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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 433 records · Page 24Linked to original sources

[Ambulatory long-term prevention of thromboembolism with low-molecular weight heparin].

Patients with severe bleeding complications and other side effects on conventional anticoagulants and strong indication for further anticoagulation were treated with a low molecular weight heparin fragment (Tedelparin). In this paper we report the experiences in 30 patients, who were anticoagulated 1-11 months with this compound. All patients injected themselves a dose ranging from 1 X 2,500 to 1 X 20,000 anti factor Xa units per day. Within 132 months of treatment one patient with good compliance developed thromboembolism. Four patients had bad compliance. Two of them experienced rethrombosis 1 and 8 weeks after starting therapy. Severe haemorrhages did not occur. Two patients had one minor bleeding complication each. Both patients developed several times per year severe haemorrhages with conventional anticoagulants. All excessive subcutaneous haematomas and indurations of the adipose tissue at the injection site of conventional heparin disappeared completely. Low molecular weight heparin can be regarded as an alternative anticoagulant in patients with severe bleeding and other complications on oral anticoagulants and conventional heparin.

Adult↗

Import of honeybee prepromelittin into the endoplasmic reticulum: structural basis for independence of SRP and docking protein.

Honeybee prepromelittin is correctly processed and imported by dog pancreas microsomes. Insertion of prepromelittin into microsomal membranes, as assayed by signal sequence removal, does not depend on signal recognition particle (SRP) and docking protein. We addressed the question as to how prepromelittin bypasses the SRP/docking protein system. Hybrid proteins between prepromelittin, or carboxy-terminally truncated derivatives, and the cytoplasmic protein dihydrofolate reductase from mouse were constructed. These hybrid proteins were analysed for membrane insertion and sequestration into microsomes. The results suggest the following: (i) The signal sequence of prepromelittin is capable of interacting with the SRP/docking protein system, but this interaction is not mandatory for membrane insertion; this is related to the small size of prepromelittin. (ii) In prepromelittin a cluster of negatively charged amino acids must be balanced by a cluster of positively charged amino acids in order to allow membrane insertion. (iii) In general, a signal sequence can be sufficient to mediate membrane insertion independently of SRP and docking protein in the case of short precursor proteins; however, the presence and distribution of charged amino acids within the mature part of these precursors can play distinct roles.

Animals↗

Import of frog prepropeptide GLa into microsomes requires ATP but does not involve docking protein or ribosomes.

Frog prepropeptide GLa, a precursor to a secretory protein containing 64 amino acids, was processed and imported by dog pancreas microsomes. These events did not depend on either docking protein or on the presence of ribosomes. A hybrid protein between the first 60 amino acids of prepropeptide GLa and an unrelated peptide of 49 amino acids fused to the carboxy terminus, however, behaved like a typical secretory protein precursor with regard to docking protein dependence. This suggests that independence of the need for docking protein, in the case of prepropeptide GLa, can be attributed to the size of the precursor protein. Processing and import of prepropeptide GLa by microsomes were ATP dependent. Therefore, import of proteins into the endoplasmic reticulum (ER) includes an ATP-requiring step not involving a ribosome/ribosome receptor or signal recognition particle (SRP)/docking protein interaction.

Adenosine Triphosphate↗

The ATP requiring step in assembly of M13 procoat protein into microsomes is related to preservation of transport competence of the precursor protein.

M13 procoat protein is processed to transmembrane coat protein by dog pancreas microsomes after completion of synthesis and in the absence of the signal recognition particle (SRP)/docking protein system. ATP is required for fast and efficient processing of procoat protein by microsomes in a reticulocyte lysate. Requirement for ATP is also observed in the absence of ribosomes or docking protein. This indicates the existence of a unique assembly pathway for procoat protein into microsomes which depends on ATP but does not depend on the SRP/docking protein and ribosome/ribosome receptor systems. We suggest that the ATP requirement is linked to a so far unknown component of the reticulocyte lysate, acting on transport competence of precursor proteins.

Adenosine Triphosphate↗

Clinical effects of intravenous iloprost in patients with intermittent claudication.

In a randomized patient-blind study iloprost or hydroxy-ethyl starch 200/0.5 were given i.v. 5 h daily for 2 weeks to 24 patients suffering from severe intermittent claudication due to peripheral vascular disease. An increase in pain-free walking distance of more than 50% occurred in 6 of 11 patients after the iloprost infusions and in 7 of 12 patients after HES treatment. No significant effects on haemodynamic or clinical chemistry tests were observed.

Aged↗

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↗

[Prevention of thromboembolism with low-molecular weight heparin in pregnancy].

