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In vivo anti-tumor activity of murine hematopoietic stem cells expressing a p185HER2-specific chimeric T-cell receptor gene

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journal of Microbiology and Immunology 2006年第2期4卷 117-124页

作者： jIAN MIN YANG MICHAEL S FRIEDMAN MARIANNE T HUBEN jENNIFER FULLER QIAO LI ALFRED E CHANG james j mule KEVIN T MCDONAGH Department of Hematology Changhai Hospital the Second Military Medical University Shanghai P. R. China Department of Internal Medicine University of Michigan Medical School Ann Arbor Michigan USA Department of Surgery University of Michigan Medical School Ann Arbor Michigan USA Division of Hematology Oncology and Blood and Marrow Transplantation Department of Internal Medicine University of Kentucky College of Medicine Lexington Kentucky USA

We have confirmed efficient anti-tumor activities of the peripheral lymphocytes transduced with a p185HEH2-specific chimeric T-cell receptor gene both in murine and in human in our previous studies. To further test the feasibility of chimeric T-cell receptor in a bone marrow transplantation model, we first, made two routine tumor cell lines： MT901 and MCA-205, to express human p185HER2 by retroviral gene transduction. Murine bone marrow cells were retrovirally transduced to express the chimeric T-cell receptor and gene-modified bone marrow cells were transplanted into lethally irradiated mouse. Six months post transplantation, p185HER2-positive tumor ceils： MT-901/HER2 or MCA-205/ HER2 was subcutaneously or intravenously injected to make mouse models simulating primary breast cancer or pulmonary metastasis. The in vivo anti-tumor effects were monitored by the size of the subcutaneous tumor or counting the tumor nodules in the lungs after India ink staining. The size of the subcutaneous tumor was significantly inhibited and the number of pulmonary nodules were significantly decreased in mouse recipients transplanted with chimeric T-cell receptor modified bone marrow cells compared with the control group. Our results suggest the efficient in vivo anti-tumor activities of chimeric T-cell receptor gene modified bone marrow cells.

关键词： Gene therapy Retrovirus Chimeric T-cell receptor Murine Hematopoietic stem cell Immunotherapy

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An analytical model to estimate the time delay to reach spontaneous ignition considering heat loss in oil reservoirs

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Petroleum Science 2024年第4期21卷 2469-2474页

作者： james j.Sheng Er-Long Yang College of Petroleum Engineering Northeast Petroleum University

During air injection into an oil reservoir, an oxidation reaction generates some heat to raise the reservoir temperature. When the reservoir temperature reaches an ignition temperature, spontaneous ignition occurs. There is a time delay from the injection to ignition. There are mixed results regarding the feasibility of spontaneous ignition in real-field projects and in laboratory experiments. No analytical model is available in the literature to estimate the oxidation time required to reach spontaneous ignition with heat *** paper discusses the feasibility of spontaneous ignition from theoretical points and experimental and field project observations. An analytical model considering heat loss is proposed. Analytical models with and without heat loss investigate the factors that affect spontaneous ignition. Based on the discussion and investigations, we find that it is more difficult for spontaneous ignition to occur in laboratory experiments than in oil reservoirs; spontaneous ignition is strongly affected by the initial reservoir temperature, oil activity, and heat loss; spontaneous ignition is only possible when the initial reservoir temperature is high, the oil oxidation rate is high, and the heat loss is low.

关键词： Spontaneous ignition Time delay Air injection Heat loss Low temperature oxidation Combustion

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Tumor Antigen Specific Activation of Primary Human T-Cells Expressing a Virally Encoded Chimeric T-Cell Receptor Specific for p185HER2

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journal of Microbiology and Immunology 2004年第4期2卷 272-277页

作者：杨建民 Michael S FRIEDMAN Christopher M REYNOLDS Marianne T HUBEN Lee WILKE jennifer FULLER 李桥 Zelig ESHHAR james j mule Kevin T MCDONAGH Department of Hematology Changhai Hospital The Second Millitay Medical University Shanghai 200433 China Departments of Internal Medicine Departments of Surgery Departments of Internal Medicine University of Michigan Medical School Ann Arbor MI 48109 and De- partment of Chemical Immunology the Weizmann Institute of Science Israel

