检索结果-南通市图书馆

Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

Bone Research 2023年第4期11卷 737-750页

作者： Lindsey H.Remark Kevin Leclerc Malissa Ramsukh Ziyan Lin Sooyeon Lee Backialakshmi Dharmalingam lauren Gillinov Vasudev V.Nayak Paulo El Parente Margaux Sambon Pablo j.Atria Mohamed A.E.Ali Lukasz Witek Alesha B.Castillo Christopher Y.Park Ralf H.Adams Aristotelis Tsirigos Sophie M.Morgani Philipp Leucht Department of Orthopaedic Surgery NYU Robert I.Grossman School of MedicineNew YorkNYUSA Applied Bioinformatics Laboratories NYU Grossman School of MedicineNew YorkNYUSA Institute of Comparative Molecular Endocrinology Ulm UniversityUlmGermany Max Planck Institute for Molecular Biomedicine Department of Tissue Morphogenesisand University of MünsterFaculty of MedicineD-48149 MünsterGermany Department of Biochemistry and Molecular Biology University of Miami Miller School of MedicineMiamiFLUSA Department of Pathology NYU Robert I.Grossman School of MedicineNew YorkNYUSA Biomaterials Division New York University College of DentistryNew YorkNYUSA Hansjörg Wyss Department of Plastic Surgery NYU Grossman School of MedicineNew York UniversityNew YorkNYUSA Department of Biomedical Engineering Tandon School of EngineeringNew York UniversityBrooklynNYUSA Department of Cell Biology NYU Robert I.Grossman School of MedicineNew YorkNYUSA

Skeletal stem and progenitor cells(SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.

关键词： Notch skeletal elevated

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Ropinirole Implants Reverse MPTP-Induced Parkinsonism in Rhesus Monkeys

引用

Pharmacology & Pharmacy 2013年第3期4卷 1-8页

作者： Steven j. Siegel lauren Nagy Torben Skarsfeldt Mark Pierce Carol O’ Neill Robert Lin Lori Langhamer jeffery H. Kordower Department of Psychiatry University of Pennsylvania Philadelphia USA NuPathe Inc. Conshohocken USA Rush Medical Center Chicago USA

Purpose: We compared efficacy and side effects of ropinirole implants with oral ropinirole in parkinsonian monkeys. Methods: Twenty monkeys received injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP) to render them parkinsonian. Monkeys were then placed into 3 groups based upon clinical rating scores (CRS). Group 1 received oral ropinirole and placebo implants. Group 2 receivedropinirole implants that released 1/9th of the animals’ optimal daily oral dose and oral placebo. Group 3 received placebo implants and oral placebo. Monkeys were assessed for pharmacokinetic data, CRS, Global Dyskinesia Rating Scale, and skin irritation. Results: For the ropinirole implant group, the activity pattern was similar to that seen pre-MPTP;which extended through the weekends and was greater than control treated parkinsonian monkeys. Oral ropinirole yielded a high degree of variability for activity, with values following oral dosing being higher than the pre-MPTP periodbut levels similar to placebo treated parkinsonian animals during weekends, which were excluded from oral dosing. Implants and oral treatment achieved significant improvement in CRS between 11 - 60 days and 4 - 60 days respectively. Conclusion: Low dose ropinirole implants have the potential to provide continuous clinical improvement in bradykinesia with fewer “off periods” and lower risk for medication-induced psychosis than oral medication.

关键词： Ropinirole Implant Parkinson’s Disease MPTP Pharmacokinetic Dyskinesia

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma

引用

Bioactive Materials 2020年第3期5卷 624-635页

作者： Gloria B.Kim Virginia Aragon-Sanabria lauren Randolph Hali jiang joshua A.Reynolds Becky S.Webb Achuthamangalam Madhankumar Xiaojun Lian james R.Connor jian Yang Cheng Dong Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA16802United States Department of Neurosurgery M.S.Hershey Medical CenterThe Pennsylvania State UniversityHersheyPA17033United States

