055 TOLL样受体家族与LPS信号转导

细菌脂多糖(LPS)可激活巨噬细胞、内皮细胞等引起一些炎症介质的释放,最终可导致机体的损伤甚至休克死亡.在这一过程中LPS如何被机体细胞识别并启动细胞反应已引起高度重视.十几年来研究已明确LBP/CD14、CD11/CD18可使LPS解聚并被运送和结合到细胞表面,但是这些分子缺乏信号转导的功能.近二三年发现了一种功能性的LPS跨膜受体--Toll样受体家族.Toll样受体被认为是其它LPS受体的协同受体或接头受体(adaptor receptor),正是这种受体直接将LPS的刺激信号向细胞内传递,其胞浆区具有与IL-1受体同源的结构,其作用涉及炎症因子主要是细胞因子级联反应中的基因激活及反应基因的调节.     

TLR4与糖尿病肾病的研究进展

糖尿病肾病(diabetic nephropathy,DN)的发病机制尚不明确,近年来大量研究表明,Toll样受体4(Toll-like receptor 4,TLR4)与DN密切相关.TLR4通过髓样分化因子88(myeloid differentiation factor 88,MyD88)依赖性和非依赖性等途径激活下游信号分子,引发一系列的炎症反应,最终导致DN的发生与发展.     

TOLL样受体家族与LPS信号转导

细菌脂多糖 (LPS)可激活巨噬细胞、内皮细胞等引起一些炎症介质的释放 ,最终可导致机体的损伤甚至休克死亡。在这一过程中LPS如何被机体细胞识别并启动细胞反应已引起高度重视。十几年来研究已明确LBP CD14、CD11 CD18可使LPS解聚并被运送和结合到细胞表面 ,但是这些分子缺乏信号转导的功能。近二三年发现了一种功能性的LPS跨膜受体———Toll样受体家族。Toll样受体被认为是其它LPS受体的协同受体或接头受体 (adaptorreceptor) ,正是这种受体直接将LPS的刺激信号向细胞内传递 ,其胞浆区具有与IL 1受体同源的结构 ,其作用涉及炎症因子主要是细胞因子级联反应中的基因激活及反应基因的调节     

Toll样受体4信号转导研究进展

Toll样受体4(TLR4)作为LPS信号转导受体,在与LPS反应时可形成一个由TLR4和MD 2构成的复合体,其在细胞内的信号转导依赖于不同的接头蛋白。在早期反应时,TLR4依赖MyD88和Mal可导致NF кB激活;而在后期反应中,通过TRIF和TRAM可引起NF кB和IRF3的迟发激活。由此诱导细胞因子、化学趋化因子和其他转录因子的表达。     

LPS受体及信号转导研究进展

内毒素脂多糖 (L PS)可激活单核 /巨噬细胞 ,产生一系列炎症反应 ,而 L PS跨膜信号转导是引起细胞效应的关键。本文主要综述 L PS结合蛋白 (L BP) ,L PS受体 (m CD14、s CD14 )以及 Toll样受体 (TL Rs)在 L PS激活细胞及信号跨膜传递中的重要作用。推测 L PS/L BP与细胞膜 CD14结合后 ,TL Rs以细胞外富含亮氨酸片段的重复序列识别 L PS,将 L PS的刺激信号跨膜转导 ,激活 NF- κB信号途径导致效应基因的表达     

人类Toll样受体信号转导途径及其介导的免疫作用

人类Toll样受体（TLR）是近年来发现的一类新的细胞表面信号传导跨膜受体,是人体固有免疫和适应性免疫的桥梁。TLR4组织分布较广泛,激活后通过TLR4-NF-κB信号途径促进细胞因子合成、激活T细胞、调节Th1／Th2免疫反应的平衡,从而调节机体的免疫状态。进一步研究TLR4的信号转导途径及其在疾病发展过程中的表达情况,可以为临床预防和治疗疾病提供新的思路和方法。     

TOLL样受体家族与LPS信号转导

细菌脂多糖（LPS）可激活巨噬细胞、内皮细胞等引起一些炎症介质的释放,最终可导致机体的损伤甚至休克死亡。在这一过程中LPS如何机体细胞识别并启动细胞反应已引起高度重视。十几年来研究已明确LBP／CD14、CD11／CD18可使LPS解聚并被运送和结合到细胞表面,但是这些分子缺乏信号转导的功能。近二三年发现了一种功能性的LPS跨膜受体－－Toll样受体家族。Toll样受体被认为是其它LPS受体的协同受体或接头受体（adaptor receptor）,正是这种受体直接将LPS的刺激信号向细胞内传递,其胞浆区具有与IL－1受体同源的结构,其作用涉及炎症因子主要是细胞因子级联反应中的基因激活及反应基因的调节。     

024 Toll样受体-一个新发现的介导天然免疫的古老家族(上)

Toll样蛋白是近年在人和小鼠细胞上发现的跨膜信号传递受体家族,它在进化上高度保守.本文介绍了它在人类的家族成员、组织表达分布和分子结构特征,重点介绍了TLR2、TLR4的胞内信号转导途径.     

LPS诱导的EGFR活化促进肠上皮细胞中COX-2的表达

坏死性小肠结肠炎(necrotizing enterocolitis,NEC)是一种由于对菌群的过度炎症反应而导致肠坏死的新生儿疾病,是导致早产儿死亡的主要肠道疾病。细菌脂多糖(lipopolysaccharide,LPS)通过Toll样受体4(Toll-like receptor 4,TLR4)调节炎症反应,是NEC发病机制的关键分子。然而,LPS也诱导环氧合酶-2(cyclooxygenase-2,COX-2)的生成,COX-2能通过影响肠细     

Toll样受体—一个新发现的介导天然免疫的古老家族(上)

Toll样蛋白是近年在人和小鼠细胞上发现的跨膜信号传递受体家族 ,它在进化上高度保守。本文介绍了它在人类的家族成员、组织表达分布和分子结构特征 ,重点介绍了TLR2、TLR4的胞内信号转导途径     

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.     

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.     

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.     

'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 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.