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Haemopoietic-cell transplantation (HCT) is an intensive therapy used to treat high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. The main complication of HCT is graft-versus-host disease (GVHD), an immunological disorder that affects many organ systems, including the gastrointestinal tract, liver,(More)
Puberty onset is initiated by activation of neurons that secrete gonadotropin-releasing hormone (GnRH). The timing and progression of puberty may depend upon temporal coordination of two opposing central mechanisms--a restraint of GnRH secretion before puberty onset, followed by enhanced stimulation of GnRH release to complete reproductive maturation during(More)
Classic experiments have shown that ovulation and estrous cyclicity are under circadian control and that surgical ablation of the suprachiasmatic nuclei (SCN) results in estrous acyclicity in rats. Here, we characterized reproductive function in the circadian Clock mutant mouse and found that the circadian Clock mutation both disrupts estrous cyclicity and(More)
It is well known that estrogen (E2) stimulates expression of progesterone receptors (PRs), thereby inducing responsiveness of several tissues to the actions of progesterone (P). Recent studies have also suggested, however, that biological actions previously ascribed to E2 alone may also be mediated by activation of E2-induced PRs, even independently of(More)
Progesterone's (P4) negative feedback actions in the female reproductive axis are exerted in part by suppression of hypothalamic GnRH release. Here we show that P4 can inhibit GnRH release by a mechanism independent of a nuclear P4 receptor (PR(A/B)). Injections of P4, but not vehicle, allopregnanolone, or dexamethasone, acutely suppressed LH levels in both(More)
No validated biomarkers exist for acute graft-versus-host disease (GVHD). We screened plasma with antibody microarrays for 120 proteins in a discovery set of 42 patients who underwent transplantation that revealed 8 potential biomarkers for diagnostic of GVHD. We then measured by enzyme-linked immunosorbent assay (ELISA) the levels of these biomarkers in(More)
Peripheral administration of N-methyl-D,L-aspartate (NMA), an analogue of the excitatory amino acid aspartate, elicits LH and prolactin (PRL) release in rats, most likely by increasing endogenous releasing-hormone secretion. These experiments were carried out to assess the degree to which NMA stimulates FSH and to analyze the relationship between endocrine(More)
W e are writing as scientists and editors of leading peer-reviewed journals that have published important contributions in the study of endocrine disrupting chemicals (EDCs). By signing this editorial, we affirm that regulatory decisions on EDCs should be made based on the best available science and expertise that involves, among others, reproductive(More)
Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard initial therapy, yet only 25% to 41% of patients completely respond. This randomized, 4-arm, phase 2 trial was designed to identify the most promising agent(s) for initial therapy for aGVHD. Patients were(More)
Dendritic cells (DCs) have been shown to be a promising adjuvant for inducing immunity to cancer. We evaluated tumor lysate-pulsed DC in a Phase I trial of pediatric patients with solid tumors. Children with relapsed solid malignancies who had failed standard therapies were eligible. The vaccine used immature DC (CD14-, CD80+, CD86+, CD83-, and HLA-DR+)(More)