BACKGROUND & AIMS: :A structure-activity relationship (SAR) study was performed principally at the N1 position of N1-arylsulfonyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-diaminocyclohexanes, a new family of calcilytics acting at the calcium sensing receptor (CaSR). The most active compound in this series was the 4-(trifluoromethoxy)benzenesulfonyl derivative 7e, which displayed an IC50 of 5.4 +/- 0.5 microM with respect to the inhibition of calcium-induced tritiated inositol phosphate ([3H]IP) accumulation in Chinese hamster ovarian (CHO) cells expressing the CaSR. Replacement of the sulfonamide linkage of this compound by a carboxamide led to a 6-fold increase in activity (7m, IC50 = 0.9 +/- 0.2 microM). Among the carboxamides synthesized, one of the most active compounds was the 4-chlorophenylcarboxamide (1S,2S,1'R)-7n (Calhex 231, IC50 = 0.33 +/- 0.02 microM). The absolute configuration of (1S,2S,1'R)-7n was deduced from an X-ray crystallographic study of one of the diastereomers of compound 7d. The stereochemical preference for the (1S,2S,1'R)-isomers can be rationalized on the basis of a three-dimensional model of the calcilytic binding pocket of the CaSR. Removal of the C-1' methyl group or replacement of the 1-naphthyl group by a 2-naphthyl or biphenyl moiety led to appreciable loss of calcilytic activity. Compounds 7e, 7m, and Calhex 231 did not stimulate [3H]IP accumulation in CHO cells expressing or not expressing the CaSR.

背景与目标： : 主要在N1-arylsulfonyl-N2-[1-(1-萘基) 乙基]-trans-1，2-二氨基环己烷的N1位置进行了构效关系 (SAR) 研究，作用于钙感应受体 (CaSR) 的新的钙离子家族。该系列中最具活性的化合物是4-(三氟甲氧基) 苯磺酰基衍生物7e，在表达CaSR的中国仓鼠卵巢 (CHO) 细胞中，对钙诱导的tri化肌醇磷酸 ([3H]IP) 积累的抑制作用显示出5.4/- 0.5微米的IC50。用甲酰胺代替该化合物的磺酰胺键导致6倍活动增加 (7m，IC50 = 0.9 +/- 0.2微米)。在合成的甲酰胺中，最具活性的化合物之一是4-氯苯基甲酰胺 (1S，2S，1'R)-7n (Calhex 231，IC50 = 0.33 +/- 0.02微米)。(1S，2S，1'R)-7n是根据对化合物7d的非对映异构体之一的x射线晶体学研究得出的。(1S，2S，1'R)-异构体可以在CaSR的煅烧结合袋的三维模型的基础上合理化。C-1甲基的去除或2-萘基或联苯部分取代1-萘基导致煅烧活性的明显损失。化合物7e，7m，并且Calhex 231不刺激表达或不表达CaSR的CHO细胞中的 [3H]IP积累。

BACKGROUND & AIMS: UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin (EPO) for growth and survival. We isolated a novel subline, UT-7/GM after long-term culture of UT-7 with GM-CSF. The hemoglobin concentration and gamma-globin and EPO-receptor mRNA levels were significantly higher in EPO-treated UT-7/GM cells than in untreated cells. In contrast, the platelet factor 4 and glycoprotein IIb mRNA levels were much higher in thrombopoietin (TPO)-treated UT-7/GM cells than in untreated cells. Some TPO-treated cells had morphologically mature megakaryocytic characteristics such as a developed demarcation membrane in the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM is a bipotential cell line that can be induced to differentiate into erythroid and megakaryocytic lineages by EPO and TPO, respectively. Moreover, a minority of UT-7/GM cells acquired a high hemoglobin concentration by treatment with TPO, suggesting that TPO in part induced the erythroid differentiation of the UT-7/GM cells. Interestingly, GM-CSF inhibited the EPO- or TPO-induced erythroid differentiation and the TPO-induced megakaryocytic differentiation of UT-7/GM cells. These results support the hypothesis that cytokines influence the programming of gene expression required for lineage commitment or differentiation.

