Biomedical subjects

H J Metzner

Publications and source records attributed to H J Metzner.

5 recordsLinked to original sources

PubMed1999

Effect of factor XIII on endothelial barrier function.

The effect of factor XIII on endothelial barrier function was studied in a model of cultured monolayers of porcine aortic endothelial cells and saline-perfused rat hearts. The thrombin-activated plasma factor XIII (1 U/ml) reduced albumin permeability of endothelial monolayers within 20 min by 30 +/- 7% (basal value of 5.9 +/- 0.4 x 10(-6) cm/s), whereas the nonactivated plasma factor XIII had no effect. Reduction of permeability to the same extent, i.e., by 34 +/- 9% could be obtained with the thrombin-activated A subunit of factor XIII (1 U/ml), whereas the iodoacetamide-inactivated A subunit as well as the B subunit had no effect on permeability. Endothelial monolayers exposed to the activated factor XIII A exhibited immunoreactive deposition of itself at interfaces of adjacent cells; however, these were not found on exposure to nonactivated factor XIII A or factor XIII B. Hyperpermeability induced by metabolic inhibition (1 mM potassium cyanide plus 1 mM 2-deoxy-D-glucose) was prevented in the presence of the activated factor XIII A. Likewise, the increase in myocardial water content in ischemic-reperfused rat hearts was prevented in its presence. This study shows that activated factor XIII reduces endothelial permeability. It can prevent the loss of endothelial barrier function under conditions of energy depletion. Its effect seems related to a modification of the paracellular passageways in endothelial monolayers.

Animals↗

PubMed1998

Two non-proline cis peptide bonds may be important for factor XIII function.

The structure of recombinant human cellular factor XIII zymogen was solved in its monoclinic crystal form and refined to an R-factor of 18.3% (Rfree = 23.6%) for all data between 40.0 and 2.1 A resolution. Two non-proline cis peptide bonds were detected. One is between Arg310 and Tyr311 close to the active site cysteine residue (Cys314) and the other is between Gln425 and Phe426 at the dimerization interface. The structure and the role of these cis peptides are discussed in the light of their possible importance for factor XIII function.

Amino Acid Sequence↗

PubMed1998

Characterization of factor VIII/von Willebrand factor concentrates using a modified method of von Willebrand factor multimer analysis.

In order to provide patients with von Willebrand disease a factor VIII (FVIII)/von Willebrand factor (vWF) concentrate of reproducible quality, an SDS-agarose gel electrophoresis method has been established to determine the content of the high molecular weight multimers (band 11 and higher) of vWF. This method has been used to characterize the content of high molecular weight vWF multimers in Humate P/Haemate P, a commercial FVIII/vWF concentrate. The average content of high molecular weight vWF multimers of 47 batches of Humate P/Haemate P has been determined to be 84.1% of the corresponding bands in normal human plasma. Use of this multimer analysis method for the characterization of five further commercial products revealed clear differences with respect to the high molecular weight vWF multimer content. Furthermore, there is a linear correlation (r2 = 0.73) between the content of high molecular weight vWF multimers and the specific activity of vWF (determined as vWF:RCoF/vWF:Ag). The method described here for analysis of the content of high molecular weight vWF multimers is a reliable and reproducible method to characterize this class of factor concentrates with respect to vWF multimer composition.

Electrophoresis↗

PubMed1996

Therapeutic factor XIII preparations and perspectives for recombinant factor XIII.

With the increasing availability of human plasma this source was used to substitute for the production of factor XIII concentrate from placenta. Prior to changing the source material, the virus safety in accordance with the Committee for Proprietary Medicinal Products (CPMP) guidelines and the half-life were investigated. Concerning the virus safety, the following cumulative log 10 clearance factors were obtained: human immunodeficiency virus (HIV) > or = 18.9, herpes simplex virus (HSV-1) > or = 21.5, polio > or = 19.1, bovine viral diarrhea virus (BVDV) > or = 13.3. Half-life studies of factor XIII from plasma in comparison with factor XIII from placenta were done in rabbits by determination of the antigen and in patients with congenital factor XIII deficiency by determination of the activity and antigen. In rabbits, the terminal half-life of the antigen was 78.2 hours for factor XIII from placenta and 87.0 hours for factor XIII from plasma. In patients the half-lives were similar: 9.2 days for activity and antigen of factor XIII from plasma and 8.5 days (activity) versus 9.4 days (antigen) for the placenta-derived factor XIII. Some further clinical studies with factor XIII concentrates are also reviewed. Newer developments concerning recombinant factor XIII, its expression, characterization, and properties are summarized. Concerning the physicochemical data, the behavior in plasma was characterized by the formation of high-molecular-weight complexes, and first in vivo results, the recombinant factor XIII product was comparable to the naturally occurring material.

Amino Acid Sequence↗

PubMed1990

Crystallization of blood coagulation factor XIII by an automated procedure.

Both recombinant blood coagulation factor XIII alpha-chain and factor XIII isolated from human placenta have been crystallized using a novel robotic system for the automatic screening of crystallization conditions. The monoclinic and orthorhombic crystals obtained are suitable for X-ray analysis.

Crystallization↗