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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 505 records · Page 28Linked to original sources
PubMed1980

Stauffer's syndrome in renal cell carcinoma evidence for intravascular coagulation.

In 40 patients with non-metastasising (n = 31) and metastasising (n = 9) renal cell carcinoma, evidence of Stauffer's syndrome (increase in alkaline serum phosphatase and prolongation of prothrombin time) was found in 18 patients. Prolongation of prothrombin time was not due to depletion of vitamin K-dependent coagulation factors or manifest fibrinolysis, but due to the presence of circulating fibrinogen fibrinmonomer-FDP complexes. Ethanol gelation test was found to be positive in 28/40 subjects and soluble fibrin monomer complexes were increased in 38/40 patients. The resulting disturbance of fibrinogen-fibrin conversion was reflected by an increase in thrombin coagulase time and reptilase time. These findings suggests a state of latent compensated intravascular coagulation (presumably triggered within the vascular tumor). For diagnostic purposes the most sensitive indicator is thrombin coagulase time. Thrombin coagulase time normalised after tumor resection and was positive in patients with recurrent metastases. The increase in alkaline serum phosphatase was due to an increase in the hepatic isoenzyme. Such an increase was much more common than the elevation of total alkaline serum phosphatase. Regan's isoenzyme was only found in 1 subject. In parallel, gamma-GT was elevated in 24 patients. The study shows that Stauffer's syndrome occurs more frequently than commonly assumed when thrombin coagulase time, gamma-GT and the hepatic isoenzyme of alkaline serum phosphatase are determined in patients with renal cell carcinoma. DIC and low grade fibrinolysis may account for the coagulation abnormalities of the syndrome.

Adenocarcinoma↗
PubMed1980

Transport of proteins into mitochondria. Posttranslational transfer of ADP/ATP carrier into mitochondria in vitro.

The mitochondrial ADP/ATP carrier is an integral transmembrane protein of the inner membrane. It is synthesized on cytoplasmic ribosomes. Kinetic data suggested that this protein is transferred into mitochondria in a posttranslational manner. The following results provide further evidence for such a mechanism and provide information on its details. 1. In homologous and heterologous translation systems th newly synthesized ADP/ATP carrier protein is present in the postribosomal supernatant. 2. Analysis by density gradient centrifugation and gel filtration shows, that the ADP/ATP carrier molecules in the postribosomal fraction are present as soluble complexes with apparent molecular weights of about 120 000 and 500 000 or larger. The carrier binds detergents such as Triton X-100 and deoxycholate forming mixed micelles with molecular weights of about 200 000-400 000. 3. Incubation of a postribosomal supernatant of a reticulocyte lysate containing newly synthesized ADP/ATP carrier with mitochondria isolated from Neurospora spheroplasts results in efficient transfer of the carrier into mitochondria. About 20-30% of the transferred carrier are resistant to proteinase in whole mitochondria. The authentic mature protein is also largley resistant to proteinase in whole mitochondria and sensitive after lysis of mitochondria with detergent. Integrity of mitochondria is a preprequisite for translocation into proteinase resistant position. 4. The transfer in vitro into a proteinase-resistant form is inhibited by the uncoupler carbonyl-cyanide m-chlorophenylhydrazone but not the proteinase-sensitive binding. These observations suggest that the posttranslational transfer of ADP/ATP carrier occurs via the cytosolic space through a soluble oligomeric precursor form. This precursor is taken up by intact mitochondria into an integral position in the membrane. These findings are considered to be of general importance for the intracellular transfer of insoluble membrane proteins. They support the view that such proteins can exist in a water-soluble form as precursors and upon integration into the membrane undergo a conformational change. Uptake into the membrane may involve the cleavage of an additional sequence in some proteins, but this appears not to be a prerequisite as demonstrated by the ADP/ATP carrier protein.

Adenosine Diphosphate↗
PubMed1980

Biogenesis of glyoxysomes. Synthesis and intracellular transfer of isocitrate lyase.