背景与目标： UT-7是一种人类巨核细胞白血病细胞系，其生长和存活绝对依赖于interleukin-3，粒细胞-巨噬细胞集落刺激因子 (gm-csf) 或促红细胞生成素 (EPO)。在用gm-csf长期培养UT-7后，我们分离了一个新的子系UT-7/GM。在EPO处理的UT-7/GM细胞中，血红蛋白浓度以及 γ-珠蛋白和EPO受体mRNA水平显着高于未处理的细胞。相比之下，血小板生成素 (TPO) 处理的UT-7/GM细胞中的血小板因子4和糖蛋白IIb mRNA水平远高于未处理的细胞。某些经TPO处理的细胞具有形态成熟的巨核细胞特征，例如细胞质和多小叶核中的分界膜发达。这些发现表明，UT-7/GM是一种双能细胞系，可以分别通过EPO和TPO诱导分化为红系和巨核细胞系。此外，少数UT-7/GM细胞通过用TPO处理获得高血红蛋白浓度，表明TPO部分诱导了UT-7/GM细胞的红系分化。有趣的是，gm-csf抑制EPO或TPO诱导的红细胞分化和TPO诱导的UT-7/GM细胞的巨核细胞分化。这些结果支持以下假设: 细胞因子会影响谱系承诺或分化所需的基因表达编程。

BACKGROUND & AIMS: :Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4+ T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG. The effect of CD28 blockade on lupus nephritis onset, survival, production of anti-ds DNA antibodies and costimulatory molecules was evaluated. CD28 blockade prevented the development of lupus nephritis and prolonged survival during the 3-month treatment and 12 weeks after. Furthermore, the production of anti-ds DNA autoAbs was decreased. Lastly, the protective effect of CD28 blockade was associated with increased intrarenal expression of the immunoregulatory molecule, Indoleamine 2, 3-dioxygenase, of the co-inhibitory receptor programmed cell-Death - 1 (PD-1) and of its ligand programmed death ligand - 1 (PDL-1).In conclusion, CD28 blockade prevented the development of lupus nephritis in NZB/NZW F1 mice. This immunomodulatory strategy is a promising candidate for SLE therapy in humans.

背景与目标： 系统性红斑狼疮 (SLE) 是一种慢性全身性炎症性疾病。抗狼疮标志双链DNA (ds DNA) 的自身抗体 (autoAbs) 是通过自身反应性b细胞和CD4 T细胞之间的相互作用产生和维持的。该相互作用由CD28/CD80-86/CTLA-4轴控制。在这里，我们研究了在SLE的鼠模型中，选择性阻断CD28-CD80/86共刺激相互作用是否可以缓解狼疮性肾炎的发展。为此，用anti-CD28 Fab' 片段或对照Fab'-IgG处理NZB/nzwf1小鼠3个月。评估了CD28阻断对狼疮性肾炎发作，存活，抗ds DNA抗体和共刺激分子产生的影响。CD28阻断可防止狼疮性肾炎的发展，并在3个月的治疗和12周后延长生存期。此外，抗ds DNA autoAbs的产生减少了。最后，CD28阻断的保护作用与免疫调节分子吲哚胺2,3-双加氧酶，共抑制性受体程序性细胞死亡-1 (PD-1) 及其配体程序性死亡配体-1 (PDL-1) 的肾内表达增加有关。总之，CD28阻断阻止了NZB/NZW F1小鼠狼疮性肾炎的发展。这种免疫调节策略是人类SLE治疗的有希望的候选者。

