BACKGROUND & AIMS: While the choice of stationary phase, organic modifier, and gradient strength can have significant effects on biomolecule separations, mobile phase additives can also have a significant effect on the chromatographic selectivity, recovery, efficiency and resolution. Given the importance of stationary phase coverage, the beneficial, silanol-masking properties of amines, and the potential for selectivity modification through ion-pair interactions, cyclohexylamine was examined as a mobile phase additive and compared with triethylamine and trifluoroacetic acid. Greatly improved separation was possible when cyclohexylamine was used as compared with phosphate buffer, and cyclohexylamine did not require purification before use, while triethylamine required distillation before 'clean' chromatograms were obtained.

背景与目标： 固定相，有机改性剂和梯度强度的选择可能对生物分子分离产生重大影响，而流动相添加剂也可能对色谱的选择性，回收率，效率和分离度产生重大影响。考虑到固定相覆盖的重要性，胺的有益硅烷醇掩蔽特性以及通过离子对相互作用进行选择性修饰的潜力，我们将环己胺作为流动相添加剂进行了研究，并将其与三乙胺和三氟乙酸进行了比较。与磷酸盐缓冲液相比，使用环己胺可以大大提高分离度，并且在使用前不需要纯化环己胺，而在获得“干净”色谱图之前，需要对三乙胺进行蒸馏。

BACKGROUND & AIMS: :Infection with H pylori leads to a persistent chronic inflammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between H pylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of the world. Prevalence rates in Western countries are decreasing, especially in younger people (< 10%); and a decline in distal gastric adenocarcinoma has been observed. Risk groups in Western countries still show considerably higher risk of developing cancer, especially in patients infected with cagA+ strains and in persons harboring genetic polymorphism of the IL-1B promoter (-511T/T) and the corresponding IL-1 receptor antagonist (IL-1RN*2). Thus, general eradication of all infected persons in Western countries not recommended and is limited to risk groups in order to achieve a risk reduction. In contrast, infection rates and cancer prevalence are still high in East Asian countries. A prevention strategy to treat infected persons may avoid the development of gastric cancer to a large extent and with enormous clinical importance. However, studies in China and Japan indicate that prevention of gastric cancer is effective only in those patients that do not display severe histological changes such as atrophy and intestinal metaplasia. Thus, prophylactic strategies to prevent gastric cancer in high risk populations such as China should therefore especially aim at individuals now at younger age when the histological alterations caused by the bacterial infection was still reversible. In countries with a low prevalence of gastric cancer, risk groups carrying cagA+ strains and IL-1 genetic polymorphisms should be identified and treated.

背景与目标： 幽门螺杆菌感染导致胃粘膜持续性慢性炎症，从而增加了远端胃腺癌的风险。大量研究已确定幽门螺杆菌感染与胃癌风险之间存在明显的相关性。但是，不建议普遍根除，因为在世界不同地区，癌症的预防和治疗时间仍然存在争议。西方国家的患病率正在下降，尤其是在年轻人中（<10％）；并且已经观察到远端胃腺癌的下降。西方国家的风险人群仍然显示出罹患癌症的高得多的风险，尤其是在感染cagA株的患者以及具有IL-1B启动子（-511T / T）和相应的IL-1受体拮抗剂（IL- 1RN * 2）。因此，不建议在西方国家全面消灭所有感染者，并且仅限于风险人群，以实现降低风险的目的。相反，东亚国家的感染率和癌症患病率仍然很高。治疗感染者的预防策略可以在很大程度上避免胃癌的发展，并且具有巨大的临床意义。但是，在中国和日本的研究表明，胃癌的预防仅对那些没有表现出严重的组织学改变（例如萎缩和肠化生）的患者有效。因此，在中国这样的高风险人群中，预防胃癌的预防策略应特别针对年龄较小的人群，因为这些年龄段的细菌感染引起的组织学改变仍然是可逆的。在胃癌患病率较低的国家，应识别和治疗携带cagA毒株和IL-1遗传多态性的危险人群。

BACKGROUND & AIMS: Genomic instability at simple repeated sequences has been observed in various types of human cancers and is considered an important mechanism in tumorigenesis. Alterations at microsatellite loci have been reported scattered throughout the genome. Recently, the transforming growth factor-beta receptor type II (TGF-beta RII) and the insulin-like growth factor II receptor (IGF-IIR) genes were shown to have inactivating mutations within coding microsatellite sequences. The demonstration of mutations in two growth regulatory genes supports the idea that other regulatory genes with repeat sequences may also be targets in tumours with defective mismatch repair. We examined genes involved in tumour suppression, cell adhesion and cell cycle regulation for mutations at small repeat sequences in replication error positive gastrointestinal cancers. Several polymorphisms were found which exhibited instability, but no other instability was present in the regions examined.

