再生障碍性贫血骨髓及外周血高水平Flt3配体的来源及意义

目的：研究再生障碍性贫血（AA）患者骨髓及外周血高水平FL（Flt3配体）的来源和影响因素。方法：采用常规ELISA法测定AA患者骨髓和外周血FL含量，应用单色和双色免疫荧光标记流式细胞仪分析FL的分泌细胞及其受体Flt3的表达，并观察AA患者淋巴细胞经PHA激发后环胞菌（CyA)对FL分泌的影响。结果：AA患者骨髓和外周血FL含量显著升高，为正常的25倍以上，外周血和骨髓浓度无区别；正常人CD3^ 细胞内贮存有大量FL，而AA患者CD3^ 细胞以膜型FL为主，胞内基本无FL存在；淋巴细胞经PHA活化后可分泌FL，CyA可抑制FL的分泌，结论：AA患者骨髓和外周血FL水平显著升高，主要由CD^＋细胞产生。     

再生障碍性贫血患者骨髓及外周血T、NK细胞膜分子和可溶性分子动态变化

目的研究T淋巴细胞及免疫分子在再生障碍性贫血（AA）致病中的作用及其与临床疗效的相关性。方法应用免疫荧光染色技术和流式细胞仪分析AA骨髓及外周血T淋巴细胞表型，ELISA测定骨髓和外周血白介素-2及其可溶性受体（IL-2，sIL-2R）、可溶性Fas配体（sFas-L）和Flt3配体（FL）的水平。结果（1）AA病人骨髓和外周血CD8+细胞百分率增加，CD4/CD8比例下降；骨髓血CD25+和HLA-DR+细胞百分率增多，急性AA增加尤为显著（P<0.01）；骨髓血中CD16+或CD56+细胞百分率也明显增多（P<0.05）。（2）所有AA患者骨髓及外周血IL-2含量均显著升高，绝大部分患者的sFas-L含量增加，FL水平升高尤为显著，高达正常水平的20倍。IL-2、sFas-L和FL的含量与临床疗效密切相关，经治疗有效的患者骨髓和外周血的IL-2、sFas-L和FL水平明显下降，但FL仍不能降至正常水平。结论T细胞的异常活化，多种免疫分子表达的异常升高，以及产生针对自身造血干/祖细胞的细胞毒效应，是AA造血功能衰竭的主要原因。     

脂多糖肺损伤CD4~+T细胞及其亚型T_(H1)、T_(H2)细胞的凋亡

目的　观察CD4 + T细胞及其亚型TH1 、TH2 细胞的凋亡变化 ,从TH1 、TH2 凋亡的角度探讨脂多糖肺损伤时机体抗炎、致炎反应的分子机制。方法　静脉注射脂多糖制作大鼠脂多糖肺损伤模型。分离、提纯外周血与BALF中T淋巴细胞 ,抗大鼠CD4 FITC标记、流式细胞仪分选后 ,通过流式细胞仪检测及荧光显微镜检查 ,观察外周血与BALF中CD4 + T淋巴细胞凋亡变化 ;应用免疫组织化学技术及TUNEL法双染动态观察外周血与BALF中TH1 、TH2 细胞凋亡的变化。结果　①脂多糖 (LPS)致伤后 ,外周血与BALF中CD4 + T淋巴细胞进行性减少 ,与正常对照组比较差异非常显著 ,与该类细胞凋亡比例之间呈显著负相关关系 ,提示CD4 + T细胞呈时间依赖性凋亡性减少。地塞米松 (DEX)组与LPS组比较 ,CD4 + T细胞比例及凋亡百分数无显著差异 ;②LPS致伤后 ,外周血与BALF中IFN γ阳性细胞 (TH1 细胞 )与IL 4阳性细胞 (TH2 细胞 )数目均减少 ,与各自凋亡细胞的比例呈显著的负相关关系。DEX组IFN γ阳性细胞、IL 4阳性细胞数目均减少 ,IFN γ阳性细胞中凋亡细胞的百分数明显增加 ,与对照组比较差异非常显著 (P <0 .0 1)。IL 4阳性细胞中凋亡细胞的百分数亦增加 ,但幅度小于IFN γ阳性细胞。LPS致伤后 ,大鼠肺组织水肿及炎性病变程度进行性加重 ,     

IFN-α联合GM-CSF在无血清培育条件下诱生DC的研究

本研究分别采用IFN α联合粒单系集落刺激因子 (GM CSF)及IL 4联合GM CSF在无血清培育条件下从正常人及多发性骨髓瘤 (MM)患者外周血单个核细胞中诱生树突状细胞 (DC) ,并对其形态、功能及免疫表型进行比较。结果表明IFN α联合GM CSF能与IL 4联合GM CSF同样有效地诱导产生DC ,所得的DC在形态、免疫表型及功能上无明显差异 (P >0 0 5 ) ,正常人和MM患者的外周血单个核细胞经诱生所获得的DC在免疫表型及功能上亦无明显差异 (P >0 0 5 )。     

