慢性粒细胞白血病肿瘤干细胞的免疫调节功能

目的 研究慢性粒细胞白血病(CML)骨髓来源的肿瘤干细胞的免疫学特征,比较其与正常人来源的间充质干细胞(MSC)是否存在免疫功能的异常.方法 分离正常人和CML患者骨髓中的MSC,MLR法检测其对T细胞增殖的影响,流式细胞术检测其对T细胞周期、凋亡的作用情况.结果 CML和正常志愿者骨髓来源的MSC的细胞形态和表型没有差异,CML患者来源的MSC抑制T细胞增殖能力和抑制T细胞停留在G0/G1期的作用均减弱(CML MSC组74.5%±1.2%,BMSC组94.0%±1.9%,P＜0.05),CML患者抑制T细胞凋亡的作用增强(CMLMSC组8.36%±1.31%,BMSC组14.10%±0.65%,P＜0.05).结论 CML患者骨髓来源的MSC存在明显的免疫调节功能缺陷,如果使用CML患者自体的MSC移植治疗可能不是一种很好的选择,对于CML患者最好是选用异基因的MSC移植.     

慢性粒细胞白血病肿瘤干细胞的免疫功能

背景：研究认为间充质干细胞可能是骨髓造血微环境的免疫保护位点。由于慢性粒细胞白血病存在造血微环境异常和免疫异常,所以推测间充质干细胞可能在慢性粒细胞白血病的病理过程中扮演了一个重要角色。 目的：观察慢性粒细胞白血病骨髓来源的肿瘤干细胞的免疫学特征,比较其与正常人来源的间充质干细胞是否存在免疫功能的异常。 方法：分离正常人和慢性粒细胞白血病患者的骨髓间充质干细胞,分别检测它们对T细胞周期、活化、抑制和增殖的作用。 结果与结论：慢性粒细胞白血病和正常志愿者骨髓来源的间充质干细胞形态和表型没有差异,慢性粒细胞白血病患者来源的间充质干细胞抑制T细胞增殖的作用减弱,抑制T细胞周期及活化的能力减弱,慢性粒细胞白血病患者抑制T细胞凋亡的作用增强。提示慢性粒细胞白血病患者骨髓来源的间充质干细胞存在明显的免疫调节功能缺陷,如果使用慢性粒细胞白血病患者自体的间充质干细胞移植治疗可能不是一种很好的选择,对于骨髓增生异常综合征患者最好是选用异基因的间充质干细胞移植。     

骨髓增生异常综合征来源的间充质干细胞对T细胞亚群的影响

目的:观察骨髓增生异常综合征(MDS)患者来源的间充质干细胞(MSC)对混合淋巴细胞反应体系中的T淋巴细胞亚群的影响.方法:将MDS来源的MSC,按照不同比例加入双向混合淋巴细胞培养体系中共同孵育,3 d后采用流式细胞术(FCM)和ELISA法检测其表面抗原以及上清液中细胞因子的变化.结果:MDS来源的MSC能明显抑制共孵育体系中的CD8 +T细胞亚群和IFN-γ的分泌,轻度抑制IL- 4的分泌,与正常来源的MSC抑制性没有统计学意义.结论:MSC在体外能明显抑制CD8 +T细胞(CTL)和Th1细胞,轻度抑制Th2细胞.     

骨髓和脂肪来源的间充质干细胞免疫调节作用的比较研究

本研究中我们分离骨髓和脂肪的间充质干细胞,分别检测它们对T细胞周期、活化、抑制和增殖的作用情况,研究脂肪来源(adipose-derived mesenchemal stem cell,AMSC)和骨髓来源(bone marrow derived mesenchemal stem cell,BMSC)间充质干细胞的免疫学特征,比较它们是否存在免疫功能的差异,结果显示AMSC和BMSC均具有抑制T细胞增殖的能力,在有丝分裂原刺激和MLR的T细胞增殖中均具有剂量依赖性的,在1∶2时有极强的抑制作用,但是在1∶100时这种作用基本消失,在共培养时AMSC和BMSC都可使更多的T细胞被抑制在G0/G1期,同时也可以抑制T细胞的早期活化,但是上述作用AMSC均较BMSC弱,但是AMSC并不具有抑制T细胞凋亡的作用,而两者在Th0向Th1或Th2分化中所起的作用是基本相似的,主要抑制Th0向Th1细胞(IL-2和IFN-γ生成细胞)的分化,而对向Th2细胞(IL-4和IL-10生成细胞)分化没有明显的影响。所以,AMSC和BMSC具有类似的免疫调节作用,因AMSC取材方便而成为更佳的材料来源。     

骨髓和脂肪来源间充质干细胞的免疫调节作用

背景：脂肪来源的间充质干细胞是否具有和骨髓来源间充质干细胞类似的免疫调节作用? 目的：观察骨髓来源和脂肪来源间充质干细胞的免疫学特征。 方法：分离骨髓和脂肪来源的间充质干细胞,分别检测它们对T细胞周期、活化、抑制和增殖的作用情况。 结果与结论：骨髓来源和脂肪来源的间充质干细胞同样具有抑制T细胞增殖的能力,在有丝分裂原刺激和混合淋巴细胞反应的T细胞增殖中这种作用都是具有剂量依赖性的,在1︰2时有极强的抑制作用,但是在1︰100时这种作用基本消失,在共培养时骨髓来源和脂肪来源的间充质干细胞都可以使更多的T细胞被抑制在G0/G1期,同时也可以抑制T细胞的早期活化,但是上述作用脂肪来源的间充质干细胞均较骨髓来源间充质干细胞弱,且脂肪来源的间充质干细胞并不具有抑制T细胞凋亡的作用。     

