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101.
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Daniel L. Schwartz Ian Tagge Katherine Powers Sinyeob Ahn Rohit Bakshi Peter A. Calabresi R. Todd Constable John Grinstead Roland G. Henry Govind Nair Nico Papinutto Daniel Pelletier Russell Shinohara Jiwon Oh Daniel S. Reich Nancy L. Sicotte William D. Rooney 《Journal of magnetic resonance imaging : JMRI》2019,50(3):878-888
103.
Charlie C. Park Catherine Hooker Jonathan C. Hooker Emily Bass William Haufe Alexandra Schlein Yesenia Covarrubias Elhamy Heba Mark Bydder Tanya Wolfson Anthony Gamst Rohit Loomba Jeffrey Schwimmer Diego Hernando Scott B. Reeder Michael Middleton Claude B. Sirlin Gavin Hamilton 《Journal of magnetic resonance imaging : JMRI》2019,49(1):229-238
104.
Sun James J. Perera Bhathika Henley William Angus-Leppan Heather Sawhney Indermeet Watkins Lance Purandare Kiran N. Eyeoyibo Mogbeyiteren Scheepers Mark Lines Geraldine Winterhalder Robert Ashby Samantha De Silva Ravindu Miller Jonjo Philpott David E. Ashwin Chris Howkins Joshua Slater Harriet Medhurst David Shankar Rohit 《Journal of neurology》2022,269(5):2761-2761
Journal of Neurology - 相似文献
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Preparation and comparative evaluation of 99mTc‐HYNIC‐cNGR and 99mTc‐HYNIC‐PEG2‐cNGR as tumor‐targeting molecular imaging probes
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![点击此处可从《Journal of labelled compounds & radiopharmaceuticals》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kusum Vats Drishty Satpati Rohit Sharma Chandan Kumar Haladhar Dev Sarma Sharmila Banerjee 《Journal of labelled compounds & radiopharmaceuticals》2018,61(2):68-76
The tripeptide sequence asparagine‐glycine‐arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC‐c(NGR) and HYNIC‐PEG2‐c(NGR), were synthesized, radiolabeled with 99mTc, and evaluated in CD13‐positive human fibrosarcoma HT‐1080 tumor xenografts. The radiotracers, 99mTc‐HYNIC‐c(NGR) and 99mTc‐HYNIC‐PEG2‐c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being ?2.33 ± 0.05 and ?2.61 ± 0.08. The uptake of 2 radiotracers 99mTc‐HYNIC‐c(NGR) and 99mTc‐HYNIC‐PEG2‐c(NGR) was similar in nude mice bearing human fibrosarcoma HT‐1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of 99mTc‐labeled HYNIC peptide could not be modulated through introduction of PEG2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention. 相似文献
107.
Sahithi Ravuluri Rohit Bansal Nidhi Chhabra Anurag S. Rathore 《Pharmaceutical research》2018,35(7):142
Purpose
To understand non-enzymatic hydrolytic fragmentation of a monoclonal antibody therapeutic under temperature stressed conditions and investigating possible mechanism for the same.Methods
The mAb therapeutic was incubated at 50°C in phosphate buffer at pH 6.5 and fragmentation was monitored at different ionic strengths under stressed conditions. The incubated mAb was sampled at regular time intervals by analytical Size Exclusion Chromatography (SEC).Results
It was observed that 57% of the mAb product fragmented over 4 days into two fragment species – Fc-Fab and Fab with molecular weights of 97 KDa and 47 KDa, respectively, as measured by mass spectrometry (MS) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The fragmentation rate was slow initially and then accelerated with time. No change in % aggregate level was observed in this duration, implying that degradation was primarily via fragmentation at high temperature. Kinetics of hydrolytic fragmentation was hypothesized and SEC data was fitted to estimate the kinetic rate constants. While degradation of the monomer into fragment species was non-Arrhenius with a negative activation energy, further degradation of Fab-Fc fragments into Fab or Fc fragments followed Arrhenius Law with an activation energy of 2.1 and 15.38 kcal/mol, respectively.Conclusion
High temperature (50°C) causes mAb to cleave at the hinge region to form Fab-Fc and Fab/Fc, as confirmed by dynamic light scattering, SDS-PAGE, SEC, and MS. A kinetic model for hydrolytic fragmentation has been proposed. The results are expected to assist end users in formulation development as well as in monitoring stability of biotherapeutic products.108.
Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice
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![点击此处可从《The Journal of clinical investigation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Morioka T Asilmaz E Hu J Dishinger JF Kurpad AJ Elias CF Li H Elmquist JK Kennedy RT Kulkarni RN 《The Journal of clinical investigation》2007,117(10):2860-2868
Obesity is characterized by hyperinsulinemia, hyperleptinemia, and an increase in islet volume. While the mechanisms that hasten the onset of diabetes in obese individuals are not known, it is possible that the adipose-derived hormone leptin plays a role. In addition to its central actions, leptin exerts biological effects by acting in peripheral tissues including the endocrine pancreas. To explore the impact of disrupting leptin signaling in the pancreas on beta cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (Pdx1) promoter. The KOs exhibited improved glucose tolerance due to enhanced early-phase insulin secretion, and a greater beta cell mass secondary to increased beta cell size and enhanced expression and phosphorylation of p70S6K. Similar effects on p70S6K were observed in MIN6 beta cells with knockdown of the ObR gene, suggesting crosstalk between leptin and insulin signaling pathways. Surprisingly, challenging the KOs with a high-fat diet led to attenuated acute insulin secretory response to glucose, poor compensatory islet growth, and glucose intolerance. Together, these data provide direct genetic evidence, from a unique mouse model lacking ObRs only in the pancreas, for a critical role for leptin signaling in islet biology and suggest that altered leptin action in islets is one factor that contributes to obesity-associated diabetes. 相似文献
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