual proteins which, either as enzymes, enzyme effectors or blocking ligands, acting as single agents or in synergistic conjunction with other venom components, modify vital structures of the prey organism to destroy their biological function. Predominantly neurotoxic venoms paralyze respiratory activity by pre- or postsynaptic blockade of neuromuscular transmission. Predominantly haemocytotoxic snake venoms contain components which interact with proteins of the haemostasis, kallikrein or complement system, causing blood volume loss, hypotension or intravascular coagulation which finally lead to circulatory failure. Several isolated snake venom proteins with a known mode of action have found practical application as pharmaceutical agents, diagnostic reagents or preparative tools in the field of haemostaseology, neurobiology and complement research.

Animals↗
PubMed1994

Isolation and characterization of Textarin, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom.

The venom of P. textilis contains two different enzymes which convert human prothrombin into thrombin. Prothrombin activation by Textarin, a serine proteinase containing a calcium-binding molecule site, with a molecular mass of 50,000 to 53,000 Da and I.P. 5.5, separated from crude venom by either barium citrate adsorption or hydroxyl apatite chromatography, is strongly stimulated by phospholipid and calcium ions. A second activator, found in the supernatant of barium citrate adsorbed venom solution, activates prothrombin in the absence of any co-factor. Human plasma coagulation induced by Textarin, phospholipid and calcium ions is affected by lupus anticoagulants. Textarin may thus be used for the detection of lupus anticoagulants in patient plasma samples.

Amino Acid Sequence↗
PubMed1991

Heparin cofactor II: experimental approach to a new assay and clinical results.

By a series of experiments it could be shown that an activity test of heparin cofactor II (HC II) is only specific after a complete depletion of antithrombin III. Also when dermatan sulfate which does not enhance the action of AT III is used for the activation of HC II there is a considerable influence on the remaining thrombin activity which alters the test results. Furthermore, in a system which contains plasma as well as thrombin the formation of a clot is likely to occur which by its opacity influences photometric results. A chromogenic substrate assay is described which excludes the influence of these variables. This assay was used to examine the activity of HC II in healthy persons as well as in patients. Three members of a family were found who had a heterozygous deficiency of HC II without any history of thrombosis. On the other hand, a total of 16 patients with heterozygous deficiency of HC II suffered from recurrent thromboembolic episodes. For this reason it is assumed that a deficiency of HC II has a certain importance in the occurrence of thrombophilia though it is apparently less thrombogenic than a deficiency of other inhibitors.

Antibodies↗
PubMed1991

Endothelium-dependent relaxant effect of thrombocytin, a serine proteinase from Bothrops atrox snake venom, on isolated pig coronary arteries.

Since thrombin causes an endothelium-dependent relaxation of precontracted pig coronary arteries, the ability of thrombocytin, a serine proteinase from the venom of the common lancehead, Bothrops atrox, to induce endothelium-dependent changes in the vascular tone was investigated. Relaxation of pig coronary rings did not appear in vessels denuded of the endothelium. Thrombocytin (0.1-2.0 micrograms/ml) caused an endothelium-dependent, reversible, transient relaxation of PGF2 alpha-precontracted arteries which could be blocked by heparin and relatively high concentrations of alpha-NAPAP, a synthetic competitive thrombin inhibitor. Indomethacin and hirudin did not influence the relaxant effect. Both the thrombocytin- and bradykinin-induced relaxation were diminished by the guanylate cyclase inhibitor methylene blue and by NG-monomethyl-L-arginine. The thrombocytin-induced relaxation was absent in de-endothelialized vessels. Thrombocytin was able to induce aggregation of human blood platelets in Tyrode's solution at the same concentration range as used for the relaxation. Batroxobin neither relaxed precontracted arteries nor aggregated human blood platelets in vitro. The present studies show that the serine proteinase thrombocytin is not only able to aggregate platelets but may also release endothelium-derived relaxing factor from the vascular endothelium.

