Objective: Fetal hemoglobin (HbF) levels in the hemolysates obtained from infants who died from sudden infant death syndrome (SIDS) are reported to be markedly increased compared with controls. This finding could have been explained by increased HbF synthesis caused by episodes of hypoxemia in the SIDS infants. A prospective study in a group of infants being monitored at home after an apparent life-threatening event (ALTE) and considered at increased risk for SIDS was conducted with an improved ribonuclease protection assay. The ribonuclease protection assay allowed for the quantitation of [gamma/(gamma+beta)]-globin mRNAs, which has a highly significant correlation with the levels of HbF synthesis.
Methods: Thirty-five infants who were admitted for an ALTE were included in the study. All infants were at home under surveillance with a cardiorespiratory monitor and followed in an apnea clinic with monthly appointments. Seventy-three blood samples were obtained between 38 and 61 weeks of postconceptional age. For control purposes, a similar group of 37 normal infants (99 samples) whose HbF synthesis was previously determined were included.
Results: Mean [gamma/(gamma+beta)]-globin mRNAs were increased in the ALTE group at 42 to 45 and 46 to 49 weeks of postconceptional age (mean: 55.2 +/- 17.4% and 33.9 +/- 14%) in comparison with HbF synthesis in controls (mean: 42.6 +/- 13.7% and 23.6 +/- 9.8%).
Conclusions: The data obtained in this report from infants who were considered at risk for SIDS show that HbF synthesis is increased between 42 and 49 weeks of postconceptional age. Determining HbF synthesis as described in this study may have value as a marker for episodes of hypoxemia for certain infants who are at risk for SIDS.
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http://dx.doi.org/10.1542/peds.112.4.e285 | DOI Listing |
Nature
January 2025
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
C-H activation is the most direct way of functionalizing organic molecules. Many advances in this field still require specific directing groups to achieve the necessary activity and selectivity. Developing C-H activation reactions directed by native functional groups is essential for their broad application in synthesis.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Centre for Stem Cell Research (CSCR), A Unit of InStem Bengaluru, Christian Medical College Campus, Vellore, Tamil Nadu, 632002, India.
Background: Sickle cell disease (SCD) and β-thalassemia patients with elevated gamma globin (HBG1/G2) levels exhibit mild or no symptoms. To recapitulate this natural phenomenon, the most coveted gene therapy approach is to edit the regulatory sequences of HBG1/G2 to reactivate them. By editing more than one regulatory sequence in the HBG promoter, the production of fetal hemoglobin (HbF) can be significantly increased.
View Article and Find Full Text PDFScience
November 2024
Dana-Farber/Boston Children's Hospital Cancer and Blood Disorder Center, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Down-regulation of BCL11A protein reverses the fetal (HbF, αγ) to adult (HbA, αβ) hemoglobin switch and is exploited in gene-based therapy for hemoglobin disorders. Because of reliance on ex vivo cell manipulation and marrow transplant, such therapies cannot lessen disease burden. To develop new small-molecule approaches, we investigated the state of BCL11A protein in erythroid cells.
View Article and Find Full Text PDFJ Clin Med
November 2024
Instituto de Investigación, Transferencia e Innovación (ITEI), Universidad Internacional de La Rioja (UNIR), 26006 Logroño, Spain.
The Special Issue Diamine Oxidase Deficiency: Prevalence, consequences, and solutions brings together a series of groundbreaking studies that explore the role of four single-nucleotide polymorphisms (SNPs) (rs10156191, rs1049742, rs1049793, and rs2052129) of the Diamine Oxidase (DAO) across various medical conditions, with a special focus on its influence on histamine metabolism [...
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Center of Expertise in Hemoglobinopathies and Their Complications, Thalassemia and Sickle Cell Disease Unit, Hippokration General Hospital, 41221 Athens, Greece.
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