BACKGROUND & AIMS: :The antigens in normal human skin defined by antibodies in patients with bullous pemphigoid (BP) were studied by Western immunoblots. Eighteen (90%) of 20 BP sera reacted to a 230-kD antigen. Seven (35%) of the sera reacted to a 160-kD antigen. Two of these reacted only to the 160-kD antigen and five also reacted to the 230-kD antigen. Antibodies to the 160-kD antigen were not present in 25 control sera obtained from normal individuals or patients with other bullous diseases. The 160-kD antigen was present in epidermal extracts of four different specimens of normal human skin but not in dermal extracts or extracts of control cells including melanoma, fibroblasts, lung carcinoma, and colon carcinoma. Monospecific sera with antibodies to either the 230-kD or to the 160-kD antigen reacted solely to their respective target antigens, but not to both, in extracts of epidermis that contained both antigens. The 160-kD antigen broke down to a 140-kD fragment, while the 230-kD antigen was unchanged in the absence of protease inhibitors. Western blot affinity purified antibody to the 160-kD antigen bound only to the basement membrane zone on the epidermal side of 1M NaCl split skin. These results indicate that a 160-kD antigen is a normal component of the basement membrane zone of human skin. The antigen is located on the epidermal side of skin split with 1M NaCl. It is a minor BP antigen, antibodies to which are present in some patients with BP.

背景与目标： ：通过Western免疫印迹研究了大疱性天疱疮（BP）患者中抗体定义的正常人皮肤中的抗原。 20个BP血清中有18个（90％）与230 kD抗原反应。七分之三（35％）的血清与160-kD抗原反应。其中两个仅与160-kD抗原反应，另外五个也与230-kD抗原反应。从正常个体或患有其他大疱性疾病的患者获得的25个对照血清中不存在针对160-kD抗原的抗体。 160-kD抗原存在于正常人皮肤的四个不同标本的表皮提取物中，但不存在于包括黑色素瘤，成纤维细胞，肺癌和结肠癌的真皮提取物或对照细胞提取物中。在包含两种抗原的表皮提取物中，具有针对230-kD或针对160-kD抗原的抗体的单特异性血清仅与它们各自的靶抗原发生反应，但与两种抗原均不发生反应。 160 kD抗原分解为140 kD片段，而230 kD抗原在不存在蛋白酶抑制剂的情况下保持不变。 Western blot亲和纯化的针对160-kD抗原的抗体仅与1M NaCl分裂皮肤的表皮侧的基膜区结合。这些结果表明160-kD抗原是人皮肤基底膜区的正常成分。抗原位于用1M NaCl分裂的皮肤的表皮侧。它是次要的BP抗原，某些BP患者中存在针对该抗体的抗体。

BACKGROUND & AIMS: The involvement of antigen-specific T cells in the pathogenesis of collagen diseases is still controversial. The final stages of collagen diseases are usually characterized by the dominance of inflammation. Therefore, antigen non-specific factors, such as inflammatory cytokines, probably play an important role in this process. On the other hand, the methods available to analyze the antigen-specific aspects of the immune response are still limited. Here we review our novel system of T cell clonality analysis based on the idea that activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Using this method, dynamic changes of clonal accumulation of T cells could be evaluated during antigenic stimulation in vivo and in vitro. The significance of antigen-specific T cell clones in collagen diseases is discussed using data obtained from patients with rheumatoid arthritis and systemic lupus erythematosus.