Glioblastoma(GBM),the deadliest form of brain cancer,presents long-standing problems due to its *** antigen receptor(CAR)T cell immunotherapy has emerged as a powerful strategy to treat ***-13-receptor-α2(IL13Rα2),present in over 75%of GBMs,has been recognized as an attractive candidate for antiglioblastoma ***,we propose a novel multidisciplinary approach to target brain tumors using a combination of fluorescent,therapeutic nanoparticles and CAR T cells modified with a targeted-quadruplemutant of IL13(TQM-13)shown to have high binding affinity to IL13Rα2-expressing glioblastoma cells with low off-target ***-alkyne cycloaddition conjugation of nanoparticles to the surface of T cells allowed a facile,selective,and high-yielding clicking of the *** clicked onto T cells were retained for at least 8 days showing that the linkage is stable and promising a suitable time window for in vivo delivery.T cells clicked with doxorubicin-loaded nanoparticles showed a higher cytotoxic effect in vitro compared to bare T *** vitro and in vivo T cells expressing TQM-13 served as delivery shuttles for nanoparticles and significantly increased the number of nanoparticles reaching brain tumors compared to nanoparticles *** work represents a new platform to allow the delivery of therapeutic nanoparticles and T cells to solid tumors.

关键词： Glioblastoma T cells Nanoparticles Targeted drug delivery Citrate polymers Fluorescence

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

传热学

传热学

引用

1984年

作者：（美）查普曼（A.j.chapman）何用梅译

来源：汇雅图书（南通市图书馆... 评论

在线全文

汇雅图书（南通市图书馆）

学校读者我要写书评

暂无评论

Improved Outcomes in Gallbladder Cancer with Early Diagnosis and Negative Nodal Status

引用

journal of Cancer Therapy 2012年第2期3卷 137-145页

作者： lauren Smithson Christopher Keto Lorenzo Ferguson Sumet Silapaswan Michael j. jacobs Ramachandra Kolachalam jeffrey C. Flynn Vijay K. Mittal Department of Surgery Providence Hospital and Medical Centers Southfield USA Department of Surgery Providence Hospital and Medical Centers Southfield USA.

Background: Gallbladder cancer (GBC) is a rare disease of the hepatobiliary tract characterized by silent presentation, poor prognosis, and limited therapy. Current imaging modalities, clinical symptoms and laboratory values are of limited value in diagnosis and tumour markers are used as a clinical adjunct. Five year survival is 5% - 12% and a majority of patients survive less than 1 year. Early identification, negative nodal status, and extended cholecystectomy improve survival;adjuvant therapy does not appear to play a role. Objective: To evaluate the effects of stage and nodal status of GBC on survival by analyzing clinical and radiological factors leading to preoperative diagnosis and appropriate subsequent management. Results: Forty-three patients (31 female, 12 male) had primary GBC. Average age was 69 years. The most common presenting symptom was pain (65%). Fifteen (35%) patients presented with acute cholecystitis;9 were suspicious for a mass. Ultrasound and computed tomography were the imaging modalities most often used. Preoperative diagnoses were made in only 7 (16%) patients, whereas 16 (37%) patients were diagnosed intra-operatively and 20 (47%) post-operatively. Adjuvant chemotherapy was offered in 16 (37%) patients. Average survival was 28 months (range 0.5 - 238 months), with a 5-year survival of 13% across all stages. Early GBC (stages 1 - 2) had a 5-year survival of 43%, and late GBC (stages 3 - 4) had no survival at 5 years, with an average survival of 9 months. Positive nodes decreased survival. Conclusion: Our results mirror what has been reported in the literature. Most patients presented with acute cholecystitis, with confounding clinical data, but few were preoperatively diagnosed with GBC. Imaging was rarely diagnostic. Late stage GBC, as well as node-positive status, had dismal outcomes with low 1-year and 5-year survival rates. Improved preoperative suspicion of early GBC would allow for more intentional curative resections, before nodes

关键词： Gallbladder Carcinoma Node Status Survival

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Using Geographic Information Systems (GIS) for Targeted National Recruitment of Community-Dwelling Caregivers Managing Dementia-Related Behavioral and Psychological Symptoms: A Recruitment Approach for a Randomized Clinical Trial

引用

journal of Geographic Information System 2021年第3期13卷 302-317页

作者： Danny L. Scerpella Nicole G. Bouranis Melinda j. Webster Maria Dellapina Sokha Koeuth lauren j. Parker Helen C. Kales Laura N. Gitlin School of Public Health Johns Hopkins University Baltimore USA College of Nursing and Health Professions Drexel University Philadelphia USA Department of Psychiatry University of California-Davis Sacramento USA

