A transgenic mouse model reproduces human hereditary systemic amyloidosis.

Amyloidoses are rare life-threatening diseases caused by protein misfolding of normally soluble proteins. The fatal outcome is predominantly due to renal failure and/or cardiac dysfunction. Because amyloid fibrils formed by all amyloidogenic proteins share structural similarity, amyloidoses may be studied in transgenic models expressing any amyloidogenic protein. Here we generated transgenic mice expressing an amyloidogenic variant of human apolipoprotein AII, a major protein of high density lipoprotein. According to amyloid nomenclature this variant was termed STOP78SERApoAII. STOP78SER-APOA2 expression at the physiological level spontaneously induced systemic amyloidosis in all mice with full-length mature STOP78SER-ApoAII identified as the amyloidogenic protein. Amyloid deposits stained with Congo red were extracellular, and consisted of fibrils of approximately 10 nm diameter. Renal glomerular amyloidosis was a major feature with onset of renal insufficiency occurring in mice older than six months of age. The liver, heart and spleen were also greatly affected. Expression of STOP78SER-APOA2 in the liver and intestine in mice of the K line but not in other amyloid-laden organs showed they present systemic amyloidosis. The amyloid burden was a function of STOP78SER-APOA2 expression and age of the mice with amyloid deposition starting in two-month-old high-expressing mice that died from six months onwards. Because STOP78SER-ApoAII conserved adequate lipid binding capacity as shown by high STOP78SER-ApoAII amounts in high density lipoprotein of young mice, its decrease in circulation with age suggests preferential deposition into preformed fibrils. Thus, our mouse model faithfully reproduces early-onset hereditary systemic amyloidosis and is ideally suited to devise and test novel therapies.

Pathologic features of necrotizing adenoviral prostatitis in an AIDS patient.

Adenovirus has been implicated as a cause of opportunistic infections in immunocompromised patients, frequently with multiorgan involvement and a fatal outcome. We describe a case of necrotizing adenoviral prostatitis in a 35-year-old man with terminal AIDS and generalized adenoviral infection. The histopathologic findings of intraacinar necrotizing inflammation, prominent viral nuclear inclusions in residual epithelium, and mild T-lymphocyte and macrophageal inflammatory reaction were observed in the prostate. The presence of adenovirus was confirmed by electron microscopy and immunohistochemistry. Squamous metaplasia was present in the surrounding acini. This case of adenoviral prostatitis appears to be the first report of its kind in medical literature and demonstrates another aspect of the diversity of organ manifestations seen in this infection. This lesion should be included in the differential diagnosis of necrotizing prostatic diseases.