背景与目标： 抗原特异性T细胞是否参与胶原蛋白疾病的发病机制仍存在争议。胶原蛋白疾病的最后阶段通常以炎症占优势为特征。因此，抗原非特异性因子，例如炎性细胞因子，可能在此过程中起重要作用。另一方面，可用于分析免疫应答的抗原特异性方面的方法仍然有限。在这里，我们基于激活的抗原特异性T细胞应在淋巴细胞群体中形成累积克隆的想法，回顾了我们的T细胞克隆性分析的新系统。使用这种方法，可以在体内和体外抗原刺激过程中评估T细胞克隆积累的动态变化。利用类风湿性关节炎和系统性红斑狼疮患者获得的数据，讨论了抗原特异性T细胞克隆在胶原蛋白疾病中的重要性。

BACKGROUND & AIMS: :Continuous changes in the length of smooth muscles require a highly organized sarcolemmal structure. Yet, smooth muscle cells also adapt rapidly to altered environmental cues. Their sarcolemmal plasticity must lead to profound changes which affect transmembrane signal transduction as well as contractility. We have established porcine vascular and human visceral smooth muscle cultures of epithelioid and spindle-shaped morphology and determined their plasma membrane properties. Epithelioid cells from both sources contain a higher ratio of cholesterol to glycerophospholipids, and express a less diverse range of lipid-associated annexins. These findings point to a reduction in efficiency of membrane segregation in epithelioid cells. Moreover, compared to spindle-shaped cells, cholesterol is more readily extracted from epithelioid cells with methyl-beta-cyclodextrin and its synthesis is more susceptible to inhibition with lovastatin. The inability of epithelioid cells to process vasoactive metabolites, such as angiotensin or nucleotides further indicates that contractile properties are impaired. Phenotypic plasticity extends beyond the loss of smooth muscle cell marker genes. The plasma membrane has undergone profound functional changes which are incompatible with cyclic foreshortening, but might be important in the development of vascular disease.

背景与目标： ：平滑肌长度的连续变化需要高度组织化的肌膜结构。然而，平滑肌细胞也能迅速适应变化的环境提示。它们的肌膜可塑性必须导致深刻的变化，从而影响跨膜信号转导和收缩。我们已经建立了上皮样和纺锤形形态的猪血管和人内脏平滑肌培养物，并确定了它们的质膜特性。来自两种来源的上皮样细胞都含有较高的胆固醇与甘油磷脂比例，并且表达的脂质相关膜联蛋白的变化范围较小。这些发现表明上皮样细胞中膜分离的效率降低。此外，与纺锤形细胞相比，胆固醇更容易通过甲基-β-环糊精从上皮样细胞中提取，并且其合成更容易受到洛伐他汀的抑制。上皮样细胞不能处理血管活性代谢产物，例如血管紧张素或核苷酸，这进一步表明收缩特性受到损害。表型可塑性超出了平滑肌细胞标记基因丧失的范围。质膜已经发生了深刻的功能变化，这与循环缩短不相容，但是在血管疾病的发展中可能很重要。

BACKGROUND & AIMS: Prostate-specific antigen (PSA), a glycoprotein initially thought to be produced only by the epithelial cells of the prostate, has recently been found in 30% of female breast tumours using immunofluorometry. Our aim was to localize PSA immunohistochemically in a selected group of 27 paraffin-embedded breast tissues. A scoring system was developed for the histological assessment of PSA positivity within the breast tissue. One pathologist (DH) scored, classified and graded all tumours. Site-specific PSA staining was noted in the histology slides. Intense staining was identified in apocrine metaplasia and within the lining ductal epithelium of cystically dilated ducts. The epithelium in lesions of sclerosing adenosis was also frequently positive for PSA staining. Hyperplastic ductal epithelium (especially of mild degree) occasionally stained positive, as did normal breast ducts. Better differentiated tumours showed PSA staining [e.g. mucinous carcinoma (colloid)]. If an infiltrating duct carcinoma showed staining for PSA, adjacent intraductal carcinoma was also noted to stain positively, if present.

