A retrospective study of immunochemical fecal occult blood testing for colorectal cancer detection.

BACKGROUND: Colonoscopic examination is the common pathway for positive screening tests detecting colorectal lesions. We evaluated a specific, quantitative high-throughput automatic immunochemical fecal occult blood test (Auto iFOBT) method for colorectal cancer (CRC) screening and to determine its concordance with physician assessments informed by complete colonoscopy, the gold-standard technique for evaluation of the colonic mucosa. METHODS: 1200 CRC symptomatic patients were recruited for a retrospective investigation. Colorectal neoplasia were localized by colonoscopy and cancer outcomes were enumerated according to severity. In addition, stool samples were collected and analyzed by Auto iFOBT to derive sensitivity, specificity, and positive predictive value. Qualitative colonoscopy and Auto iFOBT results were correlated, as were cancer severities and quantitative hemoglobin concentrations. RESULTS: Ninety-one patients were found positive for CRC; 50 mucosal, 20 submucosal, and 21 advanced. At standard cutoff, sensitivity was 60%, 90%, and 95%, respectively. Specificity and positive predictive value for all neoplasia and cancers were 89.6% and 86.4%, and 60.9% and 33.7%, respectively. Cancer severities could be approximated roughly according to hemoglobin concentrations. CONCLUSIONS: Specific qualitative 2-day Auto iFOBT is an accurate tool for the detection of colorectal cancer and therefore provides the basis for a large-scale screening program.

Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease.

Citrullinated proteins are the products of a posttranslational process in which arginine residues undergo modification into citrulline residues when catalyzed by peptidylarginine deiminases (PADs) in a calcium ion-dependent manner. In our previous report, PAD2 expressed mainly in the rat cerebrum became activated early in the neurodegenerative process. To elucidate the involvement of protein citrullination in human neuronal degeneration, we examined whether citrullinated proteins are produced during Alzheimer's disease (AD). By Western blot analysis with antimodified citrulline antibody, citrullinated proteins of varied molecular weights were detected in hippocampal tissues from patients with AD but not normal humans. Two of the citrullinated proteins were identified as vimentin and glial fibrillary acidic protein (GFAP) by using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. Interestingly, PAD2 was detected in hippocampal extracts from AD and normal brains, but the amount of PAD2 in the AD tissue was markedly greater. Histochemical analysis revealed citrullinated proteins throughout the hippocampus, especially in the dentate gyrus and stratum radiatum of CA1 and CA2 areas. However, no citrullinated proteins were detected in the normal hippocampus. PAD2 immunoreactivity was also ubiquitous throughout both the AD and the normal hippocampal areas. PAD2 enrichment coincided well with citrullinated protein positivity. Double immunofluorescence staining revealed that citrullinated protein- and PAD2-positive cells also coincided with GFAP-positive cells, but not all GFAP-positive cells were positive for PAD2. As with GFAP, which is an astrocyte-specific marker protein, PAD2 is distributed mainly in astrocytes. These collective results, the abnormal accumulation of citrullinated proteins and abnormal activation of PAD2 in hippocampi of patients with AD, strongly suggest that PAD has an important role in the onset and progression of AD and that citrullinated proteins may become a useful marker for human neurodegenerative diseases.

Nine new secoiridoid glucosides from Jasminum nudiflorum.

Phytochemical study of the leaves of Jasminum nudiflorum has led to the isolation of nine new secoiridoid glucosides, jasnudiflosides F-L (1-7), nudifloside D (8) and isooleoacteoside (9). The structures of these compounds were elucidated on the basis of chemical and spectroscopic evidence.