Animals↗
PubMed1991

Hirudin for diagnostic purposes.

Hirudin serves as a versatile tool for the control of thrombin activity in hemostaseology. It may be added in excess to blood, plasma or test mixtures to prevent catalytic and nonenzymatic effects of thrombin. It may be used to quench thrombin activity upon extensive or limited action. Unlike heparin-antithrombin III complex which exclusively inhibits alpha-and gamma-thrombin, hirudin also inhibits meizothrombin, a precursor of alpha-thrombin. Thus, hirudin may be used for the detection of meizothrombin as well as for the prevention of its action in plasma samples. In conjunction with chromogenic substrates, hirudin may serve to discriminate between actions mediated by thrombin, its precursors, cofactors and effectors and actions of other enzyme systems. The principle of this hirudin application is exemplified for factor-V- and factor-VIII-dependent anticoagulant activity of protein C.

Amino Acid Sequence↗
PubMed1991

Effects of snake venoms on hemostasis.

Proteins found in venoms, especially of the Viperidae snake family, exert, often with a narrow specificity, activating, inactivating, or other converting effects on different components of the hemostatic and fibrinolytic systems, respectively. Some purified snake venom proteins have become valuable tools in basic research and in diagnostic procedures in hemostaseology. "Procoagulant" as well as "anticoagulant" venom components have been identified in in vitro test systems. "Procoagulant" snake venom components may cause in vivo, upon massive application as in the case of snake-bite of small prey animals, intravascular coagulation leading to circulatory arrest and rapid death. Smaller doses of procoagulant venom components applied to large organisms as in the case of snake-bite accidents in humans, may cause a consumption coagulopathy with localized or generalized bleeding. Highly purified, specific fibrinogen coagulant venom proteinases are used in human medicine to produce therapeutic defibrinogenation. These practically nontoxic venom enzymes may act synergistically with other components aggravating their toxic effects.

Animals↗
PubMed1990

Chicken growth-associated protein (GAP)-43: primary structure and regulated expression of mRNA during embryogenesis.

Growth-associated protein (GAP)-43 is a neuron-specific phosphoprotein whose expression is associated with axonal outgrowth during neuronal development and regeneration. In order to investigate the expression of this gene product in the early developing nervous system we have isolated and sequenced a cDNA for chicken GAP-43. The predicted amino acid sequence for chicken GAP-43 displays extensive similarity to that of the mammalian protein, particularly in the amino-terminal region, to which functional domains of the protein have been assigned. The cDNA hybridizes with two RNAs of differing molecular weights on Northern blots; both appear to be regulated similarly. These RNAs first appear in the brain on embryonic day 3 (E3), suggesting that GAP-43 begins to be expressed when neuroblasts become post-mitotic. In situ hybridization analysis reveals that GAP-43 RNA is expressed by several neural structures in the chick embryo, including derivatives of the neural tube, neural crest, and neuroectodermal placodes.

Amino Acid Sequence↗
PubMed1989

On the significance of animal experiments in toxinology.

In increasing areas of the world, there is considerable controversy over the use of animals in scientific research. Ethical, scientific and economic reasons require a reduction in animal experiments as well as animal numbers, a refinement of existing methods and, wherever possible, a replacement of in vivo methods by in vitro test systems. By scoping on papers published in Toxicon between 1980 and 1986, the current situation of animal experimentation in toxinology is evaluated. Fundamental research and antivenin production are reviewed and special reference is given to the experiments involved in drug registration by the example of batroxobin, a purified serine proteinase from Bothrops moojeni venom used as a defibrinogenating agent. Although the ethical question is the most important motif, a reduction in the number of animal experiments can be achieved more pragmatically: the scientific community must learn to constantly ask whether the intention behind an experimental series justifies the use of animals or not. This learning process can be supported by special educational programmes at university level, by making financial support dependent on questionnaires concerning the planned animal experimentation, by including respective questions in the application files for grants, and by ethical guidelines that form an integral part in the instruction for authors of scientific journals.