背景与目标： 前列腺特异性抗原（PSA）是一种最初被认为仅由前列腺上皮细胞产生的糖蛋白，最近在30％的女性乳腺肿瘤中使用免疫荧光法发现了这种蛋白。我们的目标是通过免疫组化将PSA定位在27个石蜡包埋的乳腺组织的选定组中。开发了评分系统用于乳腺组织内PSA阳性的组织学评估。一名病理学家（DH）对所有肿瘤进行了评分，分类和分级。组织学幻灯片中记录了位点特异性PSA染色。在顶泌化生和囊性扩张管的衬里导管上皮中鉴定到强染色。硬化性腺病病灶中的上皮也常对PSA染色呈阳性。增生性导管上皮（特别是轻度导管）偶尔染色呈阳性，正常乳腺导管也是如此。分化更好的肿瘤表现出PSA染色[例如粘液癌（胶体）]。如果浸润性导管癌显示PSA染色，则也可以发现邻近的导管内癌也呈阳性染色。

BACKGROUND & AIMS: :In order to provide accurate prognosis and developmental intervention to newborns, new methods of assessing cerebral functions are needed. The non-invasive technique of functional magnetic resonance imaging (fMRI) can be considered as the leading technique for functional exploration of the infant's brain. Several studies have previously applied fMRI in both healthy and diseased newborns with different sensory and cognitive tasks. In this chapter, the methodological issues that are proper to the use of fMRI in the newborn are detailed. In addition, an overview of the major findings of previous fMRI studies is provided, with a focus on notable differences from those in adult subjects. More specifically, the functional responses and the localization of cortical activations in healthy and diseased newborns are discussed. We expect a rapid expansion of this field and the establishment of fMRI as a valid clinical diagnostic tool in the newborn.

背景与目标： ：为了给新生儿提供准确的预后和发育干预，需要评估脑功能的新方法。功能性磁共振成像（fMRI）的非侵入性技术可以被认为是婴儿大脑功能性探索的主要技术。先前有几项研究将功能磁共振成像应用于具有不同感觉和认知任务的健康和患病新生儿。在本章中，将详细介绍适合于新生儿使用fMRI的方法学问题。此外，提供了以前的功能磁共振成像研究的主要发现的概述，重点是与成人受试者的显着差异。更具体地说，讨论了健康和患病新生儿的功能反应和皮质激活的定位。我们期望这一领域的快速发展和功能磁共振成像作为新生儿有效的临床诊断工具的建立。

BACKGROUND & AIMS: :Assessment of wound healing is a complex task, especially when the lesion is associated to significant (full thickness) loss of the skin. The clinical observation, essentially subjective and highly dependent on the observer's experience, creates difficulties in the comparison of results. Scoring scales were introduced in the clinical practice to create comparable semi-quantitative data and promote better management of resources, but its usefulness in a clinical perspective is still limited. New non-invasive biometric methodologies, although infrequently used, have opened new possibilities. While complementing the clinical observation and contributing to therapeutic decisions and prognosis, they may also help to look further into the pathophysiological mechanisms of scarring drugs rehabilitation. Following previous work in this arena, the authors review, the state-of-the-art of cutaneous wound healing clinical and biometric follow up, proposing a diagnosis correlation for the most relevant descriptors found in both strategies in order to fully characterise the different stages of the healing process.

背景与目标： ：伤口愈合的评估是一项复杂的任务，尤其是当病变与皮肤的严重（全层）损失有关时。临床观察本质上是主观的，并且高度依赖观察者的经验，因此在比较结果时会遇到困难。在临床实践中引入了评分量表，以创建可比较的半定量数据并促进更好的资源管理，但其在临床上的实用性仍然有限。尽管不经常使用新的非侵入式生物统计方法，但也开辟了新的可能性。在补充临床观察并有助于治疗决策和预后的同时，它们还可能有助于进一步研究疤痕药物康复的病理生理机制。在此领域的先前工作之后，作者回顾了最新的皮肤伤口愈合临床和生物测定学随访情况，提出了两种策略中最相关的描述符的诊断相关性，以全面表征不同的阶段愈合过程。

