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The findings of the present study demonstrated that patients with an initial diagnosis of IPF occasionally acquire MPO-ANCA, which develops to MPA during the disease course of IPF. The presence of pulmonary eosinophilia and low attenuation areas on computed tomography scans might be predictive of MPO-ANCA positive conversion.

De novo adipogenesis at the implanted site of a basement membrane extract (Matrigel) was induced through controlled release of basic fibroblast growth factor (bFGF). bFGF was incorporated into biodegradable gelatin microspheres for its controlled release. When the mixture of Matrigel and bFGF-incorporated gelatin microspheres was implanted subcutaneously into the back of mice, a clearly visible fat pad was formed at the implanted site 6 weeks later. Histologic examination revealed that the de novo formation of adipose tissue accompanied with angiogenesis was observed in the implanted Matrigel at bFGF doses of 0.01, 0.1, and 1 microg/site, the lower and higher doses being less effective. The de novo formation induced by the bFGF-incorporated microspheres was significantly higher than that induced by free bFGF of the same dose. The mRNA of a lipogenesis marker protein, glycerophosphate dehydrogenase, was detected in the formed adipose tissues, biochemically indicating de novo adipogenesis. Free bFGF, the bFGF-incorporated gelatin microspheres, or Marigel alone and bFGF-free gelatin microspheres with or without Matrigel did not induce formation of adipose tissue. This de novo adipogenesis by mixture of Matrigel and the bFGF-incorporated gelatin microspheres will provide a new idea for tissue engineering of adipose tissue.

This paper investigates the controlled release of hepatocyte growth factor (HGF) by biodegradable gelatin hydrogels and their HGF-induced angiogenic effect. Hydrogels of different degradabilities were prepared through chemical crosslinking gelatin with varied amounts of glutaraldehyde. When the gelatin hydrogels were radioiodinated and subcutaneously implanted into the back of mice, the remaining radioactivity of the hydrogels decreased with time. However, the remaining period became longer when the concentration of glutaraldehyde used for hydrogel preparation increased. Following implantation of gelatin hydrogels incorporating 125I-labeled HGF, the HGF radioactivity retained in the mouse subcutis for longer time periods as the glutaraldehyde concentration becomes higher. The time profile of HGF remaining in every gelatin hydrogel was in good accordance with that of hydrogel degradation, indicating HGF release as a result of hydrogel biodegradation. The gelatin hydrogel incorporating HGF histologically induced angiogenic change around the implanted hydrogel. Gelatin hydrogels incorporating 5 and 10 microg HGF significantly enhanced the number of capillaries newly formed around the implanted site. This was in marked contrast to free HGF of same dose form and HGF-free, empty gelatin hydrogel. The gelatin hydrogel incorporating HGF induced VEGF around the implanted site. In vitro bioassay revealed that HGF molecules interacting with gelatin, still exhibited the biological activity. The interacted HGF would be released from gelatin hydrogels only when they were degraded to generate water-soluble gelatin fragments. It is possible that the HGF associating gelatin fragments of bioactivating, results in induced angiogenic effect.

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