背景与目标： 在各种类型的人类癌症中已经观察到简单重复序列的基因组不稳定性，并且被认为是肿瘤发生的重要机制。据报道，微卫星基因座的改变分散在整个基因组中。最近，研究表明转化生长因子β受体II型（TGF-βRII）和胰岛素样生长因子II受体（IGF-IIR）基因在编码微卫星序列中具有失活突变。两个生长调节基因突变的证明支持了这样的想法，即具有重复序列的其他调节基因也可能是错配修复缺陷的肿瘤的靶标。我们检查了涉及复制抑制阳性胃肠道癌中小重复序列突变的肿瘤抑制，细胞粘附和细胞周期调控的基因。发现了几个表现出不稳定性的多态性，但在检查的区域中没有其他不稳定性。

BACKGROUND & AIMS: :The pathogenicity of the plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria depends on a type III secretion system which is encoded by the 23-kb hrp (hypersensitive response and pathogenicity) gene cluster. Expression of the hrp operons is strongly induced in planta and in a special minimal medium and depends on two regulatory proteins, HrpG and HrpX. In this study, DNA affinity enrichment was used to demonstrate that the AraC-type transcriptional activator HrpX binds to a conserved cis-regulatory element, the plant-inducible promoter (PIP) box (TTCGC-N(15)-TTCGC), present in the promoter regions of four hrp operons. No binding of HrpX was observed when DNA fragments lacking a PIP box were used. HrpX also bound to a DNA fragment containing an imperfect PIP box (TTCGC-N(8)-TTCGT). Dinucleotide replacements in each half-site of the PIP box strongly decreased binding of HrpX, while simultaneous dinucleotide replacements in both half-sites completely abolished binding. Based on the complete genome sequence of Xanthomonas campestris pv. vesicatoria, putative plant-inducible promoters consisting of a PIP box and a -10 promoter motif were identified in the promoter regions of almost all HrpX-activated genes. Bioinformatic analyses and reverse transcription-PCR experiments revealed novel HrpX-dependent genes, among them a NUDIX hydrolase gene and several genes with a predicted role in the degradation of the plant cell wall. We conclude that HrpX is the most downstream component of the hrp regulatory cascade, which is proposed to directly activate most genes of the hrpX regulon via binding to corresponding PIP boxes.

背景与目标： ：植物致病性细菌Xanthomonas campestris pv的致病性。 vesicatoria依赖于由23-kb hrp（过敏反应和致病性）基因簇编码的III型分泌系统。 hrp操纵子的表达在植物和特殊的基本培养基中强烈诱导，并依赖于两种调节蛋白HrpG和HrpX。在这项研究中，DNA亲和力富集用于证明AraC型转录激活因子HrpX与保守的顺式调控元件，即植物诱导型启动子（PIP）框（TTCGC-N（15）-TTCGC）结合，四个hrp操纵子的启动子区域。当使用缺少PIP盒的DNA片段时，未观察到HrpX的结合。 HrpX还绑定到包含不完整的PIP盒（TTCGC-N（8）-TTCGT）的DNA片段。 PIP盒每个半位中的二核苷酸替换强烈降低了HrpX的结合，而两个半位中同时进行的二核苷酸替换则完全消除了结合。基于Xanthomonas campestris pv的完整基因组序列。在几乎所有的HrpX激活基因的启动子区域中，鉴定出了由vesptoria组成的假定的植物诱导型启动子，该启动子由PIP框和-10个启动子组成。生物信息学分析和逆转录-PCR实验揭示了新的HrpX依赖性基因，其中包括NUDIX水解酶基因和几个在植物细胞壁降解中具有预测作用的基因。我们得出的结论是，HrpX是hrp调节级联的最下游组件，建议通过与相应的PIP盒结合直接激活hrpX regulon的大多数基因。