BACKGROUND & AIMS: :Tumor-infiltrating stroma cells (TISC) as well as tumors themselves are thought to be involved in tumor-related immunosuppression, which is one of the critical mechanisms of tumor escape from immune surveillance. However, preparation of TISC is difficult because of the small proportion of TISC in established tumors. Thus, the cells thought to be involved in tumor-related immunosuppression are generally prepared from spleens or draining lymph nodes in tumor-bearing mice. In this study, we developed a method for directly preparing TISC from established tumors in order to analyze their function. Using green fluorescent protein (GFP) transgenic (Tg) mice and C57BL/6 mice transplanted with bone marrow (BM) cells of GFPTg mice, we detected three subpopulations of TISC: one is compatible with immature myeloid cells (ImC) derived from BM and the two other subpopulations, CD11b(+) cells and CD11b(-) cells, do not originate from BM. The TISC including these subpopulations but not each subpopulation independently after culturing with tumors in the presence of GM-CSF could suppress T cell proliferation induced by anti-CD3. In our system, tumors did not inhibit T cell responses directly, but unknown factors from tumors affected immunosuppression by TISC.

背景与目标： ：肿瘤浸润基质细胞（TISC）以及肿瘤本身都被认为与肿瘤相关的免疫抑制有关，这是肿瘤逃避免疫监视的关键机制之一。然而，由于在已建立的肿瘤中TISC的比例很小，因此TISC的制备是困难的。因此，通常被认为与肿瘤相关的免疫抑制有关的细胞是从荷瘤小鼠的脾脏或引流淋巴结中制备的。在这项研究中，我们开发了一种从已建立的肿瘤中直接制备TISC的方法，以分析其功能。使用绿色荧光蛋白（GFP）转基因（Tg）小鼠和移植有GFPTg小鼠骨髓（BM）细胞的C57BL / 6小鼠，我们检测到TISC的三个亚群：一个与源自BM的未成熟髓样细胞（ImC）相容。其他两个亚群CD11b（）细胞和CD11b（-）细胞并非源自BM。在存在GM-CSF的情况下与肿瘤培养后，TISC包括这些亚群，但并非每个亚群独立地抑制由抗CD3诱导的T细胞增殖。在我们的系统中，肿瘤并未直接抑制T细胞反应，但来自肿瘤的未知因素影响了TISC的免疫抑制。

BACKGROUND & AIMS: :We investigated the functional significance of extraradical mycorrhizal networks produced by geographically different isolates of the arbuscular mycorrhizal fungal (AMF) species Glomus mosseae and Glomus intraradices. A two-dimensional experimental system was used to visualize and quantify intact extraradical mycelium (ERM) spreading from Medicago sativa roots. Growth, phosphorus (P) and nitrogen (N) nutrition were assessed in M. sativa plants grown in microcosms. The AMF isolates were characterized by differences in extent and interconnectedness of ERM. Phenotypic fungal variables, such as total hyphal length, hyphal density, hyphal length per mm of total or colonized root length, were positively correlated with M. sativa growth response variables, such as total shoot biomass and plant P content. The utilization of an experimental system in which size, growth rate, viability and interconnectedness of ERM extending from mycorrhizal roots are easily quantified under realistic conditions allows the simultaneous evaluation of different isolates and provides data with a predictive value for selection of efficient AMF.

背景与目标： ：我们调查了丛枝菌根真菌（AMF）物种Glomus mosseae和Glomus intraradices的地理上不同的分离物产生的自由基外菌根网络的功能意义。二维实验系统用于可视化和量化从紫花苜蓿根部传播的完整的根外菌丝体（ERM）。在微观世界中评估了苜蓿植物的生长，磷（P）和氮（N）营养。 AMF分离株的特征是ERM的程度和相互连接性不同。表型真菌变量，例如总菌丝长度，菌丝密度，每毫米总或定殖根长度的菌丝长度，与苜蓿生长反应变量（如总枝生物量和植物P含量）呈正相关。在实际条件下容易量化从菌根根延伸的ERM的大小，生长速度，生存力和相互联系的实验系统，可以同时评估不同的分离物，并为选择有效AMF提供具有预测价值的数据。

