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61.
CK2 as a positive regulator of Wnt signalling and tumourigenesis 总被引:10,自引:0,他引:10
Seldin DC Landesman-Bollag E Farago M Currier N Lou D Dominguez I 《Molecular and cellular biochemistry》2005,274(1-2):63-67
62.
Background
Combat-related posttraumatic stress disorder (PTSD) can be a difficult condition to treat and has been associated with serious medical and economic issues among U.S. military veterans. Distinguishing between treatment responders vs. non-responders in this population has become an important public health priority. This study was conducted to identify pre-treatment characteristics of U.S. veterans with combat-related PTSD that might contribute to favorable and unfavorable responses to high value treatments for this condition.Method
This study focused on 805 patients who completed a VHA PTSD residential program between 2000 and 2007. These patients completed the PTSD Clinical Checklist at pre-treatment, post-treatment, and a four-month follow-up assessment. Latent growth curve analysis (LCGA) was incorporated to determine trajectories of changes in PTSD across these assessments and whether several key clinical concerns for this population were associated with their treatment responses.Study Findings
LCGA indicated three distinct trajectories in PTSD outcomes and identified several clinical factors that were prospectively linked with changes in veterans'' posttraumatic symptomatology. When compared to a group with high PTSD symptom severity that decreased over the program but relapsed at follow-up (41%), the near half (48.8%) of the sample with an improving trajectory had less combat exposure and superior physical/mental health. However, when compared to a minority (10.2%) with relatively low symptomatology that also remained somewhat stable, patients in the improving group were younger and also reported greater combat exposure, poorer physical/mental health status, and more problems with substance abuse before the start of treatment.Conclusions
Findings suggest that veterans are most likely to benefit from residential treatment in an intermediate range of symptoms and risk factors, including PTSD symptom severity, history of combat exposure, and comorbid issues with physical/mental health. Addressing these factors in an integrative manner could help to optimize the effectiveness of treatments of combat-related PTSD in many cases. 相似文献63.
Phylogeny of the Drosophila saltans species group based on combined analysis of nuclear and mitochondrial DNA sequences 总被引:2,自引:0,他引:2
Nucleotide sequences from two nuclear loci, alcohol dehydrogenase and
internal transcribed spacer-1 of the nuclear ribosomal DNA repeats, and two
mitochondrial genes, cytochrome oxidase I and cytochrome oxidase II, were
determined from nine species in the Drosophila saltans species group. The
partition homogeneity test and partitioned Bremer support were used to
measure incongruence between phylogenetic hypotheses generated from
individual partitions. Individual loci were generally congruent with each
other and consistent with the previously proposed morphological hypothesis,
although they differed in level of resolution. Since extreme conflict
between partitions did not exist, the data were combined and analyzed
simultaneously. The total evidence method gave a more resolved and highly
supported phylogeny, as indicated by bootstrap proportions and decay
indices, than did any of the individual analyses. The cordata and elliptica
subgroups, considered to have diverged early in the history of the D.
saltans group, were sister taxa to the remainder of the saltans group. The
sturtevanti subgroup, represented by D. milleri and D. sturtevanti,
occupies an intermediate position in this phylogeny. The saltans and
parasaltans subgroups are sister clades and occupy the most recently
derived portion of the phylogeny. As with previous morphological studies,
phylogenetic relationships within the saltans subgroup were not
satisfactorily resolved by the molecular data.
相似文献
64.
Reini W Bretveld Chris MG Thomas Paul TJ Scheepers Gerhard A Zielhuis Nel Roeleveld 《Reproductive biology and endocrinology : RB&E》2006,4(1):30
Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system
through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference
with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide
exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function
of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation:
1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition
and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms
are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation
of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies,
exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy,
spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal
function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity,
it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining
the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive
effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in
this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both
in toxicological and epidemiological settings. 相似文献
65.
66.
