BACKGROUND & AIMS: We report on an association study between a tetranucleotide repeat polymorphism in the GABR beta1 gene and manic-depressive illness in a Spanish population. This gene may be an important candidate for bipolar affective disorders since severe GABergic alterations have been described in patients. Although our results do not reveal a clear evidence for association between manic-depressive illness and GABR beta1, we have found significant differences between patients and controls in the female subpopulation.

背景与目标： 我们报告了GABR beta1基因中的四核苷酸重复多态性与西班牙人群的躁狂抑郁症之间的关联研究。该基因可能是双相情感障碍的重要候选者，因为已在患者中描述了严重的GAB能改变。尽管我们的结果并未显示出躁狂抑郁症与GABR beta1之间存在关联的明确证据，但我们发现女性亚人群中的患者与对照组之间存在显着差异。

BACKGROUND & AIMS: PURPOSE:A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues. EXPERIMENTAL DESIGN:Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models. RESULTS:Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (

BACKGROUND & AIMS: :Passive immunity against gastrointestinal infections has recently been successfully applied as prophylaxis and therapy in patients in a variety of virally and bacterially induced infections. Campylobacter jejuni is frequently associated with acute diarrhoea in humans, and several species of animals have been shown to transmit the disease, although birds have been implicated as the main source of infection. We used bovine and chicken immunoglobulin preparations from the milk and eggs, respectively, of immunized animals for prophylactic and therapeutic treatment of chickens infected with C. jejuni. A marked prophylactic effect (a >99% decrease in the number of bacteria) was noted using either antibody preparation, whereas the therapeutic efficacy, i.e. when antibodies were given after the infection was established, was distinctly lower (80-95%) as judged by faecal bacterial counts. These observations may serve as a starting point for experiments aimed at elimination of the infection in an industrial or farm setting. It may also encourage future attempts to treat, prophylactically or therapeutically, patients with Campylobacter-induced diarrhoea.

背景与目标： ：最近，针对胃肠道感染的被动免疫已成功应用于各种病毒和细菌引起的感染的预防和治疗中。空肠弯曲菌常与人类急性腹泻有关，尽管鸟类被认为是主要的感染源，但已显示出几种动物可传播这种疾病。我们分别使用免疫动物的牛奶和鸡蛋中的牛和鸡免疫球蛋白制剂对空肠弯曲杆菌感染的鸡进行预防和治疗。两种抗体制剂均具有显着的预防作用（细菌数量减少> 99％），而判断的治疗效果（即在感染确定后给予抗体）则明显较低（80-95％）通过粪便细菌计数。这些观察结果可作为旨在消除工业或农场感染的实验的起点。它还可能鼓励将来尝试预防性或治疗性弯曲杆菌引起的腹泻患者。

BACKGROUND & AIMS: OBJECTIVES:Cases of hypophosphataemia (often coincident with renal dysfunction) have been reported in HIV-infected patients taking tenofovir disoproxil fumarate (TDF), but randomized placebo-controlled trials of HIV-infected persons with normal baseline renal function have found a comparable incidence of hypophosphataemia in the TDF and placebo groups. We assessed the incidence of grade 2 and higher hypophosphataemia in the HIV Outpatient Study (HOPS). METHODS:We analysed a prospective cohort of patients who initiated either a TDF-containing highly active antiretroviral therapy (HAART) regimen [TDF-exposed (TDF+) group; n = 165] or a TDF-sparing HAART regimen [TDF-unexposed (TDF-) group; n = 90], and who had normal baseline phosphate and creatinine values. RESULTS:The TDF+ and TDF- groups had comparable median follow-up times (10.9 vs 8.8 months, respectively; P = 0.18) and number of phosphate measurements (median = 3 for both) and were similar on most clinical and demographic factors. During follow up, 12.7% of TDF+vs 6.7% of TDF-patients developed grade 2 hypophosphataemia (2.0-2.4 mg/dL), and 2.4% of TDF+ patients vs 0% of TDF-patients developed grade 3 hypophosphataemia (1.0-1.9 mg/dL); none developed grade 4 hypophosphataemia (<1.0 mg/dL). The incidence of grade 2 or higher hypophosphataemia was 16.7 per 100 person-years among TDF+ patients vs 8.0 per 100 person-years among TDF-patients (P = 0.11). CONCLUSIONS:The incidence of hypophosphataemia was somewhat elevated in HOPS patients who took TDF-containing HAART compared with those who took TDF-sparing HAART during the first 1 to 2 years of observation, but the difference was not statistically significant. Longer follow-up of a larger population is needed to determine if this trend towards an association achieves statistical significance and to evaluate the clinical consequences of hypophosphataemia.

