STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice

Deregulated activation of STAT3 is frequently associated with many human hematological and epithelial malignancies, including gastric cancer. While exaggerated STAT3 signaling facilitates an antiapoptotic, proangiogenic, and proproliferative environment for neoplastic cells, the molecular mechanisms leading to STAT3 hyperactivation remain poorly understood. Using the gp130(Y757F/Y757F) mouse model of gastric cancer, which carries a mutated gp130 cytokine receptor signaling subunit that cannot bind the negative regulator of cytokine signaling SOCS3 and is characterized by hyperactivation of the signaling molecules STAT1 and STAT3, we have provided genetic evidence that IL-11 promotes chronic gastric inflammation and associated tumorigenesis. Expression of IL-11 was increased in gastric tumors in gp130(Y757F/Y757F) mice, when compared with unaffected gastric tissue in wild-type mice, while gp130(Y757F/Y757F) mice lacking the IL-11 ligand-binding receptor subunit (IL-11Ralpha) showed normal gastric STAT3 activation and IL-11 expression and failed to develop gastric tumors. Furthermore, reducing STAT3 activity in gp130(Y757F/Y757F) mice, either genetically or by therapeutic administration of STAT3 antisense oligonucleotides, normalized gastric IL-11 expression and alleviated gastric tumor burden. Surprisingly, the genetic reduction of STAT1 expression also reduced gastric tumorigenesis in gp130(Y757F/Y757F) mice and coincided with reduced gastric inflammation and IL-11 expression. Collectively, our data have identified IL-11 as a crucial cytokine promoting chronic gastric inflammation and associated tumorigenesis mediated by excessive activation of STAT3 and STAT1.     

Role of self-efficacy and behaviour change

Behaviour change is an important concept in relation to health promotion and disease prevention. Self-efficacy has been identified as an important determinant of health behaviour, future health behaviour and health behaviour change. In order to effectively facilitate behaviour change, it is essential that interventions are research based, and emphasize the utility of theory in practice. The effective practice of health promotion and disease prevention requires a full understanding of the processes of patient behaviour. This article presents the role of the nurse in influencing health-related behaviour change. Self-efficacy and related but distinct theories that underpin behaviour change are discussed. The empirical evidence that supports the link between self-efficacy and predictions of health behaviours is also examined.     

Gamma interferon responses induced by a panel of recombinant and purified mycobacterial antigens in healthy,non-mycobacterium bovis BCG-vaccinated Malawian young adults

We have previously shown that young adults living in a rural area of northern Malawi showed greater gamma interferon (IFN-gamma) responses to purified protein derivatives (PPD) prepared from environmental mycobacteria than to PPD from Mycobacterium tuberculosis. In order to define the mycobacterial species to which individuals living in a rural African population have been exposed and sensitized, we tested T-cell recognition of recombinant and purified antigens from M. tuberculosis (38 kDa, MPT64, and ESAT-6), M. bovis (MPB70), M. bovis BCG (Ag85), and M. leprae (65 kDa, 35 kDa, and 18 kDa) in >600 non-M. bovis BCG-vaccinated young adults in the Karonga District of northern Malawi. IFN-gamma was measured by enzyme-linked immunosorbent assay (ELISA) in day 6 supernatants of diluted whole-blood cultures. The recombinant M. leprae 35-kDa and 18-kDa and purified native M. bovis BCG Ag85 antigens induced the highest percentages of responders, though both leprosy and bovine tuberculosis are now rare in this population. The M. tuberculosis antigens ESAT-6 and MPT64 and the M. bovis antigen MPB70 induced the lowest percentages of responders. One of the subjects subsequently developed extrapulmonary tuberculosis; this individual had a 15-mm-diameter reaction to the Mantoux test and responded to M. tuberculosis PPD, Ag85, MPT64, and ESAT-6 but not to any of the leprosy antigens. We conclude that in this rural African population, exposure to M. tuberculosis or M. bovis is much less frequent than exposure to environmental mycobacteria such as M. avium, which have antigens homologous to the M. leprae 35-kDa and 18-kDa antigens. M. tuberculosis ESAT-6 showed the strongest association with the size of the Mantoux skin test induration, suggesting that among the three M. tuberculosis antigens tested it provided the best indication of exposure to, or infection with, M. tuberculosis.     

Response rates for providing a blood specimen for HIV testing in a population-based survey of young adults in Zimbabwe

Background  

To determine differences among persons who provided blood specimens for HIV testing compared with those who did not among those interviewed for the population-based Zimbabwe Young Adult Survey (YAS).     