Balamurugan A Lewis MJ Kitchen CM Robertson MN Shiver JW Daar ES Pitt J Ali A Ng HL Currier JS Yang OO 《Journal of virology》2008,82(6):2784-2791
Vaccination for human immunodeficiency virus type 1 (HIV-1) remains an elusive goal. Whether an unsuccessful vaccine might not only fail to provoke detectable immune responses but also could actually interfere with subsequent natural immunity upon HIV-1 infection is unknown. We performed detailed assessment of an HIV-1 gag DNA vaccine recipient (subject 00015) who was previously uninfected but sustained HIV-1 infection before completing a vaccination trial and another contemporaneously acutely infected individual (subject 00016) with the same strain of HIV-1. Subject 00015 received the vaccine at weeks 0, 4, and 8 and was found to have been acutely HIV-1 infected around the time of the third vaccination. Subject 00016 was a previously HIV-1-seronegative sexual contact who had symptoms of acute HIV-1 infection approximately 2 weeks earlier than subject 00015 and demonstrated subsequent seroconversion. Both individuals reached an unusually low level of chronic viremia (<1,000 copies/ml) without treatment. Subject 00015 had no detectable HIV-1-specific cytotoxic T-lymphocyte (CTL) responses until a borderline response was noted at the time of the third vaccination. The magnitude and breadth of Gag-specific CTL responses in subject 00015 were similar to those of subject 00016 during early chronic infection. Viral sequences from gag, pol, and nef confirmed the common source of HIV-1 between these individuals. The diversity and divergence of sequences in subjects 00015 and 00016 were similar, indicating similar immune pressure on these proteins (including Gag). As a whole, the data suggested that while the gag DNA vaccine did not prime detectable early CTL responses in subject 00015, vaccination did not appreciably impair his ability to contain viremia at levels similar to those in subject 00016. 相似文献
67.
Jutras I Houde M Currier N Boulais J Duclos S LaBoissière S Bonneil E Kearney P Thibault P Paramithiotis E Hugo P Desjardins M 《Molecular & cellular proteomics : MCP》2008,7(4):697-715
Macrophages are immune cells that function in the clearance of infectious particles. This process involves the engulfment of microbes into phagosomes where these particles are lysed and degraded. In the current study, we used a large scale quantitative proteomics approach to analyze the changes in protein abundance induced on phagosomes by interferon-gamma (IFN-gamma), an inflammatory cytokine that activates macrophages. Our analysis identified 167 IFN-gamma-modulated proteins on phagosomes of which more than 90% were up-regulated. The list of phagosomal proteins regulated by IFN-gamma includes proteins expected to alter phagosome maturation, enhance microbe degradation, trigger the macrophage immune response, and promote antigen loading on major histocompatibility complex (MHC) class I molecules. A dynamic analysis of IFN-gamma-sensitive proteins by Western blot indicated that newly formed phagosomes display a delayed proteolytic activity coupled to an increased recruitment of the MHC class I peptide-loading complex. These phagosomal conditions may favor antigen presentation by MHC class I molecules on IFN-gamma-activated macrophages. 相似文献
68.
69.
Current evidence indicates an immunostimulating role for complex carbohydrates, i.e., polysaccharides, from several plant sources. In the present work, we determined the specific in vivo effects, with time of administration, of one such compound, a neutral arabinogalactan from larch not only on immune (lymphoid) cells, but also on natural killer (NK) lymphoid cells, as well as a variety of other hemopoietic cells in both the bone marrow and spleen of healthy, young adult mice. The latter were injected daily (i.p.) with arabinogalactan (500 microg in 0.1 ml pH 7.2 phosphate buffered saline-PBS) for 7 or 14 days. Additional, aged (1 1/2-2 yr) mice were similarly injected for 14 days only. Control mice were given the PBS vehicle in all cases, following the above injection regimen. Animals from all groups were sampled 24 h after the final injection and the immune and hemopoietic cell populations in the bone marow and spleen were assessed quantitatively. The results indicated that immediately following either 7 or 14 days of arabinogalactan administration to young, adult mice, lymphoid cells in the bone marrow were significantly decreased (p < 0.004; p < 0.001, respectively) relative to controls but remained unchanged at both time intervals in the spleen. NK cells, after 7 days of arabinogalactan exposure, were also decreased significantly in the bone marrow (p < 0.02), but unchanged in the spleen. After 14 days' exposure to the polysaccharide, NK cells in the bone marrow had returned to normal (control) levels, but were increased in the spleen (p < 0.004) to levels greater than 2-fold that of control. Among other hemopoietic cell lineages, none was influenced in the bone marrow or spleen by one-week administration of arabinogalactan; however, after two-week exposure, precursor myeloid cells and their mature (functional) progeny (granulocytes), were significantly reduced in the spleen (p < 0.043; p < 0.006, respectively), as were splenic monocytes (p < 0.001). These lineages in the bone marrow, however, remained steadfastly unaltered even after 14 days of continuous exposure to the agent. Of the vast cascade of cytokines induced in the presence of this polysaccharide, it appears that immunopoiesis- and hemopoiesis-inhibiting ones are most prevalent during at least the first two weeks of daily exposure. 相似文献
70.