BACKGROUND & AIMS: :The site-1 determinant of the hemagglutinin molecule of influenza virus (A/PR/8/34) is one of several immunodominant sites in the BALB/c Th cell response to Ha. A synthetic peptide comprising this T cell site (HA110-120), a panel of analogs containing single substitutions in this determinant, and homologs truncated at the amino- or carboxyl-terminal were used to examine the fine specificities of 15 T cells specific for site-1 in the context of I-Ed. The results indicate that every residue within the minimal determinant plays a role in the T cell recognition process, as single substitutions at any of these positions affected the ability of the peptide to stimulate at least some site 1-specific T cells. For the majority of the residues examined, substitutions had dissimilar effects on distinct T cells, indicating that the substituted residues were affecting recognition in a receptor-specific manner. Each of the 15 T cells examined had a distinct fine specificity pattern, suggesting that the BALB/c T cell repertoire for this site is likely to exceed 100 distinct clonotypes.

背景与目标： 流感病毒血凝素分子（A / PR / 8/34）的1位点决定簇是BALB / c Th细胞对Ha的免疫应答中的几个免疫优势位点之一。包含该T细胞位点的合成肽（HA110-120），在该决定簇中包含单个取代基的一组类似物以及在氨基或羧基端被截短的同源物用于检查15个对该位点特异性的T细胞的精细特异性在I-Ed中为-1。结果表明，最小决定簇内的每个残基都在T细胞识别过程中起作用，因为这些位置中任何一个的单取代都会影响肽刺激至少一些位点1特异性T细胞的能力。对于所检查的大多数残基，取代对不同的T细胞的影响不同，表明取代的残基以受体特异性方式影响识别。检查的15个T细胞中的每一个都有独特的精细特异性模式，这表明该位点的BALB / c T细胞库可能超过100种不同的克隆型。

BACKGROUND & AIMS: How an increase in blood pressure, in and of itself, induces hypertensive nephrosclerosis is unclear. In an earlier study we found that leukocyte infiltration, proximal tubular cell proliferation, matrix deposition and interstitial fibrosis occur in the unclipped kidney of 2 K 1 C Goldblatt hypertensive rats. In this study we tested the hypothesis that the cell surface adhesion molecule ICAM-1 is expressed on the vascular endothelium and tubular epithelium of unclipped kidneys at 4 weeks. As a positive control, we examined the clipped kidney as well. We found that systolic blood pressure was significantly elevated in renovascular hypertensive rats compared to sham-operated controls after 4 weeks (198 +/- 5 mmHg vs 121 +/- 2 mmHg, P < 0.001). Furthermore, quantitative (densitometry) measurements showed that ICAM-1 expression on vascular endothelium and on tubular cells was significantly increased in unclipped kidneys compared to controls (P < 0.05). The same was true for monocyte and granulocyte infiltration (P < 0.05). These same variables were even more prominent in the clipped kidneys, compared to unclipped and control kidneys (P < 0.05). Our data show that ICAM-1 is expressed in unclipped kidneys exposed to hypertension as well as in clipped kidneys exposed to ischemia. We suggest that mechanical injury induced by increased blood pressure is responsible for an inflammatory adhesion molecule-mediated response and concomitant renal injury.

背景与目标： 血压升高本身如何引起高血压性肾硬化尚不清楚。在较早的研究中，我们发现2 K 1 C Goldblatt高血压大鼠的未切除肾脏中发生白细胞浸润，近端肾小管细胞增殖，基质沉积和间质纤维化。在这项研究中，我们测试了以下假设：第4周，细胞表面粘附分子ICAM-1在未切除的肾脏的血管内皮和肾小管上皮细胞中表达。作为阳性对照，我们还检查了修剪的肾脏。我们发现，与假手术对照组相比，肾血管性高血压大鼠的收缩压在4周后显着升高（198 /-5 mmHg与121 /-2 mmHg，P <0.001）。此外，定量（密度测定）测量结果显示，与对照相比，未切除的肾脏在血管内皮和肾小管细胞上的ICAM-1表达显着增加（P <0.05）。单核细胞和粒细胞浸润也是如此（P <0.05）。与未修剪的和对照的肾脏相比，这些相同的变量在修剪的肾脏中甚至更为突出（P <0.05）。我们的数据表明，ICAM-1在暴露于高血压的未切除的肾脏以及暴露于缺血的切除的肾脏中表达。我们认为，血压升高引起的机械损伤是炎症粘附分子介导的反应和伴随的肾损伤的原因。