Low-grade pure and mixed cerebral astrocytomas treated in the CT scan era

Summary From 1974 to 1992, 63 patients diagnosed with low-grade pure or mixed oligo-astrocytoma were seen and treated at our institution. All patients underwent CT scan pre-operatively. There were 20 female and 43 males ranging in age from 12 to 73 years (median age of 33 years). 15 patients had a stereotactic biopsy as the only surgical procedure. 34 had a partial tumor resection and 14 a gross total tumor resection.43 patients were treated with post-operative radiotherapy whereas 20 patients underwent surgery only as part of the initial management. 50 to 60 Gy (median 59.4 Gy) were given with daily fractions of 1.8 to 2 Gy. Tumor volume ranged from 3.4 to 441 cm³. Median tumor volume was larger for radiotherapy treated patients.Median follow-up was 54 months (range of 4 to 240 months). The overall 10 and 15 actuarial survival rates were 37% and 25% respectively. The 5 year survival rate for patients treated at initial diagnosis with surgery alone was 66% and it was 67.3% for patients treated with radiation therapy (P = NS). Prognostic factors having independant significant impact on survival were: extent of surgery, age, gender and tumor volume.As well, survival for patients with low-grade astrocytoma in the CT scan era appears to be improved compared to historical controls in the literature.     

Changing the minimum legal drinking age--its effect on a central city emergency department

AIMS: To quantify the effect of a recent national law change on the presentation of ethanol intoxicated patients to a central city Emergency Department (ED). METHODS: All records of ethanol intoxicated patients presenting to the ED for twelve months before and after the change to the minimum legal drinking age were studied. Each patient was classified as having laboratory confirmed intoxication, clinical suspicion only, or no record of intoxication. Three age groups were identified, 15-17 year olds, eighteen and nineteen year olds and over 20 year olds. Within each age group the proportion of presentations with ethanol intoxication was compared across the two time periods. RESULTS: The number of intoxicated 18 and 19 year olds increased in the twelve months after the national law change from 66 to 107 (52 to 80 for laboratory confirmed intoxication and fourteen to 27 for clinical suspicion only). This represented an increase in the proportion of presentations in this age group with intoxication (p=0.009) from 2.9% to 4.4%, a 50% increase (RR=1.51, 95%CI 1.11-2.03). There was no evidence of an increase in the proportion intoxicated for those over nineteen years (3.4% vs 3.3%, p=0.48, RR=0.97, 95%CI=0.89-1.06) although the numbers increased slightly (963 to 992). However there was a worrying trend for an increase in the 15-17 year olds, with numbers increasing from 72 to 95 and the proportion increasing from 5.0% to 6.7% (p=0.07, RR=1.35, 95%CI=0.98-1.88). CONCLUSION: The recent lowering of the minimum legal drinking age from 20 to eighteen years has resulted in increased presentations to the ED of intoxicated eighteen and nineteen year olds. A similar trend was seen in the 15-17 year olds.     

Cellular imaging with zif268 expression in the rat nucleus accumbens and frontal cortex further dissociates the neural pathways activated following the retrieval of contextual and cued fear memory

Quantitative in situ hybridization revealed that the expression of the plasticity-associated gene zif268 was increased in specific regions of the rat frontal cortex and nucleus accumbens following fear memory retrieval. Increased expression of zif268 was observed in neurons in the core of the nucleus accumbens during the retrieval of contextual and discrete cued fear associations. In contrast, zif268 expression was additionally induced in neurons of the nucleus accumbens shell and the anterior cingulate cortex during the retrieval of contextual but not cued fear memories. No changes in the expression of this gene were seen in the ventral medial prefrontal cortex or ventral and lateral regions of the orbitofrontal cortex that were correlated specifically with the retrieval of fear memory. These experiments demonstrate the specific and dissociable activation of limbic cortical-ventral striatal regions that accompanies cued and contextual fear. These data, together with those previously published by our laboratory (Hall, J., Thomas, K.L. & Everitt, B.J. (2001) J. Neurosci., 21, 2186-2193), suggest that retrieval of contextual fear memories activates a wider limbic cortical-ventral striatal neural circuitry than does retrieval of cued fear memories. Moreover, the expression of zif268 may contribute to plasticity and reconsolidation of fear memory in these dissociable pathways.     

Patient perspectives on involvement in cancer research in the UK

The patient's perspective is offered to identify the benefits of patient involvement in the research process so that it will lead to research that is reliable and relevant to cancer patients' needs. A brief outline of recent consumer involvement in research and initiatives being undertaken in the UK will provide a guide for those seeking to consider what has already been achieved. Practical suggestions are offered to those seeking to facilitate this mode of working. A wider conceptual approach suggests the interrelationships that should be built, through networks of communication, so that efficient, effective, economic and equitable health care may be provided to all those suffering from cancer. This should lead to an appreciation of work that still needs to be undertaken to achieve progress.