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Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in mS and EAE

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世界最新医学信息文摘 2016年第11期 8-8页

作者： marloes van Zwam Ruth Huizinga marie-José melief Annet F.wierenga-wolf marjan van meurs Jane S.Voerman Knut P.H.Biber hendrikus w.g.m.boddeke Uta E.H?pken Christian meisel Andreas meisel Ingo Bechmann Rogier Q.Hintzen Bert A.‘t Hart Sandra Amor Jon D.Laman Leonie A.Boven

Drainage of central nervous system(CNS) antigens to the brain-draining cervical lymph nodes(CLN) is likely crucial in the initiation and control of autoimmune responses during multiple sclerosis(mS). we demonstrate neuronal antigens within CLN of mS patients. In monkeys and mice with experimental autoimmune encephalomyelitis(EAE) and in mouse models with non-inflammatory CNS damage, the type and extent of CNS damage was associated with the frequencies of CNS antigens within the cervical lymph nodes. In addition, CNS antigens drained to the spinal-cord-draining lumbar lymph nodes. In human mS CLN, neuronal antigens were present in pro-inflammatory antigen-presenting cells(APC), whereas the majority of myelincontaining cells were anti-inflammatory. This may reflect a different origin of the cells or different drainage mechanisms. Indeed, neuronal antigen-containing cells in human CLN did not express the lymph node homing receptor CCR7, whereas myelin antigen-containing cells in situ and in vitro did. Nevertheless, CLN from EAE-affected CCR7-deficient mice contained equal amounts of myelin and neuronal antigens as wild-type mice. we conclude that the type and frequencies of CNS antigens within the CLN are determined by the type and extent of CNS damage. Furthermore, the presence of myelin and neuronal antigens in functionally distinct APC populations within mS CLN suggests that differential immune responses can be evoked.

关键词： Neuroinflammation Immune regulation Autoreactive Tcells Tolerance Chemokines Cytokines

Design and implementation of a platform for configuring clinical dynamic safety checklist applications

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Frontiers of Information Technology & Electronic Engineering 2018年第7期19卷 937-946页

作者： Shan NAN Xu-dong LU Pieter VAN gORP hendrikus H.m.KORSTEN Richard VDOVJAK Uzay KAYmAK Hui-long DUAN Department of Biomedical Engineering Zhejiang University Hangzhou 310027 China School of Industrial Engineering Eindhoven University of Technology Eindhoven 5600 MB the Netherlands Department of Aneasthiaology and Intensive-Care Catharina Ziekenhuis Eindhoven 5623 E J the Netherlands Philips Research Eindhoven Eindhoven 5656 AE the Netherlands

In recent years, it has been demonstrated that checklists can improve patient safety significantly. To facilitate the effective use of checklists in daily practice, both the medical community and the informatics community propose to implement checklists in dynamic checklist applications that can be integrated into the clinical workflow and that is specific to the patient context. However, it is difficult to develop such applications because they are tightly intertwined with the content of specific checklists. we propose a platform that enables access to dynamic checklist applications by configuring the infrastructures provided in the platform. Then, the applications can be developed without time-consuming programming work. we define a number of design criteria regarding point of care and clinical processes by analyzing the existing checklist applications and the lessons learned from ***, by applying rule-based clinical decision support and workflow management technologies, we design technical mechanisms to satisfy the design criteria. A dynamic checklist application platform is designed based on these mechanisms. Finally, we build a platform in various design cycle iterations, driven by multiple clinical cases. By applying the platform, we develop nine comprehensive dynamic checklist applications with 242 dynamic *** results demonstrate both the feasibility and the overall generic nature of the proposed approach. we propose a novel platform for configuring dynamic checklist applications. This platform satisfies the general requirements and can be easily configured to satisfy different scenarios in which safety checklists are used.

关键词： Checklist workflow Clinical decision support Process management Patient safety

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Unspecified live kidney donation by urological patients

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world Journal of Transplantation 2020年第8期10卷 215-222页

作者： Sebastiaan Ceuppens hendrikus J A N Kimenai Karel w J Klop willij C Zuidema michiel g H Betjes willem weimar Jan N m IJzermans Frank J m F Dor Robert C minnee Division of Transplant Surgery Department of SurgeryErasmus MC University Medical CenterRotterdam 3015GDNetherlands Department of Internal medicine Nephrology and Kidney Transplant UnitRotterdam 3000CANetherlands Imperial College Renal and Transplant Unit Hammersmith HospitalImperial College Healthcare NHS TrustLondon W120HSUnited Kingdom

