Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregn...Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites.In species with invasive hemochorial placentation,these uterine natural killer(uNK)cells,via secretion of cytokines,chemokines,mucins,enzymes and angiogenic growth factors,contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis.In humans,uNK cells have the phenotype CD56^(bright) CD16^(dim) and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy.Gene expression studies indicate that CD56^(bright) CD16^(dim) uterine and circulating cells are functionally distinct.In humans but not mice or other species with post-implantation decidualization,uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility.Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function,achieved via interferon(IFN)-c secretion.During spiral arterial modification,branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict.The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance,high-volume channels.Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women.Here we briefly review key information concerning uNK cell functions from studies in rodents,summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized,pregnant mouse model for in vivo investigations of human 展开更多
Humanized mouse models that have received human cells or tissue transplants are extremely useful in basic and applied human disease research. Highly immunodeficient mice, which do not reject xenografts and support cel...Humanized mouse models that have received human cells or tissue transplants are extremely useful in basic and applied human disease research. Highly immunodeficient mice, which do not reject xenografts and support cell and tissue differentiation and growth, are indispensable for generating additional appropriate models. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rynull gene （e.g., NOD/SCID/7c＂uu and Rag2nu＂ycnun mice）. These strains show not only a high rate of human cell engraftment, but also generate well-differentiated multilineage human hematopoietic cells after human hematopoietic stem cell （HSC） transplantation. These humanized mice facilitate the analysis of human hematology and immunology in vivo. However, human hematopoietic cells developed from HSCs are not always phenotypically and functionally identical to those in humans. More recently, a new series of immunodeficient mice compensates for these disadvantages. These mice were generated by genetically introducing human cytokine genes into NODISCIDI？cn＂u and Rag2nulITcnUll mice. In this review, we describe the current knowledge of human hematopoietic cells developed in these mice. Various human disease mouse models using these humanized mice are summarized.展开更多
A robust animal model for "hypothesis-testing/mechanistic" research in human immunology and immuno-pathology should meet the following criteria.First,it has well-studied hemato-lymphoid organs and target cel...A robust animal model for "hypothesis-testing/mechanistic" research in human immunology and immuno-pathology should meet the following criteria.First,it has well-studied hemato-lymphoid organs and target cells similar to those of humans.Second,the human pathogens establish infection and lead to relevant diseases.Third,it is genetically inbred and can be manipulated via genetic,immunological and pharmacological means.Many human-tropic pathogens such as HIV-1 fail to infect murine cells due to the blocks at multiple steps of their life cycle.The mouse with a reconstituted human immune system and other human target organs is a good candidate.A number of human-mouse chimeric models with human immune cells have been developed in the past 20 years,but most with only limited success due to the selective engraftment of xeno-reactive human T cells in hu-PBL-SCID mice or the lack of significant human immune responses in the SCID-hu Thy/Liv mouse.This review summarizes the current understanding of HIV-1 immuno-pathogenesis in human patients and in SIV-infected primate models.It also reviews the recent progress in the development of humanized mouse models with a functional human immune system,especially the recent progress in the immunodeficient mice that carry a defective gammaC gene.NOD/SCID/gammaC-/(NOG or NSG) or the Rag2-/-/gammaC-/double knockout (DKO) mice,which lack NK as well as T and B cells (NTB-null mice),have been used to reconstitute a functional human immune system in central and peripheral lymphoid organs with human CD34+ HSC.These NTB-hu HSC humanized models have been used to investigate HIV-1 infection,immuno-pathogenesis and therapeutic interventions.Such models,with further improvements,will contribute to study human immunology,human-tropic pathogens as well as human stem cell biology in the tissue development and function in vivo.展开更多
目的探讨人性化情感干预对慢性精神分裂症患者的康复效果。方法将118例慢性精神分裂症患者根据入院时间分为观察组和对照组各59例,对照组采用传统护理模式,观察组按计划实施人性化情感干预护理,具体包括医院支持、社会支持及社会活动三...目的探讨人性化情感干预对慢性精神分裂症患者的康复效果。方法将118例慢性精神分裂症患者根据入院时间分为观察组和对照组各59例,对照组采用传统护理模式,观察组按计划实施人性化情感干预护理,具体包括医院支持、社会支持及社会活动三方面。分别于入院15d及入院60d采用阴性症状量表(scale for assessment of negative symptoms,SANS)、简明精神病量表(brief psychiatric rating scale,BPRS)及住院患者护士观察量表(nurses’observation scale for inpatient evaluation,NOSIE)评定两组患者的干预效果。结果入院后60d,除思维贫乏外,观察组患者SANS总分及各因子分均低于对照组;BPRS总分及思维障碍、活动障碍因子分低于对照组;NOSTE总分及积极因子分高于对照组,消极因子分低于对照组,差异均有统计学意义(P<0.05)。结论人性化情感干预能降低慢性精神分裂症患者的焦虑、抑郁症状,使患者感受到社会和家庭的关怀,促使患者走出自我封闭状态。展开更多
基金These studies were supported by awards from the Natural Sciences and Engineering Research Council,Canada,the Canadian Institutes of Health Research and the Canada Research Chairs Program to BAC and a Province of Ontario/Queen’s Postdoctoral Fellowship award to JHZ.
