BACKGROUND & AIMS: AIM:To investigate the dynamic alteration of telomerase expression during development of hepatocellular carcinoma (HCC) and its diagnostic implications in liver tissues or peripheral blood mononuclear cells for HCC. METHODS:Dynamic expressions of liver telomerase during malignant transformation of hepatocytes were observed in Sprague-Dawly (SD) rats fed with 0.05% of 2-fluoenyacetamide (2-FAA). Total RNA and telomerase were extracted from rat or human liver tissues. The telomerase activities in livers and in circulating blood were detected by a telomeric repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA), and its diagnostic value was investigated in patients with benign or malignant liver diseases. RESULTS:The hepatoma model displayed the dynamic expression of hepatic telomerase during HCC development. The telomerase activities were consistent with liver total RNA levels (r = 0.83, P<0.01) at the stages of degeneration, precancerosis, and cancerization of hepatocytes. In HCC patients, the telomerase levels in HCC tissues were significantly higher than in their adjacent non-cancerous tissues, but liver total RNA levels were lower in the former than in the latter. Although the circulating telomerase of HCC patients was abnormally expressed among patients with chronic liver diseases, the telomerase activity was a non-specific marker for HCC diagnosis, because the incidence was 15.7% in normal control, 25% in chronic hepatitis, 45.9% in liver cirrhosis, and 85.2% in HCC, respectively when absorbance value of telomerase activity was more than 0.2. If the value was over 0.6, the incidence was 60% in HCC group and 0% in any of the others (P<0.01) except in two cases with liver cirrhosis. However, the combination of circulating telomerase with serum alpha-fetoprotein level could increase the positive rate and the accuracy (92.6%, 125 of 135) of HCC diagnosis. CONCLUSION:The overexpression of telomerase is associated with HCC development, and its abnormality in liver tissues or in peripheral blood could be a useful marker for diagnosis and prognosis of HCC.

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BACKGROUND & AIMS: :The aim of this study was to assess the clinical value of serum oestradiol concentration 8 days after embryo transfer (D8E2) and beta-human chorionic gonadotrophin (HCG-beta) concentration 12 days after embryo transfer (D12HCG-beta) in the prediction of pregnancy and the outcome of pregnancy following assisted reproduction, taking into account the day of transfer, which was either day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by giving quantitative and reliable predictive information instead of non-specific uncertainties. A total of 2035 embryo transfer cycles performed between January 2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic pregnancy and first-trimester abortions were classified as non-viable pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing pregnancies (OP). Significantly higher D8E2 and D12HCG-beta were obtained in D5 transfers compared with D3 transfers with regard to pregnancy and OP (P

BACKGROUND & AIMS: :Intracranial aneurysms (IAs) can be related to or associated with some vascular anatomic variations, lesions, diseases, or systemic disorders in which a causative or predisposing factor(s) in aneurysm formation can be identified. This article includes flow-related, infectious, traumatic iatrogenic, and neoplastic aneurysms and aneurysms related to systemic disorders and drug abuse. In some conditions, IAs associated with other disorders are true aneurysms. Most of them, however, are false aneurysms. Characteristics and management of these unusual aneurysms are discussed.

背景与目标： : 颅内动脉瘤 (IAs) 可能与某些血管解剖变异，病变，疾病或全身性疾病有关或与之相关，在这些疾病中可以识别出动脉瘤形成的病因或诱发因素。本文包括与血流相关的，感染性的，创伤性的医源性的，肿瘤性的动脉瘤和与全身性疾病和药物滥用有关的动脉瘤。在某些情况下，与其他疾病相关的IAs是真正的动脉瘤。但是，其中大多数是假性动脉瘤。讨论了这些异常动脉瘤的特征和处理。

