| 1. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 2. |
- Butler, Geraldine, et al.
(författare)
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Evolution of pathogenicity and sexual reproduction in eight Candida genomes.
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 459:7247, s. 657-62
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Tidskriftsartikel (refereegranskat)abstract
- Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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| 3. |
- Couch, Fergus J., et al.
(författare)
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AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study
- 2007
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:7, s. 1416-1421
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Tidskriftsartikel (refereegranskat)abstract
- The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
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| 4. |
- Soranzo, Nicole, et al.
(författare)
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A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 38-1182
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Tidskriftsartikel (refereegranskat)abstract
- The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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| 5. |
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| 6. |
- Babbin, Brian A., et al.
(författare)
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Non-muscle myosin IIA differentially regulates intestinal epithelial cell restitution and matrix invasion
- 2009
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Ingår i: American Journal of Pathology. - : Elsevier. - 0002-9440 .- 1525-2191. ; 174:2, s. 436-448
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial cell motility is critical for self-rejuvenation of normal intestinal mucosa, wound repair, and cancer metastasis. This process is regulated by the reorganization of the F-actin cytoskeleton, which is driven by a myosin II motor. However, the role of myosin II in regulating epithelial cell migration remains poorly understood. This study addressed the role of non-muscle myosin (NM) IIA in two different modes of epithelial cell migration: two-dimensional (2-D) migration that occurs during wound closure and three-dimensional (3-D) migration through a Matrigel matrix that occurs during cancer metastasis. Pharmacological inhibition or siRNA-mediated knockdown of NM IIA in SK-CO15 human colonic epithelial cells resulted in decreased 2-D migration and increased 3-D invasion. The attenuated 2-D migration was associated with increased cell adhesiveness to collagen and laminin and enhanced expression of beta1-integrin and paxillin. On the 2-D surface, NM IIA-deficient SK-CO15 cells failed to assemble focal adhesions and F-actin stress fibers. In contrast, the enhanced invasion of NM IIA-depleted cells was dependent on Raf-ERK1/2 signaling pathway activation, enhanced calpain activity, and increased calpain-2 expression. Our findings suggest that NM IIA promotes 2-D epithelial cell migration but antagonizes 3-D invasion. These observations indicate multiple functions for NM IIA, which, along with the regulation of the F-actin cytoskeleton and cell-matrix adhesions, involve previously unrecognized control of intracellular signaling and protein expression.
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| 7. |
- Heard-Costa, Nancy L, et al.
(författare)
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NRXN3 is a novel locus for waist circumference : a genome-wide association study from the CHARGE Consortium
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000539-
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Tidskriftsartikel (refereegranskat)abstract
- Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4×10−7)]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3×10−8 for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4×10−6, 0.024 z-score units (0.10 kg/m2) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07–1.19; p = 3.2×10−5 per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
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| 8. |
- Morgan-Richards, Mary, et al.
(författare)
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Bird evolution: testing the Metaves clade with six new mitochondrial genomes
- 2008
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 8:20
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evolutionary biologists are often misled by convergence of morphology and this has been common in the study of bird evolution. However, the use of molecular data sets have their own problems and phylogenies based on short DNA sequences have the potential to mislead us too. The relationships among clades and timing of the evolution of modern birds (Neoaves) has not yet been well resolved. Evidence of convergence of morphology remain controversial. With six new bird mitochondrial genomes (hummingbird, swift, kagu, rail, flamingo and grebe) we test the proposed Metaves/Coronaves division within Neoaves and the parallel radiations in this primary avian clade. Results: Our mitochondrial trees did not return the Metaves clade that had been proposed based on one nuclear intron sequence. We suggest that the high number of indels within the seventh intron of the beta-fibrinogen gene at this phylogenetic level, which left a dataset with not a single site across the alignment shared by all taxa, resulted in artifacts during analysis. With respect to the overall avian tree, we find the flamingo and grebe are sister taxa and basal to the shorebirds (Charadriiformes). Using a novel site-stripping technique for noise-reduction we found this relationship to be stable. The hummingbird/swift clade is outside the large and very diverse group of raptors, shore and sea birds. Unexpectedly the kagu is not closely related to the rail in our analysis, but because neither the kagu nor the rail have close affinity to any taxa within this dataset of 41 birds, their placement is not yet resolved. Conclusion: Our phylogenetic hypothesis based on 41 avian mitochondrial genomes ( 13,229 bp) rejects monophyly of seven Metaves species and we therefore conclude that the members of Metaves do not share a common evolutionary history within the Neoaves.