BACKGROUND & AIMS: OBJECTIVE:The mechanism behind the epidemiologically evident inverse relation between Helicobacter pylori seropositivity and risk of oesophageal adenocarcinoma (OAC) remains obscure. Severe corpus gastritis is unlikely to be in the causal pathway. With the hypothesis of a uniformly low risk, the associations of OAC with duodenal ulcer and gastric ulcer were explored, both linked to H pylori infection but with different patterns of bacterial colonisation and intragastric acidity. Possible associations of oesophageal squamous cell carcinoma (OSCC) with these ulcer types were also addressed. DESIGN AND PATIENTS:Retrospective cohorts of 61,548 and 81,379 unoperated patients with duodenal ulcer and gastric ulcer, respectively, recorded in the Swedish Inpatient Register since 1965, were followed from the first hospitalisation until the date of any cancer, death, emigration, definitive surgery, or 31 December 2003. Standardised incidence ratios (SIRs), with 95% CIs, expressed relative risk of oesophageal cancer, compared with the Swedish population matched for age, sex and calendar period. RESULTS:Contrary to expectation, patients with duodenal ulcer had a significant 70% excess risk of OAC (SIR 1.7, 95% CI 1.1 to 2.5). Gastric ulcer was unrelated to OAC (SIR 1.1, 95% CI 0.6 to 1.7). Although duodenal ulcer was non-significantly associated with a small excess of OSCC (SIR 1.3, 95% CI 0.96 to 1.8), gastric ulcer was linked to 80% increased risk (SIR 1.8, 95% CI 1.4 to 2.3). CONCLUSION:The inverse association between H pylori and OAC does not pertain to all infections. The pattern of gastric colonisation and/or impact on acidity may be important. With the reservation for the possibility of confounding, this study also provides some support for the importance of intragastric environment in the aetiology of OSCC.

背景与目标： 目的：幽门螺杆菌血清阳性与食管腺癌（OAC）风险之间的流行病学证据呈负相关。严重的胃炎胃炎不太可能在因果关系中。假设风险均一，探讨了OAC与十二指肠溃疡和胃溃疡的相关性，两者均与幽门螺杆菌感染有关，但细菌定植和胃内酸度不同。食管鳞状细胞癌（OSCC）与这些溃疡类型的可能关联也得到了解决。
设计和患者：自1965年以来在瑞典住院患者登记表中记录的分别有61,548和81,379例未手术的十二指肠溃疡和胃溃疡患者的回顾性队列，从首次住院治疗直至癌症，死亡，移民，定型手术，或2003年12月31日。与年龄，性别和日历时期相匹配的瑞典人口相比，具有95％CI的标准发生率（SIR）表示食道癌的相对风险。
结果：与预期相反，十二指肠溃疡患者发生OAC的风险显着增加70％（SIR 1.7，95％CI 1.1至2.5）。胃溃疡与OAC无关（SIR 1.1，95％CI 0.6至1.7）。尽管十二指肠溃疡与OSCC的少量过量无显着相关性（SIR 1.3，95％CI 0.96至1.8），但胃溃疡与80％的风险增加相关（SIR 1.8，95％CI 1.4至2.3）。
结论：幽门螺杆菌与OAC之间的负相关并不适用于所有感染。胃定植的模式和/或对酸度的影响可能很重要。由于保留了混淆的可能性，本研究还为胃内环境在OSCC病因中的重要性提供了一些支持。

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: :The prevalence of mRNAs coding for the sea urchin embryo regulatory factors P3A1 and P3A2 was measured by single-strand probe excess solution hybridization. P3A1 and P3A2 are not homologous proteins, though they both bind specifically to a particular cis-regulatory sequence. Interaction at this target site is known to be required for lineage-specific expression of an aboral ectoderm-specific gene and probably for several other genes as well. Genome blot hybridizations show that both factors are encoded by single-copy genes. Maternal mRNAs for both factors are present at less than 10(3) molecules per egg, which places them in the rare mRNA class. During development to the mesenchyme blastula stage, the amount of P3A1 mRNA (per embryo) increases severalfold while that of P3A2 remains approximately constant. Specification of the aboral ectoderm founder cells and of their initial patterns of gene expression must occur during early to mid-cleavage stage. Therefore, the regulatory proteins needed for this process must be produced by this stage. We show that the quantities of the P3A proteins that can be synthesized from the numbers of mRNA molecules present in the large blastomeres of the early embryo are sufficient to be functional, because these proteins will be accumulated in the nuclei. Thus maternal P3A1 or P3A2 proteins asre not required, nor were these detected in earlier studies. Furthermore, differential spatial (as well as temporal) distribution of both of these newly synthesized factor species could result from the unequal cleavage pattern utilized in the sea urchin egg.