Two patients were anticoagulated during pregnancy with the low molecular weight heparin Kabi 2165 because of side effects on conventional heparin. One patient had to be treated because of deep vein thrombosis in the first pregnancy and the other patient because of a Björk Shiley mitral valve prosthesis. The first patient had developed cutaneous allergic reactions to different conventional heparins and the second patient suffered from extensive local haematomas because of subcutaneous injection of heparin. The doses of the low molecular heparin were 1 X 5000 (patient 1) and 1 X 10,000 (patient 2) anti factor Xa units. The treatment period was 27 and 20 weeks, respectively. No thromboembolism or bleeding occurred. The low molecular weight heparin could not be detected in the umbilical vein or in the breast milk.

Adult↗

[Anticoagulation with low molecular-weight heparin in patients with prosthetic heart valve replacements].

In six patients with prosthetic heart valve replacement anticoagulation was performed with low molecular weight heparin for 4-58 weeks. The treatment was indicated because of one or more severe cerebral or gastrointestinal bleeding complications during therapy with oral anticoagulants or conventional heparin. The dose of the low molecular weight heparin ranged individually from 2,500 to 12,000 units once a day subcutaneously and was adjusted on the basis of the general bleeding tendency of the patient and the specific anticoagulant effect on factor Xa. Under this treatment no heart valve thrombosis occurred. Two minor bleeding complications were observed in two patients. All patients suffered previously from severe bleeding complications with conventional anticoagulants. One additional patient, who had been treated one year earlier with the low molecular weight heparin, again experienced embolism during treatment with only 1 X 5,000 anti factor Xa units per day. We conclude that anticoagulation with low molecular weight heparin may be recommended for patients with prosthetic heart valve replacement and severe bleeding problems with conventional anticoagulants. In patients with recurrent embolism higher doses should be administered.

Adult↗

[Neutralization of low molecular weight heparin Kabi 2165 by protamine chloride].

Low molecular weight (LMW) heparin Kabi 2165 possesses improved pharmacodynamic properties compared with conventional heparin. It is currently investigated in the prophylaxis of thromboembolism. The neutralization of Kabi 2165 by protamine chloride was analysed after i.v. injection of both the agent and the antidot in healthy persons. The anticoagulant effects of the LMW heparin on the activated partial thromboplastin time, thrombin, and thromboelastography are completely and immediately suppressed by protamine chloride. The inhibition of factor Xa is antagonized up to 50%-60%. The bleeding time remained unaffected. The data indicate that protamine chloride may be used in clinical situations as an antidot to the LMW heparin Kabi 2165. A rebound phenomenon of the anticoagulant effect does not occur.

Blood Coagulation↗

Import of honeybee prepromelittin into the endoplasmic reticulum. Requirements for membrane insertion, processing, and sequestration.

Honeybee prepromelittin is correctly processed and imported by dog pancreas microsomes. Membrane insertion of prepromelittin, assayed as signal sequence removal by signal peptidase, is not dependent on signal recognition particle and docking protein. However, a previously uncharacterized proteinaceous component of the microsomal membrane is required for completion of membrane transfer of promelittin. Furthermore, membrane insertion of prepromelittin is not coupled to translation. These data suggest the signal sequence, in addition to its role in membrane recognition, has a more general function for membrane insertion, cotranslational import of proteins is not an intrinsic feature of microsomes, and at least in certain cases, proteinaceous membrane components are involved in membrane transfer.

Amino Acid Sequence↗

Phenprocoumon metabolites in human plasma; characterization by HPLC and GC-MS.

Pooled plasma from patients receiving phenprocoumon anticoagulant therapy was extracted and the following substances were characterized: phenprocoumon, and its 7-hydroxy,4'-hydroxy and 6-hydroxy derivatives; they were identified by HPLC and after methylation by quartz capillary GC-MS using the electron impact and selective ion monitoring modes. This is the first occasion when phenprocoumon metabolites have been identified in plasma; they were unconjugated and in much lower concentrations (43.2 and 2 ng/ml for the 7,4' and 6-hydroxy derivatives, respectively) than the original compound (2000 ng/ml).

4-Hydroxycoumarins↗

Malignant fibrous histiocytoma associated with peripheral blood eosinophilia. In vitro studies demonstrating tumor-derived eosinophilopoietic activity.

Peripheral blood eosinophilia is a well-recognized paraneoplasia in many kinds of hematological and nonhematological malignancies. We report the case of a patient with a malignant fibrous histiocytoma. With increasing tumor burden, the patient developed a marked peripheral blood eosinophilia. Using an in vitro assay for growth of eosinophilic colonies, both the serum and the tumor of the patient proved to contain an eosinophilopoietic activity.

Cell Division↗