Animal Experimentation↗
PubMed1989

[Snake venom proteins in hemostasis: new results].

Biological features of venomous snakes as well as biochemical properties and actions of their venoms which serve for prey acquisition, indicate the vertebrates' haemostasis system as a vulnerable target for snake venom actions. Components exerting a specific, either stimulating or inactivating effect on basal membrane or endothelial cells of the vascular wall, on platelets, on almost every step of plasma coagulation or fibrinolysis respectively, have been isolated and purified from snake venoms. Snake venom proteins acting with a defined specificity on cellular or plasmatic components of the human haemostatic system are being used in coagulation and aggregation tests, in photometric assays in conjunction with chromogenic substrates as well as in immunological systems as biochemical tools for research and diagnostic purposes.

Blood Coagulation↗
PubMed1989

[Psychoanalysis and psychotherapy management in Austria].

In a study on the psychotherapeutic provision in Austria the participation of the psychoanalysts was also researched. All over Austria there is a lack of psychotherapists in numbers and regionally. Long term psychotherapy except for a few special institutions are free of charge for the client. In private practice however the patients have to pay heavily. Non-medical psychotherapists are not eligible for refunds by the health insurance system. Almost 4/5 of all psychotherapists belong to a non-medical profession (e.g. psychologists). Only about 1/5 are medical doctors who work as psychotherapists on the basis of a therapeutic training. Psychoanalysts in Austria primarily work as psychoanalytic oriented psychotherapists and to a lesser extent as psychoanalysts.

Austria↗
PubMed1988

Isoelectric focusing of Protac, the protein C activator from copperhead (Agkistrodon contortrix) venom: a note on experimental problems.

The isoelectric point of Protac was recently estimated to be at pH 3. However, further investigations using different experimental procedures revealed that Protac, due to its particular binding properties, is able to form complexes with carrier ampholytes. Thus, the actual isoelectric point of Protac was found to be in the basic region.

Crotalid Venoms↗
PubMed1988

Practical application of the protein C activator Protac from Agkistrodon contortrix venom.

The protein C activator Protac from A. contortrix venom is being investigated as a potential antithrombotic agent and as a tool for the preparation of activated protein C. Its established major application is the zymogen activation in functional protein C determinations based on either a clotting assay or a chromogenic substrate technique. The sensitivity of the activated partial thromboplastin time as an indicator reaction for Protac activated protein C depends on the contact activator component of the reagent. Protein C dose-response increased in the following order: kaolin greater than ellagic acid greater than sulfatide. This phenomenon is due to a competition of molecular affinities between Protac, plasma components and the different activating surfaces.

Crotalid Venoms↗
PubMed1987

Characterization of the protein C activator Protac from the venom of the southern copperhead (Agkistrodon contortrix) snake.

A single chain glycopeptide with a molecular weight of approximately 37,000, an isoelectric point of 3.0 +/- 0.2 and a carbohydrate content of approximately 20% was isolated from the venom of the southern copperhead Agkistrodon contortrix contortrix. It was capable of converting zymogen protein C in plasma of man and various vertebrates into its activated form, a serine proteinase which exerts an anticoagulant effect. Conversion of the zymogen protein C into the active proteinase was demonstrated by measuring the prolongation of the activated partial thromboplastin time due to proteolytic degradation of factors Va and VIIIa by the activation product, as well as by direct measurement of the generated enzyme activity by means of a synthetic chromogenic substrate. Intravenous injection of the venom protein C activator into rabbits caused prolonged activated partial thromboplastin time. Repeated subcutaneous injections led to formation of an antibody which formed, with purified protein C activator as well as with crude A. contortrix venom, a precipitating complex devoid of protein C activator potency. As revealed by activity measurements and by immunodiffusion experiments, the venoms of various A. contortrix, A. bilineatus subspecies contain similar protein C activators.

Animals↗