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51.
Polyspecificity is defined as the ability of a given antibody molecule to bind a large panel of structurally diverse antigens. A fraction of circulating IgG in all healthy individuals acquires promiscuous antigen-binding activity only after a transient exposure to certain protein destabilizing factors. The molecular mechanisms of this phenomenon are not well understood. Exposures to protein destabilizing agents are common steps in immunoglobulin isolation and purification processes. We performed kinetic and thermodynamic analyses using surface plasmon resonance-based technique in order to characterize the interactions of a single mouse monoclonal antibody to its cognate antigen before and after induction of promiscuous antigen-binding activity. The obtained results, suggest that enhanced antigen binding activity induced by exposure to mild denaturing condition resulted from an increase in the structural flexibility of the antigen-binding site. Further pH and ionic strength-dependence analyses of the antibody/antigen interactions demonstrated that the transition to promiscuous antigen-binding was accompanied by a change in the type of non-covalent forces involved in the complex formation. Moreover, from this study, it is evident that an antibody molecule could use two distinct thermodynamic pathways for binding to the same antigen while retaining the same value of the binding affinity. The obtained results may contribute to the understanding of the molecular mechanisms that lay behind natural antibody polyspecificity. 相似文献
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53.
Extramedullary hematopoiesis (EMH) is most often associated with underlying hematologic disorders, such as myeloproliferative neoplasms and thalassemia. EMH in the setting of solitary fibrous tumor (SFT) is exceedingly rare, with only 3 cases reported to date in the English literature. Herein, we describe our experience with a unique case of SFT arising in the breast with intratumoral foci of EMH in a 57‐year‐old woman who presented with an incidentally found right axillary mass on routine screening mammography. To the best of our knowledge, this is the first reported case of mammary SFT with concurrent intratumoral EMH. 相似文献
54.
Varalakshmi Boreddy Kiranmyai V. S. Aparna Bitla Ram Rapur Rao P. V. L. N. Srinivas Kumar Vishnubotla Siva 《International urology and nephrology》2020,52(5):917-921
International Urology and Nephrology - Osteopontin (OPN) is evolving as a novel biomarker of injury, overall survival and renal outcome in critically ill patients with acute kidney injury (AKI),... 相似文献
55.
56.
Daniel Y.C. Heng J. Connor Wells Brian I. Rini Benoit Beuselinck Jae-Lyun Lee Jennifer J. Knox Georg A. Bjarnason Sumanta Kumar Pal Christian K. Kollmannsberger Takeshi Yuasa Sandy Srinivas Frede Donskov Aristotelis Bamias Lori A. Wood D. Scott Ernst Neeraj Agarwal Ulka N. Vaishampayan Sun Young Rha Jenny J. Kim Toni K. Choueiri 《European urology》2014
Background
The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic renal cell carcinoma (mRCC) in the era of targeted therapy.Objective
To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies.Design, setting, and participants
Retrospective data from patients with synchronous mRCC (n = 1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not.Outcome measurements and statistical analysis
OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria.Results and limitations
Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo (p < 0.0001). When adjusted for IMDC criteria to correct for imbalances, the HR of death was 0.60 (95% confidence interval, 0.52–0.69; p < 0.0001). Patients estimated to survive <12 mo may receive marginal benefit from CN. Patients who have four or more of the IMDC prognostic criteria did not benefit from CN. Data were collected retrospectively.Conclusions
CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times <12 mo or four or more IMDC prognostic factors may not benefit from CN. This information may aid in patient selection as we await results from randomized controlled trials.Patient summary
We looked at the survival outcomes of metastatic renal cell carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors. 相似文献57.