Biosynthesis of isocitrate lyase, a tetrameric enzyme of the glyoxysomal matrix, was studied in Neurospora crassa, in which the formation of glyoxysomes was induced by a substitution of sucrose medium by acetate medium. 1. Translation of Neurospora mRNA in reticulocyte lysates yields a product which has the same apparent molecular weight as the subunit of the functional enzyme. Using N-formyl[35S]methionyl-tRNAfMet as a label, the translation product shows the same apparent size which indicates that the amino terminus has no additional "signal'-type sequence. 2. Read-out systems employing free and membrane-bound polysomes show that only free ribosomes are active in the synthesis of isocitrate lyase. 3. Isocitrate lyase synthesized in reticulocyte lysate is released into the supernatant and is soluble in a monomeric form. It interacts with Triton X-100 to form mixed micells in contrast to the functional tetrameric form. 4. Transfer of isocitrate lyase synthesized in vitro into isolated glyoxysomes is suggested by results of experiments in which supernatants from reticulocyte lysates are incubated with a particle fraction isolated from acetate-grown cells. No transfer occurs when particles from non-induced cells are employed. Resistance to added proteinase is used as a criterion for transmembrane transfer. The data support a post-translational transfer mechanism for isocitrate lyase. They suggest that isocitrate lyase passes through a cytosolic precursor pool as a monomer and is transferred into glyoxysomes.

Animals↗
PubMed1980

Paradoxical effect of high and low dose aspirin in experimental arterial thrombosis.

The effect of different dosage regimens of aspirin was investigated in an experimental model of arterial thrombosis. A paradoxical effect with an increase of the arterial thrombus growth could be seen after a first single dose of 100 mg aspirin/kg body weight. When the high dose of aspirin was given repeatedly, a thrombus size minor than under low dose aspirin therapy with 10 mg/kg body weight has been observed. Our experimental thrombosis experiments do not provide sufficient evidence to support antithrombotic therapy with low doses of aspirin.

Animals↗
PubMed1980

Biphasic initial phase of platelet aggregation inhibition after oral aspirin.

For one hour after the ingestion of 1 g aspirin the pharmacodynamics of acetylsalicylic acid with regard to the inhibition of platelet aggregation were studied in nine healthy male volunteers. Plasma salicylic acid (SA) and acetylsalicylic acid (ASA) levels were measured, and platelet aggregation was controlled by the collagen-induced aggregation. It took 12 - 24 minutes till the maximum of platelet aggregation inhibition was reached; maximal inhibition was only observed with ASA levels above 4.5 /microgram/ml and total ASA levels above 10 /microgram/ml. At that time already more than 50% of the total ASA were hydrolysed to minimally active SA. In spite of further increasing ASA levels inhibition of platelet aggregation decreased again. The different sensitivity of platelet- and vessel wall cyclooxygenase to aspirin does not explain our findings.

Administration, Oral↗
PubMed1979

[Urokinase treatment of phlegmasia coerulea dolens (author's transl)].

Fibrinolysis treatment with urokinase was successfully undertaken in two patients, aged 71 and 76 years, with phlegmasia coerulea dolens. In the first case, with necrosis in the fore-foot, there was significant regression of the necrotic area, but a later limited amputation was still necessary. In the second, with severe heart failure, recurrent pulmonary emboli and hyperosmolar uncontrolled diabetes mellitus, complete healing was achieved. Venous thrombectomy was not possible in these two patients because of the duration of the thrombosis in the veins of the pelvic region, necrosis had already occurred, and the patients' general condition was so serious. The advanced age and arteriosclerotic changes argued against streptokinase treatment. Mean urokinase maintenance dosage of 1000-1500 IU/kg X h, with simultaneous administration of heparin at about 20 U/kg X h, produced no significant side-effects. Minor gastro-intestinal bleeding did not require stoppage of urokinase administration.

Aged↗
PubMed1979

Congenital factor VII deficiency. A report of four new cases.

Four new cases with congenital homozygous factor VII deficiency are described. Factor VII levels were reduced to less than 1%, 3%, 8% and 10%, respectively. The incidence and severity of bleeding symptoms were well correlated with the measured factor VII activity. In the severe case of factor VII deficiency (less than 1%) a home treatment program was started because of severe recurrent hemarthroses. This entailed transfusions of 20 U/kg body weight prothrombin complex or factor VII concentrate in case of acute bleeding approximately every three weeks. These transfusions have been carried out successfully without any problems. In contradiction, two brothers with hypoproconvertinemia (factor VII 8% and 10% respectively) reached an age of more than 70 years. Despite replacement therapy postoperative bleeding followed one appendectomy, whereas no postoperative bleeding followed patients requiring Achilles tendon lengthening and an above knee amputation and only slight bleeding followed a tonsillectomy. Based on our experience we suggest that in patients with factor VII deficiency of less than 10%, when undergoing surgery, should be maintained a minimal factor VII activity of 10--15% during the first three postoperative days.

