Development of a plasma- and albumin-free recombinant von Willebrand factor.

Baxter has developed a recombinant therapy for treating von Willebrand's disease. Recombinant VWF is co-expressed with the rFVIII in CHO cells used to produce the rFVIII product Advate. This rVWF is used as a drug component for a rVWF-rFVIII complex drug product. CHO cells produce partially processed and partially un-processed rVWF still containing the pro-peptide. In order to make a consistent preparation containing mature and processed rVWF only rVWF is exposed to recombinant furin to remove the pro-peptide. Recombinant VWF and furin are produced under serum- and protein-free conditions. It is highly purified by a series of chromatographic steps and formulated in a protein-free buffer and has a homogeneous multimer distribution. The specific activity is higher in rVWF than in commercial plasma-derived VWF-FVIII complex products. SDS agarose electrophoretic analysis shows the presence of ultra-high molecular weight multimers. The FVIII-binding capacity and affinity of rVWF to FVIII is comparable to VWF in plasma. Carbohydrate analysis shows an intact glycosylation pattern. Recombinant VWF binds to collagen and promotes platelet adhesion under shear stress. It stabilizes endogenous FVIII in VWF-deficient knock-out mice as seen by a secondary rise in murine FVIII.

[Prevalence of goiter in the Aachen area. Ultrasound volumetry of the thyroid gland of 1,336 adults in an endemic goiter region]. / Strumaprävalenz im Raum Aachen. Sonographische Volumetrie der Schilddrüse bei 1336 Erwachsenen in einem Strumaendemiegebiet.

AIM: The aim of the study was to assess the prevalence of thyroid enlargement by ultrasonic volume measurements. RESULTS: 1336 adults living in the iodine-deficient area of Aachen, West Germany (760 females, 576 males, mean age: 54.05 +/- 16.09 years) were included in the investigation. The ultrasonic examination was carried out in patients who did not suffer from thyroid disease at the time of study. RESULTS: The thyroid volume was age-dependent and varied from 13.3 +/- 10.4 ml in patients < 21 years to 29.9 +/- 24.3 ml in patients > 70 years. The prevalence of thyroid enlargement ranged from 14.3% in young people to 51.3% in the elderly. There was no difference in the volumes of the left and right thyroid lobe. The prevalence of thyroid enlargement was higher in females compared to males (p < 0.05). Retrosternal thyroid mass was detected in 25% of all patients > 70 years. CONCLUSION: There is evidence of a high prevalence of thyroid enlargement in iodine-deficient areas.

The induction of organ-specific antibodies during the graft-vs.-host reaction.

During the parent (P) into F1 hybrid graft-vs.-host reaction (GVHR), nuclear, leukocyte and erythrocyte autoantibodies are commonly seen. The specificity of these autoantibodies is reminiscent of those found in systemic lupus erythematosus (SLE) patients and SLE-prone mice. Organ-specific antibodies, however, including thyro-globulin (Tg) antibodies do not arise spontaneously. There have been conflicting reports about the ability of exogenous Tg to induce an anti-Tg response during the GVHR. We have re-examined this question in greater detail. Using the murine P----F1 GVHR system, the results of this work demonstrate that mouse thyroglobulin (MTg)-specific antibodies can be induced during a GVHR. However, mice must both be undergoing a GVHR, and have received exogenous MTg. The highest autoantibody response occurs if mice are injected with mouse thyroid extract or purified MTg at the time of P----F1 cell transfer. The anti-MTg response is MTg dose dependent. The ability to induce anti-MTg antibody was not major histocompatibility complex restricted, for both the DBA/2----B6D2F1 (low responder H-2 haplotypes to MTg), and AKR or DBA/2----AKD2F1 (high/low responder----high responder haplotype) GVHR gave similar responses. The anti-MTg titers peaked between days 7-10 and declined thereafter. In contrast, antibodies to dsDNA were not present at this early time, but developed after several weeks. We conclude that organ-specific autoantibodies can be induced during a GVHR if the appropriate antigen(s) are presented near the time of GVHR induction.