BACKGROUND & AIMS: :Cyclic and congenital neutropenia are caused by mutations in the human neutrophil elastase (HNE) gene (ELA2), leading to an immunodeficiency characterized by decreased or oscillating levels of neutrophils in the blood. The HNE mutations presumably cause loss of enzyme activity, consequently leading to compromised immune system function. To understand the structural basis for the disease, we implemented methods from bioinformatics to analyze all the known HNE missense mutations at both the sequence and structural level. Our results demonstrate that the 32 different mutations have diverse effects on HNE structure and function, affecting structural disorder and aggregation tendencies, stability maintaining contacts, and electrostatic properties. A large proportion of the mutations are located at conserved amino acids, which are usually essential in determining protein structure and function. The majority of the disease-causing HNE missense mutations lead to major structural changes and loss of stability in the protein. A few mutations also affect functional residues, leading into decreased catalytic activity or altered ligand binding. Our analysis reveals the putative effects of all known missense mutations in HNE, thus allowing the structural basis of cyclic and congenital neutropenia to be elucidated. We have employed and analyzed a set of some 30 different methods for predicting the effects of amino acid substitutions. We present results and experience from the analysis of the applicability of these methods in the analysis of numerous genes, proteins, and diseases to reveal protein structure-function relationships and disease genotype-phenotype correlations.

背景与目标： ：循环性和先天性中性粒细胞减少症是由人中性粒细胞弹性蛋白酶（HNE）基因（ELA2）突变引起的，导致免疫缺陷，其特征是血液中中性粒细胞水平降低或振荡。 HNE突变可能导致酶活性下降，因此导致免疫系统功能受损。为了了解该疾病的结构基础，我们采用了生物信息学的方法来分析序列和结构水平上所有已知的HNE错义突变。我们的结果表明，这32种不同的突变对HNE的结构和功能有多种影响，影响结构异常和聚集趋势，保持接触的稳定性以及静电性质。很大一部分突变位于保守氨基酸上，这通常是决定蛋白质结构和功能所必需的。大多数引起疾病的HNE错义突变会导致主要的结构变化和蛋白质稳定性的损失。一些突变也影响功能性残基，导致催化活性降低或配体结合改变。我们的分析揭示了HNE中所有已知错义突变的推定作用，从而阐明了周期性和先天性中性粒细胞减少症的结构基础。我们已经采用并分析了一组约30种不同的方法来预测氨基酸取代的影响。我们提供了对这些方法在众多基因，蛋白质和疾病分析中的适用性进行分析的结果和经验，以揭示蛋白质结构与功能的关系以及疾病的基因型与表型的相关性。

BACKGROUND & AIMS: Transgenic mice expressing high levels of the BclxL or Bcl2 proteins in the male germinal cells show a highly abnormal adult spermatogenesis accompanied by sterility. This appears to result from the prevention of an early and massive wave of apoptosis in the testis, which occurs among germinal cells during the first round of spermatogenesis. In contrast, sporadic apoptosis among spermatogonia, which occurs in normal adult testis, is not prevented in adult transgenic mice. The physiological early apoptotic wave in the testis is coincident, in timing and localization, with a temporary high expression of the apoptosis-promoting protein Bax, which disappears at sexual maturity. The critical role played by the intracellular balance, probably hormonally controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in normal mouse testis) in this early apoptotic wave is shown by the occurrence of a comparable testicular syndrome in mice defective in the bax gene. The apoptotic wave appears necessary for normal mature spermatogenesis to develop, probably because it maintains a critical cell number ratio between some germinal cell stages and Sertoli cells, whose normal functions and differentiation involve an elaborate network of communication.