背景与目标： ：通过单链探针过量溶液杂交测量编码海胆胚胎调节因子P3A1和P3A2的mRNA的发生率。尽管P3A1和P3A2都与特定的顺式调控序列特异性结合，但它们不是同源蛋白。已知该靶标位点的相互作用是特定于宗族的外胚层特异性基因的谱系表达所必需的，并且可能还需要其他几个基因。基因组印迹杂交显示这两个因子均由单拷贝基因编码。每个鸡蛋的母体mRNA均少于10（3）个分子，这使它们处于罕见的mRNA类中。在发育到间充质囊阶段期间，P3A1 mRNA（每个胚胎）的数量增加了几倍，而P3A2的数量则保持大致恒定。胎盘外胚层基础细胞及其基因表达的初始模式的规范必须在卵裂早期至中期进行。因此，必须在该阶段生产该过程所需的调节蛋白。我们表明，可以从早期胚胎的大型卵裂球中存在的mRNA分子数量合成的P3A蛋白数量足以发挥功能，因为这些蛋白将积聚在细胞核中。因此，不需要母体P3A1或P3A2蛋白，也不需要在早期研究中检测到这些蛋白。此外，这两种新合成的因子物种在空间（以及时间）上的差异分布可能是由于海胆卵中使用的不均等卵裂模式造成的。

BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌症疼痛患者中吗啡连续静脉输注（CIVI）与吗啡连续皮下输注（CSCI）的剂量，疗效和副作用。符合条件的患者被转到姑息治疗计划，并接受稳定剂量的吗啡CIVI。该设计是患者内部的单向交叉。其中每个患者提供了从吗啡从CIVI切换到CSCI之前和之后的数据。 “救援”剂量是根据需要每2小时给予的每小时剂量的50％。吗啡通过McGaw / AccuPro容量输注泵静脉内（i.v.）和皮下（s.c.）输注。获得包括副作用和疼痛评估在内的基线数据后，每天对患者进行两次毒性和止痛效果评估。连续48个小时具有稳定CIVI剂量的患者以与静脉内（i.v.）阶段相同的剂量转入CSCI。稳定剂量定义为无剂量变化，在过去24小时内有四个或更少的急救剂量，疼痛等级为无或轻度。如果连续96个小时保持这些标准，则认为CIVI等于CSCI。入组患者57例，其中40例可评估（女性15例，男性25例）。中位年龄为67岁（范围为30-83岁）。在整个静脉内维持稳定剂量后，所有40位参与者阶段，跨到南卡罗来纳州相并保持在s.c.至少持续48小时。在整个静脉内，有32名患者维持了稳定的剂量。和s.c.阶段。平均稳定i.v.剂量（第2天）为5.05 mg / hr，平均稳定s.c.剂量（第4天）为5.7 mg / hr（P = 0.01）。第2天的平均急救剂量为每24小时0.83，而第4天为每24小时0.80（P = 0.6）。第2天的平均类别疼痛评分为0.83，第4天的平均疼痛评分为0.85（P = 0.7）。第2天的平均视觉模拟量表（VAS）为22.9毫米，而第4天为17.6毫米（P = 0.1）。第2天的副作用的平均发生率为1.7，而第4天的平均发生率为2.0（P = 0.2）。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点的局部毒性（轻度红斑）的报道，需要进行部位改变。我们所有的40名患者均通过CIVI和CSCI吗啡可以很好地控制疼痛。在没有保持相同i.v.的八位参与者中和s.c.剂量较高时，所有患者均具有足够的疼痛控制能力，并且在较高的s.c.下具有相似的副作用。吗啡剂量。这些数据表明和s.c.当以连续输注方式给药时，对于大多数患者而言，这两种途径均具有镇痛作用。疼痛控制和副作用状况非常相似且可以接受。南卡罗来纳州吗啡是静脉注射的绝佳替代品。需要胃肠外吗啡治疗的住院患者和门诊患者中的吗啡疼痛。

BACKGROUND & AIMS: :In this review, we focused on our studies of cancer dormancy in a murine B cell lymphoma and human breast cancer. Lifelong dormancy was induced in syngeneic mice by prior immunization to the idiotype of the tumor cell (TC) Ig before TC challenge. The mice maintained approximately 10(6) lymphoma cells in their spleen throughout their lifetime despite replication of the TCs at a reduced rate. Recurrences occurred randomly. Because of the balance between replication and cell death, we hypothesized that a similar balance might occur in long-term survivors of breast cancer when the risk of recurrences is very low. We developed a sensitive assay for circulating tumor cells (CTCs) which none were found in normal age-matched women. One third of patients, 7-22 years after mastectomy and without any evidence of disease, had CTCs. The half-life of these CTCs could be deduced from other studies as probably 2-3 hours. Hence, there was a precise balance between replication of TCs (presumably from micrometastases) and cell death. Therefore, a major population of clinically cured breast cancer patients have a chronic disease controlled by their own physiological mechanisms. We speculate on underlying mechanisms based both on studies in experimental models and clinical trials.