背景与目标： 目的：已经报道了接受替诺福韦二富马酸富马酸酯（TDF）感染HIV的患者发生低血磷的情况（通常与肾功能不全同时发生），但基线肾功能正常的HIV感染者的随机安慰剂对照试验发现TDF和安慰剂组的低磷血症。我们在HIV门诊研究（HOPS）中评估了2级和更高的低血磷的发生率。
方法：我们分析了开始采用含TDF的高活性抗逆转录病毒疗法（HAART）方案[TDF暴露（TDF）组）的患者的前瞻性队列研究。 n = 165]或保留TDF的HAART方案[未暴露TDF（TDF-）的组； n = 90]，并且基线磷酸盐和肌酐值正常。
结果：TDF和TDF-组的中位随访时间（分别为10.9和8.8个月； P = 0.18）和磷酸盐测量次数（两者的中位数= 3）具有可比性，并且在大多数临床和人口统计学因素上相似。在随访期间，TDF的12.7％与TDF的患者的6.7％发生了2级低血磷（2.0-2.4 mg / dL），TDF的2.4％vs TDF的患者中出现了3级的低血磷（1.0-1.9 mg） / dL）;没有一个发生4级低血磷（<1.0 mg / dL）。 TDF患者中2级或更高水平低血磷的发生率为每100人年16.7人，而TDF患者为每100人年8.0人（P = 0.11）。
结论：在观察的头1至2年中，与含TDF的HAART的HOPS患者相比，接受含TDF的HAART的HOPS患者的低磷酸盐血症发生率有所升高，但差异无统计学意义。需要对更大的人群进行更长时间的随访，以确定这种联系趋势是否达到统计学意义并评估低血磷的临床后果。

BACKGROUND & AIMS: :Neoadjuvant or adjuvant multimodality therapy in oesophageal cancer is introduced in an effort to improve prognosis. However, in a substantial fraction of patients there is no response to this non-surgical therapy. Non-invasive imaging modalities such as computed tomography (CT), endoscopic ultrasound (EUS) and 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) have been evaluated for assessing patient response to therapy, and these are described in this review. Currently, FDG-PET seems to be the best available tool for neoadjuvant therapy response assessment in oesophageal cancer.

背景与目标： ：在食管癌中引入新辅助或辅助多模治疗以改善预后。但是，在相当一部分患者中，对这种非手术疗法没有任何反应。已评估了计算机断层扫描（CT），内窥镜超声（EUS）和18F-2-氟-2-脱氧-d-葡萄糖正电子发射断层扫描（FDG-PET）等非侵入性成像方式，以评估患者对治疗的反应，并在这篇评论中对此进行了描述。目前，FDG-PET似乎是食管癌新辅助治疗反应评估的最佳可用工具。

BACKGROUND & AIMS: :Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.

背景与目标： ：Rhodopseudomonas palustris是一种紫色的兼性光养细菌，它利用氢气作为电子供体，在光养植物生长过程中固定二氧化碳，或在固氮过程中合成氨气。它还使用氢作为电子补充剂，以在光异养生长期间将氧化的碳化合物（例如苹果酸）完全同化到细胞材料中。 R. palustris基因组预测膜结合的镍铁摄取氢化酶和几种调节蛋白来控制氢化酶的合成。与氢化酶基因簇直接相邻的还有一个新的传感器激酶基因（RPA0981）。在这里，我们显示帕氏疟原虫调节传感器氢化酶HupUV与传感器激酶响应调节蛋白对HoxJ-HoxA共同作用，以响应氢气激活氢化酶表达。转录组分析表明，HupUV-HoxJA调节系统还控制编码预测的二羧酸转运系统，推定的甲酸盐转运蛋白和谷氨酰胺合成酶的基因的表达。 RPA0981在抑制氢化酶合成方面作用很小。我们还确定了两组分系统RegS-RegR抑制摄取氢化酶的表达，可能是响应细胞内氧化还原状态的变化。转录组分析表明，与缺乏摄取氢酶的突变菌株相比，当在固氮条件下在苹果酸上光异养生长时，利用氢的pal.ris细胞中约有30个基因差异表达。由此看来，还原剂以氢的形式的循环利用对R. palustris的基因表达没有广泛的非特异性影响。

BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.