BACKGROUND & AIMS: :Methionine adenosyltransferase (MAT) is involved in folate-mediated one-carbon metabolism, which is essential for preimplantation embryos in terms of both short-term periconceptional development and long-term phenotypic programming beyond the periconceptional period. Here, our immunofluorescence analysis of bovine oocytes and preimplantation embryos revealed the consistent expression of MAT2A (the catalytic subunit of the ubiquitously expressed-type of MAT isozyme) during this period. Addition of the MAT2A inhibitor FIDAS to the culture media of bovine preimplantation embryos reduced their blastocyst development, revealing the particular importance of MAT2A in successful blastocyst development. Exploration of MAT2A-associated genomic regions in bovine blastocysts using chromatin immunoprecipitation and sequencing (ChIP-seq) identified candidate MAT2A-associated genes implicated not only in short-term periconceptional embryo development, but also in long-term phenotypic programming during this period in terms of growth, metabolism, and immune functions. These results suggest the critical involvement of MAT2A in the periconceptional period in life-long programming of health and disease as well as successful preimplantation development.

背景与目标： : 蛋氨酸腺苷转移酶 (MAT) 参与叶酸介导的单碳代谢，这对于植入前胚胎的短期围术期发展和围术期以后的长期表型编程都是必不可少的。在这里，我们对牛卵母细胞和植入前胚胎的免疫荧光分析揭示了在此期间MAT2A (MAT同工酶普遍表达类型的催化亚基) 的一致表达。在牛植入前胚胎的培养基中添加MAT2A抑制剂FIDAS会降低其胚泡发育，从而揭示了MAT2A在成功胚泡发育中的特殊重要性。使用染色质免疫沉淀和测序 (ChIP-seq) 探索牛囊胚中的MAT2A-associated基因组区域，确定了候选MAT2A-associated基因，不仅涉及短期内胚胎发育，而且还涉及在此期间生长，代谢和免疫功能方面的长期表型编程。这些结果表明，MAT2A在围手术期的关键参与了健康和疾病的终生规划以及成功的植入前发展。

BACKGROUND & AIMS: BACKGROUND:The Nutrition Embedded Evaluation Programme Impact Evaluation (NEEP-IE) study is a cluster randomised controlled trial designed to evaluate the impact of a childcare centre-based integrated nutritional and agricultural intervention on the diets, nutrition and development of young children in Malawi. The intervention includes activities to improve nutritious food production and training/behaviour-change communication to improve food intake, care and hygiene practices. This paper presents the rationale and study design for this randomised control trial. METHODS:Sixty community-based childcare centres (CBCCs) in rural communities around Zomba district, Malawi, were randomised to either (1) a control group where children were attending CBCCs supported by Save the Children's Early Childhood Health and Development (ECD) programme, or (2) an intervention group where nutritional and agricultural support activities were provided alongside the routine provision of the Save the Children's ECD programme. Primary outcomes at child level include dietary intake (measured through 24-h recall), whilst secondary outcomes include child development (Malawi Development Assessment Tool (MDAT)) and nutritional status (anthropometric measurements). At household level, primary outcomes include smallholder farmer production output and crop-mix (recall of last production season). Intermediate outcomes along theorised agricultural and nutritional pathways were measured. During this trial, we will follow a mixed-methods approach and undertake child-, household-, CBCC- and market-level surveys and assessments as well as in-depth interviews and focus group discussions with project stakeholders. DISCUSSION:Assessing the simultaneous impact of preschool meals on diets, nutrition, child development and agriculture is a complex undertaking. This study is the first to explicitly examine, from a food systems perspective, the impact of a preschool meals programme on dietary choices, alongside outcomes in the nutritional, child development and agricultural domains. The findings of this evaluation will provide evidence to support policymakers in the scale-up of national programmes. TRIAL REGISTRATION:ISRCTN registry, ID: ISRCTN96497560 . Registered on 21 September 2016.

