Viruses as co-factors for the initiation or exacerbation of lung fibrosis

Idiopathic pulmonary fibrosis (IPF) remains exactly that. The disease originates from an unknown cause, and little is known about the mechanisms of pathogenesis. While the disease is likely multi-factorial, evidence is accumulating to implicate viruses as co-factors (either as initiating or exacerbating agents) of fibrotic lung disease. This review summarizes the available clinical and experimental observations that form the basis for the hypothesis that viral infections may augment fibrotic responses. We review the data suggesting a link between hepatitis C virus, adenovirus, human cytomegalovirus and, in particular, the Epstein-Barr gammaherpesvirus, in IPF. In addition, we highlight the recent associations made between gammaherpesvirus infection and lung fibrosis in horses and discuss the various murine models that have been used to investigate the contribution of gammaherpesviruses to fibrotic progression. We review the work demonstrating that gammaherpesvirus infection of Th2-biased mice leads to multi-organ fibrosis and highlight studies showing that gammaherpesviral infections of mice either pre- or post-fibrotic challenge can augment the development of fibrosis. Finally, we discuss potential mechanisms whereby viral infections may amplify the development of fibrosis. While none of these studies prove causality, we believe the evidence suggests that viral infections should be considered as potential initiators or exacerbating agents in at least some cases of IPF and thereby justify further study

Hb Leslie, an unstable hemoglobin due to deletion of glutaminyl residue beta 131 (H9) occurring in association with beta0-thalassemia, HbC, and HbS

Abstract A new unstable hemoglobin, Hb Leslie, has been observed in three generations of a Georgia family. The propositus, a 42-yr-old black veteran with hemolytic anemia and splenomegaly, has a hemoglobin variant with an electrophoretic mobility similar to that of hemoglobin F. The variant comprises about 85% of the total hemoglobin and was isolated by chromatography. Chemical analysis has identified the abnormality as a deletion of the glutaminyl residue in position 131 (H9) of the beta-chain. Deletion of this critical residue which participates in the alpha1beta1 contact causes decreased stability of the hemoglobin without significant changes in functional properties or morphologic abnormalities in the erythrocyte. Family studies revealed hemoglobin Leslie occurring in combination with beta0-thalassemia, HbS, and HbC. All persons with the various Hb Leslie combinations, including the propositus, have no clinical manifestations other than anemia. In some the anemia is fully compensated. There is no history of drug- associated hemolysis.</jats:p

Hb Leslie, an unstable hemoglobin due to deletion of glutaminyl residue beta 131 (H9) occurring in association with beta0-thalassemia, HbC, and HbS

A new unstable hemoglobin, Hb Leslie, has been observed in three generations of a Georgia family. The propositus, a 42-yr-old black veteran with hemolytic anemia and splenomegaly, has a hemoglobin variant with an electrophoretic mobility similar to that of hemoglobin F. The variant comprises about 85% of the total hemoglobin and was isolated by chromatography. Chemical analysis has identified the abnormality as a deletion of the glutaminyl residue in position 131 (H9) of the beta-chain. Deletion of this critical residue which participates in the alpha1beta1 contact causes decreased stability of the hemoglobin without significant changes in functional properties or morphologic abnormalities in the erythrocyte. Family studies revealed hemoglobin Leslie occurring in combination with beta0-thalassemia, HbS, and HbC. All persons with the various Hb Leslie combinations, including the propositus, have no clinical manifestations other than anemia. In some the anemia is fully compensated. There is no history of drug- associated hemolysis.</jats:p