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| 9. |
- Petri, Michelle, et al.
(författare)
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Systemic lupus international collaborating clinics renal activity/response exercise - Development of a renal activity score and renal response index
- 2008
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 58:6, s. 1784-1788
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To develop a measure of renal activity in systemic lupus erythematosus and use it to develop a renal response index. Methods. Abstracted data from the medical records of 215 patients with lupus nephritis were sent to 8 nephrologists and 29 rheumatologists for rating. Seven nephrologists and 22 rheumatologists completed the ratings. Each physician rated each patient visit with respect to renal disease activity (none, mild, moderate, or severe). Using the most commonly selected rating for each patient as the gold standard, stepwise regression modeling was performed to identify the variables most related to renal disease activity, and these variables were then used to create an activity score. This activity score could then be applied to 2 consecutive visits to define a renal response index. Results. The renal activity score was computed as follows: proteinuria 0.5-1 gm/day (3 points), proteinuria >1-3 gm/day (5 points), proteinuria >3 gm/day (11 points), urine red blood cell count > 10/high-power field (3 points), and urine white blood cell count >10/high-power field (I point). The chance-adjusted agreement between the renal response index derived from the activity score applied to the paired visits and the plurality physician response rating was 0.69 (95% confidence interval 0.59-0.79). Conclusion. Ratings derived from this index for rating of renal response showed reasonable agreement with physician ratings in a pilot study. The index will require further refinement, testing, and validation. A data-driven approach to create renal activity and renal response indices will be useful in both clinical care and research settings.
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| 10. |
- Plunkett, Jevon, et al.
(författare)
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Mother's Genome or Maternally-Inherited Genes Acting in the Fetus Influence Gestational Age in Familial Preterm Birth
- 2009
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Ingår i: Human Heredity. - : S. Karger AG. - 1423-0062 .- 0001-5652. ; 68:3, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- Objective: While multiple lines of evidence suggest the importance of genetic contributors to risk of preterm birth, the nature of the genetic component has not been identified. We perform segregation analyses to identify the best fitting genetic model for gestational age, a quantitative proxy for preterm birth. Methods: Because either mother or infant can be considered the proband from a preterm delivery and there is evidence to suggest that genetic factors in either one or both may influence the trait, we performed segregation analysis for gestational age either attributed to the infant (infant's gestational age), or the mother (by averaging the gestational ages at which her children were delivered), using 96 multiplex preterm families. Results: These data lend further support to a genetic component contributing to birth timing since sporadic (i.e. no familial resemblance) and nontransmission (i.e. environmental factors alone contribute to gestational age) models are strongly rejected. Analyses of gestational age attributed to the infant support a model in which mother's genome and/or maternally-inherited genes acting in the fetus are largely responsible for birth timing, with a smaller contribution from the paternally-inherited alleles in the fetal genome. Conclusion: Our findings suggest that genetic influences on birth timing are important and likely complex. Copyright (C) 2009 S. Karger AG, Basel
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| 11. |
- Ross, Owen A., et al.
(författare)
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Genomic investigation of alpha-synuclein multiplication and parkinsonism
- 2008
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 63:6, s. 743-750
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Copy number variation is a common polymorphic phenomenon within the human genome. Although the majority of these events are non-deleterious they can also be highly pathogenic. Herein we characterize five families with parkinsonism that have been identified to harbor multiplication of the chromosomal 4q21 locus containing the a-synuclein gene (SNCA). Methods: A methodological approach using fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) 250K SNP microarrays was used to characterize the multiplication in each family and to identify the genes encoded within the region. The telomeric and centromeric breakpoints of each family were further narrowed using semiquantitative polymerase chain reaction with microsatellite markers and then screened for transposable repeat elements. Results: The severity of clinical presentation is correlated with SNCA dosage and does not appear to be overtly affected by the presence of other genes in the multiplicated region. With the exception of the Lister kindred, in each family the multiplication event appears de novo. The type and position of Alu/LINE repeats are also different at each breakpoint. Microsatellite analysis demonstrates two genomic mechanisms are responsible for chromosome 4q21 multiplications, including both SNCA duplication and recombination. Interpretation: SNCA dosage is responsible for parkinsonism, autonomic dysfunction, and dementia observed within each family. We hypothesize dysregulated expression of wild-type (alpha-synuclein results in parkinsonism and may explain the recent association of common SNCA variants in sporadic Parkinson's disease. SNCA genomic duplication results from intraallelic (segmental duplication) or interallelic recombination with unequal crossing over, whereas both mechanisms appear to be required for genomic SNCA triplication.
