Kell blood group activity of gram-negative bacteria

To understand better the relationships between blood-group antigens and bacterial constituents, examples of 23 gram-negative bacteria (representing the 10 genera Citrobacter, Edwardsiella, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Serratia, and Shigella) were tested for the presence of Kl-like antigens by hemagglutination-inhibition (HAI) assays against both IgG and IgM anti-Kl. Saline-suspended whole organisms, cell-free culture media, and disrupted organisms were used to test for such antigens in, on, and secreted by the microorganisms examined. Disrupted organisms of an isolate of Shigella sonnei nonspecifically inhibited IgG anti-Kl as well as IgG antibodies of the specificities Kpb, Fya, S, and c. However, only Escherichia coli 0125:B15, subtype 12808, had specific K1-like activity (no activity with other IgG [(k, Kpb, Jka, Fya, S, c] and IgM [A, B, M, P1] antibodies). Disrupted organisms inhibited IgM but not IgG anti-K1 in the HAI assay. A second subtype, E. coli 0125:B15, subtype 12809, exhibited no K1-like activity. These findings support the report of K1 activity in cell-free broth cultures of E. coli 0125:B15 (subtype unspecified). Thus, although not all E. coli 0125:B15 possesses K1-like activity, the finding of such activity in at least one E. coli subtype confirms the idea that bacterial components may play a role in the production of naturally occurring antibodies directed against non-ABO red cell antigens.     

Modulation of the gait deficit in arthritic rats by infusions of muscimol and bicuculline

Gait analysis in the adjuvant-induced arthritic rat model of chronic pain was used to examine the role of GABA(A) receptors in the development of pain. Drug solutions were administered continuously at 5+/-0.75 microl/h for 14 days via Alzet osmotic pumps (2ML2) placed under the skin of the back. The GABA(A) receptor agonist, muscimol, produces a dose-dependent reversal of the gait deficits seen in arthritic rats without reducing the tibiotarsal joints inflammatory edema or the histological picture of joint erosion and inflammation. The higher infusion rate for muscimol, 20 microg/h, caused the gait for the arthritic rats to be indistinguishable from that of normal non-arthritic rats. In normal, non-arthritic rats, muscimol did not show any effect on gait. The GABA(A) receptor antagonist bicuculline showed small but significant exacerbation of stride length (P < 0.05) single and double stance time (P < 0.05) and swing time deficits (P < 0.05) in the arthritic rats, but no changes in measures of gait in the normal control rat. The results suggest that the development of arthritic pain is increased in the absence of GABA(A) receptor tone and that increasing GABA(A) receptor tone can reduce arthritic pain but does not affect the disease process.     

Anaphylaxis after treatment with recombinant factor VIII

BACKGROUND: Treatment of hemophilia patients with recombinant factor VIII concentrates has not previously been associated with anaphylaxis. STUDY DESIGN AND METHODS: A 5-week-old boy with severe hemophilia A developed dyspnea, cyanosis, hypotension, and a diffuse urticarial rash following treatment with a recombinant factor VIII (Recombinate). To identify the cause of anaphylaxis in this patient, the vial lot was examined for the presence of endotoxin, and a checkerboard immunoblotting technique was used to test serum and/or plasma samples from the patient and mother for the presence of antibodies (IgA, IgG, IgE, and IgM) to Recombinate-related antigens (recombinant factor VIII, von Willebrand factor, human serum albumin, Chinese hamster ovary proteins, bovine serum albumin, mouse monoclonal anti-human factor VIII, polyethylene glycol 3350), and to ethylene oxide, the agent used to sterilize the infusion equipment. RESULTS: No immune response directed against the Recombinate-related antigens or ethylene oxide that could be associated with the anaphylactic reaction was identified. Endotoxin was not present upon rabbit pyrogen testing of the therapeutic product. CONCLUSION: These studies failed to show any association between Recombinate and the onset of the allergic reaction. This seems to be the first reported case of anaphylaxis following the infusion of a recombinant form of factor VIII concentrate.     

Survivin与Caspase-3在妊娠期高血压疾病患者胎盘组织中的表达及意义

目的：研究凋亡相关蛋白Survivin（生存素）和Caspase-3（半胱氨酸蛋白酶-3）在妊娠高血压疾病（HDCP）患者胎盘细胞中的表达情况,探讨其与HDCP发生发展的相关性,为进一步明确HDCP的发病机制提供研究依据。方法：随机选取60例HDCP患者（其中子痫前期轻度28例,子痫前期重度32例,分别为轻度组、重度组）胎盘组织和30例健康孕妇（对照组）胎盘组织,采用免疫组化S—P法检测胎盘组织中Sur-vivin和Caspase-3的表达,并用图像分析系统对染色结果进行分析。结果：①Survivin在重度组表达显著低于轻度组及对照组,差异有显著性（P〈0.01）;轻度组与对照组比较,无显著性差异（P〉0.05）;②Caspase-3表达在轻度组与重度组显著高于对照组,差异均有显著性（P〈0.01）;重度组高于轻度组,差异有显著性（P〈0.01）。③Survivin与Caspase-3在两组胎盘组织中表达呈负相关（R=-0.413,P〈0.01）。结论：在HDCP患者胎盘组织中Survivin表达下调、Caspase-3表达上调,HDCP的发病机制可能与Survivin及Cas-pase-3表达变化有关。     

Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome

Aberrant epigenetic alterations in the genome such as DNA methylation and chromatin remodeling play a significant role in breast cancer development. Since epigenetic alterations are considered to be more easily reversible compared to genetic changes, epigenetic therapy is potentially very useful in reversing some of these defects. Methylation of CpG islands is an important component of the epigenetic code, and a number of genes become abnormally methylated in breast cancer patients. Currently, several epigenetic-based synthetic drugs that can reduce DNA hypermethylation and histone deacetylation are undergoing preclinical and clinical trials. However, these chemicals are generally very toxic and do not have gene specificity. Epidemiological studies have shown that Asian women are less prone to breast cancer due to their high consumption of soy food than the Caucasian women of western countries. Moreover, complementary/and or alternative medicines are commonly used by Asian populations which are rich in bioactive ingredients known to be chemopreventive against tumorigenesis in general. Examples of such agents include dietary polyphenols, (-)-epigallocatechin-3-gallate (EGCG) from green tea, genistein from soybean, isothiocyanates from plant foods, curcumin from turmeric, resveratrol from grapes, and sulforaphane from cruciferous vegetables. These bioactive components are able to modulate epigenetic events, and their epigenetic targets are known to be associated with breast cancer prevention and therapy. This approach could facilitate the discovery and development of novel drugs for the treatment of breast cancer. In this brief review, we will summarize the epigenetic events associated with breast cancer and the potential of some of these bioactive dietary components to modulate these events and thus afford new therapeutic or preventive approaches.     

乌审旗3000名妇女宫颈癌筛查结果分析

目的：了解乌审旗妇女宫颈癌及癌前病变的发病现状,探讨子宫颈液基细胞学（Thinprep paptest,TCT）结合阴道镜检查的诊断价值。方法：对3 000名乌审旗妇女进行TCT筛查,对TCT阳性（细胞学TBS分类为不典型鳞状细胞以上）的妇女进行阴道镜及镜下多点活组织检查（活检）,分析TCT阳性者的阴道镜检查及活检结果,比较TCT阳性者中不同年龄段患者的活检结果。结果：3 000名受检者中,TCT阳性537例（17.9%）,其中经活检证实为宫颈上皮内瘤变（cervical intraepthelial neoplasia,CIN）190例（6.3%）,宫颈浸润癌2例（0.07%）,537例TCT阳性者中,阴道镜检查正常264例（49.2%）,其中活检结果为CIN34例,阴道镜的假阴性率为12.9%,异常273例（50.8%）,其中活检结果为湿疣34例,CIN或浸润癌158例,阴道镜与活检的诊断符合率达70.3%（192/273）。TCT为轻度鳞状上皮内病变、高度鳞状上皮内病变、鳞状细胞癌的病例与活检的诊断符合率分别为50.4%,88.3%和2/2,假阳性率则分别为49.6%、11%和0。537例TCT阳性者中,2030岁组、3140岁组,4147岁组的CIN检出率分别为33.7%、44.5%2、6.7%（P〈0.05）。结论：乌审旗妇女CIN的发生率高,是宫颈癌的高发人群。TCT结合阴道镜检查是较好的宫颈癌筛查手段之一。     

不明原因慢性咳嗽诊治现状及分析

目的:研究和探讨不明原因慢性咳嗽的诊治现状。方法:对我院呼吸科门诊2006年1月~2008年12月间诊治的138例不明原因慢性咳嗽患者的病因诊断、治疗情况进行分析研究,对相关数据进行统计学处理。结果:138例不明原因慢性咳嗽按病因分类,鼻后滴流综合征(PNDS)最多,占35.5%,咳嗽变异型哮喘(CVA)占27.5%,胃—食管返流性咳嗽(GERC)占12.3%,嗜酸粒细胞性支气管炎(EB)占10.9%,变应性咳嗽(AC)占8.7%,感冒后咳嗽占5.1%。其中116例被误诊,误诊率84.1%,确诊后121例经治疗1~8周治愈,治愈率87.7%。结论:不明原因慢性咳嗽易被疏忽和误诊,明确病因诊断,规范治疗是关键。     

Synthesis and biological evaluation of a novel anti-malarial lead

Abstract  

Malaria is re-emerging in many tropical areas of the world and is often fatal due to drug resistance, leading to about a million deaths each year. Multiple drug resistance has required new efforts in drug discovery and development. Thus, the search for new drugs operating by novel mechanisms of action is receiving increased attention. Herein we report the synthesis and biological evaluation of a novel anti-malarial with micromolar activity against resistant strains of the parasite.