Perianal abscess formation in infants who are younger than 12 months is a separate entity from abscess formation in older age groups. In this largest study to date, a combined center series of patients who presented to 2 academic pediatric hospitals with infantile perianal abscess, local hygiene and systemic antibiotics without surgical drainage minimized formation of fistula in ano.

Abstract:To study amyloid ␤-protein (A␤) production and aggregation in vivo, we created two transgenic (Tg) mouse lines expressing the C-terminal 100 amino acids of human amyloid precursor protein (APP): Tg C100.V717F and Tg C100.WT. Western blot analysis showed that human APP-C100 and A␤ were produced in brain and some peripheral tissues and A␤ was produced in serum. Using antibodies specific for the A␤ C terminus we found that Tg C100.V717F produced a 1.6-fold increase in A␤42/A␤40 compared with Tg C100.WT. Approximately 30% of total brain A␤ (ϳ122 ng/g of wet tissue) was water-soluble. The remaining 70% of A␤ partitioned into the particulate fraction and was completely sodium dodecyl sulfate-soluble. In contrast, human Alzheimer's disease brain has predominantly sodium dodecyl sulfate-insoluble A␤. Immunohistochemistry with an A␤(5-8) antibody showed that A␤ or A␤-containing fragments accumulated intracellularly in the hippocampus of aged Tg C100.V717F mice. The soluble A␤ levels in Tg brain are similar to those in normal human brain, and this may explain the lack of microscopic amyloid deposits in the Tg mice. However, this mouse model provides a system to study the intracellular processing and accumulation of A␤ or A␤-containing fragments and to screen for compounds directed at the ␥-secretase activity. Key Words: Alzheimer's disease -Amyloid ␤-protein-Amyloid precursor protein-C100 -Transgenic mouseProcessing. J. Neurochem. 72, 2479 -2487 (1999).Alzheimer's disease (AD) is characterized neuropathologically by amyloid plaques, neurofibrillary tangles, cerebrovascular amyloid, and neuronal degeneration (Glenner and Wong, 1984;Masters et al., 1985). The principal component of the plaques is the 4-kDa amyloid ␤-protein A␤, which is proteolytically derived from the amyloid precursor protein (APP) (Kang et al., 1987).Two major forms of A␤ are found. The 40-amino acid peptide (A␤40) is the predominant form that is produced during normal metabolism of APP. The longer A␤42 species is a minor product and is more cytotoxic and prone to aggregation than A␤40 (Hilbich et al., 1991;Jarrett et al., 1993;Roher et al., 1996). Mutations associated with familial AD (FAD) that are located adjacent to the N terminus of A␤ increase the levels of both A␤40 and A␤42 (Hardy, 1997). Mutations near the C terminus of A␤ or mutations in another FAD-associated gene, presenilin, increase the level of A␤42 (Hardy, 1997). These data indicate that APP processing and A␤ release, particularly the ␥-secretase process releasing the long A␤, play an important role in the etiology of AD.The A␤ fragment is generated by sequential cleavage of APP by ␤-secretase at the N terminus of A␤ followed by ␥-secretase at the A␤ C terminus. Cleavage of APP by ␤-secretase between Met 671 and Asp 672 results in secretion of an ectodomain sAPP␤, which is a truncated APP form ending with Met 671 (Seubert et al., 1993;Li et al., 1998a), and a fragment of ϳ12 kDa, C100 or A4CT

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