The regulation of exogenous and endogenous class I MHC genes in a human tumor cell line, K562

Previous studies have implied the existence of a trans-dominant intracellular repressor able to down-regulate the expression of the entire family of class I MHC genes in the genome of the K562 erythroleukemia cell line. This study demonstrates, however, that the transfection of human or murine class I genes into K562 cells leads to the cell surface expression of the transfected MHC gene product in all situations, even when several kilobases of 5' flanking sequence were included in the transfected genes. The endogenous cellular class I MHC genes remained repressed in the transfected cells. These findings suggest that repression of class I MHC gene expression in K562 may not be mediated predominantly by a trans-dominant repressor of MHC gene expression; rather, other more complex regulatory influences might exist.     

Lung tumor-associated derepressed alloantigen coded for by the K region of the H-2 major histocompatibility complex

Transplacental induction of lung tumors in C3HfeB/HeN (C3Hf) strain mice can be readily achieved with the carcinogen 1-ethyl-1-nitrosourea. Several of these tumors express, as a tumor-associated transplantation antigen (TATA), a normal tissue alloantigen present in strain A and C3H/HeN (C3H) mice. In the present study it was shown that the tumor-associated alloantigen on the C3Hf-derived lung tumor 85 was present in all mice of H-2(a) and H-2(k) haplotypes tested and in CBA (532) strain mice (H-2(ka) haplotype). Studies using congenic-resistant and recombinant strains of mice indicated that the genetic locus controlling the expression of this antigen was either within or to the left of the H-2K region of the major histocompatibility complex (MHC). Thus the antigen was expressed in B10.A (4R) mice (kkbbbb MHC haplotype) but not in B10 (bbbbbb) or B10.AQR mice (qkkddd). The antigen was expressed in all tissues tested of C3H and A strain mice. It was not detected on any tissue tested including embryo tissue of C3Hf mice or mice of MHC haplotype other than H-2(k) or H-2(a). Because C3Hf strain mice were originally derived from C3H strain mice (H-2(k)), the MHC haplotype of C3Hf mice has been provisionally designated H-2(kb). The finding of a tumor-associated change in the expression of a H-2K region-coded antigen is consistent with the concept that MHC-coded antigens may act as targets for immunological surveillance of tumors.     

Effectiveness of education for gastric cancer patients: A controlled prospective trial comparing interactive vs. lecture-based programs

Objective

Although patient education may enhance knowledge, coping with illness, and quality of life among cancer patients, it is uncertain which didactic method is most effective. We compared the impact of an interactive, patient-oriented group program to a lecture-based, information-only program in gastric cancer patients.

Methods

In this prospective, controlled trial, 121 gastric cancer patients attending inpatient rehabilitation after surgical treatment received either the interactive intervention or lectures providing information. The outcomes were patients’ disease-related knowledge, active coping with illness, and quality of life (QoL) at the end of their stay and 6 and 12 months thereafter.

Results

Both groups improved their knowledge and QoL during rehabilitation; however, knowledge was significantly higher in the interactive group compared to the lecture group. This difference was maintained at the 6- and 12-months follow-ups. In addition, the interactive group proved superior to the lecture group regarding active coping with illness and QoL at the end of rehabilitation, but not during follow-up.

Conclusions

A structured, interactive patient education program proved superior to lecture-based provision of information in regards to short-term and long-term knowledge as well as short-term coping and QoL.

Practice implications

In gastric cancer patients, interactive patient education seems preferable over lectures.     

丹参酮ⅡA对神经祖细胞系C17．2的保护作用

目的:了解丹参酮ⅡA对神经祖细胞系C17.2的保护作用,探讨其可能的作用机制。方法:本实验于2005年起在广州血液中心器官移植配型中心实验室进行。C17.2祖细胞系由澳大利亚新南威尔士大学解剖教研室David Walsh博士惠赠。将C17.2细胞以1×109L-1的密度接种,用含10%胎牛血清IMDM,37℃、体积分数为0.05CO2、饱和湿度的CO2培养箱培养,接近融合的C17.2细胞用含0.1mmol/LEDTA的胰酶室温消化,按1∶3的比例传代。C17.2细胞以5×107L-1的密度接种于96孔板或25cm2的培养瓶中,用含10%胎牛血清IMDM培养过夜后,加入含4g/L AAPH(水溶性偶氮引发剂2,2'-偶氮二(2-脒基丙烷)二盐酸盐)无血清的IMDM培养基培养建立神经细胞凋亡模型。C17.2细胞以5×103/孔的密度接种于96孔板中,用含10%胎牛血清IMDM培养过夜后,加入含4g/LAAPH无血清的IMDM培养基培养。对照组不加入丹参酮ⅡA,实验组分别加入0.02,0.05,0.1,0.2mg/L丹参酮ⅡA培养8h,噻唑蓝法检测细胞活性:细胞活性的相对值=(实验组吸光度值/对照组吸光度值)×100%,流式细胞仪检测细胞凋亡。结果:①AAPH处理8h后,C17.2细胞被过氧化损害,大多数细胞失去正常的形态,细胞呈圆形,脱落。加入丹参酮ⅡA后,细胞形态基本保持正常,少数细胞呈圆形。②C17.2细胞在IMDM的培养液中,细胞数量是含4g/L AAPH无血清的IMDM培养基条件下的2.5～3倍。浓度为0.02,0.05,0.1mg/L的丹参酮ⅡA对C17.2细胞有保护作用,质量浓度大于0.2mg/L丹参酮ⅡA对C17.2细胞保护作用降低。③AAPH作用前大部分C17.2细胞的线粒体完整,有少量的早期凋亡细胞和凋亡细胞,AAPH作用后凋亡细胞总数、凋亡细胞明显增加。丹参酮ⅡA处理组可以明显减少早期凋亡细胞。结论:在体外丹参酮ⅡA对神经细胞具有抗凋亡的作用,可以保护神经细胞。     