Adolescent↗
PubMed1978

Nitrogenase X: Mössbauer and EPR studies on reversibly oxidized MoFe protein from Azotobacter vinelandii OP. Nature of the iron centers.

Under anaerobic conditions the molybdenum-iron protein (MoFe protein) from Azotobacter vinelandii can be reversibly oxidized with thionine. Electron paramagnetic resonance studies reveal that the oxidation proceeds in two distinct phases: the MoFe protein can be oxidized by four electrons without loss of the EPR signal from the S = 3/2 cofactor centers. A second oxidation step, involving two electrons, leads to the disappearance of the cofactor EPR signal. In order to correlate the events during the thionine titration with redox reactions involving individual iron centers we have studied the MoFe proteins from A vinelandii and Clostridium pasteurianum with Mössbauer spectroscopy. Spectra were taken in the temperature range from 1.5 K to 200 K in applied magnetic fields of up to 54 kG. Analysis of the Mössbauer data allows us to draw three major conclusions: (1) the holoprotein contains 30 +/- 2 iron atoms. (2) Most probably, 12 iron atoms belong to two, apparently identical, iron clusters (labeled M) which we have shown previously to be structural components of the iron and molybdenum containing cofactor of nitrogenase. The M-centers can be stabilized in three distinct oxidation states, MOXe- in equilibrium MNe- in equilibrium MR. The diamagnetic (S = 0) state MOX is attained by oxidation of the native state MN with either thionine or oxygen. MR is observed under nitrogen fixing conditions. (3) The data strongly suggest that 16 iron atoms are associated with four iron centers which we propose to call P-clusters. Each P-cluster contains four spin-coupled iron atoms. In the native protein the P-clusters are in the diamagnetic state PN, yielding the Mössbauer signature which we have labeled previously 'components D and Fe2+'. Three irons of the D-type and one iron of the Fe2+-type appear to comprise a P-cluster. A one-electron oxidation yields the paramagnetic state POX. Although the state POX is characterized by half-integral electronic spin a peculiar combination of zero-field splitting parameters and spin relaxation renders this state EPR-silent. Spectroscopically, the P-clusters are novel structures; there is, however, evidence that they are closely related to familiar 4Fe-4S centers.

Azotobacter↗
PubMed1978

The effect of bezafibrate on the fibrinolytic enzyme system and the drug interaction with racemic phenprocoumon.

The influence of a new hypolipidaemic agent, bezafibrate, on anticoagulant requirements and fibrinolysis was studied in 15 patients with hyperlipidaemia on long-term treatment with racemic phenprocoumon. Our results suggest a dose-dependent augmentation of the anticoagulant response to the coumarin drug. Treatment with bezafibrate at 450 and 600 mg daily required a reduction of the phenprocoumon dose by 18.5 and 33.5%, respectively. Correspondingly, the serum level of phenprocoumon decreased by 11.6 and 35.3%. No evidence for an altered drug elimination of racemic phenprocoumon could be found during treatment with bezafibrate. The results support the hypothesis that bezafibrate and analogous hypolipidaemic drugs enhance the response to oral anticoagulant drugs by increasing the affinity of the receptor site for coumarins or the rate of degradation of the vitamin-K-dependent clotting factors. The investigation of the fibrinolytic enzyme system demonstrated an increase of the fibrinolytic activity by enhancing the activity of the plasminogen activator. The lysis time for euglobulin clot was reduced significantly, plasma fibrinogen only moderately. The antiplasmin activity could not be altered substantially by a decrease of alpha1-antitrypsin and a slight increase of alpha2-macroglobulin. In contrast with the inhibition of platelet function the effect of bezafibrate on the fibrinolytic enzyme system showed no dose dependence.

4-Hydroxycoumarins↗