BACKGROUND & AIMS: :Gastric muscle contractions grind and mix solid/liquid meal within the stomach, and move it into the bowels at a controlled rate. Contractions are of two types: slow volume-reducing contractions of the proximal stomach (the fundus), and peristaltic contraction waves in the distal stomach (the antrum). Fundic squeeze maintains gastro-duodenal pressure difference to drive gastric emptying. Emptying is generally assumed to proceed from the antrum to the fundus, so that ingested drugs can take hours to enter the small intestines and activate. Antral contraction waves (ACW), in contrast, generate fluid motions that break down and mix gastric content. Using a computer model of the human stomach, we discover a new function of these contraction waves apart from grinding and mixing. In coordination with fundic contraction, antral contraction waves move liquid content from the fundus along a very narrow path to the duodenum through the center of the antrum. Using physiological data, we show that this gastric emptying "Magenstrasse" (stomach road) can funnel liquid gastric content from the farthest reaches of the fundus directly to the intestines within 10 min. Consequently, whereas drugs (tablets, capsules, liquid) released off the Magenstrasse may require hours to enter the duodenum, at low concentration, when released on the Magenstrasse the drug can enter the duodenum and activate within 10 min-at high concentration. This discovery might explain observed high variability in drug initiation time, and may have important implications to both drug delivery and digestion, as well as to other wall-driven emptying of elastic containers.

背景与目标： : 胃肌肉收缩在胃内研磨和混合固体/液体食物，并以受控的速度将其移入肠道。收缩有两种类型: 近端胃 (眼底) 的缓慢减容收缩和远端胃 (胃窦) 的蠕动收缩波。胃底挤压可维持胃十二指肠压差，以驱动胃排空。排空一般假设是从胃窦到眼底进行，这样摄入的药物可能需要几个小时才能进入小肠并激活。相反，窦收缩波 (ACW) 会产生分解并混合胃内容物的液体运动。使用人类胃的计算机模型，除了研磨和混合之外，我们还发现了这些收缩波的新功能。与胃底收缩相协调，胃窦收缩波将液体含量从眼底沿非常狭窄的路径穿过胃窦中心到达十二指肠。使用生理数据，我们表明这种胃排空的 “Magenstrasse” (胃路) 可以在10分钟内将液体胃内容物从最远处的眼底直接漏斗到肠道。因此，尽管从Magenstrasse释放的药物 (片剂，胶囊，液体) 可能需要数小时才能进入十二指肠，但在低浓度下，当在Magenstrasse上释放时，药物可以进入十二指肠并在10分钟内激活-高浓度。这一发现可能解释了观察到的药物起始时间的高变异性，并且可能对药物输送和消化以及其他壁驱动的弹性容器排空具有重要意义。

BACKGROUND & AIMS: :Orphan medicinal products (OMPs) are targeted at the diagnosis, prevention or treatment of rare diseases and have a special status in European law. This status brings incentives for pharmaceutical companies to invest in OMP development. The goal of the legislation is to encourage the development of more treatments for life-threatening rare disorders, but increased availability of OMPs raises important issues surrounding the public funding of very expensive treatments by national health services. In this article we review OMPs and the incentives for their development and discuss the challenges presented by funding these treatments.

背景与目标： : 孤儿药品 (OMPs) 针对罕见疾病的诊断，预防或治疗，在欧洲法律中具有特殊地位。这种状态为制药公司投资OMP开发带来了动力。该立法的目标是鼓励为危及生命的罕见疾病开发更多的治疗方法，但是omp的可用性增加引发了围绕国家卫生服务机构为非常昂贵的治疗提供公共资金的重要问题。在本文中，我们回顾了omp及其发展的诱因，并讨论了资助这些治疗带来的挑战。

BACKGROUND & AIMS: Focal and segmental sclerosed lesions in the glomeruli are found in several pathological entities and more often are found in the corticomedullary junction where renal blood flow and filtration pressure is maximal. Experimental data suggest that hyperfiltration injury results in focal and segmental glomerulosclerosis (FSGS). In keeping with this concept, malignant hypertension is a known cause of nephrotic-range proteinuria and nephrotic syndrome pathalobically represented by FSGS. We report a case of unilateral renal artery stenosis associated with nephrotic syndrome and FSGS in the contralateral kidney only. The kidney with the stenosed renal artery showed normal glomeruli with juxtaglomerular hyperplasia, suggesting that protection from hyperfiltration injury was provided by the presence of high-grade stenosis. Serum creatinine concentration, blood pressure, and proteinuria normalized after aorto-renal bypass surgery. This case shows the importance of hemodynamic factors on the pathogenesis of secondary FSGS and the progression of renal disease.

