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.
Thirty six bacteria were isolated from various sourcesc (soil, starch, cooked rice and other foods) and subjected to a series of primary screening tests to obtain the optimal isolation to production of amylase. The volume of producing zone by logal indicator for (Seven) isolates of the secondary screening by measuring the enzymatic activity and specific enzymatic activity. The isolate A4 was found to be the most efficient for production of amylase. Then this isolate was diagnosed through microscopic, vitek 2 system technique. in addition by gentic diagnesis through gene 16s of the genes nitrogen bases by use the polymerase chain reaction (PCR) which reached 1256 bases. In comparison to the available information at the National Center for
... Show MoreCadmium has been known to be harmful to human healthy , manily Via contaminated drinking water , food supplies , tobacco and industrial pollutant . The aim of this study was to determine the toxicity of new Cadmium (II) complex ( Bis[ 5- ( P- nitrophenyl ) – ? 4 – Phenyl- 1,2,4- triazole -3- dithiocarbamatohydrazide] cadmium (II) Hydra ( 0.5) and compare it with anticancer drug cyclophosphamide ( CP) in female albino mice . This complex causes to several alterations in Enzymatic activity of Glutamate Pyruvate Transaminase (GPT) and Alkaline Phosphatase (ALP ) in three organs after the treatment of mice with different doses of a new cadmium (II) complex ( 0.09 / 0.25ml , 0.18/ 0.5ml and 0.25mg /0.7 ml /30 gm of mous
... Show MoreAccording to so many previous studies, lack of sufficient information during prescribing steps may lead to medication errors. Thus, the presence of the clinical pharmacist during routine rounding process in the ward with intervention of patient care plan may reduce the probability of adverse drug events (ADEs).This study evaluate role of the clinical pharmacists, as a member of medical team with the physician, on ADEs and report their interventions in the internal medicine unit. This study was designed to compare between two groups of patients, those receiving care from a rounding team (physician, nurse, and clinical pharmacist) (study or intervention group with 51 patient); and those receiving c
... Show MoreThe dependence of the energy losses or the stopping power for the ion contribution in D- T hot plasma fuels upon the corresponding energies and the related penetrating factorare arrive by using by a theoretical approximation models. In this work we reach a compatible agreement between our results and the corresponding experimental results.
The current study aims to determine the extent of SOMO's interest in strategic alignment operations and whether this interest is sufficient to be reflected in enhancing its organizational reputation. The field of research was in the oil marketing company SOMO. The managers in the top management within this company were targeted and the questionnaire was used as a data collection tool. The study population (109), (105) questionnaires were distributed, (94) questionnaires and (11) questionnaires were not retrieved, and the valid questionnaires had reached (91) and the analytical and descriptive approach was used for the study, the current research found to find A direct relationship and a positive effect of strategic
... Show MoreAbstract:
This study is considerated one of many Studies above the standing of
the Islamic Arab nation which was chosen by God from other nations all over
the world . Some of these nations used to come to the Arab nation to take
whatever useful for them from the beginning of history till now . The
researcher deals in this study with a French artist who is well-know as
August Renoir . He traveled to Algeria and lived there . He was
influenced by the Islamic culture.
The study include. from chapter . chapter one deals with the framework of
programming (out line ) . Chapter two deals with the theoretical framework .
It includes five sections. Deals with the Islamic drawings(Arabesque) . section
three deals w
Encouraging micro-enterprises for comprehensive economic development are crucial to achieve the ambitious vision 2030 of the Kingdom of Saudi Arabia.
Small and Medium enterprises are inputting around 15.5 per cent to GDP while 33 per cent contribution as a private sector to Saudi Arabia's gross domestic product (GDP). This study aims to identify the most important factors that affect the efficiency of small enterprises in Saudi Arabia. To accomplish this objective, the study was conducted for small projects via the comprehensive inventory method under the supervision of the Institute of Entrepreneurship. A total of 282 questionnaires were collected from entrepreneurs and the differentiation analysis
... Show MoreThe business environment is witnessing great and rapid developments due to the economic and technological development that has caused damage to human beings, which requires the need to reduce this damage and work to protect the environment and participate in supporting the social aspects. This requires economic resources to be realized by the economic units. Economic development in preserving the environment that has caused damage and supporting the social aspects that preserve human rights, enhance their position and satisfy their needs in society. Global professional organizations, the United Nations and stakeholder representatives have been issuing the Global Reporting Initiative (GRI) to find guidelines for the preparation of
... Show More
This research addressed the cultural factors that are affecting the communicator in international public relations in light of the theory of the cultural relativism. The research aimed to find out the nature of cultural differences between societies and how can for professionals in international public relations understanding the culture of other and communicate with him peacefully. The researcher used qualitative and interpretative methodology. Some of the important results of the research are: The Communities are affected by cultural factors that are composed from values, customs, traditions, prevailing and inherited ethic, languages, religious beliefs, fashion, gender, colors indi |