BACKgROUND Individuals with benign kidney disorders undergoing nephrectomy have three possibilities:Autotransplantation,with a certain risk of complications,but without a clear benefit;discarding the kidney;or living kidney *** To investigate whether patients with benign kidney disorders and a medical indication for nephrectomy are suitable as unspecified live kidney *** we searched all clinical data from 1994-2019 for unspecified donors and their transplant recipients(n=160).Nine of these 160 donors had pre-existing kidney disorders necessitating nephrectomy and had decided to donate their kidney anonymously after discussing the possibility of kidney *** studied the clinical course of these nine donating patients and their transplant *** Seven of nine donating patients indicated unbearable loin pain as the main complaint,one donating patient refused ureterocutaneostomy and one had two aneurysms of the renal ***,seven donating patients described absence of pain and one a significant reduction after the *** average 1-year creatinine level in the donating patients was 88μmol/L and after a median of 6.9 years the average creatinine level was 86.6μmol/*** the transplant recipients,one major complication occurred which led to death and in one transplant recipient graft function failed to normalize at first but has been stable for nine years ***,all transplant recipients are off *** Our data show that patients undergoing nephrectomy as part of treatment in selected kidney disorders can function as live kidney donors.

关键词： Unspecified donor Live kidney donation Benign kidney disorder Living donors Kidney Transplantation

公元前44—前31年间罗马与喀尔基斯关系析论

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上海师范大学学报（哲学社会科学版） 2020年第1期49卷 134-141页

作者： H.A.m.范韦理克北京大学历史系北京100871

公元前2世纪末到前1世纪初,塞琉古王朝的崩溃使近东变成了一块由众多弱小王国和公国组成的“拼图”。每一个小国的外交事务都被比其更大更强的临近政治实体——罗马和帕提亚操控,喀尔基斯公国即这些被操控的弱小国家中的一个。尽管在公... 详细信息

公元前2世纪末到前1世纪初,塞琉古王朝的崩溃使近东变成了一块由众多弱小王国和公国组成的“拼图”。每一个小国的外交事务都被比其更大更强的临近政治实体——罗马和帕提亚操控,喀尔基斯公国即这些被操控的弱小国家中的一个。尽管在公元前1世纪60年代中期,庞培已经将喀尔基斯牢牢地纳入了罗马的势力范围,但公元前1世纪50年代帕提亚王国的壮大又重新动摇了喀尔基斯统治者对罗马的忠诚,这种动摇在前44年至前31年的罗马内战期间体现得尤为明显。关注喀尔基斯公国对罗马摇摆不定的忠诚及其带来负面影响,同时,描绘两者之间的政治关系,可以阐明历史上罗马统治的基本特质:罗马帝国并非像现代国家那样拥有明确的疆域,它指的是罗马势力影响所及的范围;该范围囊括众多与之结盟的弱小王国和公国,罗马在其中拥有不同程度的权威。

关键词：喀尔基斯帕提亚罗马共和国附庸国统治者

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Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in mS and EAE

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世界最新医学信息文摘 2017年第30期 281-281页

Drainage of central nervous system(CNS) antigens to the brain-draining cervical lymph nodes(CLN) is likely crucial in the initiation and control of autoimmune responses during multiple sclerosis(mS).we demonstrate neuronal antigens within CLN of mS *** monkeys and mice with experimental autoimmune encephalomyelitis(EAE) and in mouse models with non-inflammatory CNS damage,the type and extent of CNS damage was associated with the frequencies of CNS antigens within the cervical lymph *** addition,CNS antigens drained to the spinal-cord-draining lumbar lymph *** human mS CLN,neuronal antigens were present in pro-inflammatory antigen-presenting cells(APC),whereas the majority of myelincontaining cells were *** may reflect a different origin of the cells or different drainage ***,neuronal antigen-containing cells in human CLN did not express the lymph node homing receptor CCR7,whereas myelin antigen-containing cells in situ and in vitro ***,CLN from EAE-affected CCR7-deficient mice contained equal amounts of myelin and neuronal antigens as wild-type *** conclude that the type and frequencies of CNS antigens within the CLN are determined by the type and extent of CNS ***,the presence of myelin and neuronal antigens in functionally distinct APC populations within mS CLN suggests that differential immune responses can be evoked.