背景与目标： 背景：我们检查了膀胱癌中P53基因的杂合性（LOH）缺失，并研究了P53基因在乳头状瘤恶性进展中的作用。另外，检查了复发性膀胱癌的克隆性。
方法：分析了47例患者的67例膀胱癌中P53基因的LOH。从福尔马林固定，石蜡包埋的组织中提取DNA，在P53基因的3个多态性位点处通过聚合酶链反应（PCR）进行扩增，并通过非放射性同位素单链构象多态性（Non-RI SSCP）分析。
结果：在40个信息量样本中，在13个样本中检测到LOH，其中3个7级中有4个（57％），2个23级中有9个（39％），1个10级中没有10个（10％）。在1级和2级以及1级和3级的LOH之间观察到统计学意义。对5例恶性进展的分析表明，3例（60％）在原发性肿瘤中显示LOH，2例在复发性肿瘤中显示LOH。 ，与LOH在19例（16％）的3例中未显示出恶性进展的情况相反。 4例异时复发表现为LOH。在复发性肿瘤中2个，仅在初始肿瘤中1个，在两个肿​​瘤中1个。
结论：P53基因的改变被认为与肿瘤的分级有关，并有助于膀胱癌的恶性进展。 P53基因中的LOH可作为浅表性膀胱癌预后的临床指标。

BACKGROUND & AIMS: :With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5-year overall survival (OS) was improved by the addition of rituximab-61% with rituximab-CHOP-ESHAP, compared with 43% for CHOP-ESHAP-HDT and 24% for CHOP alone (p = 0.088). Significant increases in failure-free survival (FFS) and disease-free survival (DFS) (61% and 96%), compared with CHOP-ESHAP-HDT (34% and 90%) and CHOP (16% and 44%; p = 0.002 and p < 0.001, respectively) were observed. Compared to CHOP, rituximab-CHOP-ESHAP yielded significantly superior OS (p = 0.014), FFS (p < 0.001) and DFS (p < 0.001). The survivals, however, were not significantly different from patients treated with CHOP-ESHAP-HDT. It is concluded that rituximab-ESHAP-CHOP is superior over standard CHOP and fares comparably to upfront HDT/ASCT in previously untreated patients with aggressive lymphoma. A prospective randomized controlled trial is warranted to confirm these results.

背景与目标： ：在目前可用的联合化疗方案下，根据国际预后指数（IPI）刚被诊断为侵袭性非霍奇金淋巴瘤（NHL）的患者的预后仍然不尽人意，并且迫切需要一种更具创新性的疗法来提高患者的生存率。这项研究的目的是比较利妥昔单抗与CHOP（环磷酰胺，阿霉素，长春新碱，泼尼松）和ESHAP（依托泊苷，甲基泼尼松龙，大剂量Ara-C，顺铂）联合使用时与CHOP-ESHAP和前期高剂量联合治疗的疗效在该研究所进行的两项连续治疗试验中，对新诊断为“高”和“高中度”风险性侵袭性淋巴瘤的年龄≤65岁的患者进行剂量治疗（HDT）和自体干细胞移植（ASCT）与标准CHOP的比较。在1995年5月至2002年7月之间，纳入了84例年龄在15至65岁之间，新诊断为侵袭性NHL且年龄调整后的IPI为2或3的患者。患者的中位年龄为38岁（范围15-65）。治疗组之间的基线人口统计学特征，尤其是主要的预后变量相似。接受利妥昔单抗-CHOP-ESHAP治疗的患者接受了八个周期的利妥昔单抗（第1-6周期的第1天以及第7周期的第21和28天为375 mg m（-2））加CHOP（第1、3和5周期的第3天） ）和ESHAP（周期2、4和6的第3天和周期7的第1天），间隔为21天。入组CHOP-ESHAP-HDT组（n = 23）的患者接受了三个疗程的CHOP治疗，然后切换到ESSHAP的两个或四个周期，然后进行HDT。单独接受CHOP治疗的患者（n = 25）接受了标准的八个CHOP周期治疗。与单独使用CHOP-ESHAP-HDT或CHOP相比，利妥昔单抗-CHOP-ESHAP的完全缓解率显着提高（分别为67％，44％和36％； p = 0.043）。中位随访时间为53个月，利妥昔单抗-CHOP-ESHAP加利妥昔单抗-61％改善了5年总生存（OS），相比之下，CHOP-ESHAP-HDT和43％改善了5年总生存率仅适用于CHOP（p = 0.088）。与CHOP-ESHAP-HDT（34％和90％）和CHOP（16％和44％）相比，无失败生存率（FFS）和无病生存率（DFS）显着增加（61％和96％）；分别观察到= 0.002和p​​ <0.001）。与CHOP相比，利妥昔单抗-CHOP-ESHAP产生显着优越的OS（p = 0.014），FFS（p <0.001）和DFS（p <0.001）。但是，其存活率与用CHOP-ESHAP-HDT治疗的患者无明显差异。结论是，对于先前未经治疗的侵袭性淋巴瘤患者，利妥昔单抗-ESHAP-CHOP优于标准CHOP，且其费用可与前期HDT / ASCT相提并论。必须进行前瞻性随机对照试验来证实这些结果。

