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1.
p70 lupus autoantigen binds the enhancer of the T-cell receptor beta-chain gene. 总被引:9,自引:2,他引:7 下载免费PDF全文
H Messier T Fuller S Mangal H Brickner S Igarashi J Gaikwad R Fotedar A Fotedar 《Proceedings of the National Academy of Sciences of the United States of America》1993,90(7):2685-2689
The p70 (Ku) autoantigen has been described as a nonhistone nuclear protein recognized by antibodies from lupus patients. In our studies on the regulation of T-cell receptor (TCR) beta-chain gene expression we have identified the p70 lupus autoantigen as a DNA-binding protein that binds the enhancer of the TCR beta-chain gene. This enhancer is essential for expression of the TCR beta gene. The core TCR beta enhancer contains the E3 motif, which we show here is essential for enhancer activity. The protection of the E3 motif in T cells and the marked reduction in enhancer activity when the E3 motif is mutated underline its physiological importance in regulating beta enhancer activity. The p70 lupus autoantigen gene was identified by screening T-cell lambda gt11 libraries with an E3 probe. The gene encodes a protein which binds the E3 motif in a sequence-specific manner. The identification of a 70-kDa protein as a major E3-binding protein by UV crosslinking is consistent with the conclusion that the p70 lupus autoantigen binds the beta enhancer. Finally, we have shown that T-cell nuclear proteins which bind the E3 motif bear p70 (Ku) lupus autoantigenic determinants. Together these data suggest that the p70 autoantigen binds a critical motif in the beta enhancer and probably regulates TCR beta gene expression. 相似文献
2.
Hoffmann M Gaikwad J Schmalz G Cavender A D'Souza R 《Connective tissue research》2002,43(2-3):376-380
Studying the mechanisms of molecular interactions in developing tissues demands sensitive molecular biological in vivo and in vitro techniques. Laser capture microdissection (LCM) allows for the isolation of mRNA in histological sections even from single cells, thus enabling the identification of in vivo gene expression products in closely circumscribed tissue areas. The aims of this study were to assess the optimal fixation, processing, and staining conditions to retrieve RNA from microdissected odontoblasts. Fluorometric assays and RT-PCR analysis of alpha 1(I) collagen, dentin sialophosphoprotein (Dspp), and osteocalcin (OC) confirmed that the total RNA isolated from day 0 and day 3 captured odontoblasts was sufficient in quantity and quality. Our results indicate that individual odontoblasts obtained by LCM are morphologically intact and chemically unaltered, allowing accurate molecular and biochemical analyses. 相似文献
3.
Amos S Gaikwad Rachel E Donohue M Tarek Elghetany Andrea M Sheehan Xinyan Y Lu Maria M Gramatges Kenneth L McClain Toni-Ann Mistretta Jyotinder N Punia Timothy J Moore Tatiana Goltsova Michael Cubbage Choladda V Curry 《International journal of clinical and experimental pathology》2014,7(9):6225-6230
Background: Precursor B acute lymphoblastic leukemia (B-ALL) is the most common cancer in children and overall, has an excellent prognosis. However, the Philadelphia chromosome translocation (Ph+), t(9;22)(q34;q11), is present in a small subset of patients and confers poor outcomes. CD25 (IL-2 receptor alpha chain) expression has been associated with Ph+ B-ALL in adults, but no similar study has been performed in pediatric B-ALL. Methods: A retrospective analysis of 221 consecutive pediatric patients with a diagnosis of B-ALL (blood and/or bone marrow) from 2009 to 2012 was performed to determine an association between Ph+ B-ALL and CD25 expression. A threshold of 25% was used to define positive cases for CD25 expression by flow cytometry. Results: There were 221 patients with a diagnosis of B-ALL ranging from 2 to 22 years (median, 6 years). Eight (3.6%) B-ALL patients were positive for the Philadelphia chromosome translocation (Ph+ B-ALL) and 213 were negative (Ph-negative B-ALL). CD25 expression was observed in 6 of 8 (75%) Ph+ B-ALL patients and 6 of 213 (2.8%) Ph-negative B-ALL patients. CD25 expression was significantly higher in Ph+ B-ALL compared to Ph-negative B-ALL, with median CD25 expression of 64% (range 0-93%) and 0.1% (range 0-91%), respectively (P ≤ 0.0002). Therefore, CD25 expression as a predictor of Ph+ B-ALL had 75% sensitivity, 97% specificity, 50% positive predictive value and 99% negative predictive value. Conclusions: CD25 expression is a specific and relatively sensitive marker for the identification of Ph+ B-ALL in the pediatric population. 相似文献
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Objective
To measure physical activity in children with wasting and to look for association between poor physical activity and wasting.Methods
Physical activity was measured in 56 children with wasting, using Children’s Activity Rating Scale, and compared with age- and sex-matched controls.Results
A significant association was found between poor physical activity and malnutrition as determined by weight-for-height Z Score <-2 (P=0.001) and midupper-arm circumference (P=0.002).Conclusion
Physical activity can be used as clinical parameter to assess malnutrition. 相似文献7.