细胞因子诱导不同来源的贴壁细胞分化为树突状细胞的研究

通过贴壁的方法分离胚肝、脐带血、造血动员后的外周血及正常人外周血中的树突状细胞 (DC )的前体细胞 ,体外采用细胞因子诱导 ,并对其进行形态学观察和细胞表型分析 ;同时比较了不同来源DC的增殖、分泌IL 12的能力及激发同种异体T细胞和脐带血幼稚型T细胞 (naiveTcell)的作用。实验结果表明 ,经过造血动员后的外周血细胞产生的DC数量和纯度均较高 ,而且能经体外细胞因子诱导为功能性DC ,是较理想的DC来源     

CD4~+T细胞亚群在再生障碍性贫血中的作用及机制

再生障碍性贫血(AA)是一组多种原因引起的骨髓造血功能衰竭,主要表现为全血细胞减少的综合征。CD4+T淋巴细胞在AA发病中发挥更重要作用,AA患者中Th1细胞的极化、Th17细胞的高表达及调节性T细胞(Treg)数量的减少,都与AA的发病密切相关。Th1细胞的极化和Th17细胞/Treg比例的失衡,T细胞异常活化,导致骨髓造血细胞的凋亡,也是目前AA研究的热点之一。Th22细胞的增多、Th9细胞的双向性生物学效应、滤泡辅助T细胞的辅助作用及各亚群之间的相互作用,也都提示了CD4+T细胞亚群参与AA的发病。本文在分析各亚群生物学特性和功能的基础上,重点阐述CD4+T细胞亚群与AA发病关系的研究进展。     

类风湿性关节炎患者外周血细胞内IFN-γ和IL-4的三色流式分析

目的　用全血在单个细胞水平上研究类风湿性关节炎 (RA)患者TH1 TH2 细胞因子分泌模式及其与疾病活动程度的关系。方法　用三色流式细胞术检测RA患者外周血细胞内细胞因子IFN γ和IL 4的表达情况。结果　RA患者外周血IFN γ 细胞百分率及IFN γ /IL 4 细胞比值比健康人明显增高 ,IFN γ /IL 4 比值与患者Stoke指数呈正相关 (r=0 .86 10 ,P <0 .0 1)。结论　RA患者外周血中细胞因子分泌模式朝TH1 偏移 ,IFN γ /IL 4 比值与疾病活动性相关 ,TH1 TH2 平衡在RA发病机理及疾病进程中起重要作用     

Flt3配基的生物学特性研究进展

Flt3配基(FL)是一种新近发现的、能够刺激早期造血的细胞因子。该因子通过与造血干细胞表面酪氨酸激酶受体3(Flt3)结合,刺激造血干细胞的增殖和分化,增加淋巴细胞、树突状细胞(DC)、自然杀伤(NK)细胞及体外长期培养的干细胞等的数量。若与其它造血细胞因子合用,FL的作用可以得到明显加强。最近的研究还发现,FL通过促进体内DC、NK细胞、细胞毒T细胞(CTL)的增殖、分化和成熟,发挥抗肿瘤作用。本文对FL的基因克隆及蛋白质结构作一简单介绍,并重点对近年来FL生物学特性研究状况作一综述。     

Flt3配体研究进展

Flt3配体 (FL)是新近发现的、能够刺激早期造血的细胞因子。该因子通过与酪氨酸激酶受体 3(Flt30 )结合 ,刺激造血干细胞的增殖和分化 ,增加淋巴细胞、树突状细胞 (DC)、自然杀伤 (NK)细胞及体外长期培养的干细胞等的数量。最近的研究还发现 ,FL通过促进体内DC、NK细胞、细胞毒T细胞 (CTL)的增殖、分化和成熟 ,发挥抗肿瘤作用。本文对FL的基因克隆及蛋白质结构作一简单介绍 ,并重点对近年来FL生物学特性研究状况作一综述。     

人骨髓瘤单核细胞系(M20)分泌白细胞介素1抑制因子

在体外培养骨髓瘤单核细胞系(M20)的上清液具有抑制白细胞介素1(IL1)的活性。从其上清液中分离出一种因子,该因子能抑制由IL1诱导的小鼠胸腺细胞对PHA反应的增殖,也能抑制依赖IL1的淋巴细胞和成纤维细胞的增殖,但不能抑制IL2诱导的或与IL1无关的其它细胞增殖反应。从正常人外周血单个核细胞(PBMC)     

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.     

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.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

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.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.