Context Colorectal cancer is the second leading cause of cancer death in the United States. Prevention has focused on the detection and removal of polypoid neoplasms. Data are limited on the significance of nonpolypoid colorectal neoplasms (NP-CRNs). Objectives To determine the prevalence of NP-CRNs in a veterans hospital population and to characterize their association with colorectal cancer. Design, Setting, and Patients Cross-sectional study at a veterans hospital in California with 1819 patients undergoing elective colonoscopy from July 2003 to June 2004. Main Outcome Measures Endoscopic appearance, location, size, histology, and depth of invasion of neoplasms. Results The overall prevalence of NP-CRNs was 9.35% (95% confidence interval [95% CI], 8.05%-10.78%; n=170). The prevalence of NP-CRNs in the subpopulations for screening, surveillance, and symptoms was 5.84% (95% CI, 4.13%-8.00%; n=36), 15.44% (95% CI, 12.76%-18.44%; n=101), and 6.01% (95% CI, 4.17%-8.34%; n=33), respectively. The overall prevalence of NP-CRNs with in situ or submucosal invasive carcinoma was 0.82% (95% CI, 0.46%-1.36%; n=15); in the screening population, the prevalence was 0.32% (95% CI, 0.04%-1.17%; n=2). Overall, NP-CRNs were more likely to contain carcinoma (odds ratio, 9.78; 95% CI, 3.93-24.4) than polypoid lesions, irrespective of the size. The positive size-adjusted association of NP-CRNs with in situ or submucosal invasive carcinoma was also observed in subpopulations for screening (odds ratio, 2.01; 95% CI, 0.27-15.3) and surveillance (odds ratio, 63.7; 95% CI, 9.41-431). The depressed type had the highest risk (33%). Nonpolypoid colorectal neoplasms containing carcinoma were smaller in diameter as compared with the polypoid ones (mean [SD] diameter, 15.9 [10.2] mm vs 19.2 [9.6] mm, respectively). The procedure times did not change appreciably as compared with historical controls. Conclusion In this group of veteran patients, NP-CRNs were relatively common lesions diagnosed during routine colonoscopy and had a greater association with carcinoma compared with polypoid neoplasms, irrespective of size.

The complete gene 4 nucleotide sequence was determined for rhesus rotavirus and each of 11 viral variants selected by neutralizing monoclonal antibodies. Gene 4 is 2362 bases in length and encodes a protein, VP3, of 776 amino acids with a calculated Mr of 86,500. A conserved trypsin cleavage site, located at amino acid 247, divides VP3 into VP8 and VP5. Neutralizing monoclonal antibodies directed at VP3 were used to select variants that escaped neutralization. Each variant contains a single gene 4 mutation that permits viral growth in the presence of the antibody. Variant mutations were identified in six distinct neutralization regions in VP8 and VP5. Five of the six neutralization regions were found in VP8. The VP8 regions were primarily associated with strain-specific or limited heterotypic rotavirus neutralization. One region was identified in VP5 by three monoclonal antibodies that neutralize a broad range of rotavirus serotypes. The VP5 neutralization region is largely hydrophobic and is similar to putative fusion sequences of Sindbis and Semliki Forest viruses.Rotavirus is a 70-nm icosahedral virus comprised of two capsid layers. The inner capsid, composed of proteins VP1, VP2, and VP6, contains an endogenous RNA-dependent RNA polymerase and 11 double-stranded RNA segments (1). Gene segments 4 and 9 encode the outer capsid proteins VP3 and VP7, respectively, of rhesus rotavirus (RRV) (2). VP7 (37 kDa) is a glycoprotein, and antibodies directed against VP7 neutralize the virus and specify the viral serotype (3-8). The other viral surface protein, VP3, is an 84-to 88-kDa nonglycosylated protein containing the viral hemagglutinin (9). In the presence of trypsin, VP3 is cleaved to VP5 (60 kDa) and VP8 (28 kDa), which results in enhancement of viral infectivity (10). Preliminary studies indicate that cleavage of VP3 mediates penetration of the virion into the cell (11). VP3 is also associated with restriction of virulence of certain rotavirus strains in mice (12) and humans (13). Antibodies directed at VP3 inhibit viral hemagglutination (14), neutralize the virus in vitro (14), and passively protect mice against heterologous rotavirus challenge in vivo (15). Further studies have demonstrated that VP3 effectively induces protective immunity in animals (16) and is immunogenic in young children (17).We have studied VP3 neutralization sites of the rhesus strain of simian rotavirus. RRV is serotypically identical to type 3 human rotavirus strains (18). Previously, we described a library of monoclonal antibodies (mAbs) directed against the RRV VP3 protein, which defines its functional and antigenic topography (22). mAbs directed at VP3 were used to delineate distinct neutralization domains and to demonstrate that VP3 contains both heterotypic and homotypic neutralizing epitopes. Neutralizing mAbs (N-mAbs) selecting these distinct domains were characterized by competitive binding studies and by their ability to recognize mutants that grew in the presence of N-mAbs.In this study, we have determined the full-len...

Six biochemical and genetic forms of methylmalonic acidemia have been defined previously: two (mut degrees and mut-) resulting from defects in the mutase apoenzyme, and four (cbl A, cbl B, cbl C, and cbl D) resulting from deficient adenosylcobalamin synthesis. We retrospectively surveyed the clinical presentation, response to cobalamin supplementation, and long-term outcome in the four most prevalent mutant classes by collecting detailed information on 45 patients (15 mut degrees, 5 mut-, 14 cbl A, and 11 cbl B). Most patients presented acutely with a common set of clinical and laboratory findings; however, there were significant differences between mutant classes: mut degrees patients presented earlier in infancy than did cbl A and cbl B patients; in response to cobalamin supplements, marked decreases in the concentration of methylmalonic acid in blood or urine were reported in most cbl A patients and in nearly half the cbl B patients, but not in mut degrees or mut- patients; and finally, most cbl A, cbl B, and mut- patients were still living, whereas most mut degrees patients died during the first few months of life. Our data indicate that genotypic classification of the methylmalonic acidemias has prognostic and therapeutic use as well as diagnostic value.

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