cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein

Using the yeast two hybrid system, a mouse embryo cDNA library was screened for proteins that interact with the C-terminus of the human beta-amyloid precursor protein (beta PP). A fusion protein was identified that interacts specifically with the cytoplasmic domain of beta PP and does not interact with the beta-amyloid region. The protein encoded by this partial mouse cDNA is identical to the C-terminus of the rat Fe65 protein. This mouse protein also interacts with the homologous C-terminal domains of the mouse amyloid precursor-like proteins, APLP1 and APLP2. These conserved cytoplasmic regions contain a common amino acid motif, Asn-Pro-Thr-Tyr, which has previously been shown to influence both the secretion and internalization of beta PP. Fe65 has been implicated in regulatory and cell signaling mechanisms because it contains two different motifs involved in protein binding, a WW domain (a variant of Src homology 3 domains) and a phosphotyrosine interaction domain (PID). Interestingly, the PID domain binds to the same motif present in the conserved cytoplasmic domains of the beta PP and beta PP-like proteins. RNA analyses reveal that Fe65 is predominantly expressed in brain and in the regions most affected by Alzheimer's disease (AD)-associated neuropathology. The human Fe65 mRNA was cloned from a fetal brain cDNA library. The message encodes a protein of 735 amino acids that is 95% identical to the rat Fe65 protein. The human Fe65 gene was mapped on human metaphase chromosomes to band 11p15 using fluorescence in situ hybridization.      

Pattern of proteinuria in IgA nephropathy

Summary: Proteinuria is one of the bad prognostic indices in IgA nephritis (IgAN). This study compares the pattern of protein excretion in 10 patients with IgAN (IA) with that 5 years later (IB), when they developed renal impairment or hypertension. The pattern of proteinuria was analysed by SDS-PAGE and isoelectric focusing (IEF) and assayed for orosomucoid, α-1-microglobulin, retinol-binding protein, lysozyme, beta-2-microglobulin and N-acetyl-β-D-glucosaminidase activity. The data suggest that the changing pattern of proteinuria from IgA₁ to IgA₂ may reflect hyperfiltration as well as tubular injury.     

Chronic osteomyelitis: bone and gallium scan patterns associated with active disease

Bone and gallium scans are used to assess osteomyelitis patients with prior bone disease. To refine the criteria for interpreting these scans, the data from 136 consecutive patients with clinically suspected osteomyelitis were reviewed. Active osteomyelitis was diagnosed with surgery or biopsy and culture in 49 patients, excluded with the same criteria in 16, and excluded by clinical follow-up for at least 6 months in 71. Five different scintigraphic patterns were found. The true-positive and false-positive ratios, the likelihood ratios, and posterior probabilities for active osteomyelitis in each pattern were calculated. Only one pattern (gallium uptake exceeding bone-seeking radiopharmaceutical uptake) was indicative of active disease. Other patterns slightly raised or decreased the probability of disease. The extent of these changes varies directly with the prior probability of disease, determined from patient-specific factors (e.g., clinical data, laboratory data, findings on plain films) known best by the referring clinician.