Focal dermal hypoplasia (FDH) is an X-linked dominant multisystem birth defect affecting tissues of ectodermal and mesodermal origin. Using a stepwise approach of (i) genetic mapping of FDH, (ii) high-resolution comparative genome hybridization to seek deletions in candidate chromosome areas and (iii) point mutation analysis in candidate genes, we identified PORCN, encoding a putative O-acyltransferase and potentially crucial for cellular export of Wnt signaling proteins, as the gene mutated in FDH. The findings implicate FDH as a developmental disorder caused by a deficiency in PORCN.

The group B coxsackieviruses (CVB) induce experimental pancreatitis and myocarditis in mice and are established agents of human myocarditis, especially in children. We tested the hypothesis that the development of CVB-induced myocarditis is linked to CVB-induced pancreatitis by studying the replication of different CVB strains in mice. Eight of nine genotypically different type 3 CVB (CVB3) strains induced acute pancreatitis in mice; of these, three viruses also induced acute myocarditis. One CVB3 strain was avirulent for both organs. Myocarditis was not observed in the absence of pancreatitis. The results obtained by inoculation of mice with strains of other CVB serotypes were consistent with these data. Infectious virus titers were measured in serum, pancreas, and heart as a function of time after inoculation of mice with three CVB3 strains. Each strain was representative of one of the three viral virulence phenotypes: avirulent, pancreovirulent only, and cardiovirulent. All strains replicated well and persisted in the pancreas through 8 days post-inoculation, but the cardiovirulent CVB3 strain tended to replicate to higher titer earlier and persist longer in sera, pancreatic, and cardiac tissues than the noncardiovirulent strains. Replication of the CVB3 strains were studied in two human pancreatic tumor lines and in primary human endothelial cell cultures derived from cardiac artery. Cardiovirulent strains, both individually and as a group, tended to replicate to titers as high as, or higher than, noncardiovirulent strains did in cell culture. The data are consistent with the possibility of an etiologic link between CVB-induced pancreatic and heart disease.

Influenza A pandemic (H1N1) 2009 virus RNA was detected by reverse transcription–PCR in 144 clinical samples from Bonn, Germany. A common rapid antigen–based test detected the virus in only 11.1% of these samples. The paramount feature of rapid test–positive samples was high virus concentration. Antigen-based rapid tests appear unsuitable for virologic diagnostics in the current pandemic.

No clinical or microbiological improvement was achieved by the adjunctive use of HA gel compared to SRP alone. Only SFFR was affected by the use of HA in terms of a more rapid reduction of SFFR in the test sites.

The linear, single-stranded enterovirus RNA genome is flanked at either end with a nontranslated region (NTR). By replacing the entire 5 NTR of coxsackievirus B3 (CVB3) with that from type 1 poliovirus, a progeny virus was obtained following transfection of HeLa cells. The chimeric virus, CPV/49, replicates like the parental CVB3 strain in HeLa cells but is attenuated for replication and yield in primary human coronary artery endothelial cell cultures, in a human pancreas tumor cell line, and in primary murine heart fibroblast cultures. Western blotting analyses of CPV/49 replication in murine heart fibroblast cultures demonstrate that synthesis of CPV/49 proteins is significantly slower than that of the parental CVB3 strain. CPV/49 replicates in murine hearts and pancreata, causing no disease in hearts and a minor pancreatic inflammation in some mice that resolves by 28 days postinoculation. A single inoculation with CPV/49 induces protective anti-CVB3 neutralizing antibody titers that completely protect mice from both heart and pancreatic disease when mice are challenged 28 days p.i. with genetically diverse virulent strains of CVB3. That a chimeric CVB3 strain, created from sequences of two virulent viruses, is sufficiently attenuated to act as an avirulent, protective vaccine strain in mice suggests that chimeric genome technology merits further evaluation for the development of new nonpoliovirus enteroviral vectors.The six serotypes of the group B coxsackieviruses (CVB1 to CVB6) are enteroviruses in the picornavirus family (17). The enterovirus genus also includes the group A coxsackieviruses, polioviruses (PVs), echoviruses, and several other numbered serotypes. Very similar to PV, the prototype enterovirus, in nucleotide sequence and identical in gene order, the CVB genome is 7,400 nucleotides (nt) in length. The single open reading frame encodes 11 proteins and is flanked by nontranslated regions (NTR). The 5Ј-terminal nucleotide is linked to a virus-encoded protein, and the 3Ј terminus is completed with a polyadenosine tail. The CVB are etiologically linked to a wide range of human diseases ranging from mild, common cold-like symptoms through serious and life-threatening illnesses such as meningitis and inflammatory heart disease (reviewed in reference 38).The enteroviral 5Ј NTR, at about 740 nt in length, represents 10% of the viral genome. The 5Ј NTR nucleotide sequence is well maintained among certain enterovirus groups; within the CVB, for example, primary structure is 73% conserved overall, with sequences of individual strains within serotypes much more highly conserved (44). Somewhat greater nucleotide nonidentity can occur between genomes of groups, such as between PV and CVB (26,42). Notwithstanding an overall 30% nonidentity at the primary structure level, the 5Ј NTR of CVB3 was shown to be able to functionally replace that of poliovirus type 1 (PV1) (29, 47), a finding that was confirmed later by others (57). Replacement of a PV 5Ј NTR with that from a human rhinovirus also produced infectious...