关键词： Neuroinflammation Immune regulation Autoreactive Tcells Tolerance Chemokines Cytokines

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肥胖轻度影响人类吸入麻醉药的药物动力学

麻醉与镇痛 2010年第1期6卷 9-15页

作者： hendrikus J. m. Lemmens Lawrence J. Saidman Edmond I Eger, II michael J. Laster 徐诚实(译) 岳云(校) Department of Anesthesia Stanford University School of Medicine Stanford California the Department of Anesthesia and Perioperative Care Universi of California San Francisco California 不详

背景很少有研究确定肥胖对吸入麻醉药药物动力学的影响。我们假设肥胖患者体重指数（BmI）的增加与强效吸入麻醉药在脂肪中的溶解度之间的相互影响，可能增加麻醉药的摄取量和减慢麻醉药输出浓度（FD）和吸入浓度（FI）达到稳态肺泡内... 详细信息

背景很少有研究确定肥胖对吸入麻醉药药物动力学的影响。我们假设肥胖患者体重指数（BmI）的增加与强效吸入麻醉药在脂肪中的溶解度之间的相互影响，可能增加麻醉药的摄取量和减慢麻醉药输出浓度（FD）和吸入浓度（FI）达到稳态肺泡内的浓度（FA或潮气量末浓度）的速率该假设提示肥胖对于易溶性麻醉药的影响更大（如异氟烷和地氟烷比较）。方法107例患者，ASA分级Ⅰ～Ⅲ级，应用丙泊酚诱导，注射肌肉松弛刺行气管插管，直用50％氧化亚氮行控制通气，呼气未二氧化碳维持在35—45mmHg之间．以1L／min的流量给予异氧皖或地氧烷，使其FD浓度足以维持FA在0．6mAC（兮别为0．7％或3．7％），分别于开始吸入麻醉药后5、10、20、40、60、90、120、150和180分钟时测定FD、FI及FA。结果59例患者接受异氟烷，48例患者接受地氟烷。体重指数在18～63kg／m^2之间，各麻醉组之间人口统计学变量无差异。对异氟烷而言，FD／FA或FI／FA在18个时间点中有9个与体重指数（BmI）轻微（但显著）相关，而对于地氟烷来说，FD／FA或FI／FA仅有一个时间点与体重指数（BmI）明显相关（P〈0.01）。将每组分为非肥胖患者（BmI〈30）和肥胖患者（BmI〉／30）后，应用异氟烷时肥胖患者的FD／FA或FI／FA在4个时间点较高，而非肥胖细和应用地氟烷者之间无差异。接受异氟烷的患者麻醉停药后对指令的反应时间较长，而肥胖者异氟烷和地氟烷的唤醒时间均未延长或缩短、运用BmI来标准化FI／FA和FD／FA后，异氟烷的中位数均高于地氟烷的中位数3到5倍，在血／气分配系数（3．1）、肌肉／气分配系数（4．6）、脂肪／气配配系数（5．4）的比值上具有可比性。结论BmI轻度影响FI／FA和FD／FA，麻醉药在所有组织中溶解度较大时该效应最为显著。BmI增加会增强麻醉药摄取从而增大维持肺泡内麻醉药浓度稳态时麻醉药的需要量，尤其是应用易溶性麻醉药时。但是，随着体重增加而增加的量并不大。

关键词：吸入麻醉药肥胖患者药物动力学血/气分配系数吸入浓度体重指数人类氧化亚氮

Towards medical imaging of drug photoactivation:Development of light responsive magnetic resonance imaging and chemical exchange saturation transfer contrast agents

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Smart Molecules

Smart molecules 2024年第2期2卷 129-138页

作者： Ilse m.welleman Carlijn L.F.van Beek Ioana Belcin Albert m.Schulte Rudi A.J.O.Dierckx Ben L.Feringa hendrikus H.Boersma wiktor Szymański Department of Radiology Medical Imaging CenterUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands Stratingh Institute for Chemistry University of GroningenGroningenThe Netherlands Department of Clinical Pharmacy and Pharmacology Nuclear Medicine and Molecular ImagingUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands

In recent years,the use of light to selectively and precisely activate drugs has been developed along the fundamental concepts of *** of the key methods in this field relies on transiently silencing the drug activity with photocleavable protecting groups(PPgs).To effectively utilize light-activated drugs in future medical applications,physicians will require a reliable method to assess whether light penetrates deep enough into the tissues to activate the photoresponsive theragnostic ***,we describe the development and evaluation of magnetic resonance(mR)imaging agents that allow for the detection of light penetration and drug activation in the tissues using non-invasive whole-body magnetic resonance imaging(mRI)and chemical exchange saturation transfer(CEST)-mRI *** approach relies on the use of PPg-protected mR contrast agents,which upon irradiation with light change their imaging signal.A gadolinium(III)-based mRI contrast agent is presented that undergoes a significant change in relaxivity(25%)upon uncaging,providing a reliable indicator of lightinduced cargo ***,we introduce the first light-responsive CESTmRI imaging agent,enabling positive signal enhancement(off-to-on)upon light activation,offering a novel approach to visualize the activation of photoactive agents in living *** research provides a proof-of-principle for the noninvasive,whole-body imaging of light penetration and drug activation with high temporal resolution characteristic of mR methods.

关键词： CEST mRI photochemistry photocleavable protecting groups photopharmacology