ABSTRACT
Most cases of hemolytic disease of the newborn associated with anti-Jra are mild. However, rare cases of hydrops fetalis and severe anemia have been reported. We treated a neonate with anemia who was born with maternal anti-Jra, which were detected in the umbilical cord plasma. The Jra antigens in the neonate core blood red blood cells (RBCs) exhibited extremely weak reactivity to PEG-IAT, an anti-Jra reagent. However, upon re-examination of Jra antigen using PEG-IAT at 3 months postpartum, positivity was observed. Thereafter, upon performing PCR-SSP analysis of blood relatives targeting ABCG2 at positions 376 and 421, we found that the mother was Jr(a-) with 376 T homozygosity, whereas the father was Jr(a+) with 376 C homozygosity and a carrier of a 421 C > A mutation. The first sibling, like the propositus, was Jr(a+), exhibiting 376 CT heterozygosity. However, the first sibling carried a 421 C > A mutation, whereas the propositus had no mutation at position 421. Setting the normal Jra (a+) type (376 C, 421 C) to 100 %, we identified the amount of Jra in RBC using FCM to be 82 % in the father, 31 % in the first sibling, and 69 % in the propositus. Furthermore, upon comparing peripheral blood and myelograms of the neonate at the time of birth, we found a low myeloid cells/erythroid cells ratio, undifferentiated erythroblasts, and reduced megakaryocytes. On the basis of these findings, we suggest that cell surface antigen is involved in the HDN caused by anti-Jra, and that a cytodifferentiation abnormality is present in the hematopoietic system.
ABSTRACT
As observed previously in cultured human skin fibroblasts, a decrease of hyaluronan production was also observed in group C Streptococcus equi FM100 cells treated with 4-methylumbelliferone (MU), although there was no effect on their growth. In this study, the inhibition mechanism of hyaluronan synthesis by MU was examined using Streptococcus equi FM100, as a model. When MU was added to a reaction mixture containing the two sugar nucleotide donors and a membrane-rich fraction as an enzyme source in a cell-free hyaluronan synthesis experiment, there was no change in the production of hyaluronan. On the contrary, when MU was added to the culture medium of FM100 cells, hyaluronan production in the isolated membranes was decreased in a dose-dependent manner. However, when the effect of MU on the expression level of hyaluronan synthase was examined, MU did not decrease either the mRNA level of the has operon containing the hyaluronan synthase gene or the protein level of hyaluronan synthase. Solubilization of the enzyme from membranes of MU-treated cells and addition of the exogenous phospholipid, cardiolipin, rescued hyaluronan synthase activity. In the mass spectrometric analysis of the membrane phospholipids from FM100 cells treated with MU, changes were observed in the distribution of only cardiolipin species but not of the other major phospholipid, PtdGro. These results suggest that MU treatment may cause a decrease in hyaluronan synthase activity by altering the lipid environment of membranes, especially the distribution of different cardiolipin species, surrounding hyaluronan synthase.