四肢关节专用低场强MRI评估对膝关节损伤的诊断价值

目的：分析四肢关节专用低场强MRI诊断膝关节损伤的临床应用价值。 方法：于2004-12/2005-10解放军总医院全军骨科研究所收治经手术、关节镜检查或临床证实的膝关节损伤患者40例（43个膝关节）。应用Atorscan0.2T永磁型四肢关节专用低场强磁共振机,对膝关节损伤的MRI表现进行分析。 结果：四肢关节专用低场强MRI对半月板、前交叉韧带、骨挫伤等均可作出正确诊断。 结论：四肢关节专用低场强MRI对膝关节损伤的综合诊断具有重要意义,是膝关节损伤较理想的一种非创伤性检查方法。     

Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.     

Antimicrobial activities of pomegranate rind extracts: enhancement by addition of metal salts and vitamin C

Background

Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course.

Methods/Design

The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis.

Discussion

This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia.

Trial registration

Current Controlled Trials ISRCTN01897462.     

Measuring maternal mortality: An overview of opportunities and options for developing countries

Background  

There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015.     

Endoplasmic reticulum chaperone gp96 in macrophages is essential for protective immunity during Gram‐negative pneumonia

Klebsiella pneumoniae is among the most common Gram‐negative bacteria that cause pneumonia. Gp96 is an endoplasmic reticulum chaperone that is essential for the trafficking and function of Toll‐like receptors (TLRs) and integrins. To determine the role of gp96 in myeloid cells in host defence during Klebsiella pneumonia, mice homozygous for the conditional Hsp90b1 allele encoding gp96 were crossed with mice expressing Cre‐recombinase under control of the LysM promoter to generate LysMcre‐Hsp90b1‐flox mice. LysMcre‐Hsp90b1‐flox mice showed absence of gp96 protein in macrophages and partial depletion in monocytes and granulocytes. This was accompanied by almost complete absence of TLR2 and TLR4 on macrophages. Likewise, integrin subunits CD11b and CD18 were not detectable on macrophages, while being only slightly reduced on monocytes and granulocytes. Gp96‐deficient macrophages did not release pro‐inflammatory cytokines in response to Klebsiella and displayed reduced phagocytic capacity independent of CD18. LysMcre‐Hsp90b1‐flox mice were highly vulnerable to lower airway infection induced by K. pneumoniae, as reflected by enhanced bacterial growth and a higher mortality rate. The early inflammatory response in Hsp90b1‐flox mice was characterized by strongly impaired recruitment of granulocytes into the lungs, accompanied by attenuated production of pro‐inflammatory cytokines, while the inflammatory response during late‐stage pneumonia was not dependent on the presence of gp96. Blocking CD18 did not reproduce the impaired host defence of LysMcre‐Hsp90b1‐flox mice during Klebsiella pneumonia. These data indicate that macrophage gp96 is essential for protective immunity during Gram‐negative pneumonia by regulating TLR expression. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Role of the alpAB proteins and lipopolysaccharide in adhesion of Helicobacter pylori to human gastric tissue

The attachment of the bacterial pathogen Helicobacter pylori (H. pylori) to gastric epithelial cells is commonly believed to be required for an efficient and persistent colonization of the human stomach as well as for host cell trans-membrane signaling. In the past, several putative adhesins were postulated, including the outer membrane proteins AlpAB and the bacterial lipopolysaccharide (LPS) presenting oligomeric Lewis x (Le(x)) sugar components. We investigated the AlpAB-mediated and the Le(x)-dependent binding by knockout mutagenesis in one distinct strain, H. pylori P1. We show here that the mutagenesis of either alpA and/or alpB dramatically reduced the adherence of H. pylori P1 to a given gastric biopsy section. None of these mutations influenced the surface exposure of the Le(x) antigen, suggesting that the assembly and/or presentation of LPS is independent of the AlpAB outer membrane proteins. However, a truncation of the LPS O-side chain by a galE mutation abolished the presentation of the Le(x) epitope. This Le(x)-negative strain did not show any significant reduction in its binding capacity to the gastric tissue, when compared with the corresponding wild-type strain. From these data we conclude that the AlpAB-specific adherence is independent of the composition of the LPS and that the oligomeric Le(x) structure does not confer binding to the gastric biopsy material used in this study. As the adhesion properties of our H. pylori strain P1 vary in dependence on the respective biopsy donor it is assumed that the surface-exposed Le(x) epitope recognizes a different host cell receptor than AlpAB, which was probably not present in the tissue sections used in this study.