背景与目标：

BACKGROUND & AIMS: :Between February 26, 1981, and July 30, 1987, 36 patients underwent orthotopic liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Three of the 36 recipients died within 3 mo because of graft nonfunction or surgical complications. The other 33 (92%) lived for at least 1 yr. Two of the 33 died after 12 and 14 mo, respectively, of recurrent cholangiocarcinoma that was not diagnosed before transplantation. Four other patients died of recurrent liver failure (three cases) or immunoblastic sarcoma (one case) after 14, 21, 36 and 44 mo. Twenty-seven (75%) of the patients are still alive 23 to 81 mo after transplantation. Two patients have been diagnosed as having colorectal cancer 11 and 21 mo respectively, after transplantation, for an overall incidence of 5.6% (2 of 36) and a corrected incidence of 6.5% (2 of 31) if the three early deaths and two later deaths caused by cholangiocarcinomas are excluded. It is not known whether colorectal malignancies were present but undetected at the time of transplantation or whether they developed afterward. It is clear that patients who undergo liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis should have careful follow-up of the colon, including colonoscopy and multiple biopsies of the colorectal mucosa. Whether proctocolectomy should be considered prophylactically after liver transplantation is an unresolved issue.

背景与目标： : 在1981年2月26日和1987年7月30日之间，有36例患者因溃疡性结肠炎相关的原发性硬化性胆管炎接受了原位肝移植。36名接受者中有3名因移植物无功能或手术并发症而在3个月内死亡。其他33人 (92%) 至少活了1年。33例中的2例分别在移植前未诊断出的复发性胆管癌分别在12和14个月后死亡。另外4例患者在14、21、36和44个月后死于复发性肝衰竭 (3例) 或免疫母细胞肉瘤 (1例)。移植后23至81个月，有27 (75%) 例患者仍然存活。两名患者在移植后分别被诊断为结直肠癌11和21个月，如果排除了由胆管癌引起的三例早期死亡和两例晚期死亡，则总发生率为5.6% 例 (36例中的2例) 和6.5% 例的校正发生率 (31例中的2例)。尚不清楚是否存在结直肠恶性肿瘤，但在移植时未发现，或者其后是否发展。很明显，接受肝移植治疗与溃疡性结肠炎相关的原发性硬化性胆管炎的患者应仔细随访结肠，包括结肠镜检查和结肠粘膜的多次活检。肝移植后是否应预防性考虑直肠结肠切除术是一个尚未解决的问题。

BACKGROUND & AIMS: BACKGROUND:Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic. CONTENT:We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs. SUMMARY:With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.

背景与目标：

BACKGROUND & AIMS: :Proteins encoded by MADS-box genes are important transcription factors involved in the regulation of flowering plant growth and development. Currently, no systematic information exists regarding the MADS-box family in the important tropical fruit banana. Ninety-six MADS-box genes were identified from the banana (Pahang) A genome. Phylogenetic analysis indicated that Musa acuminata MCM1-AGAMOUS- DEFICIENS-SRF (MaMADS) could be divided into MIKCc, MIKC*, Mα/β and Mγ groups. MIKCc could be further divided into 11 subfamilies, which was further supported by conserved motif and gene structure analyses. Transcriptome analysis on the Feng Jiao (FJ) and BaXi Jiao (BX) banana cultivars revealed that MaMADS genes are differentially expressed in various organs, at different fruit development and ripening stages, indicating the involvement of these genes in fruit development and ripening processes. Interactive network analysis indicated that MaMADS24 and 49 not only interacted with MaMADS proteins themselves, but also interacted with hormone-response proteins, ethylene signal transduction and biosynthesis-related proteins, starch biosynthesis proteins and metabolism-related proteins. This systematic analysis identified candidate MaMADS genes related to fruit development and ripening for further functional characterization in plants, and also provided new insights into the transcriptional regulation of MaMADS genes, facilitating the future genetic manipulation of MADS-mediated fruit development and ripening.

