Search results for "PTO"
showing 10 items of 28599 documents
Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer
2001
We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the widely expressed human MDM2 oncoprotein and were able to bypass self-tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic mice and by generating A2.1-negative, allo-A2.1-restricted human T lymphocytes. A broad range of malignant, as opposed to nontransformed cells, were killed by high-avidity transgenic mouse and allogeneic human CTLs specific for the A2.1-presented MDM2 epitope. Whereas the self-A2.1-restricted human T cell repertoire gave rise only to low-avidity CTLs unable to recognize the natural MDM2 peptide, human A2.1+ T lymphocytes were turned into efficient MDM2-specific CTLs upon exp…
Nitric oxide and sensory afferent neurones modulate the protective effects of low-dose endotoxin on rat gastric mucosal damage
1995
Pretreatment (1 h) with low doses (5-40 micrograms/kg i.p.) of Escherichia coli endotoxin dose dependently reduced the gastric mucosal damage induced by a 10 min challenge with 1 ml ethanol (50% and 100%) in conscious rats. Treatment with the nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 5 and 10 mg/kg i.p.), significantly inhibited the protective effects of endotoxin (40 micrograms/kg i.p.). The actions of L-NAME were reversed by the prior administration of L-arginine (100 mg/kg i.p.). The protective effects of endotoxin were not influenced by pretreatment with dexamethasone (5 mg/kg s.c. twice) or indomethacin (5 mg/kg s.c.). However, ablation of sensory affe…
INFLAMMATORY CYTOKINES IN ACUTE ISCHEMIC STROKE.
2008
Three major cytokines, namely, tumor necrosis factor (TNF-alpha), interleukin (IL)-1, and IL-6 are produced by cultured brain cells after various stimuli such as ischemia. Neurones, astrocytes, microglia and oligodendrocytes can produce inflammatory mediators, and cytokine receptors are expressed constitutionally throughout the Central Nervous System (CNS), albeit at low levels. Cytokines are involved in virtually every facet of stroke and they have numerous pro-inflammatory and pro-coagulant effects on endothelium. TNF-alpha expression after stroke stimulates expression of tissue factor and adhesion molecules for leukocytes, release of interleukin-1 (IL-1), nitric oxide, factor VIII/von Wi…
Novel cytokine-targeted therapies and intestinal inflammation
2009
Several cytokines have been identified as critical mediators of chronic inflammation in inflammatory bowel disease (IBD) and biological therapies that target these molecules have been developed during recent years. Thereby, anti-TNF agents have noticeably improved the treatment of patients with IBD in comparison to conventional therapy. Furthermore, initial clinical trials showed promising results with anti-IL-6 and anti-IL-12/IL-23 agents. In addition to these well-known mediators of IBD, various novel cytokines have been described as critical during the pathogenesis of IBD in recent experimental studies and therapeutic targeting of these cytokines could provide new strategies for human di…
Interaction Between Cytokines and Oxidative Stress in Acute Pancreatitis
2006
Acute pancreatitis is an inflammation initially localized in the pancreatic gland which may lead to local and systemic complications. The development of severe acute pancreatitis is mediated by pathophysiological mechanisms involved in the systemic inflammatory response, cytokines and oxidative stress being their components of major importance. Nevertheless, it is still unknown why an episode of acute pancreatitis remains mild or progresses to a severe form. Activated leukocytes are the main source of cytokines. Interleukin 1beta and tumor necrosis factor alpha (TNF-alpha) initiate and propagate almost all the consequences of the systemic inflammatory response syndrome, leading to amplifica…
New intraocular lens for achromatizing the human eye.
2007
To describe the design of a new intraocular lens (IOL) capable of correcting spherical and chromatic aberrations when implanted in the human eye.University of Murcia, Murcia, and University of Valencia, Valencia, Spain.A hybrid singlet achromatic IOL was designed. The IOL has a combination of a refractive and a diffractive surface, with 1 of the surfaces being aspherical. Optical simulations were used to model the polychromatic modulation transfer function (MTF) in pseudophakic eyes to explain the differences in optical quality afforded by the achromatic IOL. Parameters such as focus shift, optical path difference, through-focus, and robustness to tilt and decentering of achromatic IOLs wer…
A Role for Leukocyte-Derived IL-1RA in DC Homeostasis Revealed by Increased Susceptibility of IL-1RA-Deficient Mice to Cutaneous Leishmaniasis
2011
Dendritic cell (DC)-derived IL-1α/β plays a critical role in the induction of T helper type 1 (Th1)-dependent immunity against Leishmania . DCs from susceptible BALB/c mice produce less IL-1α/β when compared with resistant C57BL/6 mice, contributing to aberrant Th2 development and ultimate death of infected mice. We have extended our studies of the role of IL-1 in leishmaniasis using IL-1RA -/- BALB/c mice that are characterized by upregulated IL-1 receptor signaling. Unexpectedly, infection of IL-1RA -/- mice led to significantly worsened disease outcome with larger lesions, dramatically higher parasite burdens, and decreased IFN-γ production by antigen-specific T cells. We determined that…
Ex vivoevidence for PGE2and LTB4involvement in cutaneous leishmaniasis: relation with infection status and cytokine production
1996
SUMMARYEx vivoculture of spleen cells from BALB/c mice infected with 2 × 106Leishmania major(L.major) promastigotes were cultured with ConcanavalinA (ConA) or leishmanial antigen (L. Ag) and tested for prostaglandin E2(PGE2) and for leukotriene B4(LTB4), in order to study their involvement in the evolution of cutaneous leishmaniasis and the connexion with lymphokine-mediated responses. The data were compared with those obtained in BALB/c mice protected againstL. majorby sublethal irradiation (550 rad; cured mice). In the unprotected BALB/c mice the levels of PGE2that were responsible for the depression of interferon-γ (IFN-γ) and tumour necrosis factor-α (TNFα) Th1-associated cytokines and …
Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: impact of the cluster effect on the killing of tumor cells.
2014
Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor-associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl-TN antigen showed a significant cluster effect. It induced in mice prevailing IgG2a antibodies, which bind to MCF-7 breast tumor cells and initiate the killing of these tumor cells by activation of the complement-dependent cytotoxicity complex.
EMAS position statement: Predictors of premature and early natural menopause.
2019
Simoncini, Tommaso/0000-0002-2971-0079; Chung, Hsin-Fang/0000-0003-3261-5942; Mishra, Gita/0000-0001-9610-5904 WOS:000468709100014 PubMed ID: 31027683 Introduction: While the associations of genetic, reproductive and environmental factors with the timing of natural menopause have been extensively investigated, few epidemiological studies have specifically examined their association with premature (< 40 years) or early natural menopause (40-45 years). Aim: The aim of this position statement is to provide evidence on the predictors of premature and early natural menopause, as well as recommendations for the management of premature and early menopause and future research. Materials and methods…