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Thiopurine use associated with reduced B and natural killer cells in inflammatory bowel disease

World Journal of Gastroenterology 2017年第18期23卷 3240-3251页

作者： james d.lord.donna M Shows Translational Research Program Benaroya Research Institute Gastroenterology division Virginia Mason Medical Center

To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in *** thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease (IBd) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBd at lower doses suggests that they may selectively deplete particular lymphocyte populations. Blood cells from 19 IBd patients on a thiopurine, 19 IBd patients not on a thiopurine, and 38 matched healthy control subjects were analyzed by multiple multi-color flow cytometry panels to quantify the immune cell subsets contained therein, both as a percent of cells, and as an absolute cell count. Similar analyses were performed on colon biopsies from 17 IBd patients on a thiopurine, 17 IBd patients not on a thiopurine, and 49 healthy screening colonoscopy *** blood counts revealed lower lymphocyte, but not monocyte or granulocyte, counts in IBd patients who were taking thiopurines at the time of sampling. This reduction was restricted to Cd3-negative lymphocytes, wherein both natural killer (NK) and B cells were significantly reduced among thiopurine recipients. Among Cd19+ B cells, the transitional B cells were particularly depleted, being nearly absent in both blood and colon biopsies of thiopurine recipients. No differences were associated with thiopurine use in Cd8+ T cells, mucosa-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, gamma/delta T cells, Th1, Th17, regulatory T cells (Tregs) or naïve Cd4+ T cells. However, patients with IBd had significantly more circulating FOXP3+, Helios+ Tregs and fewer iNKT and MAIT cells than healthy *** use is associated with reduced B and NK cell, but not T cell, subpopulations in the blood of IBd patients.

关键词： Thiopurine Azathioprine Mercaptopurine Lymphocyte Natural killer cell Transitional B cell Inflammatory bowel disease

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi james d.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Light controlled imaging probes for intracellular target recognition： photochromism as a tool to enhance sensing precision

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Science China Chemistry 2017年第12期60卷 1563-1564页

作者： Tony d. james department of Chemistry University of BathBath BA2 7AYUK

Chemosensors and imaging probes have been the focus of significant research interest over the past few decades. In part due to ease of preparation and simplicity in manipulation, fluorescent probes have been extensive... 详细信息

关键词： Light controlled imaging probes for intracellular target recognition photochromism enhance sensing precision

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Portal hypertension in polycystic liver disease patients does not affect wait-list or immediate post-liver transplantation outcomes

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World Journal of Gastroenterology 2016年第45期22卷 9966-9973页

作者： Neil Rajoriya dhiraj Tripathi Joanna A Leithead Bridget K Gunson Sophie lord james W Ferguson Gideon M Hirschfield Liver Unit Queen Elizabeth Hospital Centre for Liver Research NIHR Birmingham Liver Biomedical Research Unit University of Birmingham

AIM To establish the impact of portal hypertension(PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease(PCLd) listed for liver transplantation. METHOdS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLd cohort was defined by the one or more of following parameters:(1) presence of radiological or endoscopic documented varices from our own centre or the referral centre;(2) splenomegaly(> 11 cm) on radiology inabsence of splenic cysts accounting for increased imaging size;(3) thrombocytopenia(platelets diological evidence of hepatic venous outflow obstruction from a single cyst. RESULTS Forty-seven PCLd patients(F: M = 42: 5) were listed for liver transplantation(LT)(single organ, n = 35; combined liver-kidney transplantation, n = 12) with 19 patients(40.4%) having PH. When comparing the PH group with non-PH group, the mean listing age(PH group, 50.6(6.4); non-PH group, 47.1(7.4) years; P = 0.101), median listing MELd(PH group, 12; non-PH group, 11; P = 0.422) median listing UKELd score(PH group, 48; non-PH group, 46; P = 0.344) and need for renal replacement therapy(P = 0.317) were similar. In the patients who underwent LT alone, there was no difference in the duration of ICU stay(PH, 3 d; non-PH, 2 d; P = 0.188), hospital stay length(PH, 9 d; non-PH, 10 d; P = 0.973), or frequency of renal replacement therapy(PH, 2/8; non-PH, 1/14; P = 0.121) in the immediate post-transplantation period. CONCLUSION Clinically apparent portal hypertension in patients with PCLd listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity.