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| 12. |
- Taha, Muhamed-Kheir, et al.
(författare)
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Interlaboratory Comparison of PCR-Based Identification and Genogrouping of Neisseria meningitidis
- 2005
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 43:1, s. 144-149
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Tidskriftsartikel (refereegranskat)abstract
- Twenty clinical samples (18 cerebrospinal fluid samples and 2 articular fluid samples) were sent to 11 meningococcus reference centers located in 11 different countries. Ten of these laboratories are participating in the EU-MenNet program (a European Union-funded program) and are members of the European Monitoring Group on Meningococci. The remaining laboratory was located in Burkina Faso. Neisseria meningitidis was sought by detecting several meningococcus-specific genes (crgA, ctrA, 16S rRNA, and porA). The PCR-based nonculture method for the detection of N. meningitidis gave similar results between participants with a mean sensitivity and specificity of 89.7 and 92.7%, respectively. Most of the laboratories also performed genogrouping assays (siaD and mynB/sacC). The performance of genogrouping was more variable between laboratories, with a mean sensitivity of 72.7%. Genogroup B gave the best correlation between participants, as all laboratories routinely perform this PCR. The results for genogroups A and W135 were less similar between the eight participating laboratories that performed these PCRs.
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| 13. |
- Arnetz, Bengt B., et al.
(författare)
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War-related mental health disorders among Iraqis 10 years after the 1991 Gulf War : A comparative study of soldiers and civilians living under sustained socio-environmental stress
- 2009
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Ingår i: The New Iraqi Journal of Medicine. - 1817-5562. ; 5:1, s. 9-21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior studies of mental health consequences of the Gulf War (GW) have been confined to Allied forces, limiting the ability to control for important geographically and culturally-related factors. We conducted an epidemiological mental health study among Iraqi soldiers and civilians who are still residing in Iraq. This group has been exposed to sustained socio-environmental stress. Methods: A cross-sectional sample of 742 Iraqi GW veterans and 413 civilians responded to a validated mental health survey. The response rate was 96.3%. Mental health disorders, including post traumatic stress disorder (PTSD), were classified using both self-reports and validated scales. War-related exposure was calculated using the sum score of items assessing trauma exposure. Results: Iraqi soldiers reported significantly more depression (Odds Ratio [OR] 4.9; 95% confidence interval [CI] 2.2-11.1) and anxiety (OR 3.9; 95% CI, 1.2-13.3) compared to civilians, adjusting for age, education, and smoking. Soldiers closest to Kuwait during the GW reported significantly more depression compared to soldiers deployed further away from the war epicenter (OR 104.6; 95% CI, 28.0-390.8) and anxiety (OR 4.1; 95% CI, 1.5-11.1). The highest self-reported trauma exposure occurred in the southwest of Iraq. Conclusion: Iraqi soldiers that took part in the GW are at increased risk suffering from many of the same mental health disorders plaguing Allied soldiers. Soldiers closest to Kuwait were more at risk, suggesting a direct link to war-specific environmental exposures, although self-reported trauma exposure was higher in the southwest of Iraq. The study offers additional insights into the mental health consequences of living under sustained socio-environmental stress, originating from the Iraqi war. The study points out socio-environmental factors worthy of further explorations.
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| 14. |
- Baniulis, Danas, et al.