背景与目标： 在雄性生殖细胞中表达高水平BclxL或Bcl2蛋白的转基因小鼠表现出高度异常的成年精子发生并伴有不育。这似乎是由于防止了睾丸早期大量凋亡的结果，这种情况发生在第一轮精子发生过程中的生发细胞之间。相反，在成年转基因小鼠中，不能阻止正常成年人睾丸中发生的精原细胞中的偶发性细胞凋亡。睾丸中的生理性早期凋亡波在时间和位置上是一致的，具有促凋亡的蛋白Bax的临时高表达，该蛋白在性成熟时消失。 BclxL和Bax蛋白的细胞内平衡（可能是激素控制的）（在正常小鼠的睾丸中显然不表达Bcl2）在细胞内平衡中起着至关重要的作用，这是由于在小鼠中出现了类似的睾丸综合征所致。 bax基因。凋亡波似乎是正常成熟精子发生发展所必需的，这可能是因为它在某些生细胞阶段和支持细胞之间维持了关键的细胞数比，其正常功能和分化牵涉到复杂的交流网络。

BACKGROUND & AIMS: :Cyclic AMP levels in rabbit carotid bodies incubated under control conditions, 100% O2- or 95% O2/5% CO2- equilibrated medium, are close to 1 pmol/mg wet tissue (range 0.4-2.43 pmol/mg). Isobutylmethylxanthine (0.5 mM) increases cyclic AMP levels by a factor of 14 and 8 in HEPES- and CO2/CH3O(-)-buffered medium, respectively. Forskolin (0.5-10 microM) applied during 30 min increases cyclic AMP levels in a dose-dependent manner. Incubation of carotid bodies at low O2 tensions resulted in an elevation of cyclic AMP levels both in the absence and in the presence of isobutymethylxanthine. In the latter conditions cyclic AMP increase was maximum at an O2 tension of 46 mm Hg and tended to decrease at extremely low PO2. In isobutylmethylxanthine-containing Ca2(+)-free medium, cyclic AMP increased linearly with decreasing PO2 from 66 to 13 mm Hg; the absolute cyclic AMP levels attained in Ca2(+)-free medium were smaller than those observed in Ca2(+)-containing medium at any PO2. The differences between Ca2(+)-free and Ca2(+)-containing media appear to be due to the action of released neurotransmitters in the latter conditions, because dopamine and norepinephrine, which are known to be released by hypoxia in a Ca2(+)-dependent manner, increase cyclic AMP in the carotid body. Low pH/high PCO2 and high [K+]e increase cyclic AMP levels only in Ca2(+)-containing medium. Forskolin potentiates the release of catecholamines induced by low PO2. These results suggest that cyclic AMP plays an important role in the modulation of the chemoreception process.

背景与目标： ：在对照条件下，100％O2-或95％O2 / 5％CO2平衡的培养基中孵育的兔颈动脉体中的循环AMP水平接近1 pmol / mg湿组织（0.4-2.43 pmol / mg范围）。在HEPES-和CO2 / CH3O（-）缓冲的培养基中，异丁基甲基黄嘌呤（0.5 mM）将循环AMP的水平分别提高14和8倍。在30分钟内施用的Forskolin（0.5-10 microM）以剂量依赖性方式增加循环AMP的水平。在不存在和存在异丁甲基黄嘌呤的情况下，在低O2张力下孵育颈动脉都会导致环AMP含量升高。在后一种情况下，循环AMP的增加在O2张力为46 mm Hg时最大，而在极低的PO2下趋于减少。在不含异丁基甲基黄嘌呤的不含Ca2（）的介质中，环状AMP随着PO2从66 mmHg降低到13 mm Hg而线性增加。不含Ca2（）的培养基中获得的绝对循环AMP水平要小于任何PO2含Ca2（）的培养基中观察到的绝对值。不含Ca2（）和含Ca2（）的培养基之间的差异似乎是由于后者条件下释放的神经递质的作用所致，因为已知多巴胺和去甲肾上腺素在依赖Ca2（）的情况下会通过低氧释放。方式，增加颈动脉体中的循环AMP。低pH /高PCO2和高[K] e仅在含Ca2（）的培养基中会增加循环AMP的水平。 Forskolin增强了低PO2诱导的儿茶酚胺释放。这些结果表明，环状AMP在化学感受过程的调节中起重要作用。