背景与目标： 肾小球的局灶性和节段性硬化性病变在几种病理实体中发现，而在肾血流量和过滤压力最大的皮质管交界处更常见。实验数据表明，超滤损伤会导致局灶性和节段性肾小球硬化 (FSGS)。与这个概念保持一致，恶性高血压是由FSGS病理代表的肾病范围蛋白尿和肾病综合征的已知原因。我们报告了仅在对侧肾脏中与肾病综合征和FSGS相关的单侧肾动脉狭窄病例。肾动脉狭窄的肾脏显示正常的肾小球并伴有近肾小球增生，这表明高级别狭窄的存在可保护高滤过损伤。主动脉-肾搭桥手术后血清肌酐浓度，血压和蛋白尿正常化。该病例显示了血流动力学因素对继发性FSGS发病机理和肾脏疾病进展的重要性。

BACKGROUND & AIMS: OBJECTIVE:To describe the challenge of determining the correct diagnosis in a healthy adult male patient with a recent femoral fracture and a history of multiple bone fractures. METHODS:We present clinical, radiologic, laboratory, and histopathologic details in a patient with a history of recurrent fractures associated with minimal trauma. Moreover, the various types of osteopetrosis are reviewed. RESULTS:A 34-year-old African American man was in his usual state of good health when he fell hard on concrete. Immediately after the fall, he was able to bear weight, although pain prompted him to seek medical care. Besides a personal history of multiple fractures, he had no other medical problems. He had never smoked, denied illicit drug use, and had no family history of bone disorders or recurrent fractures. Findings on physical examination were unremarkable. Radiography disclosed an incomplete femoral fracture and osteosclerosis. Bone survey revealed diffuse, symmetric osteosclerosis of both the axial and the appendicular skeleton. The long bones showed areas of almost complete obliteration of the medullary canal, along with prominent hyperostosis. Additionally, a "bone-within-bone" appearance to the thickened endosteum was noted. A bone scan demonstrated numerous areas of symmetric radiotracer uptake. Laboratory analyses were unremarkable, including a complete blood cell count, electrolytes, serum protein electrophoresis, thyrotropin, and parathyroid hormone. Total alkaline phosphatase was mildly elevated at 162 U/L (normal range, 35 to 130). Seven needles were broken during attempts to perform a bone biopsy. Histologic examination showed normal bone marrow with "woven" bone and areas of primary spongiosa within mature osteoid. Autosomal dominant osteopetrosis type 2 was diagnosed on the basis of his clinical presentation and the radiologic and pathologic findings. CONCLUSION:The preliminary diagnosis for this patient's condition was Paget's disease, and determining the correct diagnosis of osteopetosis prevented the administration of inappropriate therapy. In addition, this case report reminds the clinician that genetic disease may manifest in adulthood.

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BACKGROUND & AIMS: :Professional antigen-presenting cells (APC) are able to process and present exogenous antigen leading to the activation of T cells. Antigen-immunoglobulin (Ig)G complexes (IC) are much more efficiently processed and presented than soluble antigen. Dendritic cells (DC) are known for their ability to take up and process immune complex (IC) via FcgammaR, and they have been shown to play a crucial role in IC-processing onto major histocompatibility complex (MHC) class I as they contain a specialized cross-presenting transport system required for MHC class I antigen-processing. However, the MHC class II-antigen-processing pathway is distinct. Therefore various other professional APC, like macrophages and B cells, all displaying FcgammaR, are thought to present IC-delivered antigen in MHC class II. Nonetheless, the relative contribution of these APC in IC-facilitated antigen-presentation for MHC class II in vivo is not known. Here we show that, in mice, both macrophages and DC, but not B cells, efficiently capture IC. However, only DC, but not macrophages, efficiently activate antigen-specific MHC class II restricted CD4(+) T cells. These results indicate that mainly DC and not other professional APC, despite expressing FcgammaR and MHC class II, contribute significantly to IC-facilitated T cell activation in vivo under steady-state conditions.