We have developed and tested chimeric T-cell receptors (TCR) specific for p185HER2. In these experiments, retroviral vectors expressing the N29γ or N29ζ receptors were constructed in pRET6. Amphotropic viral producer cells were established in the GALV-based PG13 packaging cell line. Ficoll purified human peripheral blood lymphocytes (PBL) were virally transduced using an optimized protocol incorporating activation with immobilized anti-CD3/anti-CD28 monoclonal anti- bodies, followed by viral infection in the presence of fibronectin fragment CH296. Transduced cells were co-cultured with human tumor cell lines that overexpress (SK-OV-3) or underexpress (MCF7) p185HER2 to assay for antigen specific im- mune responses. Both CM+ and CD8+ T-cells transduced with the N29γ or N29ζ chTCR demonstrated HER2-specific anti- gen responses, as determined by release of Th1 like cytokines, and cellular cytotoxicity assays. Our results support the fea- sibility of adoptive immunotherapy with genetically modified T-cells expressing a chTCR specific for p185HER2.

关键词： Gene therapy retrovirus Chimeric T-cell receptor Human peripheral T-lymphocytes Immunotherapy

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转染嵌合性T细胞受体基因小鼠T淋巴细胞的体外抗肿瘤作用

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中国肿瘤生物治疗杂志 2006年第4期13卷 243-248页

作者：杨建民 Michael S Friedman 李峤 james j mule Alfred E Chang Kevin T McDonagh 第二军医大学长海医院血液内科 University of Michigan Medical SchoolAnn Arbor MI 48109-0620 USA University of Kentucky College of Medicine Lexington Ky 40536-0293 USA

目的:研究小鼠T淋巴细胞在转染嵌合性T细胞受体基因后的体外抗肿瘤作用。方法:应用重组DNA技术,将HER2特异性嵌合性T-细胞受体构建入逆转录病毒载体;转入包装细胞后,收集病毒上清,转染小鼠T淋巴细胞,转基因后的小鼠T淋巴细胞分别与HER2... 详细信息

目的:研究小鼠T淋巴细胞在转染嵌合性T细胞受体基因后的体外抗肿瘤作用。方法:应用重组DNA技术,将HER2特异性嵌合性T-细胞受体构建入逆转录病毒载体;转入包装细胞后,收集病毒上清,转染小鼠T淋巴细胞,转基因后的小鼠T淋巴细胞分别与HER2阳性(SK-OV-3)或阴性(MCF-7)的肿瘤细胞系共培养,检测其细胞因子γ干扰素释放,51Cr释放法检测CTL评价其抗肿瘤效应。结果:所构建载体经酶切鉴定符合要求,乒乓法转染包装细胞系GP+E86,检测病毒滴度为1.2×106,Retronectin结合离心法转染经抗CD3/CD28单抗活化的小鼠T淋巴细胞,转染效率可达50%以上;转染嵌合性T细胞受体基因的T淋巴细胞与HER2阳性或阴性的肿瘤细胞系共培养后可检测到HER2特异性的细胞因子γ干扰素释放,51Cr释放法测CTL可见转染嵌合性T细胞受体基因T淋巴细胞对HER2阳性的肿瘤细胞具显著杀伤效应。结论:转染嵌合性T细胞受体基因的小鼠T淋巴细胞在体外可通过细胞因子释放和CTL效应发挥显著的抗肿瘤作用。

关键词：嵌合性T细胞受体基因转染免疫治疗小鼠 T淋巴细胞

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Insm1:orchestrating cellular mimicry in the thymus medulla

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Cellular & Molecular Immunology 2024年第4期21卷 414-416页

作者： K.D.james j.E.Cowan UCL Institute of Immunity and Transplantation The Pears BuildingRowland Hill StreetLondonNW32PPUK

The thymus is the primary production site for a functional and self-tolerant T-cell *** establishment of immune tolerance is mediated by the generation and presentation of tissue-restricted self-antigens(TRAs)by medullary thymic epithelial cells(mTECs),which screen T-cell receptors for self-reactivity to eliminate autoreactive T *** studies have extended our understanding of mTEC heterogeneity by examining the mechanisms by which mTECs mimic the peripheral self[1].