Sanjay Govil Mettu Srinivas Reddy Mohamed Rela 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2014,399(6):707-716
Background
Resection of perihilar cholangiocarcinoma involves major hepatectomy including caudate lobectomy. It is technically challenging because of the complex, intimate and variable relationship between biliary and vascular structures in the liver hilum. Resectability rates vary from 30 to 80 % and about one third of patients have microscopically involved margins. However, adequately performed resections provide 5-year survival of 30–40 % and are worth pursuing.Purpose
Better understanding of anatomy, better imaging, improved surgical techniques and progress in perioperative care of these patients have pushed the limits of resection of these tumours. Many of the traditional indicators of inoperability such as bilateral involvement of second-order hepatic ducts, contralateral biliary and vascular involvement, and need for arterial resection have been overcome or are being challenged. This review discusses techniques that may increase margin-free resectability of Bismuth–Corlette type III and IV perihilar cholangiocarcinoma.Conclusion
Advanced perihilar cholangiocarcinoma requires extended liver resection and often vascular resection, despite which the margin may be compromised in about one third of patients. Right sided tumours are likely to need right trisectionectomy and portal vein resection, best served by an en bloc hilar resection or Rex-recess approach. Left-sided tumours often involve contralateral blood vessels and require left trisegmentectomy with possible right portal vein or right hepatic artery reconstruction. These tumours are best tackled by hepatobiliary surgeons with experience in microvascular techniques. Salvage procedures when arterial reconstruction is not feasible are still under evaluation. 相似文献58.
Bidya Dhar Sahu Srujana Tatireddy Meghana Koneru Roshan M. Borkar Jerald Mahesh Kumar Madhusudana Kuncha Srinivas R. Shyam Sunder R. Ramakrishna Sistla 《Toxicology and applied pharmacology》2014
Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney. 相似文献
59.
Srinivas Ganta Amit Singh Niravkumar R. Patel Joseph Cacaccio Yashesh H. Rawal Barbara J. Davis Mansoor M. Amiji Timothy P. Coleman 《Pharmaceutical research》2014,31(9):2490-2502
Purpose
Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C6-ceramide, were designed to overcome these limitations.Methods
The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780CP.Results
The nanoemulsion with particle size <150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFR-targeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC50 in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist®.Conclusion
The myrisplatin/C6-ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant Magnevist® and may be suitable as a theranostic for ovarian cancer. 相似文献60.
C. V. Srinivas P. T. Rakesh K. B. R. R. Hari Prasad R. Venkatesan R. Baskaran B. Venkatraman 《Air quality, atmosphere, & health》2014,7(2):209-227
In this study, radiation doses and lifetime attributable health risk to the members of public in a 40-km impact zone around the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) were assessed for the airborne releases that occurred during 11–31 March 2011 from the loss of coolant accident associated with the east Japan earthquake and tsunami event. High-resolution simulations with FLEXPART-WRF Lagrangian particle dispersion model were made using available source term estimates for four significant isotopes (Cs134, Cs137, I131, Xe133). Radiation risk models were adopted to estimate the health risk for leukemia, breast, thyroid, and all solid cancers using simulated distributed lifetime organ doses. The simulations indicate occurrence of hotspots in the spatial activity deposition and radiation dose distribution with high values in the northwest and south-southwest land sectors in a 40-km radius. Large activity depositions (106 to 108 Bq/m2 of Cs137 between 12 and 31 March 2011) and external air doses (10 to 100 μSv/h) are simulated in the above sectors. The simulated air dose rates are found to match with observed doses at 85 % of the monitor stations within a factor of 5. It is estimated that the groundshine and ingestion dose are the principal contributors of the effective dose. Simulated average effective dose during the first year of exposure varied as ~150 mSv in the first few kilometers to 2 mSv at 40 km. The risk incidence was estimated to be high for infants compared to the children and adult age group for all types of cancers. The first 0–20-km range of the FDNPP is characterized with high risk for all types of cancers, for example, 10 to 20 in 10,000 adults for leukemia. The analysis shows that the immediate implementation of countermeasures of evacuation in the 0–20-km zone, sheltering in the 20–40-km zone, and food restrictions by Japan actually reduced significant health risks to the population living near FDNPP. Simulated yearly distribution of total dose indicates that people of evacuated zone can be rehabilitated in about 16 years in the 5–10-km area and 7 years in the 10–20-km area with minimum risk, whereas the near reactor zone of 0–5 km and areas along the plume footprint up to 20 km in the northwest sector of FDNPP require special attention and reclamation measures for rehabilitation. This study demonstrates a total simulation-based approach for estimating the radiation risk for the Fukushima case and helps to assess the time attainment of low risk for inhabitation of the people in the affected areas. 相似文献