背景与目标： : 专业抗原呈递细胞 (APC) 能够处理和呈递导致T细胞活化的外源性抗原。抗原-免疫球蛋白 (Ig)G复合物 (IC) 比可溶性抗原更有效地处理和呈现。树突状细胞 (DC) 以其通过FcgammaR吸收和处理免疫复合物 (IC) 的能力而闻名。并且它们已被证明在IC处理到主要组织相容性复合体 (MHC) I类上起着至关重要的作用，因为它们包含MHC I类抗原处理所需的专门交叉呈递转运系统。然而，MHC II类抗原处理途径是不同的。因此，其他各种专业的APC，如巨噬细胞和b细胞，都显示FcgammaR，被认为在MHC II类中呈现IC递送的抗原。尽管如此，这些APC在体内MHC II类的IC促进抗原呈递中的相对贡献尚不清楚。在这里，我们表明，在小鼠中，巨噬细胞和DC，但不是b细胞，有效地捕获IC。然而，只有DC，但不是巨噬细胞，有效激活抗原特异性MHC II类限制性CD4(+) T细胞。这些结果表明，尽管表达FcgammaR和MHC II类，但主要是DC而不是其他专业APC，在稳态条件下对IC促进的T细胞激活有显着贡献。

BACKGROUND & AIMS: :Neutralizing antibody titers of 47 infants whose mothers sustained measles (measles group) and 70 whose mothers were vaccinated (vaccine group) were compared at birth, 4 and 8 months of age. All children had antibodies at birth and 88% at 4 months. At 8 months, 49% had antibodies in the measles group and 15% in the vaccine group (P < 0.001). The geometric mean titers were significantly lower in the vaccine group than in the measles group and the difference corresponded to the antibody loss occurring in only 1.5 months of life. This small difference may reflect past exposure to wild virus of many vaccinated mothers.

背景与目标： : 比较了47名母亲患有麻疹的婴儿 (麻疹组) 和70名母亲接种了疫苗的婴儿 (疫苗组) 的中和抗体滴度。出生，4和8个月大。所有儿童在出生时具有抗体，并在4个月时88%。在8个月时，49% 在麻疹组中有抗体，在疫苗组中有15% (P <0.001)。疫苗组的几何平均滴度显着低于麻疹组，并且该差异对应于仅在生命的1.5个月内发生的抗体丢失。这种微小的差异可能反映了许多接种疫苗的母亲过去暴露于野生病毒。

BACKGROUND & AIMS: :6-Pyruvoyltetrahydropterin synthase (PTPS) catalyzes the second step of tetrahydrobiopterin (BH4) synthesis. We previously identified PTPS orthologs (bPTPS-Is) in bacteria which do not produce BH4. In this study we disrupted the gene encoding bPTPS-I in Synechococcus sp. PCC 7942, which produces BH4-glucoside. The mutant was normal in BH4-glucoside production, demonstrating that bPTPS-I does not participate in BH4 synthesis in vivo and bringing us a new PTPS ortholog (bPTPS-II) of a bimodular polypeptide. The recombinant Synechococcus bPTPS-II was assayed in vitro to show PTPS activity higher than human enzyme. Further computational analysis revealed the presence of mono and bimodular bPTPS-II orthologs mostly in green sulfur bacteria and cyanobacteria, respectively, which are well known for BH4-glycoside production. In summary we found new bacterial PTPS orthologs, having either a single or dual domain structure and being responsible for BH4 synthesis in vivo, thereby disclosing all the bacterial PTPS homologs.