关键词： medullary eliminate restricted

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What diameter?What height?Influence of measures of average tree size on area-based allometric volume relationships

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Forest Ecosystems 2024年第1期11卷 100-109页

作者： Yilin Wang john A.Kershaw Mark j.Ducey Yuan Sun james B.McCarter Integrated Forest Mensuration and Systems Analysis Laboratory Faculty of Forestry and Environmental ManagementUniversity of New BrunswickFrederictonNBCanada Department of Natural Resources and the Environment University of New HampshireDurhamNHUSA College of Forestry Nanjing Forestry UniversityNanjing210037China Scientific Programmer RayonierYuleeFLUSA

Volume is an important attribute used in many forest management *** from 83 fixed-area plots located in central New Brunswick,Canada,are used to examine how different measures of stand-level diameter and height influence volume prediction using a stand-level variant of Honer's(1967)volume *** density was included in the models(Volume=f(Diameter,Height,Density))choice of diameter measure was more important than choice of height *** density was not included(Volume=f(Diameter,Height)),the opposite was *** models with density included,moment-based estimators of stand diameter and height performed better than all other *** models without density,largest tree estimators of stand diameter and height performed better than other *** overall best equation used quadratic mean diameter,Lorey's height,and density(root mean square error=5.26 m^3·ha^(-1);1.9%relative error).The best equation without density used mean diameter of the largest trees needed to calculate a stand density index of 400 and the mean height of the tallest 400 trees per ha(root mean square error=32.08 m^(3)·ha^(-1);11.8%relative error).The results of this study have some important implications for height subsampling and LiDAR-derived forest inventory analyses.

关键词： Allometric relationships Stand structure Volume estimation Stand-level attributes

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Outcomes following minimally invasive dorsal cheilectomy for hallux rigidus:A systematic review

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World journal of Orthopedics 2024年第6期15卷 585-592页

作者： Katherine Esser james j Butler Mackenzie Roof Nathaniel P Mercer Michael C Harrington Alan P Samsonov Andrew j Rosenbaum john G Kennedy Department of Orthopaedic Surgery University of Toledo Medical Center University of Toledo College of Medicine and Life SciencesToledoOH 43614United States Department of Orthopedic Surgery NYU Langone HealthNew YorkNY 10002United States Department of Orthopedic Surgery Albany Medical CenterAlbanyNY 12208United States

BACKGROUND Cheilectomy of the 1^(st)metatarsophalangeal joint(MTPj)is one of the most common procedures for the management of hallux ***,there is no consensus regarding outcomes following minimally invasive dorsal cheilectomy(MIDC)for the management of hallux *** To evaluate outcomes following MIDC for the management of hallux *** During November 2023,the PubMed,EMBASE and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following MIDC for the management of hallux *** Six studies were *** total,348 patients(370 feet)underwent MIDC for hallux rigidus at a weighted mean follow-up of 37.9±16.5 *** distribution of patients by Coughlin and Shurna's classification was recorded in 4 studies as follows:Ⅰ(58 patients,27.1%),Ⅱ(112 patients,52.3%),Ⅲ(44 patients,20.6%).Three studies performed an additional 1^(st)MTPj arthroscopy and debridement following *** intra-articular bone debris was observed in 100%of patients in 1 *** weighted mean American orthopedic foot and ankle society score improved from a preoperative score of 68.9±3.2 to a postoperative score of *** complication rate was 8.4%,the most common of which was persistent joint pain and ***-two failures(8.7%)were ***-three secondary procedures(8.9%)were performed at a weighted mean time of 8.6±3.2 months following the index *** This systematic review demonstrated improvements in subjective clinical outcomes together with a moderate complication rate following MIDC for the management of hallux rigidus at short-term follow-up.A moderate reoperation rate at short-term follow-up was *** marked heterogeneity between included studies and paucity of high quality comparative studies limits the generation of any robust conclusions.

关键词： Minimally invasive dorsal cheilectomy Hallux rigidus The first metatarsophalangeal joint Cheilectomy Minimally invasive surgery

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The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[^(18)F]fluoro-D-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology:A single centre retrospective study

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Asian journal of Urology 2024年第1期11卷 33-41页

作者： Anthony Franklin Troy Gianduzzo Boon Kua David Wong Louise McEwan james Walters Rachel Esler Matthew j.Roberts Geoff Coughlina john W.Yaxley Department of Urology The Wesley HospitalBrisbaneQLDAustralia Wesley Medical Research BrisbaneQLDAustralia School of Medicine The University of QueenslandBrisbaneQLDAustralia Department of Radiology Wesley Medical ImagingBrisbaneQLDAustralia Department of Urology Royal Brisbane and Women's HospitalBrisbaneQLDAustralia