Over 16 million caregivers of people living with dementia require support in a range of issues, including self-care, disease education, and guidance for how to manage behavioral and psychological symptoms of dementia (BPSD). Non-pharmacological interventions are needed to address these areas, and online applications have been shown to be safe and effective. To ensure the efficacy of such interventions, racially, ethnically, geographically, and socioeconomically diverse participants must be recruited to increase the generalizability of study outcomes. This protocol paper describes a recruitment plan using Geographic Information Systems (GIS) to reach a representative sample of caregivers across the United States for a national Phase III clinical study. Using publicly available census data from the American Community Survey (ACS), combined with location data for local aging resources such as Area Agencies on Aging (AAA), recruitment will be derived from data analysis conducted in ESRI ArcGIS v10.7.1. Datasets including age, gender, income, and education will be assessed nationally at the county and census tract spatial scale in a nine-step process to develop recruitment priority areas containing high concentrations of eligible participants living in the community. Overall, the current protocol will demonstrate the value of GIS in tailoring targeted outreach strategies to recruit community-dwelling populations through local resource institutions. This novel approach may have far-reaching implications in future recruitment initiatives and help to secure racially/ethnically diverse samples.

关键词： Geographic Information Systems Recruitment Clinical Trial GIS Dementia or Caregiving

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Substantial subpial cortical demyelination in progressive multiple sclerosis: have we underestimated the extent of cortical pathology?

引用

Neuroimmunology and Neuroinflammation 2020年第1期7卷 51-67页

作者： lauren Griffiths Richard Reynolds Rhian Evans Ryan j.Bevan Mark I.Rees Djordje Gveric james W.Neal Owain W.Howell Institute of Life Sciences Swansea University Medical SchoolSwansea UniversitySwansea SA28PPUK Department of Brain Sciences Faculty of MedicineImperial College LondonLondon W53EHUK Faculty of Medicine and Health University of SydneySydneyNew South Wales NSW 2006Australia

Aim: Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Much of the complex symptomatology relates to pathology outside the classic white matter plaque, whereby lesions of the cortical grey matter, which are difficult to resolve by conventional clinical imaging, are in part predictive of outcome. We investigated the extent of grey matter pathology in whole coronal macrosections to reassess the contribution of cortical pathology to total demyelinating lesion area in progressive MS. Methods: Twenty-two cases of progressive MS were prepared as whole bi-hemispheric macrosections for histology, immunostaining and quantitative analysis of lesion number and relative area, leptomeningeal inflammation and microglial/macrophage activation. Results: Cortical grey matter demyelination was seen in all cases, which was more extensive than in white and deep grey matter (hippocampus, thalamus and basal ganglia) and accounted for 0.8%-60.2% of the entire measurable cortical ribbon. The pattern of cortical grey matter demyelination was predominantly subpial (mean 90.9%, range 60%-100%, of total cortical grey matter lesion area) and cases with the largest areas of subpial cortical lesions had more and larger deep grey matter lesions, greater numbers of activated microglia/macrophages, both in lesions as well as in normal cortical grey matter, together with elevated leptomeningeal inflammation and lymphoid-like ;structures. White matter lesion area was unchanged when compared with the progressive MS cases with little subpial cortical demyelination. Conclusion: Analysis of whole coronal macrosections reveals cortical demyelination is more extensive than reported by conventional histological methods. Cases of progressive MS with substantial subpial cortical demyelination that is independent of underlying white matter lesion area support the implications that these lesions may in-part arise through different pathogenetic mechanisms. Biomarkers and/or i

关键词： Leptomeninges B cell follicle microglia activation normal appearing grey matter

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

乙烯利对默科特桔的疏果作用

引用

国外农学(果树) 1985年第2期 20-22页

作者： chapman j. C. 魏同许生吉

前言默科特桔(murcott)是澳大利亚昆士兰州柑桔产区的一个主栽晚熟品种,因果实纯收入高而栽培面积迅速增加。该品种由美国佛罗里达州引入,虽然其起源不清楚,但许多园艺工作者认为它是一个桔和橙的杂种(Hodgson,1967)。默科特桔树有严重... 详细信息

前言默科特桔(murcott)是澳大利亚昆士兰州柑桔产区的一个主栽晚熟品种,因果实纯收入高而栽培面积迅速增加。该品种由美国佛罗里达州引入,虽然其起源不清楚,但许多园艺工作者认为它是一个桔和橙的杂种(Hodgson,1967)。默科特桔树有严重隔年结果习性,常因此引起树势衰弱、干枯.有时全树死亡。默科特桔在大年之后,次年花量减少,座果不多。为此,Stewart等(1968)在佛州进行过调查,他们认为导致默科特桔形成大小年的主要原因是缺乏营养物质,尤其

关键词：乙烯利密度疏除 2-氯乙基膦酸植物生长调节物质疏果植株调整默科特

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Inflammatory conversion of quiescent osteoblasts by metastatic breast cancer cells through pERKl/2 aggravates cancer-induced bone destruction

