Oxytocin and oxytocinase in the obese and nonobese parturients during induction and augmentation of labor

Abstract Objective To investigate differences in oxytocin (OXT) biodistribution between nonobese and obese parturients during labor. Study Design Patients with body mass index (BMI) of either ≥ 18 ≤ 24.9 kg/m2 (“nonobese”) or ≥ 30 kg/m2 (“obese”) undergoing elective induction of labor were included (N = 25 each). Blood samples were collected at baseline (T0), and 20 minutes after maximal OXT augmentation or adequate uterine contractions (T1) for OXT and oxytocinase assays. A mixed-model repeated-measures analysis of variance was used to test for group versus time interaction and analysis of covariance to detect a difference in OXT level at T1. Data presented as mean ± standard deviation or median (interquartile range), with p < 0.05 considered significant. Results The mean BMIs (kg/m2) were 22.1 ± 1.6 and 35.9 ± 5.1 in the nonobese and obese groups, respectively. No differences were observed in either the duration of OXT infusion, total dose of OXT, or plasma OXT (pg/mL) either at T0 or T1. However, plasma oxytocinase (ng/mL) was significantly lower at T0 (1.41 [0.67, 3.51] vs. 0.40 [0.29, 1.12]; p = 0.03) in the obese group. Conclusion We provide preliminary evidence that the disposition of OXT may not be different between obese and nonobese women during labor

Clonal Deletion Prunes but Does Not Eliminate Self-Specific αβ CD8+ T Lymphocytes

SummaryIt has long been thought that clonal deletion efficiently removes almost all self-specific T cells from the peripheral repertoire. We found that self-peptide MHC-specific CD8+ T cells in the blood of healthy humans were present in frequencies similar to those specific for non-self antigens. For the Y chromosome-encoded SMCY antigen, self-specific T cells exhibited only a 3-fold lower average frequency in males versus females and were anergic with respect to peptide activation, although this inhibition could be overcome by a stronger stimulus. We conclude that clonal deletion prunes but does not eliminate self-specific T cells and suggest that to do so would create holes in the repertoire that pathogens could readily exploit. In support of this hypothesis, we detected T cells specific for all 20 amino acid variants at the p5 position of a hepatitis C virus epitope in a random group of blood donors

Peptide-MHC heterodimers show that thymic positive selection requires a more restricted set of self-peptides than negative selection

T cell selection and maturation in the thymus depends on the interactions between T cell receptors (TCRs) and different self-peptide–major histocompatibility complex (pMHC) molecules. We show that the affinity of the OT-I TCR for its endogenous positively selecting ligands, Catnb-H-2Kb and Cappa1-H-2Kb, is significantly lower than for previously reported positively selecting altered peptide ligands. To understand how these extremely weak endogenous ligands produce signals in maturing thymocytes, we generated soluble monomeric and dimeric peptide–H-2Kb ligands. Soluble monomeric ovalbumin (OVA)-Kb molecules elicited no detectable signaling in OT-I thymocytes, whereas heterodimers of OVA-Kb paired with positively selecting or nonselecting endogenous peptides, but not an engineered null peptide, induced deletion. In contrast, dimer-induced positive selection was much more sensitive to the identity of the partner peptide. Catnb-Kb–Catnb-Kb homodimers, but not heterodimers of Catnb-Kb paired with a nonselecting peptide-Kb, induced positive selection, even though both ligands bind the OT-I TCR with detectable affinity. Thus, both positive and negative selection can be driven by dimeric but not monomeric ligands. In addition, positive selection has much more stringent requirements for the partner self-pMHC

Improving DNA Vaccine Potency by Linking Marek's Disease Virus Type 1 VP22 to an Antigen

We have previously employed an intercellular spreading strategy using herpes simplex virus type 1 (HSV-1) VP22 protein to enhance DNA vaccine potency because DNA vaccines lack the intrinsic ability to amplify in cells. Recently, studies have demonstrated that the protein encoded by UL49 of Marek's disease virus type 1 (MDV-1) exhibits some degree of homology to the HSV-1 VP22 protein and features the property of intercellular transport. We therefore generated a DNA vaccine encoding MDV-1 VP22 linked to a model antigen, human papillomavirus type 16 E7. We demonstrated that compared with mice vaccinated with DNA encoding wild-type E7, mice vaccinated with MDV-1 VP22/E7 DNA exhibited a significant increase in number of gamma-interferon-secreting, E7-specific CD8(+)-T-cell precursors as well as stronger tumor prevention and treatment effects. Furthermore, our data indicated that the antitumor effect was CD8 dependent. These results suggested that the development of vaccines encoding VP22 fused to a target antigen might be a promising strategy for improving DNA vaccine potency

Additional file 1 of Postoperative and postdischarge nausea and vomiting following ambulatory eye, head, and neck surgeries: a retrospective cohort study comparing incidence and associated factors

Additional file 1: Supplementary Table 1. Summary Statistics: Patient and Operative Factors by N/V Status. Supplementary Table 2. Multivariable Adjusted Odds Ratios. Supplementary Table 3. Binary Logistic Regression for PDNV vs No PDNV