背景与目标： : 6-丙酮酸基四氢蝶呤合酶 (PTPS) 催化四氢生物蝶呤 (BH4) 合成的第二步。我们先前在不产生bh4的细菌中鉴定了PTPS直系同源物 (bPTPS-Is)。在这项研究中，我们破坏了Synechococcus sp. PCC 7942中编码bPTPS-I的基因，该基因产生了BH4-glucoside。该突变体在BH4-glucoside生产中是正常的，表明bPTPS-I在体内不参与BH4合成，并为我们带来了双峰多肽的新PTPS直系同源物 (bPTPS-II)。在体外测定了重组Synechococcus bptp-II，显示PTPS活性高于人酶。进一步的计算分析表明，分别在绿色硫细菌和蓝细菌中存在单和双模bPTPS-II直系同源物，这在BH4-glycoside生产中是众所周知的。总而言之，我们发现了新的细菌PTPS直系同源物，具有单个或双结构域结构，并负责体内BH4的合成，从而公开了所有细菌PTPS同源物。

BACKGROUND & AIMS: PURPOSE OF REVIEW:Radiotherapy is very effective in local control of Hodgkin's lymphoma. Unfortunately, long-term survivors exhibit an excess of life-threatening radiation-related late side effects. Consequently, there have been calls to cease the use of radiation in the primary treatment of Hodgkin's lymphoma, although there is also support for the judicious use of combined modality treatment. RECENT FINDINGS:Most patients treated for Hodgkin's lymphoma are being cured with modern approaches. Recent publications confirm the superior efficacy of combined modality treatment over chemotherapy alone, but the initial gain in cure rate may be outweighed by late deaths due to various treatment-related diseases. Many patients may already be cured by chemotherapy alone. Classical risk factors can be used to distinguish favourable and unfavourable subgroups of patients with Hodgkin's lymphoma, but these risk factors cannot predict outcome in individual cases. A simple test to predict the likelihood of cure in individual patients would be of great benefit. Fluoro-deoxyglucose-PET scan investigation holds this promise. SUMMARY:The present review deals with the role of radiation therapy in the treatment of Hodgkin's lymphoma.

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BACKGROUND & AIMS: :It is well-recognised that steady-state isometric muscle force is decreased following active shortening (force depression, FD) and increased following active stretch (force enhancement, FE). It has also been demonstrated that passive muscle force is increased following active stretch (passive FE). Several studies have reported that FD increases with shortening amplitude and that FE and passive FE increase with stretch amplitude. Here, we investigate whether these trends continue with further increases in shortening or stretch amplitude. Experiments were performed using in situ cat soleus muscles (n=8 for FD; n=7 for FE and passive FE). FD, FE and passive FE were measured after shortening or stretch contractions that covered as wide a range of amplitudes as practically possible without damaging the muscles. FD increased approximately linearly with shortening amplitude, over the full range of amplitudes investigated. This is consistent with the hypothesis that FD arises from a stress-induced inhibition of crossbridges. FE increased with stretch amplitude only up to a point, and then levelled off. Passive FE, and the transient increase in force at the end of stretch, showed relationships to stretch amplitude that were qualitatively very similar to the relationship for FE, increasing only until the same critical stretch amplitude had been reached. We conclude that FE and passive FE do not increase with stretch amplitude under all circumstances. This finding has important consequences for determining the mechanisms underlying FE and passive FE because any mechanism that is proposed to explain them must be able to predict it.