背景与目标： : MADS-box基因编码的蛋白质是参与调节开花植物生长发育的重要转录因子。目前，尚无有关重要热带水果香蕉中MADS-box家族的系统信息。从香蕉 (Pahang) A基因组中鉴定出96个MADS-box基因。系统发育分析表明，尖锐湿疣MCM1-AGAMOUS-SRF (MaMADS) 可分为MIKCc，MIKC *，m α/β 和m γ 组。MIKCc可以进一步分为11个亚科，这得到了保守基序和基因结构分析的进一步支持。对Feng Jiao (FJ) 和BaXi Jiao (BX) 香蕉品种的转录组分析表明，MaMADS基因在不同的果实发育和成熟阶段在各个器官中差异表达，表明这些基因参与了果实的发育和成熟过程。交互网络分析表明，MaMADS24和49不仅与MaMADS蛋白本身相互作用，而且还与激素反应蛋白，乙烯信号转导和生物合成相关蛋白，淀粉生物合成蛋白和代谢相关蛋白相互作用。该系统分析确定了与果实发育和成熟相关的候选MaMADS基因，以进一步表征植物的功能，并为MaMADS基因的转录调控提供了新的见解，从而促进了MADS介导的果实发育和成熟的未来遗传操作。

BACKGROUND & AIMS: OBJECT:The purpose of this study was to provide an evidence-based algorithm for the design, development, and implementation of a new checklist for the response to an intraoperative neuromonitoring alert during spine surgery. METHODS:The aviation and surgical literature was surveyed for evidence of successful checklist design, development, and implementation. The limitations of checklists and the barriers to their implementation were reviewed. Based on this review, an algorithm for neurosurgical checklist creation and implementation was developed. Using this algorithm, a multidisciplinary team surveyed the literature for the best practices for how to respond to an intraoperative neuromonitoring alert. All stakeholders then reviewed the evidence and came to consensus regarding items for inclusion in the checklist. RESULTS:A checklist for responding to an intraoperative neuromonitoring alert was devised. It highlights the specific roles of the anesthesiologist, surgeon, and neuromonitoring personnel and encourages communication between teams. It focuses on the items critical for identifying and correcting reversible causes of neuromonitoring alerts. Following initial design, the checklist draft was reviewed and amended with stakeholder input. The checklist was then evaluated in a small-scale trial and revised based on usability and feasibility. CONCLUSIONS:The authors have developed an evidence-based algorithm for the design, development, and implementation of checklists in neurosurgery and have used this algorithm to devise a checklist for responding to intraoperative neuromonitoring alerts in spine surgery.

背景与目标：

BACKGROUND & AIMS: :A microsomal butyrylesterase (L-I) was purified from the livers of male W rats treated with phenobarbital, and an antiserum against this purified L-I was raised in a rabbit. By the Ouchteriony double-diffusion test, a precipitin line was observed between the anti-L-I antiserum and each Triton X-100 extract of livers during development, regeneration after partial hepatectomy, and carcinogenesis and of hyperplastic nodules and hepatomas, all of which revealed L-I in their esterase isoenzyme patterns. These precipitin lines exhibited esterase activity. The fusion of the lines of these tissue extracts and that of the purified L-I indicated the presence of an antigen site common to their esterases. The extracts of adult and fetal livers and also of hepatomas resembling fetal liver in the esterase isoenzyme pattern did not produce a precipitin line with anti-L-I antiserum.

背景与目标： : 从用苯巴比妥处理的雄性W大鼠的肝脏中纯化了微粒体丁酸酯酶 (l-i)，并在兔子中产生了针对该纯化的l-i的抗血清。通过Ouchteriony双扩散试验，在肝脏的发育，部分肝切除术后的再生，癌变以及增生性结节和肝癌的发育过程中，在抗L-I抗血清和每个Triton X-100提取物之间观察到沉淀蛋白线，所有这些都在其酯酶同工酶模式中显示了L-I。这些沉淀素系表现出酯酶活性。这些组织提取物的品系与纯化的l-i品系的融合表明存在其酯酶共有的抗原位点。在酯酶同工酶模式下，成年和胎儿肝脏以及类似胎儿肝脏的肝癌的提取物不会产生具有抗L-I抗血清的沉淀蛋白。

BACKGROUND & AIMS: :A brief 21-item symptom rating scale, the Psychiatric Outpatient Rating Scale (PORS), was developed for use in outpatient clinics. On the basis of its initial use with 86 patients, it was shown to have high internal and interjudge reliability and evidence of concurrent and construct validity. Scores on the PORS correlated significantly with the Global Assessment Scale and with the number of sessions of psychotherapy. For a subsample of 45 patients rated on the PORS at the beginning and termination of psychotherapy, seven symptoms revealed highly significant improvement. The PORS appears to be a potentially useful measure of change in outpatient clinics.

