We report two large kindreds with Parkinson's disease (PD) apparently inherited in autosomal dominant fashion. Forty-one persons in four generations have been affected; we have examined 7 of them. The two kindreds originated in a single small town in southern Italy and therefore are probably related. The illness was typical for PD except for early onset at a mean age of 46.5 years and a rapid course that averaged 9.7 years from onset to death. Clinical appearance and response to levodopa were typical for PD. Only one instance of definite nonpenetrance is known. Autopsy of 2 patients in one kindred showed the pathological changes typical of PD with Lewy bodies. Disease duration among affected persons who spent most of their lives in Italy was longer than for their affected US relatives, suggesting that exogenous agents may influence the course of this genetic illness. We conclude that what is probably a single gene without an additional environmental insult can cause the pathological changes typical of PD. Our findings therefore enhance the likelihood of a significant genetic component in the cause of sporadic PD. By identifying a toxic gene product, future molecular genetic studies in our kindred(s) may provide insight into the pathogenesis of sporadic PD.

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Pneumolysin is a 471-amino-acid toxin produced byStreptococcus pneumoniae which has both cytolytic and complement activation properties. We have constructed a derivative of the type 2 S. pneumoniae strain D39 in which the portion of the pneumolysin gene encoding amino acids 55 to 437 has been deleted in-frame. The virulence of this strain (ΔPly) was compared with those of wild-type D39, a pneumolysin insertion-duplication mutant (PLN-A), and a derivative (PdT) carrying a toxin gene with three point mutations known to abolish both cytolytic activity and complement activation. PdT was intermediate in virulence between D39 and either PLN-A or ΔPly in a mouse intraperitoneal challenge model. This provides unequivocal evidence that pneumolysin has an additional property that is not abolished by point mutations which reduce cytotoxicity and complement activation to virtually undetectable levels.

Prosthetic valve endocarditis due to Legionella pneumophila occurred in a woman who had aortic and mitral valve replacements with porcine xenografts. During surgery for persistent fever and aortic regurgitation due to presumed endocarditis, she had vegetations involving both the aortic and mitral valve prostheses with a circumferential abscess of the aortic annulus. Cultures, Dieterle stain, and direct fluorescent antibody stain of valve tissue, and subsequent measurements of serum antibody levels confirmed L. pneumophila as the infecting organism. This infection occurred in the absence of pneumonia. Legionella pneumophila must be considered a potential cause of culture-negative prosthetic valve endocarditis and should be sought in appropriate clinical circumstances.