Extensive expansion and diversification of the chemokine gene family in zebrafish: Identification of a novel chemokine subfamily CX

<p>Abstract</p> <p>Background</p> <p>The chemokine family plays important roles in cell migration and activation. In humans, at least 44 members are known. Based on the arrangement of the four conserved cysteine residues, chemokines are now classified into four subfamilies, CXC, CC, XC and CX3C. Given that zebrafish is an important experimental model and teleost fishes constitute an evolutionarily diverse group that forms half the vertebrate species, it would be useful to compare the zebrafish chemokine system with those of mammals. Prior to this study, however, only incomplete lists of the zebrafish chemokine genes were reported.</p> <p>Results</p> <p>We systematically searched chemokine genes in the zebrafish genome and EST databases, and identified more than 100 chemokine genes. These genes were CXC, CC and XC subfamily members, while no CX3C gene was identified. We also searched chemokine genes in pufferfish fugu and <it>Tetraodon</it>, and found only 18 chemokine genes in each species. The majority of the identified chemokine genes are unique to zebrafish or teleost fishes. However, several groups of chemokines are moderately similar to human chemokines, and some chemokines are orthologous to human homeostatic chemokines CXCL12 and CXCL14. Zebrafish also possesses a novel species-specific subfamily consisting of five members, which we term the CX subfamily. The CX chemokines lack one of the two N-terminus conserved cysteine residues but retain the third and the fourth ones. (Note that the XC subfamily only retains the second and fourth of the signature cysteines residues.) Phylogenetic analysis and genome organization of the chemokine genes showed that successive tandem duplication events generated the CX genes from the CC subfamily. Recombinant CXL-chr24a, one of the CX subfamily members on chromosome 24, showed marked chemotactic activity for carp leukocytes. The mRNA was expressed mainly during a certain period of the embryogenesis, suggesting its role in the zebrafish development.</p> <p>Conclusion</p> <p>The phylogenic and genomic organization analyses suggest that a substantial number of chemokine genes in zebrafish were generated by zebrafish-specific tandem duplication events. During such duplications, a novel chemokine subfamily termed CX was generated in zebrafish. Only two human chemokines CXCL12 and CXCL14 have the orthologous chemokines in zebrafish. The diversification observed in the numbers and sequences of chemokines in the fish may reflect the adaptation of the individual species to their respective biological environment.</p

Repeated mitral valve replacement in a patient with extensive annular calcification

<p>Abstract</p> <p>Background</p> <p>Mitral valve replacement in the presence of severe annular calcification is a technical challenge.</p> <p>Case report</p> <p>A 47-year-old lady who had undergone mitral and aortic valve replacement for rheumatic disease 27 years before presented with dyspnea. At reoperation, extensive mitral annular calcification was hindering the disc motion of the Starr-Edwards mitral prosthesis. The old prosthesis was removed and a St Jude Medical mechanical valve was implanted after thorough annular debridement. Postoperatively the patient developed paravalvular leak and hemolytic anemia, subsequently undergoing reoperation three days later. The mitral valve was replaced with an Edwards MIRA valve, with a bulkier sewing cuff, after more aggressive annular debridement. Although initially there was no paravalvular leak, it recurred five days later. The patient also developed a small cerebral hemorrhage. As the paravalvular leak and hemolytic anemia gradually worsened, the patient underwent reoperation 14 days later. A Carpentier-Edwards bioprosthetic valve with equine pericardial patches, one to cover the debrided calcified annulus, another as a collar around the prosthesis, was used to eliminate paravalvular leak. At 7 years postoperatively the patient is doing well without any evidence of paravalvular leak or structural valve deterioration.</p> <p>Conclusion</p> <p>Mitral valve replacement using a bioprosthesis with equine pericardial patches was useful to overcome recurrent paravalvular leak due to severe mitral annular calcification.</p

Impact of maximum Standardized Uptake Value (SUVmax) evaluated by 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) on survival for patients with advanced renal cell carcinoma: a preliminary report

<p>Abstract</p> <p>Background</p> <p>In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (¹⁸F-FDG) accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax) from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) on survival for patients with advanced renal cell carcinoma (RCC).</p> <p>Methods</p> <p>A total of 26 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by ¹⁸F-FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively.</p> <p>Results</p> <p>FDG uptake was detected in 230 of 243 lesions (94.7%) excluding lung or liver metastases with diameters of less than 1 cm. The SUVmax of 26 patients ranged between 1.4 and 16.6 (mean 8.8 ± 4.0). The patients with RCC tumors showing high SUVmax demonstrated poor prognosis (<it>P </it>= 0.005 hazard ratio 1.326, 95% CI 1.089-1.614). The survival between patients with SUVmax equal to the mean of SUVmax, 8.8 or more and patients with SUVmax less than 8.8 were statistically different (<it>P </it>= 0.0012). This is the first report to evaluate the impact of SUVmax on advanced RCC patient survival. However, the number of patients and the follow-up period were still not extensive enough to settle this important question conclusively.</p> <p>Conclusions</p> <p>The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using ¹⁸F-FDG-PET/CT. ¹⁸F-FDG-PET/CT has potency as an "imaging biomarker" to provide helpful information for the clinical decision-making.</p

Gene-expression patterns during regeneration of the multi-organ complex after evisceration in the sea cucumber Eupentacta quinquesemita

Many species of sea cucumbers (Echinodermata, Holothuroidea) perform evisceration, i.e., ejection of internal organs including digestive tracts when responding to environmental stresses. After evisceration, they also show a high regenerative capacity, in which all the eviscerated organs regenerate. Especially in anterior evisceration species, the oral complex structure consisting of multiple organs, including the digestive tract and central nervous system, are reconstructed. The detailed developmental mechanisms underlying the process remains unclear, and therefore, in this study, focusing on Eupentacta quinquesemita, gene expression analyses in the regenerating tissues were carried out. For the formation of the gut tube, genes involved in mesenchymal-epithelial transition were upregulated consistently with the histological changes. Upregulation of Hox and Parahox genes along the anterior-posterior axis was observed, implying the involvement of these genes in the spatial differentiation of the digestive tract. In addition, the expression of otx, six and pax, i.e., transcription factors patterning anterior nervous tissues, was upregulated during the regeneration of the central nervous system. Taken together, these results suggest that conserved genes are co-opted to the internal organ regeneration after evisceration in sea cucumbers