Absence of mutations in the transforming growth factor-beta type II receptor in sporadic lung cancers with microsatellite instability and rare H-ras1 alleles

The transforming growth factor-beta type II receptor (RII) is commonly mutated in colon and gastric cancers with microsatellite instability (MI). We utilized our series of lung cancers with MI and rare alleles of the H-ras1 gene to determine the association between MI and RII mutations and searched the entire RII coding region in 33 lung cancers with MI by polymerase chain reaction-single-strand conformation polymorphism analysis. We found no mutations, and these data support other recent evidence that RII mutations rarely occur except in colon and gastric tumors with MI.      

Bacterial-Mediated Knockdown of Tumor Resistance to an Oncolytic Virus Enhances Therapy

Oncolytic viruses (OVs) and bacteria share the property of tumor-selective replication following systemic administration. In the case of nonpathogenic bacteria, tumor selectivity relates to their ability to grow extracellularly within tumor stroma and is therefore ideally suited to restricting the production of bacterially produced therapeutic agents to tumors. We have previously shown the ability of the type 1 interferon antagonist B18R to enhance the replication and spread of vesicular stomatitis virus (VSV) by overcoming related cellular innate immunity. In this study, we utilized nonpathogenic bacteria (E. coli) expressing B18R to facilitate tumor-specific production of B18R, resulting in a microenvironment depleted of bioactive antiviral cytokine, thus “preconditioning” the tumor to enhance subsequent tumor destruction by the OV. Both in vitro and in vivo infection by VSVΔ51 was greatly enhanced by B18R produced from E. coli. Moreover, a significant increase in therapeutic efficacy resulted from intravenous (IV) injection of bacteria to tumor-bearing mice 5 days prior to IV VSVΔ51 administration, as evidenced by a significant reduction in tumor growth and increased survival in mice. Our strategy is the first example where two such diverse microorganisms are rationally combined and demonstrates the feasibility of combining complementary microorganisms to improve therapeutic outcome.     

The unmasking of <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> pneumonia during reversal of immunosuppression: case reports and literature review

Background  

Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.     

The effect of fibrin polymers on thrombin-catalyzed plasma factor XIIIa formation

The effect of fibrin polymers on thrombin-catalyzed factor XIIIa formation was studied in afibrinogenemic plasma. Fibrin polymers derived from des A fibrinogen and des A,B fibrinogen increased sixfold the rate of thrombin-catalyzed factor XIIIa formation in the presence of EDTA. Calcium chloride accelerated factor XIIIa formation 14-fold in the presence of des A,B fibrinogen without increasing the rate of thrombin formation. Fibrinopeptides A and B had no effect on factor XIIIa formation in afibrinogenemic plasma. Des A,B fibrinogen reduced by 20- to 40-fold the thrombin concentration required to activate factor XIII. Glycyl-L-prolyl-L-arginyl-L-proline (gly-pro-arg-pro), a fibrin polymerization inhibitor, inhibited des A and des A,B fibrinogen from enhancing thrombin-catalyzed factor XIIIa formation. Gly-pro-arg- pro did not modify factor XIIIa formation in afibrinogenemic plasma and did not inhibit thrombin cleavage of the chromogenic substrate S-2238. These results demonstrate that fibrin polymers accelerate thrombin- catalyzed plasma factor XIIIa formation.     

AP-1和肿瘤的关系研究进展

转录因子AP-1(activatorprotein1),主要由Jun、Fos、ATF及JDP亚家族组成,亚家族单体以同源或异源二聚体的形式结合DNA靶序列,参与靶基因调节.对基因修饰小鼠和细胞的研究表明,AP-1参与细胞的正常生长和癌性转化过程,其在细胞中的作用取决于细胞类型、AP-1的组成和各组分的相对比例,也与刺激的种类密切相关.AP-1的活性受多种核因子调节,同时单体间也存在相互促进或拮抗作用.AP-1对各种刺激如应激、辐射或生长信号等作出生理或病理应答,参与细胞的增殖、分化和转化等过程,在肿瘤的形成、转移和侵袭中发挥重要作用,已经有学者研究通过抑制AP-1活性来发展抗肿瘤药物.     

Comparison of clinical and self-reported diagnoses for participants on a community-based arthritis self-management programme

OBJECTIVE: With the advent of community-based arthritis education programmes, it is important to determine the accuracy of participants' self-reported diagnoses. The purpose of this study was to determine the level of agreement between general practitioner (GP)-recorded and self- reported diagnoses of participants attending an Arthritis Self- Management Programme (ASMP). METHODS: Participants enrolling on the ASMP were asked to (a) identify their type of arthritis via a self- administered postal questionnaire and (b) obtain a written confirmation of their diagnosis from their GP. The sample (n = 613) comprised mainly women (83%) with a mean age of 58.8 yr (S.D. 12.6) and a mean disease duration of 15.4 yr (S.D. 12.5). RESULTS: Participants' self-reported diagnoses were confirmed by GPs in 534 cases [87.1%, 95% confidence interval (CI): 84.4 89.8%]. Confirmed diagnoses were reported by 86.9% (95% CI: 83.1-90.7%) of those with osteoarthritis (OA) and 96.1% (95% CI: 93.6 98.6%) of those with rheumatoid arthritis (RA). The concordance rate for all other types of arthritis combined was lower at 60.5% (95% CI: 49.5-71.5%). There were no significant differences with respect to age, gender, education, physical functioning, duration of disease and number of GP visits between those who correctly identified their type of arthritis and those who did not. CONCLUSIONS: This study suggests that the majority of RA and OA participants attending an arthritis education programme can correctly identify their specific type of arthritis.      

HIV Risk Behaviors of Male and Female Jail Inmates Prior to Incarceration and One Year Post-Release

Individuals cycling in and out of the criminal justice system are at high risk for contracting HIV/AIDS. Most infections are contracted in the community, not during incarceration, but little is known about the profile of risk behaviors responsible for this elevated infection rate. This study investigated pre-incarceration and post-release HIV risk behaviors in a longitudinal study of 542 male and female inmates in a Northern Virginia jail. Although there was a significant decrease in risky behavior from pre-incarceration to post-incarceration, participants reported high levels of unprotected sexual activity and risky IV drug behaviors at both time points, emphasizing the need for prevention programming among this at-risk population. Gender differences in participants’ pre-incarceration and post-release HIV risk behaviors suggest the need for gender-specific interventions to reduce overall HIV risk. Identifying specific HIV risk behaviors of jail inmates is vital to improve treatment and intervention efforts inside and outside of correctional settings.