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Biomedical subjects

Jens Klinge

Publications and source records attributed to Jens Klinge.

5 recordsLinked to original sources
PubMed2007

Postnatal respiratory distress in a dichorial twin with congenital thoracic neuroblastoma after assisted reproduction by intracytoplasmatic sperm injection.

We report on the case of a female twin with congenital thoracic neuroblastoma after conception via intracytoplasmatic sperm injection (ICSI). Birth occurred at 37 + 1-week gestation per primary sectio caesarea. Acute respiratory distress necessitated intubation and mechanical ventilation. Ultrasound and magnetic resonance imaging (MRI) showed a mass in the right upper thorax compressing the trachea. The tumor was subtotally excised and histological analysis revealed neuroblastoma. No further treatment was given. The residual primary tumor regressed spontaneously. Four years after diagnosis, both twins are healthy and normally developed.

Adult↗
PubMed2004

Epitope mapping of polyclonal clotting factor VIII-inhibitory antibodies using phage display.

Clotting factor VIII (fVIII)-inhibitory antibodies represent a major problem in the treatment of haemophilia A. To understand the inactivation mechanisms and to pave the way towards modifications of recombinant clotting factors that reduce their immunogenicity, the exact localization of immunodominant epitopes is required. Here, a random peptide phage display library was employed to identify epitopes of polyclonal fVIII antibodies isolated from patient's plasma by affinity chromatography. FVIII-binding specificity and inhibitory activity of the isolated fVIII antibodies were confirmed by ELISA and Bethesda assays. Phage selection on the individual samples yielded several phages which were displaced from binding to the respective antibody preparation by fVIII. Their homology with amino acid motifs of human fVIII and immunoprecipitation results with radioactively labelled fVIII fragments suggested putative epitopes in the A1, A2 and C1 domains of fVIII for one and in the C2 domain for another patient. Synthetic peptides corresponding to the A2, C1 and C2 domain epitopes blocked antibody binding to fVIII and partially neutralized the inhibitory activity of the respective plasma in Bethesda assays. These results provide the proof of principle that random peptide libraries can be used for the mapping of epitopes in a polyclonal antibody preparation.

Amino Acid Sequence↗
PubMed2002

Hemophilia A--from basic science to clinical practice.

This article summarizes achievements of basic research and their implementation in clinical treatment of one of the most common inherited bleeding disorders hemophilia A, which is caused by genetic deficiency of coagulation factor VIII (FVIII). We discuss the structure of FVIII, its major interactions in the intrinsic pathway of blood coagulation, and the catabolism of FVIII. We also discuss achievements in the contemporary clinical practice of treatment of hemophilia A. Replacement therapy has substantially improved by development of purification and virus inactivation procedures, allowing preparation of safe and effective therapeutic plasma-derived FVIII concentrates. We give special attention to the principles used in the development of contemporary recombinant FVIII products, which do not inherit a potential risk for viral or prion transmission. Development of FVIII inhibitory antibodies is the major complication of FVIII replacement therapy. We summarize the accumulated knowledge regarding epitopes of FVIII inhibitors and mechanisms by which they inactivate FVIII and discuss approaches to overcome the effects of inhibitors and to prevent their formation by induction of immunotolerance. We also analyze the main concepts and scientific priorities in the gene-therapeutic approach for treatment of hemophilia A.

Animals↗