BACKGROUND & AIMS: :In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains. KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580 amino-acids has a relative molecular mass (Mr) of approximately 65,000 (65 K). The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue. High levels of expression were as well found in tissue samples of other human tumours. As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes. However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.

背景与目标： ：在先前针对胰腺癌中差异表达基因的大规模筛选中，我们鉴定了在癌症中高度过表达的基因，该基因编码具有四个K同源（KH）域的新型蛋白质。 KH结构域存在于RNA结合蛋白的子集中，包括前mRNA结合（hnRNP）K蛋白和脆弱的X智力低下基因产物（FMR1）。通过荧光原位杂交（FISH），将鉴定出的名为koc（在癌症中过表达的KH域蛋白）的基因分配给7p11.5染色体。两个假基因位于6号和11号染色体上。克隆的koc cDNA具有250 bp的5'-UTR，1740 bp的ORF和2168 bp的3'-UTR。富含AU的3'非翻译区域的koc包含八个AUUUA和四个AUUUUUA重复的基序。推导的具有580个氨基酸的koc蛋白的相对分子质量（Mr）约为65,000（65 K）。与正常胰腺和慢性胰腺炎组织相比，koc转录本在胰腺癌细胞系和胰腺癌组织中高度过表达。在其他人类肿瘤的组织样本中也发现了高水平的表达。由于已经显示出KH结构域参与RNA合成和代谢的调节，我们推测koc可能通过干扰转录和/或转录后过程而在调节肿瘤细胞增殖中发挥作用。但是，koc在人肿瘤细胞中的确切作用尚不清楚，尚待阐明。

BACKGROUND & AIMS: :Oral cancer is a neoplasm with some known causes. Proliferation genes are significant among its few pathogenetic and prognostic factors. Calcyclin is a cell-cycle-related gene, the function of which is still unclear. Its expression and that of Haras and histone-H3 have been investigated in an assessment of their pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological and normal mucosa of patients with squamous cell carcinoma (SCC) and benign lesions was reverse transcribed and amplified by the polymerase chain reaction (PCR). The expression of all three genes in the pathological mucosa was enhanced in SCC only. This suggests that they may be involved in its pathogenesis and provides another parameter for the differentiation of malignant and benign lesions.

背景与目标： ：口腔癌是一种具有某些已知原因的肿瘤。增生基因在其少数致病和预后因素中很重要。钙环蛋白是与细胞周期相关的基因，其功能尚不清楚。为了评估它们在鳞状细胞癌中的致病作用，已经研究了它的表达以及Haras和组蛋白H3的表达。从鳞状细胞癌（SCC）和良性病变的病理和正常粘膜中提取的RNA通过聚合酶链反应（PCR）进行逆转录和扩增。仅在SCC中，病理黏膜中所有三个基因的表达均得到增强。这表明它们可能参与其发病机理，并为区分恶性和良性病变提供了另一个参数。