Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
The isotretinoin drug is 13-cis-retinoic acid, is the treatment of severe acne and some skin cancers and used for dermatological conditions, this study was designed to detect the toxic role of the isotretinoin on the intrauterine development after implantation in albino mice during pregnancy. There are very little studies which indicating the side-effect of this drug on intra-uterine growth, so in the present research we tried to study the toxic effect of isotretinoin on the endometrial changes of uterus during the 2nd. and 3rd. trimester of gestation in pregnant mice after treatment with single chronic dose of the Isotretinoin drug (20 mg/B.wt) from first day of gestation until 21 days the last day of gestation.
The present study exa
Background: Nicotine is the foremost chemical constituent responsible for addiction in tobacco products, in the non-ionized condition can be easily absorbed via epithelial tissue of the lung, the mouth, the nose and across the skin
Objective:The study examines the harmful effect of the nicotine which is an important component of cigarette in vitro.
Type of the study: Cross-sectional study.
Methods: Examines the harmful effect of the nicotine which is an important component of cigarette in vitro by using two types of lung cancer cell lines (H460 TP53+/+, H441 TP53-/-).
Background: Prelabour rupture of membranes is a problem that faces the obstetricians. It has many maternal and fetal sequale and its etiology and management still controversial.
Objective: To test the absolute nucleated red blood cells counts at birth in infants who are born after prelabour rupture of membranes.
Methods: A prospective study conducted in AL-Kadhymia Teaching Hospital. Hundred pregnant women were included in this study. Fifty pregnant women who had prelabour rupture of membranes considered as group (1), other fifty pregnant women with intact membranes considered as group (2) through a period of one year. Nucleated red blood cell counts of venous cord blood obtained within one hour of life from 50 infants who we
The aim of this research is to know the effect of two strategies of active learning, the five fingers and traffic signals, on the first grade intermediate level student's achievement and personal intelligence. The research sample was chosen from the Al- Mansour intermediate school for boys, including (101) students divided into three groups chosen randomly which represented the first experimental group (32) students, the second experimental group (34) students, and the control group (33) students. To achieve the research aims, the research prepared a physics achievement test containing (26) items, and a personal intelligence test containing (20) items. The psychometric characteristics, of the tests were checked up the following results were
... Show MoreThe compound chalcon originally is extracted form some plant and herbs, the studies of the antiviral activity of this compound were done in two cell line cultures the L2OB and RD, the compound relatively non toxic to both cell lines of the concentration of 32?g/ml or less ,the compound have significantly anti poliovirus activity in both L2OB cell line and RD cell line, we find that the concentration of 0.03 ?g/ml or more inhibit the 100TCDID50 of the poliovirus .The therapeutic index(TI)used in this study to evaluate the drug activity ,( TI is the ratio of dose of drug which is just toxic to the cells to the does which is just inhibit the viral multiplication, if this index more than one the margin of safety of drug is according great ) .In
... Show MorePoly vinyl alcohol has been studied for its ability to form crystallites by using annealing method. Semicrystalline films of poly vinyl alcohol (PVA) were prepared by casting 11.5 wt. % and 13 wt. % PVA aqueous solution onto glass slides at annealing temperature range 90 -120°C and duration time 15- 60 minute. This allowed the macromolecules to form crystallites, small regions of folded and compacted chains separated by amorphous regions where single PVA chain may pass through several of these crystallites. Degree of crystallinity of PVA films (hydrogels) was determined by method of density; on the other hand the swelling behavior was conducted by the determination of water uptake, wet degree of crystallinity, gel fraction and solubilit
... Show MoreIn this paper, Al and Cu Plasmas that produced by pulsed Nd:YAG laser with fundamental wave length with a pulse duration of 6 nS focused onto Al and Cu targets in atmospheric air are investigated spectroscopically. The influence of pulse laser energy on the some Al and Cu plasmas characteristics was diagnosed by using optical emission spectroscopy for the wavelength range 320-740 nm. The results observed that the increase of pulse laser energy causes to increase all plasma characteristics of both plasmas under study and shown increasing of the emission line intensity. The appearance of the atomic and ionic emission lines of an element in the emission spectrum depends on the ionization energy of target atoms. The plasma characteristics ar
... Show MoreBackground: There is plenty of evidence
suggesting that involvement of several groups of
viruses in the development and / or acceleration of
Type 1 Diabetes Mellitus (T1DM).
Objective: To analyze the T- cell proliferation in
the presence of Coxsackie virus B5 (CVB5), Polio
and Adenovirus antigens in addition to assessment
of Interferon- gamma (IFN-γ), Interleukins (IL-10
and IL-6).
Methods: In 60 Iraqi T1DM children with recent
onset of T1DM, Lymphocyte proliferation was
analyzed using Methylthiazol tetrazolium (MTT)
assay by culturing Peripheral Blood Lymphocytes
(PBLs) with Coxsackie Virus B5 (CVB5),
Adenovirus, and Polio vaccine. Serum Interferon-γ,
IL-10 and IL-6 were quantified by sandw