引用

Bone Research 2021年第4期9卷 557-570页

作者： jungho Back Minh Nam Nguyen Lu Li Saelim Lee Inkyu Lee Fancheng Chen lauren Gillinov Yeon-Ho Chung Kareme D.Alder Hyuk-Kwon Kwon Kristin E.Yu Christopher M.Dussik Ziehen Hao Michael j.Flores Yoseph Kim Izuchukwu K.Ibe Alana M.Munger Sung Wook Seo Francis Y.Lee Department of Orthopaedics&Rehabilitation Yale UniversitySchool of MedicineNew HavenCTUSA Research Center for Genetics and Reproductive Health School of MedicineVietnam National University Ho Chi Minh CityLinh Trung WardThu Due DistrictHo Chi Minh CityVietnam Department of Rehabilitation Medicine Renji HospitalSchool of MedicineShanghai JiaoTong UniversityShanghaiChina College of Medicine Dankook UniversityCheonanRepublic of Korea Department of Life Science Chung-Ang UniversitySeoulRepublic of Korea Shanghai Medical College Fudan UniversityShanghai CityChina Department of Emergency&Trauma Changhai HospitalNavy Medical UniversityShanghaiChina Biomedical Engineering Johns Hopkins UniversityBaltimoreMDUSA Department of Orthopedic Surgery Samsung Medical CenterSungkyunkwan University School of MedicineSeoulGangnam-guRepublic of Korea

Disruption of bone homeostasis caused by metastatic osteolytic breast cancer cells increases inflammatory osteolysis and decreases bone formation,thereby predisposing patients to pathological fracture and cancer *** of osteoblast function induces skeletal diseases due to the disruption of bone *** observed increased activation of pERK1/2 in osteolytic breast cancer cells and osteoblasts in human pathological specimens with aggressive osteolytic breast cancer *** confirmed that osteolytic breast cancers with high expression of pERK1/2 disrupt bone homeostasis via osteoblastic ERK1/2 activation at the bone-breast cancer *** process of inflammatory osteolysis modulates ERK1/2 activation in osteoblasts and breast cancer cells through dominant-negative MEK1 expression and constitutively active MEK1 expression to promote cancer growth within ***,an FDA-approved MEK inhibitor,not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal *** together,these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment.

关键词： pERK1/2 breast homeostasis

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

2002—2004年间与接种天花疫苗相关的神经系统不良事件

引用

世界核心医学期刊文摘(神经病学分册) 2006年第4期 1-2页

作者： Sejvar j.j. Labutta R.j. chapman L.E. 张平 Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention 1600 Clifton Rd Atlanta GA 30333 United States.Dr

Context: Neurologic illness is an infrequent but severe adverse event associated with smallpox vaccination. The reinstatement of smallpox vaccination in the United States in response to possible bioterrorism renewed concerns about vaccine-related adverse neurologic events. Objective: To determine rates and describe the clinical features of neurologic events associated with smallpox vaccination. Design and Setting: We assessed reports of adverse events obtained through active case reporting and review of data reported to the Vaccine Adverse Event Reporting System among 665 000 persons vaccinated against smallpox by the Departments of Defense (n=590 400)and Health and Human Services (n=64 600) during the 2002- 2004 US Smallpox Vaccination Program. Main Outcome Measure: Adverse neurologic events temporally associated with smallpox vaccination. Results: Between December 16, 2002, and March 11, 2004, 214 neurologic adverse events temporally associated with smallpox vaccination were reported; 111 reports involved Department of Health and Human Services and 103 involved Department of Defense vaccinees. Fifty-four percent of these events occurred within 1 week of vaccination, and 53% were among primary vaccinees. The most common neurologic adverse event was headache (95 cases), followed by nonserious limb paresthesias (n=17) or pain (n=13) and dizziness or vertigo (n=13). Serious neurologic adverse events included 13 cases of suspected meningitis, 3 cases of suspected encephalitis or myelitis, 11 cases of Bell palsy, 8 seizures (including 1 death), and 3 cases of Guillain-Barré syndrome. Among these 39 events, 27 (69% ) occurred in primary vaccinees and all but 2 occurred within 12 days of vaccination. Conclusions: During the 2002- 2004 smallpox vaccination campaign, reported neurologic events were generally mild and selflimited, and no neurologic syndrome was identified at a rate above baseline estimates. Serious neurologic adverse events, such as postvaccinal encephalitis

关键词：天花疫苗神经系统

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：