文摘Natural killer(NK)cells are found in lymphoid and non-lymphoid organs.In addition to important roles in immune surveillance,some NK cells contribute to angiogenesis and circulatory regulation.The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites.In species with invasive hemochorial placentation,these uterine natural killer(uNK)cells,via secretion of cytokines,chemokines,mucins,enzymes and angiogenic growth factors,contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis.In humans,uNK cells have the phenotype CD56^(bright) CD16^(dim) and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy.Gene expression studies indicate that CD56^(bright) CD16^(dim) uterine and circulating cells are functionally distinct.In humans but not mice or other species with post-implantation decidualization,uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility.Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function,achieved via interferon(IFN)-c secretion.During spiral arterial modification,branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict.The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance,high-volume channels.Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women.Here we briefly review key information concerning uNK cell functions from studies in rodents,summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized,pregnant mouse model for in vivo investigations of human
文摘Humanized mouse models that have received human cells or tissue transplants are extremely useful in basic and applied human disease research. Highly immunodeficient mice, which do not reject xenografts and support cell and tissue differentiation and growth, are indispensable for generating additional appropriate models. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rynull gene （e.g., NOD/SCID/7c＂uu and Rag2nu＂ycnun mice）. These strains show not only a high rate of human cell engraftment, but also generate well-differentiated multilineage human hematopoietic cells after human hematopoietic stem cell （HSC） transplantation. These humanized mice facilitate the analysis of human hematology and immunology in vivo. However, human hematopoietic cells developed from HSCs are not always phenotypically and functionally identical to those in humans. More recently, a new series of immunodeficient mice compensates for these disadvantages. These mice were generated by genetically introducing human cytokine genes into NODISCIDI？cn＂u and Rag2nulITcnUll mice. In this review, we describe the current knowledge of human hematopoietic cells developed in these mice. Various human disease mouse models using these humanized mice are summarized.
基金supported by the National Natural Science Foundation of China (Grant No. 30872365)the Ministry of Science and Technology Grants (Grant Nos. 2006CB910901 and KSCX2-YW-R-150)+1 种基金the Ministry of Health (Grant Nos. 2009ZX10604 and 2008ZX10002-011)the National Institute of Health (Grant Nos. AI080432, AI041356, AA018009 and AI077454)
文摘A robust animal model for "hypothesis-testing/mechanistic" research in human immunology and immuno-pathology should meet the following criteria.First,it has well-studied hemato-lymphoid organs and target cells similar to those of humans.Second,the human pathogens establish infection and lead to relevant diseases.Third,it is genetically inbred and can be manipulated via genetic,immunological and pharmacological means.Many human-tropic pathogens such as HIV-1 fail to infect murine cells due to the blocks at multiple steps of their life cycle.The mouse with a reconstituted human immune system and other human target organs is a good candidate.A number of human-mouse chimeric models with human immune cells have been developed in the past 20 years,but most with only limited success due to the selective engraftment of xeno-reactive human T cells in hu-PBL-SCID mice or the lack of significant human immune responses in the SCID-hu Thy/Liv mouse.This review summarizes the current understanding of HIV-1 immuno-pathogenesis in human patients and in SIV-infected primate models.It also reviews the recent progress in the development of humanized mouse models with a functional human immune system,especially the recent progress in the immunodeficient mice that carry a defective gammaC gene.NOD/SCID/gammaC-/(NOG or NSG) or the Rag2-/-/gammaC-/double knockout (DKO) mice,which lack NK as well as T and B cells (NTB-null mice),have been used to reconstitute a functional human immune system in central and peripheral lymphoid organs with human CD34+ HSC.These NTB-hu HSC humanized models have been used to investigate HIV-1 infection,immuno-pathogenesis and therapeutic interventions.Such models,with further improvements,will contribute to study human immunology,human-tropic pathogens as well as human stem cell biology in the tissue development and function in vivo.
文摘目的探讨人性化情感干预对慢性精神分裂症患者的康复效果。方法将118例慢性精神分裂症患者根据入院时间分为观察组和对照组各59例,对照组采用传统护理模式,观察组按计划实施人性化情感干预护理,具体包括医院支持、社会支持及社会活动三方面。分别于入院15d及入院60d采用阴性症状量表(scale for assessment of negative symptoms,SANS)、简明精神病量表(brief psychiatric rating scale,BPRS)及住院患者护士观察量表(nurses’observation scale for inpatient evaluation,NOSIE)评定两组患者的干预效果。结果入院后60d,除思维贫乏外,观察组患者SANS总分及各因子分均低于对照组;BPRS总分及思维障碍、活动障碍因子分低于对照组;NOSTE总分及积极因子分高于对照组,消极因子分低于对照组,差异均有统计学意义(P<0.05)。结论人性化情感干预能降低慢性精神分裂症患者的焦虑、抑郁症状,使患者感受到社会和家庭的关怀,促使患者走出自我封闭状态。
