Immunization with FimA protects against Streptococcus parasanguis endocarditis in rats.

FimA, a surface-associated protein of Streptococcus parasanguis, is associated with initial colonization of damaged heart tissue in an endocarditis model (D. Burnette-Curley, V. Wells, H. Viscount, C. Munro, J. Fenno, P. Fives-Taylor, and F. Macrina, Infect. Immun. 63:4669-4674, 1995). We have evaluated the efficacy of recombinant FimA as a vaccine in the rat model of endocarditis and investigated in vitro the mechanism for the protective role of immunization. FimA-immunized and nonimmunized control animals were catheterized to induce heart valve damage and infected intravenously with 10(7) CFU of wild-type S. parasanguis FW213 bacteria. The presence of bacteria associated with platelet-fibrin vegetations 24 h postchallenge was evaluated. Immunized rats were significantly less susceptible to endocarditis (2 cases among 34 animals) than the control group (21 cases among 33 animals) (P < 0.001). Incubation of S. parasanguis FW213 with rabbit anti-FimA immune serum decreased the mean percent adherence (0.34% of added cells) to platelet-fibrin matrix in vitro compared with that of preimmune normal serum (5.04% of added cells; P < 0.001). Adsorption of immune serum with FimA-positive S. parasanguis FW213 yielded antiserum that failed to block adherence to the platelet-fibrin matrix. We assessed the vaccine potential of FimA as a common immunogen able to provide cross-protection in streptococcal endocarditis by determining the occurrence and expression of fimA in the viridans group streptococci and enterococci. We detected the presence of fimA homologs by Southern hybridization and PCR amplification analyses and determined by immunoblotting the expression of FimA-like proteins among a variety of streptococci and enterococci that frequently cause endocarditis. Eighty-one percent (26 of 32) of streptococcal and enterococcal strains isolated from bacteremic patients expressed proteins that comigrated with FimA and were reactive with polyclonal anti-FimA serum. Streptococcal DNA from strains that were positive by Western blot (immunoblot) analysis hybridized to the full-length fimA probe. Our studies suggest that FimA immunization results in antibody-mediated inhibition of bacterial adherence, a critical early event in the pathogenesis of endocarditis. Our data demonstrate that a majority of streptococcal strains associated with endocarditis have genes that encode FimA-like proteins. Taken together, these results suggest that FimA is a promising candidate for an endocarditis vaccine.     

In vivo and in vitro MR imaging of renal tumors: histopathologic correlation and pulse sequence optimization

Magnetic resonance (MR) imaging has given mixed results in the detection of renal masses. To identify the reasons for this and to determine the optimal pulse sequences for evaluating renal tumors, the authors imaged 12 primary renal tumors in vivo and 17 in vitro at 0.35 T. Histopathologic findings for each specimen were closely correlated with the MR images. Four of seven solid tumors imaged in vivo were isointense with surrounding normal renal parenchyma at all pulse sequences. The other three tumors were hyperintense in vivo at T2-weighted sequences. At heavily T2-weighted sequences eight solid tumors were hyperintense in vitro and four were hypointense. There was no correlation between signal intensity and specific tissue type or histologic pattern for solid tumors. The five cystic tumors were well seen both in vivo and in vitro on T2-weighted images. However, the signal intensity of the cyst fluid was an unreliable indicator of benignancy. SE MR imaging at 0.35 T has significant limitations in the detection of solid renal masses.     

Agenesis of the right lobe of the liver

In five patients with agenesis of the right lobe of the liver, computed tomography or sonography demonstrated absence of the right lobe with compensatory hypertrophy of other segments. In three patients, the caudate lobe was also absent. The radiologic differential diagnosis includes lobar atrophy due to cirrhosis or hilar cholangiocarcinoma. Nineteen other cases have been reported in the world literature since 1956. This interesting congenital anomaly may be associated with biliary tract disease (12 patients), portal hypertension (seven patients), and other congenital anomalies (four patients), or it may be an incidental finding (five patients).     

Zebrafish genetics and its implications for understanding vertebrate development

The identification of genes via their mutant phenotypes is the most direct way of dissecting the molecular basis of developmental processes. While this approach has been extremely powerful in invertebrates such as Drosophila and Caenorhabditis elegans, it has until recently been lacking in vertebrates. Now two landmark studies by the groups of Nusslein-Volhard and Driever have for the first time provided the basis for a comprehensive genetic dissection of vertebrate development using the teleost fish, Danio rerio. The mutations identified in these screens look set to revolutionise our understanding of vertebrate development.      

Isolation and structural characterization of the polypeptide subunits of membrane glycoprotein IIb-IIIa from human platelets

We have previously demonstrated the isolation of platelet membrane glycoprotein IIb-IIIa by affinity chromatography with a specific monoclonal antibody. We have now separated the polypeptide subunits IIb and IIIa of the isolated glycoprotein by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis and have compared their structural features. Both IIb and IIIa contain approximately 15% carbohydrate, but IIIa contains a larger percentage of mannose residues, suggesting the presence of high mannose as well as complex N- linked oligosaccharide chains. The amino acid compositions are sufficiently similar to imply areas of sequence homology between the two subunits. To examine further the relationship between the subunits, we digested a mixture of 125I-IIb and 131I-IIIa with trypsin and then separated the radiolabeled peptides by high performance liquid chromatography. The resultant peptide maps of IIb and IIIa are completely different. This indicates that neither subunit is derived from the other and suggests that polypeptides IIb and IIIa are products of separate genes.