关键词： Polycystic liver disease Portal hypertension Liver transplantation

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Promises and paradoxes of regulatory T cells in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第40期21卷 11236-11245页

作者： james d.lord. Translational Program Benaroya Research Institute at Virginia Mason Mailstop

Since their discovery two decades ago,Cd4+Cd25+Foxp3+ regulatory T cells(Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells,which promote an immune response,Tregs actively inhibit inflammation when activated by their cognate antigen,thus raising hope that these cells could be engineered into a highly targeted,antigenspecific,immunosuppressant therapy. Although Tregs represent less than 10% of circulating Cd4+T cells,they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases. In particular,spontaneous intestinal inflammation has been shown to occur in the absence of Tregs,suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease(IBd). However,over the past decade,multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBd patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis. In this review,we will discuss the history of Tregs,what is known about them in IBd,and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit.

关键词： Foxp3 Regulatory T cells Crohn’s disease Th17 Ulce

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A new direction for Alzheimer's research

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Neural Regeneration Research 2018年第2期13卷 190-193页

作者： james d.Weinstein Marshall University School of Medicine Medical Center

despite decades of research, at present there is no curative therapy for Alzheimer＇s disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. The first change is that Alzheimer＇s disease must be considered a disease of four major pathological processes, not one. The four processes are： 1） vascular hy- poperfusion of the brain with associated mitochondrial dysfunction, 2） destructive protein inclusions, 3） uncontrolled oxidative stress, and 4） proinflammatory immune processes second- ary to microglial and astrocytic dysfunction in the brain. The second change recommended is to alter the standard cognitive measurement tools used to quantify mental decline in test patients. Specifically the dementia Severity Rating Scale （dSRS） should supersede Mini-Mental State Examination （MMSE） and other popular tests, and a measurement scale developed in research should be used to produce a linear and non-irregular baseline. Finally, accepting the concept that four etiologies cause Alzheimer＇s disease leads to the last necessary change, that new thera- pies must be employed directed against all four causes, likely as a combination. There are drugs ready to be employed in such a combinations which are available and used clinically for other purposes so can be used ＂offlabel＂ and one such combination is suggested.

关键词： Alzheimer's disease etiologies combination therapy cognitive testing failed research off-label use dementia Severity Rating Scale

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design of soft magnetic materials

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npj Computational Materials 2022年第1期8卷 17-26页

作者： Ananya Renuka Balakrishna Richard d.james Aerospace and Mechanical Engineering University of Southern CaliforniaLos AngelesCA90089USA Aerospace and Engineering Mechanics University of MinnesotaMinneapolisMN55455USA

We present a strategy for the design of ferromagnetic materials with exceptionally low magnetic hysteresis,quantified by *** this strategy,we use a micromagnetic algorithm that we have developed in previous research and which has been validated by its success in solving the“Permalloy Problem”—the well-known difficulty of predicting the composition 78.5%Ni of the lowest coercivity in the Fe–Ni system—and by the insight it provides into the“Coercivity Paradox”of ***,the design strategy predicts that cubic materials with large saturation magnetization ms and large magnetocrystalline anisotropy constant κ_(1) will have low coercivity on the order of that of Permalloy,as long as the magnetostriction constantsλ_(100),λ_(111)are tuned to special *** explicit prediction for a cubic material with low coercivity is the dimensionless number(c_(11)−c_(12))λ_(100)^(2)/(2_(κ_(1)))=81 for〈100〉easy *** results would seem to have broad potential application,especially to magnetic materials of interest in energy research.