背景与目标： ：在这篇综述中，我们集中于对小鼠B细胞淋巴瘤和人类乳腺癌的癌症休眠研究。通过在TC攻击之前先对肿瘤细胞（TC）Ig的独特型进行免疫，可以在同系小鼠中终生休眠。尽管TCs的复制率降低了，但小鼠的一生中仍在脾脏中维持着约10（6）个淋巴瘤细胞。复发随机发生。由于复制和细胞死亡之间的平衡，我们假设当复发风险非常低时，长期存活的乳腺癌患者可能会发生类似的平衡。我们开发了一种循环肿瘤细胞（CTC）的灵敏检测方法，在正常年龄的女性中均未发现。乳房切除术后7-22年且无任何疾病证据的三分之一患者患有CTC。这些CTC的半衰期可以从其他研究中推断出来，大概为2-3小时。因此，在TC的复制（可能来自微转移）和细胞死亡之间存在着精确的平衡。因此，大部分临床治愈的乳腺癌患者患有受其自身生理机制控制的慢性疾病。我们基于实验模型和临床试验研究潜在的机制。

BACKGROUND & AIMS: The GATA family of vertebrate DNA binding regulatory proteins are expressed in diverse tissues and at different times of development. However, the DNA binding regions of these proteins possess considerable homology and recognize a rather similar range of DNA sequence motifs. DNA binding is mediated through two domains, each containing a zinc finger. Previous results have led to the conclusion that although in some cases the N-terminal finger can contribute to specificity and strength of binding, it does not bind independently, whereas the C-terminal finger is both necessary and sufficient for binding. Here we show that although this is true for the N-terminal finger of GATA-1, those of GATA-2 and GATA-3 are capable of strong independent binding with a preference for the motif GATC. Binding requires the presence of two basic regions located on either side of the N-terminal finger. The absence of one of these near the GATA-1 N-terminal finger probably accounts for its inability to bind. The combination of a single finger and two basic regions is a new variant of a motif that has been previously found in the binding domains of other finger proteins. Our results suggest that the DNA binding properties of the N-terminal finger may help distinguish GATA-2 and GATA-3 from GATA-1 and the other GATA family members in their selective regulatory roles in vivo.

背景与目标： GATA家族的脊椎动物DNA结合调节蛋白在不同的组织中以及在不同的发育时期表达。但是，这些蛋白质的DNA结合区具有相当的同源性，可以识别相当相似范围的DNA序列基序。 DNA结合是通过两个结构域介导的，每个结构域都包含一个锌指。先前的结果得出的结论是，尽管在某些情况下N末端指可以有助于结合的特异性和强度，但它不能独立地结合，而C末端指对于结合既是必需的又是足够的。在这里，我们表明，尽管对于GATA-1的N端手指来说确实如此，但GATA-2和GATA-3的手指却能够强烈独立地结合，并优先选择基序GATC。绑定需要在N末端指状体的两侧都存在两个基本区域。在GATA-1 N端手指附近缺少这些手指之一可能是其无法结合的原因。单个手指和两个基本区域的组合是一个基序的新变体，该变体先前已在其他手指蛋白的结合域中发现。我们的结果表明，N末端手指的DNA结合特性可能有助于区分GATA-2和GATA-3与GATA-1和其他GATA家族成员在体内的选择性调节作用。

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织化学方法将PSA定位在27个石蜡包埋的乳腺组织中。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（尤其是轻度导管）偶尔染色为阳性，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: :Pigment-dispersing factor (PDF) is an 18-mer peptide that acts as a principal neurotransmitter of the insect circadian clock. Our previous study, utilizing anti-Uca beta-PDH polyclonal antibody (pAb) to immunolabel the optic lobe of the cricket Gryllus bimaculatus, suggested the existence of an alternative PDF-like peptide in the outer cells of the first neuropile, or lamina (La), which were much less immunoreactive than the inner cells of the second neuropile, the medulla (Me). To obtain structural information about such a PDF-like peptide, we prepared 10 anti-Gryllus PDF monoclonal (mAb) and pAb antibodies and analyzed their detailed epitope specificities. The PDFMe and PDFLa inner cells and their axonal projections were clearly immunoreactive to all these antibodies, revealing the widespread immunocytochemical organization of the PDF system in the optic lobe, as seen previously with anti-Uca beta-PDH pAb and anti-Gryllus PDF mAb, the epitope structures of which were also clarified in this study. The lamina outer cells, which we found lacked a target pdf mRNA, displayed specific immunoreactivities, indicating that the cells contain a distinct PDF-like peptide possessing both N- and C-terminal structures. These cells were not immunolabeled by some other monoclonal antibodies, however, implying that the PDFLa outer cells have a PDF isoform peptide devoid of Asn at positions 6 and 16. This isoform was also identified in a varicose arborization in the lamina. These results suggest not only the structure of the peptide, but also the possibility of additional functions of this novel PDF isoform.

