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C Boyer N Auphan F Luton J M Malburet M Barad J P Bizozzero H Reggio A M Schmitt-Verhulst 《European journal of immunology》1991,21(7):1623-1634
The fate of the T cell receptor (TcR)/CD3 complex was examined on a cytotoxic T lymphocyte (CTL) clone (KB5.C20) activated either via binding of an anti-TcR monoclonal antibody (mAb) or by a Ca2+ ionophore and phorbol 12-myristate 13-acetate (PMA). After binding of the anti-TcR mAb, electron microscopy revealed internalization through coated vesicles followed by slow degradation of the antibody as shown by use of radiolabeled mAb. The influence of activation on TcR/CD3 internalization was analyzed. The Ca2+ ionophore alone had no effect on internalization, whereas PMA induced an accelerated internalization of anti-TcR mAb. PMA-induced internalization was dependent on protein kinase C (PKC) as shown by its absence in PKC-depleted cells or in the presence of the PKC inhibitor staurosporine. Anti-TcR mAb-induced internalization was maintained in PKC-depleted cells, but unexpectedly remained sensitive to inhibition by staurosporine. The monovalent anti-TcR mAb Fab fragment is non-stimulatory for the CTL. It was poorly internalized but its internalization was induced by PMA. Surprisingly, on PKC-depleted cells, the Fab was internalized more readily than in untreated cells and this internalization was sensitive to inhibition by staurosporine. Inhibition of PMA-induced phosphorylation of gamma and epsilon subunits of CD3 was demonstrated after depletion of PKC or in the presence of staurosporine, confirming that PKC function was inhibited in those conditions. Cross-linking of the TcR via plastic-coated anti-TcR mAb led to phosphorylation of CD3 gamma and epsilon and also of zeta, known to be phosphorylated on tyrosines. All of these phosphorylation events were inhibited by treatment with staurosporine. Our results indicate that staurosporine inhibits the receptor internalization induced by anti-TcR mAb by means other than inhibition of PKC, suggesting that other kinases may control a step of this internalization process. 相似文献
3.
Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from
mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has
revealed some general genotype-phenotype correlations. Severe disease has
been associated with mutations that produce a premature termination while
more mild disease has been associated with missense mutations. Here, we
provide experimental proof for these genotype-phenotype correlations by
demonstrating that nonsense mutations fail to produce stable merlin protein
while missense mutations result in the generation of merlin proteins
defective in negative growth regulation. This inability to suppress cell
growth may result from defects in the function of merlin at several levels,
including failure to form an intramolecular complex. Based on these
findings, we propose a model for merlin growth suppression that provides a
framework for analyzing NF2 patient mutations and merlin function.
相似文献
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5.
Breast cancer detection: one versus two views 总被引:2,自引:0,他引:2
Mammographic examinations of 169 patients with 172 biopsy-proved carcinomas, and of 194 healthy subjects, were interpreted independently and retrospectively by three experienced mammographers, initially as single-view oblique examinations and 6 months later as two-view oblique-cephalocaudal examinations. For the single-view examinations of the cancer patients, 67% of the cancers were correctly recommended for biopsy, additional views were requested for 23%, and a "negative" interpretation was made for 10%. For the single-view examinations of healthy subjects, biopsy was recommended for 7% and additional views were recommended for 32%. For the two-view examinations of women with cancer, 80% of the cancers were correctly recommended for biopsy, additional views were requested for 4%, and a "negative" interpretation was made for 16%. For two-view examinations of healthy subjects, biopsy was recommended for 7% and additional views were requested for only 5%. The authors conclude that single-view screening should not be performed, because it would lead to an excessive number of "call-back" examinations of healthy patients, producing additional cost and anxiety that would outweigh any theoretical benefit. 相似文献
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7.
[Purpose] The purpose of this study was to investigate the use of smartphones by
university students in selected areas, their musculoskeletal symptoms, and the associated
hazard ratio. [Subjects and Methods] This involved the completion of a self-administered
questionnaire by dental hygiene students in Seoul, Gyeonggido, and Gyeongsangbukdo. The
292 completed copies of the questionnaire were then analyzed. [Results] The most painful
body regions after the use of smartphones were found to be the shoulders and neck. In the
musculoskeletal system, back pain was found to have a positive correlation with the size
of the smartphone’s liquid crystal display (LCD) screen, and pain in legs and feet were
found to have a negative correlation with the length of time that the smartphone was used.
As a result, it was revealed that the use of a smartphone was correlated with
musculoskeletal symptoms. [Conclusion] Therefore, in today’s environment, where the use of
smartphones is on the rise, it is necessary to improve the ways that they are used and to
develop a preventive program to alleviate the symptoms of musculoskeletal damage.Key words: Smartphone, Musculoskeletal symptoms, Prevent 相似文献
8.
The accuracy of International Classification of Diseases coding for dental problems not associated with trauma in a hospital emergency department 下载免费PDF全文
9.
DH Mallon M Kostalas FJ MacPherson A Parmar A Drysdale E Chisholm 《Annals of the Royal College of Surgeons of England》2013,95(4):258-262
Introduction
Fine needle aspiration (FNA) is a safe and quick method of diagnosing superficial lumps, which aids preoperative planning. However, FNA of the parotid gland has not gained the widespread acceptance noted in other head and neck lumps. The aim of this study was to determine the ability of FNA of the parotid gland to differentiate benign and malignant disease, and to determine the impact on surgical outcome.Methods
A retrospective analysis of 201 consecutive parotid operations with preoperative FNA in a large district hospital in the UK was performed. The diagnostic characteristics were calculated for benign and malignant disease, and the impact on surgical procedure was determined.Results
In identifying benign disease, FNA has a sensitivity of 85% and a specificity of 76%. In detecting malignant disease, FNA has a sensitivity and specificity of 52% and 92% respectively. A false positive on FNA was associated with a higher incidence of neck dissection.Conclusions
FNA is a useful diagnostic test. However, owing to low sensitivity, it is necessary to interpret it in the context of all other clinical information. 相似文献10.