Objective:To review the risk of prostate cancer(PCa)in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography(18F-FDG PET/CT)ordered at Department of Urology,The Wesley Hospital,Brisbane,QLD,Australia for non-PCa related ***:Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was *** were classified as benign,indeterminate,or malignant depending of the results of prostate-specific antigen(PSA),PSA velocity,biopsy histopathology,and three-Tesla(3 T)multiparametric MRI(mpMRI)Prostate Imaging Reporting and Data System score,or gallium-68-prostate-specific membrane antigen(68Ga-PSMA)PET/CT ***:Three percent(273/9122)of men demonstrated 18F-FDG avidity within the ***-five percent(231/273)were further investigated,including with PSA tests(227/231,98.3%),3 T mpMRI(68/231,29.4%),68Ga-PSMA PET/CT(33/231,14.3%),and prostate biopsy(57/231,24.7%).Results were considered benign in 130/231(56.3%),indeterminate in 31/231(13.4%),and malignant in 70/231(30.3%).PCa was identified in 51/57(89.5%)of the men who proceeded to biopsy,including 26/27(96.3%)men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PET/*** most common Gleason score on biopsy was greater than or equal to 4+5(14/51,27.5%).68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33(78.8%).All 13 men with a positive concordant 18F-FDG,3 T mpMRI,and 68Ga-PSMA PET/CT had PCa on *** was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups(5.7 vs.6.1;p=0.580).Conclusion:In this study,after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT,70 of the 231 cases(30.3%;0.8%of the entire cohort)had results c

关键词： Prostatecancer Positionemission tomography Multiparametric magneticresonance imaging Prostatebiopsy

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Ranking environmental and edaphic attributes driving soil microbial community structure and activity with special attention to spatial and temporal scales

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mLife 2024年第1期3卷 21-41页

作者： Vadakattu V.S.R.Gupta james M.Tiedje CSIRO Agriculture&Food UrrbraeSouth AustraliaAustralia Centre for Microbial Ecology Michigan State UniversityEast LansingMichiganUSA

The incredibly complex soil microbial communities at small scales make their analysis and identification of reasons for the observed structures *** community structure is mainly a result of the inoculum(dispersal),the selective advantages of those organisms under the habitat-based environmental attributes,and the ability of those colonizers to sustain themselves over *** soil is protective,and its microbial inhabitants have long adapted to varied soil conditions,significant portions of the soil microbial community structure are likely ***,a substantial portion of the community will not correlate to often measured soil *** suggest that the drivers be ranked on the basis of their importance to the fundamental needs of the microbes:(i)those that supply energy,i.e.,organic carbon and electron acceptors;(i)environmental effectors or stressors,i.e.,pH,salt,drought,and toxic chemicals;(ii)macro-organism associations,i.e.,plants and their seasonality,animals and their fecal matter,and soil fauna;and(iv)nutrients,in order,N,P,and probably of lesser importance,other micronutrients,and *** relevance of drivers also varies with spatial and time scales,for example,aggregate to field to regional,and persistent to dynamic populations to transcripts,and with the extent of phylogenetic difference,hence phenotypic differences in organismal *** present a summary matrix to provide guidance on which drivers are important for particular studies,with special emphasis on a wide range of spatial and temporal scales,and illustrate this with genomic and population(rRNA gene)data from selected studies.

关键词： abundance community structure diversity functional microbiome microorganisms

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Lipid nanoparticles deliver mRNA to the blood-brain barrier

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Nano Research 2024年第10期17卷 9126-9134页

作者： Yanina Kuzminich Avraham Shakked Randi Calkins Sebastian Rudden Camille jones jessie Doan Bora jang Elisa Schrader Echeverri Ryan Zenhausern Liming Lian David Loughrey Hannah E.Peck Rachelle Wiese Dorothy Koveal Philip j.Santangelo james E.Dahlman George C.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Parker H.Petit Institute for Bioengineering and Biosciences Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.Coulter Department of Biomedical Engineering Emory University School of Medicine and Georgia Institute of TechnologyAtlantaGA 30332USA

Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous *** clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains *** we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted *** data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous *** the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.

关键词： lipid nanoparticle mRNA nanomedicine central nervous system blood-brain barrier

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