背景与目标： : 众所周知，主动缩短 (力降低，FD) 后，稳态等距肌肉力降低，主动拉伸 (力增强，FE) 后，稳态等距肌肉力增加。还已证明，主动拉伸 (被动FE) 后，被动肌肉力量会增加。一些研究报告说，FD随缩短幅度而增加，FE和被动FE随拉伸幅度而增加。在这里，我们研究这些趋势是否随着缩短或拉伸幅度的进一步增加而继续。使用原位猫比目鱼肌进行实验 (FD为n = 8; FE和被动FE为n = 7)。在缩短或拉伸收缩后测量FD，FE和被动FE，这些收缩实际上覆盖了尽可能宽的振幅范围，而不会损坏肌肉。在所研究的整个振幅范围内，FD随振幅的缩短而近似线性增加。这与FD由应力诱导的交叉桥抑制引起的假设是一致的。FE仅随拉伸幅度增加到一个点，然后趋于平稳。被动FE和拉伸结束时的瞬时力增加显示出与拉伸幅度的关系，在质量上与FE的关系非常相似，仅在达到相同的临界拉伸幅度之前才增加。我们得出的结论是，在所有情况下，FE和被动FE都不会随拉伸幅度而增加。这一发现对于确定FE和被动FE的潜在机制具有重要的影响，因为提出的任何解释它们的机制都必须能够预测它。

BACKGROUND & AIMS: BACKGROUND:Flow cytometric basophil activation tests have been developed as cellular tests for in vitro diagnosis of IgE-mediated reactions. Different activation markers (CD63 or CD203c) with distinct ways of regulation have been used after stimulation with various allergens. OBJECTIVE:It was the aim of the present study to compare basophil activation tests by measuring both CD63 and CD203c upregulation in patients with insect venom allergy. MATERIALS AND METHODS:43 patients with a history of insect venom anaphylaxis were examined. A careful allergy history was taken, and skin tests and determination of specific IgE-antibodies were performed. Basophil activation tests (BAT) using CD63 or CD203c expression were done after stimulation with different concentrations of bee and wasp venom extracts. 25 healthy subjects with negative history of insect venom allergy were studied as controls. RESULTS:The CD203c protocol showed a slightly higher sensitivity than the CD63 protocol (97% vs. 89%) with regard to patients' history. The magnitude of basophil response was higher with CD203c in comparison to CD63 for both insect venoms. Specificity was 100% for the CD63 protocol and 89% for the CD203c protocol with regard to controls with negative history and negative RAST. CONCLUSION:These results support the reliability of basophil activation tests using either CD63 or CD203c as cellular tests in the in vitro diagnosis of patients with bee or wasp venom allergy with a slightly higher sensitivity for the CD203c protocol.

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BACKGROUND & AIMS: BACKGROUND:Previous studies revealed increased parietal late positive potentials (LPPs) in response to spider pictures in spider phobic individuals. This study searched for basic features of fear-relevant stimuli by investigating whether schematic spider images are sufficient to evoke differential behavioral as well as differential early and late ERP responses in spider phobic, social phobic (as a clinical control group), and non-phobic control participants. METHODS:Behavioral and electrophysiological correlates of the processing of schematic spider and flower images were investigated while participants performed a color (emotional Stroop) and an object identification task. Stimuli were schematic pictures of spiders and flowers matched with respect to constituting visual elements. RESULTS:Consistent with previous studies using photographic spider pictures, spider phobic persons showed enhanced LPPs when identifying schematic spiders compared to schematic flowers. In addition, spider phobic individuals showed generally faster responses than the control groups. This effect was interpreted as evidence for an increased general behavioral hypervigilance in this anxiety disorder group. Furthermore, both phobic groups showed enhanced P100 amplitudes compared to controls, which was interpreted as evidence for an increased (cortical) hypervigilance for incoming stimuli in phobic patients in general. Finally, all groups showed faster identification of and larger N170 amplitudes in response to schematic spider than flower pictures. This may reflect either a general advantage for fear-relevant compared to neutral stimuli, or might be due to a higher level of expertise in processing schematic spiders as compared to the more artificially looking flower stimuli. CONCLUSION:Results suggest that schematic spiders are sufficient to prompt differential responses in spider-fearful and spider-non-fearful persons in late ERP components. Early ERP components, on the other hand, seem to be modified by anxiety status per se, which is consistent with recent theories on general hypervigilance in the anxiety disorder spectrum.

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