免疫细胞的代谢重编程及其对免疫功能的影响

免疫细胞代谢机制研究是免疫代谢研究的一个重要方向。免疫细胞在增殖、分化以及效应功能的执行等过程中会发生代谢重编程现象。本文综述了不同类型的免疫细胞静息或激活状态下的代谢通路。     

三种脂溶性维生素的免疫调节作用及其研究进展

维生素A、维生素D和维生素E是主要的三种脂溶性维生素,通常人们只认识到它们预防夜盲症、促进骨骼生长和抗衰老等一些营养保健作用,而对其刺激免疫细胞、调节细胞因子和增强免疫功能等方面的作用及其重要性却知之甚少.近年来研究表明:维生素A是T细胞生长、分化、激活过程中不可缺少的因子,其对体液免疫和细胞免疫都有明显的促进作用;维生素D[1,25(OH)2D3]是一种新的神经内分泌一免疫调节激素,对组织和细胞均有影响,主要对细胞免疫具有重要的调节作用;而维生素E则增强了免疫系统的功能,可以降低机体对传染病和肿瘤的易感性.临床上适量补充上述维生素有助于免疫功能恢复正常,可起到防病治病的作用.     

维生素D与妊娠糖尿病

维生素D具有广泛的生理作用,近期动物以及人体研究提示维生素D能够改善胰岛素抵抗及胰岛β细胞功能。本文总结了孕期维生素D的代谢状况及其在糖代谢中的作用机制,并综述维生素D与妊娠糖尿病相关性的研究结果。但现有研究结果并不一致,还需要设计良好的随机对照试验探索补充维生素D能否降低妊娠糖尿病的发生率或改善孕期糖代谢。     

维生素D对免疫细胞影响的研究进展

维生素D属固醇类衍生物,是维持人体生命稳定的一种营养素.活性维生素D通过与维生素D受体(vitamin D receptor,VDR)结合而发挥生物学效应.自VDR和1α-羟化酶(cytochrome P450 27B1,CYP27B1)在免疫细胞中被发现以来,维生素D的免疫调节作用便引起了人们极大关注.研究表明,维生...     

1,25(OH)2VD3及其类似物在自身免疫性内分泌疾病中的应用

1,25(OH)2VD3是维生素D3在体内的活性代谢产物,通过与细胞核上的受体结合发挥着维持钙磷平衡的作用.近年的研究发现,1,25(OH)2vD3尚可作用于免疫系统,在一定程度上发挥着免疫调节作用.内分泌系统疾病大多是遗传、免疫、环境等因素相互作用的结果,目前缺乏有效的治疗手段;而活性维生素D3免疫调节作用的发现为各种内分泌疾病提供了新的治疗理念.     

NKG2D及其配体在白血病免疫监视中的作用

NKG2D是免疫细胞表面的激活性受体,在机体的抗肿瘤免疫、抗感染免疫以及自身免疫病的发生中发挥重要作用。NKG2D识别肿瘤细胞表面的配体,激活效应细胞,产生有效的抗肿瘤免疫应答,是肿瘤免疫监视机制之一。近来研究发现白血病细胞表达多种NKG2D配体,参与白血病的免疫监视。本文就NKG2D及其配体对白血病免疫监视和免疫逃逸的作用作一综述。     

维生素D在儿童呼吸系统疾病中的研究进展

维生素D是人体不可缺少的营养素之一,具有广泛的生物学效应.维生素D不仅调节钙磷代谢,促进骨骼钙化,还作为重要的免疫调节因子在固有免疫应答和适应性免疫应答中发挥着重要作用,与呼吸系统疾病发生、发展密切相关.近年研究表明,维生素D缺乏可使免疫细胞增殖和分化偏移而产生异常免疫反应,增加呼吸系统疾病易感性和严重程度.儿童是维生素D缺乏的高危人群,深入研究维生素D的免疫调节功能,将为治疗儿童呼吸系统疾病提供理论基础.     

肺炎衣原体感染在冠心病发生发展中的作用机制

肺炎衣原体(Chlamydia pneumoniae,TWAR株)是常见的呼吸道感染病原体.近年来,越来越多的研究,包括血清流行病学、免疫细胞化学染色、多聚酶链式反应、药物干预试验等都支持肺炎衣原体在冠心病(Corona-ry Heart Disease,CHD)发生发展中的重要作用.其作用机制与脂质代谢异常、免疫复合物沉积、内皮细胞损伤、血液凝固性异常等多因素有关.     

精氨酸代谢对肿瘤生长及肿瘤免疫的影响

氨基酸代谢在疾病发生发展中的重要性逐渐被认知,其中精氨酸代谢与肿瘤的关系已成为研究热点。精氨酸作为条件性必需氨基酸,在肿瘤的发生、生长、转移过程中发挥重要作用。肿瘤免疫抑制性微环境的形成以及髓系免疫细胞的表型变化、成熟程度和功能状态都与精氨酸代谢密不可分。本文针对国内外上述相关研究成果,主要总结了精氨酸代谢在肿瘤生长、抗肿瘤免疫中的作用,归纳了肿瘤免疫微环境中的髓系免疫细胞类型、功能以及靶向精氨酸代谢途径的肿瘤治疗策略。     

维生素D干预糖尿病周围神经病变机制的研究进展

维生素D作为一种脂溶性类固醇激素,其缺乏可能引发心血管疾病、肿瘤和自身免疫性疾病等,且与糖尿病和糖尿病周围神经病变(DPN)的发生发展有关。许多研究观察了低维生素D水平与DPN之间的关系,发现维生素D通过与维生素D受体结合,促进神经因子分泌,调控神经细胞生长和修复,通过调控相关信号通路、参与神经细胞生长和分化等直接作用机制,以及拮抗高糖毒性、调节糖代谢,降低炎性因子,抗氧化应激,调节脂代谢,抗动脉粥样硬化,改善凝血功能,延缓微血管病变发生等间接作用机制干预DPN的发生发展。     

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.     

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.     

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.     

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.