Despite the presence of tumor Ag-specific CD8 ؉ T cells in the peripheral blood, metastatic melanoma often evades immune-mediated destruction. Even after therapeutic efforts to expand Ag-specific T-cell populations, the correlation between magnitude of response and clinical efficacy has been weak. Because the migratory phenotype of tumor Ag-specific effector T cells may determine their ability for tumor control, we hypothesized that the expression of CC or CXC chemokine receptor (CCR) molecules on activated CD8؉ T cells may define phenotypes associated with more effective control of melanoma progression and prolonged survival. In a retrospective evaluation of patient isolates, CCR expression was determined for activated CD8 ؉ T cells derived from the peripheral blood or tumor-involved lymph nodes of 52 patients with stage III or IV metastatic melanoma. In patients with stage III disease, expression of CXCR3 by CD8 ؉ CD45RO ؉ cells was significantly associated with enhanced survival. This was a stage-specific effect, because it was not observed in patients with stage IV disease. In addition, CCR4 and CXCR3 were highly coexpressed and associated with enhanced survival in stage III patients; however, CXCR3 seems to be the dominant receptor associated with clinical outcome. These findings support the hypothesis that the host immune system affects cancer progression and control, and that measures of CCR status of circulating lymphocytes may have prognostic value.
The contribution of interferon-gamma (IFN-gamma) to immunity from amebiasis was assessed in a three-year prospective study of children 2-5 years of age in an urban slum of Dhaka, Bangladesh. IFN-gamma produced by peripheral blood mononuclear cells stimulated with soluble amebic antigen was measured upon enrollment. Thirty-one of the 209 enrolled children had Entamoeba histolytica-associated diarrhea. Children who produced higher than the median level of IFN-gamma (median = 580 pg/mL) had longer survival without E. histolytica diarrhea/dysentery (log rank test P = 0.03) and a reduction in the risk of E. histolytica diarrhea/dysentery by more than half (Cox proportional hazard regression = 0.45, P = 0.04). When adjusted for stunting, the association between IFN-gamma and the time to the first episode of E. histolytica-associated diarrhea remained marginally significant (Cox proportional hazard regression = 0.49, P = 0.07). We conclude that production of IFN-gamma is linked to nutritional status and predicts future susceptibility to symptomatic amebiasis.
BackgroundReceiving extraneous articles in response to a query submitted to MEDLINE/PubMed is common. When submitting a multi-word query (which is the majority of queries submitted), the presence of all query words within each article may be a necessary condition for retrieving relevant articles, but not sufficient. Ideally a relationship between the query words in the article is also required. We propose that if two words occur within an article, the probability that a relation between them is explained is higher when the words occur within adjacent sentences versus remote sentences. Therefore, sentence-level concurrence can be used as a surrogate for existence of the relationship between the words.In order to avoid the irrelevant articles, one solution would be to increase the search specificity. Another solution is to estimate a relevance score to sort the retrieved articles. However among the >30 retrieval services available for MEDLINE, only a few estimate a relevance score, and none detects and incorporates the relation between the query words as part of the relevance score.ResultsWe have developed "Relemed", a search engine for MEDLINE. Relemed increases specificity and precision of retrieval by searching for query words within sentences rather than the whole article. It uses sentence-level concurrence as a statistical surrogate for the existence of relationship between the words. It also estimates a relevance score and sorts the results on this basis, thus shifting irrelevant articles lower down the list.In two case studies, we demonstrate that the most relevant articles appear at the top of the Relemed results, while this is not necessarily the case with a PubMed search. We have also shown that a Relemed search includes not only all the articles retrieved by PubMed, but potentially additional relevant articles, due to the extended 'automatic term mapping' and text-word searching features implemented in Relemed.ConclusionBy using sentence-level matching, Relemed can deliver higher specificity, thus eliminating more false-positive articles. By introducing an appropriate relevance metric, the most relevant articles on which the user wishes to focus are listed first. Relemed also shrinks the displayed text, and hence the time spent scanning the articles.
Cognitive function was assessed in 191 Bangladeshi children 6-9 years of age using verbal and nonverbal tests. These scores were added to a health surveillance database that was compiled over the four previous years that includes incidence of diarrhea and Entamoeba histolytica infection and nutritional status. The associations of diarrhea, malnutrition, and social factors with cognitive scores were analyzed statistically, and associations between diarrhea and test scores were controlled for the influence of social factors. Cognitive scores were negatively associated with stunting during school age, as well as the height-for-age and weight-for-age scores at study enrollment. Incidence of diarrhea was associated with nonverbal test scores before, but not after, controlling for socioeconomic factors. Generally E. histolytica infection was not found to independently influence scores, except that E. histolytica-associated dysentery was associated with lower test scores while dysentery of any etiology was not. Thus, malnutrition during the school age years, but not diarrhea or E. histolytica infection, was associated with a lower level of cognitive functioning. This suggested that intervention during school age years may be able to mitigate the cognitive deficiencies associated with malnutrition.
In this pilot study modafinil was well-tolerated and effective for fatigue in patients with cancer. Improvements were also seen in mood, quality of life, and functional status.
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