BACKGROUND & AIMS: :Despite the successful identification of several relevant genomic loci, the underlying molecular mechanisms of schizophrenia remain largely unclear. We developed a computational approach (NETBAG+) that allows an integrated analysis of diverse disease-related genetic data using a unified statistical framework. The application of this approach to schizophrenia-associated genetic variations, obtained using unbiased whole-genome methods, allowed us to identify several cohesive gene networks related to axon guidance, neuronal cell mobility, synaptic function and chromosomal remodeling. The genes forming the networks are highly expressed in the brain, with higher brain expression during prenatal development. The identified networks are functionally related to genes previously implicated in schizophrenia, autism and intellectual disability. A comparative analysis of copy number variants associated with autism and schizophrenia suggests that although the molecular networks implicated in these distinct disorders may be related, the mutations associated with each disease are likely to lead, at least on average, to different functional consequences.

背景与目标： ：尽管成功鉴定了几个相关的基因组位点，但精神分裂症的潜在分子机制仍不清楚。我们开发了一种计算方法（NETBAG），该方法可以使用统一的统计框架对与疾病相关的多种遗传数据进行综合分析。使用无偏倚的全基因组方法获得的这种方法用于精神分裂症相关遗传变异的应用，使我们能够鉴定出与轴突导向，神经元细胞移动性，突触功能和染色体重塑有关的几个内聚基因网络。形成网络的基因在大脑中高度表达，在产前发育过程中大脑表达更高。所确定的网络在功能上与先前与精神分裂症，自闭症和智力障碍有关的基因有关。对与自闭症和精神分裂症有关的拷贝数变异的比较分析表明，尽管与这些独特疾病有关的分子网络可能是相关的，但与每种疾病有关的突变可能至少平均而言导致不同的功能后果。

BACKGROUND & AIMS: :The Shozu Herpes Zoster (SHEZ) Study was designed to clarify the incidence of and predictive and immunological factors for herpes zoster in a defined community-based Japanese population. As part of this series, a total of 5683 residents aged ≥50 years received a varicella-zoster virus (VZV) skin test with VZV antigen, and 48 h later, the erythema and oedema were assessed by measuring the longest diameter. The diameters of both the erythema and oedema decreased with the increasing age of the subject. Sixty-three subjects contracted herpes zoster within a year after receiving the VZV skin test. Analysis of the herpes zoster incidence rate vs. the skin test reaction revealed that the shorter the diameter of erythema or oedema, the greater the likelihood of herpes zoster. These results demonstrated that the VZV skin test is an excellent surrogate marker for predicting the risk of herpes zoster.

背景与目标： ：Shozu疱疹带状疱疹（SHEZ）研究旨在阐明在特定的以社区为基础的日本人群中带状疱疹的发病率以及预测性和免疫学因素。作为该系列的一部分，共有5683名年龄≥50岁的居民接受了带有VZV抗原的水痘-带状疱疹病毒（VZV）皮肤测试，并且48小时后，通过测量最长直径来评估红斑和浮肿。红斑和水肿的直径随受试者年龄的增加而减小。接受VZV皮肤测试后一年内，六十三名受试者患了带状疱疹。带状疱疹发病率与皮肤试验反应的关系分析表明，红斑或水肿的直径越短，带状疱疹的可能性就越大。这些结果表明，VZV皮肤测试是预测带状疱疹风险的出色替代指标。