关键词： magnetic cubic exceptional

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distinct MLT asymmetry of auroral kilometric radiation observed by the FAST satellite

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Earth and Planetary Physics 2025年第1期9卷 188-193页

作者： JiaWen Tang Sai Zhang FuLiang Xiao HongMing Yang Si Liu YiHua He Chang Yang YuYue Jin ZhouKun deng Ping Li Archie james Johnston School of Physics and Electronic Sciences Changsha University of Science and TechnologyChangsha 410114China Hunan Province Higher Education Key Laboratory of Modeling and Monitoring on the Near-Earth Electromagnetic Environments Changsha University of Science and TechnologyChangsha 410114China School of Electrical and Information Engineering Changsha University of Science and TechnologyChangsha 410114China

Auroral Kilometric Radiation(AKR)is a common radio emission,which can contribute to the magnetosphere−ionosphere−atmosphere *** emissions have been observed in all magnetic planet magnetospheres of the solar *** this study,using observations from the FAST satellite from 30 August 1996 to 9 September 2001,the distribution of AKR in altitude=500−4500 km and invariant latitude(|ILAT|)=60°−80°has been analyzed.63045 AKR samples have been identified with~48%(52%)samples on the dayside(nightside).Of considerable interest,there is a distinct MLT asymmetry with the high occurrence rate in MLT=05−08 and 18−22(02−05 and 12−17)in the northern(southern)*** distinct MLT asymmetry is associated with the direction of Bxof the interplanetary magnetic *** addition,the occurrence rate on the nightside clearly increases as the index *** study further enriches *** and understanding of AKR in the magnetosphere as well as other similar radio emissions.

关键词： asymmetry auroral kilometric radiation interplanetary magnetic field

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Biodiversity of Arbuscular Mycorrhizal (AM) fungi in mangroves of Goa in West India

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Journal of Forestry Research 2013年第3期24卷 515-523页

作者： james d'Souza Bernard Felinov Rodrigues department of Botany Goa UniversityGoa 403 206 India

Seventeen mangrove species of eight families at seven river- ine and fringe habitats in Goa West India were surveyed for Arbuscular Mycorrhizal （AM） fungal diversity. Sixteen species were found to be mycorrhizal and one species showed no AM fungal colonization. AM root colonization was recorded at all seven sites and ranged from 6%-77%. Maximum root colonization was recorded in Excoecaria agal- locha （77%） and minimum colonization in Avicennia marina （6%）. Paris-type colonization was predominant at all sites. Auxiliary cells were recorded in roots of Acanthus ilicifolius, Ceriops tagal and Sonneretia alba. AM fungal root colonization and spore density varied by plant species and site. Site average spore density ranged from 1.84 spores.g^-1 to 0.54 spores.g-1 of soil. In total, 28 AM fungal species of five genera, viz. Glomus, Acaulospora, Scutellospora, Gigaspora and Entrophospora, were recovered. Glomus was the dominant genus, three species of which were sporocarpic forms. Maximum site species richness （SR） ranged from 16 to 5. Species richness was maximum in A. ilicifolius where seven species of three genera were recovered. Based on relative abun- dance （RA） and isolation frequency （IF）, two common species, viz. G. intraradices and A. laevis, were recovered from all seven sites.

关键词： Glomus intraradices root colonization Paris type sporedensity rhizosphcre

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Special issue on “Molecular Sensors and Molecular Logic Gates”

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Frontiers of Chemical Science and Engineering 2022年第1期16卷 1-3页

作者： Luling Wu Tony d.james department of Chemistry University of BathBath BA27AYUK

This issue of Frontiers of Chemical Science and Engineering highlights recent progress toward fluorescent probes that was originally conceived to coincide with 7th Conference on Molecular Sensors and Molecular Logic Gates(MSMLG 2020)to celebrate the career of Seiji Shinkai and hosted by Anthony Czarnik at the University of Nevada in ***,that meeting was cancelled due to the pandemic associated with ***,this collection of research and review papers will now serve as an introduction to MSMLG 2022 which will be in dublin,Ireland on 7–10 June 2022,where Thorfinnur Gunnlaugsson will be the local *** collection of papers contained in this special issue covers in vitro and in vivo applications and illustrates the potential for practical sensing and imaging of disease-related species.

关键词： Sensors Logic Molecular

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