Transgenic mouse lineages were established that carry the normal (M) or mutant (Z) alleles of the human $\alpha _{1}$-antitrypsin ($\alpha _{1}$-Pi) gene. All of the $\alpha _{1}$-Pi transgenic mice ...expressed the human protein in the liver, cartilage, gut, kidneys, lymphoid macrophages, and thymus. The human M-allele protein was secreted normally into the serum. However, the human Z-allele protein accumulated in several cell types, but particularly in hepatocytes, and was found in serum in tenfold lower concentrations than the M-allele protein. Mice in one lineage carrying the mutant Z allele expressed high levels of human $\alpha _{1}$-Pi RNA and displayed significant runting (50% of normal weight) in the neonatal period. This lineage was found to have $\alpha _{1}$-Pi--induced liver pathology in the neonatal period, concomitant with the accumulation of human Z protein in diastase-resistant cytoplasmic globules that could be revealed in the Periodic acid-Schiff reaction (PAS). The phenotype of mice in the strain expressing high levels of the Z allele is remarkably similar to human neonatal hepatitis, and this strain may prove to be a useful animal model for studying this disease.
One hundred five patients were enrolled in a 12‐week, randomized, prospective, double‐blind, placebo‐controlled trial of recombinant human γ‐interferon (rHuγ‐IFN) for the treatment of rheumatoid ...arthritis. Fifty‐four patients received rHuγ‐IFN and 51 received placebo. Forty‐two patients in each group completed the 12‐week trial. Some clinical improvement occurred in both groups of patients. Although the improvement with rHuγ‐IFN was greater than that with placebo, the differences were generally not statistically significant.
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