背景与目标： : 开发了一个简短的21项症状评定量表，即精神科门诊评定量表 (PORS)，用于门诊。根据86例患者的首次使用，它被证明具有较高的内部和中间信度以及并发和结构效度的证据。PORS的得分与全球评估量表和心理治疗次数显着相关。对于在心理治疗开始和终止时对PORS进行评分的45名患者的子样本，有7种症状显示出显着改善。PORS似乎是衡量门诊诊所变化的潜在有用指标。

BACKGROUND & AIMS: :Cervical screening attendance among women aged 25-29 years in England is lower than at older ages. There is some evidence that pre-notification leaflets motivate women who have not yet considered their response to a health intervention. We aimed to identify key information to motivate young women at their first cervical screening invitation. Six focus groups were conducted, five with young women aged 17-25 registered with a General Practice in Manchester, UK, and one with Practice nurses. Some women took part in two further groups to discuss leaflet design. There was low awareness of the purpose or procedures of cervical screening, and most women were de-motivated by reports of bad experiences. Some intended to be screened, but not immediately after invitation. Screening was viewed as a test for a cancer that affected older women. Since none of the participants believed that they had cervical cancer, screening seemed unnecessary. We conclude that the perception that screening is unimportant when you are young needs to be challenged. Women also need to be better informed of screening procedures. A pre-notification leaflet incorporating key information was designed and will be tested in a randomized trial of complex interventions within the routine cervical screening programme.

背景与目标： : 英格兰25-29岁女性的子宫颈筛查出勤率低于老年人。有证据表明，预先通知的传单会激励尚未考虑对健康干预措施做出反应的妇女。我们的目标是确定关键信息，以激励年轻女性首次接受子宫颈筛查邀请。进行了六个重点小组，其中五个是在英国曼彻斯特注册的17-25岁的年轻女性，其中一个是执业护士。一些妇女参加了另外两个小组，讨论传单设计。人们对宫颈筛查的目的或程序的认识不足，大多数妇女因不良经历的报道而缺乏动力。有些人打算放映，但不是在邀请后立即放映。筛查被视为对影响老年妇女的癌症的测试。由于没有参与者相信自己患有宫颈癌，因此筛查似乎没有必要。我们得出的结论是，年轻时筛查不重要的看法需要受到挑战。妇女还需要更好地了解筛查程序。设计了包含关键信息的预通知传单，并将在常规子宫颈筛查计划中进行复杂干预的随机试验中进行测试。

BACKGROUND & AIMS: :Development is a dynamic process occurring at the microscopic scale. The ability to see how it unfolds in detail is invaluable not only for helping us appreciate its full complexity but also to experimentally dissect its mechanisms. The sophistication of experimental approaches and imaging technologies has increased over the past decade at an astounding pace. In this review we highlight and discuss several studies that illustrate the latest advances in the application of live-imaging to dissect plant development.

背景与目标： : 发展是一个在微观尺度上发生的动态过程。了解其详细展开的能力不仅有助于我们理解其全部复杂性，而且还可以通过实验剖析其机制，这是无价的。在过去的十年中，实验方法和成像技术的复杂性以惊人的速度增长。在这篇综述中，我们重点介绍并讨论了几项研究，这些研究说明了活体成像在解剖植物发育中的最新进展。

