Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sequences of 42 transcripts, expressed with IgM, IgG and IgA and cloned from the mesenteric lymph node of a newborn piglet, are described. Forty transcripts used either DHA and DHB and their FR4 were identical to the single swine germline JH. The low frequency of somatic mutation made it possible to identify 35/41 as originating from five putative germline VH genes, of which VHA, VHB and VHC accounted for > 85%. The remaining six transcripts were hybrids of these five germline genes. The most 3' functional VH gene (VH2 = VHB) was the only one exclusively expressed with IgM although VHA, of unknown location in the genome, accounted for half of all transcripts. Junctional diversity in CDR3 was extensive and asymmetrical, in that D-J joining contributed more diversity than V-DJ joining. Reading frame II was used twice as frequently as frame III and the CDR3 generated using the former would have a higher expected R/S ratio. This study indicated that the expressed VH repertoire of the newborn piglet is restricted and nearly germline although junctional diversity is mature and better developed than in fetal mice. The hybrid clones suggest that swine compensate for their < 20 VH genes and single JH by using somatic gene conversion. There was no evidence for exclusive or preferential expression of the most 3' VH gene as occurs in chickens and rabbits respectively, and switching to downstream constant regions probably occurs in utero, even in the theoretical absence of environmental antigens and maternal regulatory molecules. Preferential VHA expression is probably a selection phenomenon.
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PMID:Molecular characterization of VDJ transcripts from a newborn piglet. 877 47

Pulmonary arterial hypertension (PAH) is a debilitating and deadly disease with no known cure. Heart failure is a major comorbidity and a common cause of the premature death of patients with PAH. Increased asymmetrical right ventricular hypertrophy and septal wall thickening compress the left ventricular cavity and elicit diastolic heart failure. In this study, we used the Sugen5416/hypoxia/normoxia-induced PAH rat to determine whether altered pyridine nucleotide signaling in the failing heart contributes to 1) increased oxidative stress, 2) changes in metabolic phenotype, 3) autophagy, and 4) the PAH-induced failure. We found that increased reactive oxygen species, metabolic maladaptation, and autophagy contributed to the pathogenesis of right ventricular remodeling and hypertrophy that lead to left ventricular diastolic dysfunction. In addition, arterial elastance increased in PAH rats. Glucose-6-phosphate dehydrogenase is a major source of pyridine molecule (nicotinamide adenine dinucleotide phosphate), which is a substrate for nicotinamide adenine dinucleotide phosphate oxidases in the heart. Dehydroepiandrosterone, a 17-ketosteroid that reduces pulmonary hypertension and right ventricular hypertrophy, inhibited glucose-6-phosphate dehydrogenase, decreased oxidative stress, increased glucose oxidation and acetyl-coA, and reduced autophagy in the hearts of PAH rats. It also decreased arterial stiffness and improved left ventricular diastolic function. These findings demonstrate that pyridine nucleotide signaling, at least partly, mediates PAH-induced diastolic heart failure, and that reduction of glucose-6-phosphate dehydrogenase-derived nicotinamide adenine dinucleotide phosphate is beneficial to improve left ventricle diastolic function.
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PMID:Increased reactive oxygen species, metabolic maladaptation, and autophagy contribute to pulmonary arterial hypertension-induced ventricular hypertrophy and diastolic heart failure. 2526 98