骨髓间充质干细胞对肝病的治疗作用

骨髓间充质干细胞（MSCs）是一群具有多向分化潜能的成体干细胞,具有抑制T细胞活化、调节异体移植的免疫耐受等免疫特性。肝移植是各种晚期肝病的主要治疗方法,但由于器官来源的缺乏和伴随的免疫排斥反应,其应用受到限制。研究证明骨髓是肝祖细胞的来源之一,在一定的条件下,骨髓间充质干细胞能够分化为功能性肝细胞并分泌相关细胞因子,促进肝细胞的再生,为临床治疗各种肝损害提供了新的途径。     

骨髓间充质干细胞抑制再生障碍性贫血患者外周血T细胞增殖的实验研究

背景：既往研究发现骨髓间充质干细胞具有免疫抑制作用,而再生障碍性贫血患者存在T淋巴细胞异常活化及增殖。 目的：体外分析骨髓间充质干细胞对再生障碍性贫血患者外周血T淋巴细胞增殖的抑制作用。 方法：分离再生障碍性贫血患者外周血T淋巴细胞,行羧基荧光素乙酰乙酸琥珀酰亚胺酯(CFDA SE)荧光染色,与体外培养扩增的骨髓间充质干细胞按3︰1比例直接接触法及Transwell法共培养,加入植物血凝素(PHA)刺激T淋巴细胞增殖,并设阴性及阳性对照。流式细胞术检测各组T细胞增殖情况,评价骨髓间充质干细胞对T淋巴细胞增殖的影响。 结果与结论：CFDA SE染色分析显示,直接接触组T细胞增殖较阳性对照组明显减低(P < 0.01);Transwell组T细胞增殖亦较阳性对照组减低(P < 0.05);直接接触组T细胞增殖较Transwell组明显减低(P < 0.01)。骨髓间充质干细胞可能通过直接接触及分泌某些细胞因子方式抑制再生障碍性贫血患者异常增殖的T细胞,以直接接触方式发挥主要作用。     

骨髓增生异常综合征中的T细胞免疫

骨髓增生异常综合征(myelodysplastic syndromes,MDS)是一组肿瘤性疾病,以骨髓无效造血并向急性髓系白血病转化的风险为特点.流行病学显示自身免疫性疾病的患者发生MDS风险增加,为二者存在共同病因的假设提供了依据.MDS骨髓微环境中存在T细胞过度活化的现象.部分低危组MDS治疗药物具有抑制T细胞免疫机制,而高危组MDS的去甲基化药物则增强T细胞的抗肿瘤免疫反应,特别是免疫检查点抑制剂正在MDS中进行临床实验.因此,MDS中T细胞免疫失调的双重作用值得深思,充分认识T细胞免疫异常在M D S发病机制中的作用是形成新治疗方法的理论基础.     

人骨髓MSC对PHA活化T细胞周期以及表型和细胞因子分泌的影响

目的研究人骨髓间充质干细胞(MSC)对T细胞周期和活化的影响,探讨MSC对T细胞增殖抑制的作用机制。方法Ficoll密度梯度离心法分离纯化人骨髓MSC,体外扩增培养3代后用于实验。应用流式细胞术分析MSC对PHA作用下T细胞周期和早期表型CD25、CD69表达的影响,ELISA法检测细胞因子水平。结果人骨髓MSC体外可使PHA刺激下的T细胞滞留于细胞周期的G0/G1期,下调活化T细胞早期表型CD25、CD69的表达,抑制IL-2、IFN-r的分泌。结论人骨髓MSC体外可通过对T细胞周期的影响抑制其活化和增殖。     

骨髓和脂肪来源的间充质干细胞免疫调节作用的比较

目的比较脂肪源间充质干细胞(AMSCs)和骨髓来源间充质干细胞(BMSCs)的免疫调节能力的差异。方法用流式细胞仪分析AMSCs和BMSCs的表型。通过MSCs和淋巴细胞共培养体系,检测MSCs对T细胞增殖、周期、活化、凋亡以及Th细胞分化的影响。结果表型分析结果显示AMSCs和BMSCs的表型基本一致。AMSCs和BMSCs都能抑制T细胞的增殖和早期活化,并在调节辅助性T细胞亚群的分化上作用类似。但在MSC对活化后T细胞的凋亡影响方面,BMSCs能够抑制活化T细胞的凋亡,而AMSC没有这种作用。结论 AMSCs和BMSCs对T淋巴细胞的影响基本类似,其对活化T细胞凋亡影响的差异还有待进一步的机制研究。     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

HLA genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.     

État de l’art : nouveaux anticoagulants et transfusion

Direct oral anticoagulants (DOAC) are indicated for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism. As any anticoagulant, they are associated with a bleeding risk. Management of DOAC-induced bleeding is challenging. Idarucizumab, antidote for dabigatran, is currently available and is part of the therapeutic strategy, whereas antidotes for anti-Xa agents are under development. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. We propose an update on DOAC-associated bleeding management, integrating the availability of idarucizumab and the critical place of DOAC concentration measurements.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.