Harish Saluja Vipin Dehane Yogesh Kini Uma Mahindra Prafful Gaikwad 《Journal of maxillofacial and oral surgery》2013,12(3):312-314
Aim of the study was to find out the number of miniplates used by Indian Oral and Maxillofacial Surgeons for parasymphysis fractures. A survey was done among Oral and Maxillofacial Surgeons of India at the 34th annual meeting of Association of Oral and Maxillofacial Surgeons of India. Four questions were given to each individual to find out their opinion regarding use of miniplates in parasymphysis fractures. Eighty-eight per cent of Indian surgeons were in favour of using intra-operative or post-operative intermaxillary fixation. Thirty-eight per cent responded in favour of using single miniplate for parasymphysis fracture instead of using two miniplates. Fifty-four per cent maxillofacial surgeons use various modifications depending on different conditions. Forty-two per cent of maxillofacial surgeons accepted that lower arch bar can be used as a tension band. Use of miniplates for the treatment of parasymphysis fracture varies from centre to centre and from surgeon to surgeon. Though miniplates are best used following Champy’s principle, still many surgeons use single miniplate. Arch bars placed for intermaxillary fixation can be used as a tension band, again eliminating the need for upper plate. 相似文献
8.
Background
Even after several novel therapeutic approaches, the number of people with diabetic nephropathy (DN) still continues to increase globally, this suggest to find novel therapeutic strategies to prevent it completely. Recent reports, are indicating the ubiquitin proteasome system alterations in DN. Recently, we also showed that, histone H2AK119 mono-ubiquitination (H2AK119-Ub) found to regulate Set7, a key epigenetic enzyme in the development of renal fibrosis under type 1 diabetic condition. Hence, we aimed to study the role of a known 20 s proteasome inhibitor Aspirin, on histone ubiquitination in the progression of DN.Methods
Male Wistar rats were rendered diabetic using a single dose of Streptozotocin (55 mg kg?1, ip). After 4 weeks, diabetic animals were grouped into respective groups and the drug, aspirin, low dose (25 mg kg?1 day?1), high dose (50 mg kg?1 day?1) was administered through po route. At the end of the study, kidneys from all the groups were collected and processed separately for glomerular isolation, protein isolation, and for histopathological studies.Results
Aspirin administration, reduced the protein expression of Mysm1, increased the protein expression of H2AK119-Ub and thereby reduced the Set7 protein expression in glomeruli isolated from diabetic animals and prevented renal fibrosis.Conclusions
In conclusion, our results are clearly indicating that, aspirin prevents renal fibrosis in diabetic animals through decreasing the expression of Mysm1, increasing the expression of H2AK119-Ub and thereby decreasing the protein expression of Set7, which is a novel mechanism. Moreover, this mechanism may lay down a novel strategy to prevent DN completely in future. 相似文献9.
M. S. Shaikh J. Rana D. Gaikwad U. Leartsakulpanich Premlata K. Ambre R. R. S. Pissurlenkar E. C. Coutinho 《Indian journal of pharmaceutical sciences》2014,76(2):116-124
Plasmodium falciparum dihydrofolate reductase is an important target for antimalarial chemotherapy. The emergence of resistance has significantly reduced the efficacy of the classic antifolate drugs cycloguanil and pyrimethamine. In this paper we report new dihydrofolate reductase inhibitors identified using molecular modelling principles with the goal of designing new antifolate agents active against both wild and tetramutant dihydrofolate reductase strains three series of trimethoprim analogues were designed, synthesised and tested for biological activity. Pyrimethamine and cycloguanil have been reported to loose efficacy because of steric repulsion in the active site pocket produced due to mutation in Plasmodium falciparum dihydrofolate reductase. The synthesised molecules have sufficient flexibility to withstand this steric repulsion to counteract the resistance. The molecules have been synthesised by conventional techniques and fully characterised by spectroscopic methods. The potency of these molecules was evaluated by in vitro enzyme specific assays. Some of the molecules were active in micromolar concentrations and can easily be optimised to improve binding and activity. 相似文献
10.
Kanwaljeet Garg Pankaj Kumar Singh Bhawani Shankar Sharma Poodipedi Sarat Chandra Ashish Suri Manmohanjit Singh Rajinder Kumar Shashank Sarad Kale Nalin Kumar Mishra Shailesh K Gaikwad Ashok Kumar Mahapatra 《Child's nervous system》2014,30(5):873-883