背景与目标： ：色素分散因子（PDF）是一种18-mer肽，可作为昆虫生物钟的主要神经递质。我们先前的研究使用抗Uca beta-PDH多克隆抗体（pAb）免疫标记bi Gryllus bimaculatus的视神经叶，这表明在第一个神经堆或椎板（Laina）的外层细胞中存在另一种PDF样肽），其免疫反应性比第二神经堆髓质（Me）的内部细胞低。为了获得有关此类PDF样肽的结构信息，我们制备了10种抗Gryllus PDF单克隆（mAb）和pAb抗体，并分析了其详细的表位特异性。 PDFMe和PDFLa内细胞及其轴突投影显然对所有这些抗体具有免疫反应性，揭示了视神经上PDF系统的广泛免疫细胞化学组织，如先前在抗Uca beta-PDH pAb和抗Gryllus PDF mAb中所见，在本研究中也阐明了其表位结构。我们发现缺乏目标pdf mRNA的层状外层细胞表现出特异性的免疫反应性，表明该细胞含有具有N和C端结构的截然不同的PDF样肽。这些细胞没有被其他一些单克隆抗体免疫标记，但是，这意味着PDFLa外层细胞在位置6和16处都具有不含Asn的PDF同工型肽。这些结果不仅表明了肽的结构，而且还暗示了这种新型PDF同工型具有其他功能的可能性。

BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： ：据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了低氧刺激是否影响基质和胰腺癌细胞。我们的研究结果表明，缺氧显着提高了胰腺癌（PK8）和成纤维细胞（MRC5）中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用由低氧MRC5细胞制备的条件培养基（低氧条件培养基）培养低氧PK8细胞时，侵袭性进一步加快。在缺氧条件下，PK8细胞中的MMP-2，MMP-7，MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子（HGF）分泌，这导致PK8细胞中c-Met磷酸化的升高。相反，通过从低氧条件培养基中除去HGF，可以降低PK8细胞的癌浸润，MMP活性和c-Met磷酸化升高。在免疫组织化学研究中，在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达，因此表明在癌细胞和基质细胞中均存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统，从而促进了胰腺癌的侵袭性侵袭性特征。

BACKGROUND & AIMS: :Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type, and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal-type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor-suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials.

背景与目标： ：尽管在对抗胃癌方面取得了长足的进步，但它仍然是由特殊的组织学和分子学特征定义的复杂致死性疾病。本研究的目的是研究pRb2 / p130，VEGF，EZH2，p53，p16（INK4A），p27（KIP1），p21（WAF1），Ki-67的表达，并分析它们与临床病理因素的可能关系。通过免疫组织化学检查了47例患者的表达模式，其中27例为肠型，20例为弥散型，平均随访56个月，并通过Western blot检测AGS，N87，KATO-III和YCC-2 ，-3，-16个胃细胞系。总体而言，胃癌显示EZH2与高水平的p53，Ki-67和细胞质pRb2 / p130相关（分别为P <0.05和P <0.01）。在肠型中发现EZH2表达增加，并且与远处转移的风险相关（分别为P <0.05和P <0.01），表明该蛋白可能在这种类型的癌症中具有预后价值。有趣的是，观察到p27（KIP1）表达水平与晚期疾病和转移的风险之间存在强烈的负相关（P <0.05），而p21（WAF1）和低度胃癌（G1）的表达水平之间呈正相关。肿瘤（P <0.05），证实了这些肿瘤抑制基因在胃癌中的传统接受作用。最后，在核pRb2 / p130的表达水平与低度（G1）胃肿瘤的表达水平之间发现了直接相关性，具有统计学意义（P <0.05）。总之，这些数据可能有助于进一步阐明与两种主要胃癌组织学类型及其侵袭潜能有关的致病机制。