Browsing by Subject "Hemoglobin"

Now showing 1 - 3 of 3
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    A Class I Haemophilus ducreyi Strain Containing a Class II hgbA Allele Is Partially Attenuated in Humans: Implications for HgbA Vaccine Efficacy Trials
    (American Society for Microbiology, 2019-07) Leduc, Isabelle; Fortney, Kate R.; Janowicz, Diane M.; Zwickl, Beth; Ellinger, Sheila; Katz, Barry P.; Lin, Huaiying; Dong, Qunfeng; Spinola, Stanley M.; Microbiology and Immunology, School of Medicine
    Haemophilus ducreyi causes chancroid and is a major cause of cutaneous ulcers in children. Due to environmental reservoirs, both class I and class II H. ducreyi strains persist in cutaneous ulcer regions of endemicity following mass drug administration of azithromycin, suggesting the need for a vaccine. The hemoglobin receptor (HgbA) is a leading vaccine candidate, but its efficacy in animal models is class specific. Controlled human infection models can be used to evaluate vaccines, but only a class I strain (35000HP) has been characterized in this model. As a prelude to evaluating HgbA vaccines in the human model, we tested here whether a derivative of 35000HP containing a class II hgbA allele (FX548) is as virulent as 35000HP in humans. In eight volunteers infected at three sites with each strain, the papule formation rate was 95.8% for 35000HP versus 62.5% for FX548 (P = 0.021). Excluding doses of FX548 that were ≥2-fold higher than those of 35000HP, the pustule formation rate was 25% for 35000HP versus 11.7% for FX548 (P = 0.0053). By Western blot analysis, FX548 and 35000HP expressed equivalent amounts of HgbA in whole-cell lysates and outer membranes. The growth of FX548 and 35000HP was similar in media containing hemoglobin or hemin. By whole-genome sequencing and single-nucleotide polymorphism analysis, FX548 contained no mutations in open reading frames other than hgbA. We conclude that by an unknown mechanism, FX548 is partially attenuated in humans and is not a suitable strain for HgbA vaccine efficacy trials in the model.
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    Perspective: Will We Ever Know the Optimal Hgb Level in ESRD?
    (American Society of Nephrology, 2018-10) Wish, Jay B.; Medicine, School of Medicine
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    S‐Nitroso‐L‐cysteine and ventilatory drive: A pediatric perspective
    (Wiley, 2022) Hubbard, Dallin; Tutrow, Kaylee; Gaston, Benjamin; Pediatrics, School of Medicine
    Though endogenous S‐nitroso‐l‐cysteine (l‐CSNO) signaling at the level of the carotid body increases minute ventilation (v̇E), neither the background data nor the potential clinical relevance are well‐understood by pulmonologists in general, or by pediatric pulmonologists in particular. Here, we first review how regulation of the synthesis, activation, transmembrane transport, target interaction, and degradation of l‐CSNO can affect the ventilatory drive. In particular, we review l‐CSNO formation by hemoglobin R to T conformational change and by nitric oxide (NO) synthases (NOS), and the downstream effects on v̇E through interaction with voltage‐gated K+ (Kv) channel proteins and other targets in the peripheral and central nervous systems. We will review how these effects are independent of—and, in fact may be opposite to—those of NO. Next, we will review evidence that specific elements of this pathway may underlie disorders of respiratory control in childhood. Finally, we will review the potential clinical implications of this pathway in the development of respiratory stimulants, with a particular focus on potential pediatric applications.