BACKGROUND & AIMS: :Dermatophagoides farinae-, ovalbumin- and lactalbumin-specific IgG, IgG1, IgG4, IgA and IgM were evaluated in 161 healthy children [Group 1], 84 children with bronchial asthma and/or allergic rhinitis but without atopic dermatitis [Group 2], and 54 children with atopic dermatitis but without bronchial asthma and allergic rhinitis [Group 3]. We also studied D. farinae-, egg-white-, and milk-specific IgE of children with allergic diseases. D. farinae-specific IgG, IgG1, IgG4 and IgA in Groups 2 and 3 increased until 5 years of age and thereafter they remained constant. After 2 years of age, D. farinae-specific IgG, IgG1, IgG4 and IgA in Group 2 were higher than those in Groups 1 and 3. Ovalbumin- and lactalbumin-specific IgG, IgG1, IgG4 and IgA in Groups 2 and 3 increased until 1 year of age and thereafter decreased. Until 1 year of age, ovalbumin- and lactalbumin-specific IgG, IgG1 and IgG4 in Groups 3 were higher than those in Groups 1 and 2. D. farinae-, ovalbumin- and lactalbumin-specific IgM were constant in all ages of all groups. These results suggest that atopic dermatitis in young children is related to food-specific immunoglobulins and that respiratory allergic diseases in older children is related to D. farinae-specific immunoglobulins.

背景与目标： : 在161名健康儿童中评估了粉尘螨，卵白蛋白和乳蛋白特异性IgG，IgG1，IgG4，IgA和IgM [第1组]，84名患有支气管哮喘和/或过敏性鼻炎但没有特应性皮炎的儿童 [第2组]，54例儿童特应性皮炎，但无支气管哮喘和过敏性鼻炎 [第3组]。我们还研究了患有过敏性疾病的儿童的D. farinae-，蛋清-和牛奶特异性IgE。D.第2组和第3组的farinae特异性IgG，IgG1，IgG4和IgA增加至5岁，此后保持恒定。2岁后，第2组的粉菌特异性IgG，IgG1，IgG4和IgA高于第1和第3组。第2组和第3组的卵白蛋白和乳白蛋白特异性IgG，IgG1，IgG4和IgA升高至1岁，此后降低。直到1岁，第3组的卵白蛋白和乳白蛋白特异性IgG，IgG1和IgG4均高于第1组和第2组。D.在所有年龄段的所有年龄段中，farinae-，卵白蛋白-和乳白蛋白特异性IgM都是恒定的。这些结果表明，幼儿的特应性皮炎与食物特异性免疫球蛋白有关，而大龄儿童的呼吸道过敏性疾病与D. farinae特异性免疫球蛋白有关。

BACKGROUND & AIMS: :Direct clonal analysis of tissue and organ maturation in vivo is a critical step in the interpretation of in vitro cell precursor-progeny relationships. We have developed a method to analyze clonal progenitor contributions in vivo using ES cells stably expressing separate fluorescent proteins and placed into normal blastocysts to form tetrachimeras. Here we applied this method to the analysis of embryonic yolk sac blood islands. In most vertebrates, yolk sac blood islands are the initial sites of appearance of hematopoietic and endothelial cells. It has been proposed that these lineages arise from a common clonal progenitor, the hemangioblast, but this hypothesis has not been tested directly in physiological development in vivo. Our analysis shows that each island has contributions from multiple progenitors. Moreover, contribution by individual hemangioblast progenitors to both endothelial and hematopoietic lineages within an island, if it happens at all, is an infrequent event.

背景与目标： : 体内组织和器官成熟的直接克隆分析是解释体外细胞前体-后代关系的关键步骤。我们已经开发了一种方法，可以使用稳定表达单独荧光蛋白的ES细胞来分析体内克隆祖细胞的贡献，并将其放入正常的胚泡中以形成四眼虫。在这里，我们将该方法应用于胚胎卵黄囊血岛的分析。在大多数脊椎动物中，卵黄囊血岛是造血和内皮细胞出现的初始部位。有人提出，这些谱系来自常见的克隆祖细胞，即血管母细胞，但该假设尚未在体内生理发育中直接得到检验。我们的分析表明，每个岛屿都有多个祖先的贡献。此外，单个成血管细胞祖细胞对岛内内皮和造血谱系的贡献 (如果发生的话) 是罕见的。