(författare)
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Monoclonal antibody CL5 recognizes the amino terminal domain of human phagocyte flavocytochrome b558 large subunit, gp91phox
- 2005
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 74:4, s. 337-347
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Tidskriftsartikel (refereegranskat)abstract
- Human phagocyte flavocytochrome b558 (Cytb) is a heterodimeric integral membrane protein that serves as the electron transferase of the β-nicotinamide adenine dinucleotidephosphate, reduced (NADPH)-oxidase, an enzyme complex important in the host defense function of phagocytic cells. In this study, we report the characterization of monoclonal antibody (mAb) CL5 that is specific for the large subunit, gp91phox, of the oxidase protein. This antibody recognizes gp91phox by immunoblot analysis of membrane extracts and samples of the immunopurified gp91phox/p22 phox heterodimer, prepared on anti-p22phox affinity matrices. Phage display analysis confirmed this specificity, indicating that the CL5 epitope contains the region 135-DPYSVALSELGDR of gp91phox. The antibody was used to probe for the presence of gp91phox in membrane preparations from neutrophils of patients with nine genetically distinct forms of X-linked chronic granulomatous disease (CGD). The causative mutations included missense errors as well as nonsense errors that result in premature termination of gp91phox synthesis. Analysis of the CGD samples by immunoblotting indicated that CL5 recognizes only the full-length wild-type and two missense mutations, consistent with the absence of stable short gp91 phox peptide expression in CGD neutrophils. Interestingly, CL5 was also shown to be cross-reactive with cytosolic and membrane-bound gelsolin, identified by purification, mass spectrometry and immunoblot analysis. CL5 probably cross-reacts with the sequence 771-DPLDRAMAEL in the C-terminus of gelsolin. We conclude that mAb CL5 is a useful probe for detection of full length and possibly truncated N-terminal fragments of gp91phox from membranes of Cytb-producing cells. © Blackwell Munksgaard 2005.
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| 15. |
- Baniulis, Danas, et al.
(författare)
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Unusual polyclonal anti-gp91phox peptide antibody interactions with X-linked chronic granulomatous disease-derived human neutrophils are not from compensatory expression of Nox proteins 1, 3, or 4
- 2005
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 74:3, s. 241-249
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Tidskriftsartikel (refereegranskat)abstract
- To obtain topological information about human phagocyte flavocytochrome b558 (Cytb), rabbit anti-peptide antibodies were raised against synthetic peptides mimicking gp91phox regions: 1-9 (MGN), 30-44 (YRV), 150-159 (ESY), 156-166 (ARK), 247-257 (KIS-1, KIS-2). Following affinity purification on immobilized peptide matrices, all antibodies but not prebleed controls recognized purified detergent-solubilized Cytb by enzyme-linked immunosorbent assay (ELISA). Affinity-purified antibodies recognizing KIS, ARK and ESY but not YRV, MGN or prebleed IgG specifically detected gp91phox in immunoblot analysis. Antibodies recognizing MGN, ESY, ARK and KIS but not YRV or the prebleed IgG fraction labeled intact normal neutrophils. Surprisingly, all antibodies, with the exception of YRV and pre-immune IgG controls, bound both normal and Cytb-negative neutrophils from the obligate heterozygous mother of a patient with X-linked chronic granulomatous disease (X-CGD) and all neutrophils from another patient lacking the gp91phox gene. Further immunochemical examination of membrane fractions derived from nine genetically unrelated patients with X-CGD, using an antibody that recognizes other Nox protein family members, suggests that the unusual reactivity observed does not reflect the compensatory expression of gp91phox homologs Nox1, 3 or 4. These results suggest that an unusual surface reactivity exists on neutrophils derived from X-linked chronic granulomatous disease patients that most likely extends to normal neutrophils as well. The study highlights the need for caution in interpreting the binding of rabbit polyclonal antipeptide antibodies to human neutrophils in general and, in the specific case of antibodies directed against Cytb, the need for Cytb-negative controls.
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| 16. |
- Bidartondo, Martin, et al.
(författare)
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Preserving accuracy in GenBank
- 2008
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Ingår i: Science. ; 319:5870
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 17. |
- Blom, Anna M, et al.
(författare)
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A Novel Non-Synonymous Polymorphism (p.Arg240His) in C4b-Binding Protein Is Associated with Atypical Hemolytic Uremic Syndrome and Leads to Impaired Alternative Pathway Cofactor Activity.
- 2008
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Ingår i: Journal of Immunology. - 1550-6606. ; 180:9, s. 6385-6391
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Tidskriftsartikel (refereegranskat)abstract
- Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, and copy number variation in complement factors and inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism in the complement inhibitor C4b-binding protein (C4BP) alpha-chain (c.719G>A; p.Arg240His), which is associated with aHUS. This heterozygous change was found in 6/166 aHUS patients compared with 5/542 normal (chi2 = 6.021; p = 0.014), which was replicated in a second cohort of aHUS patients in which we found 5/170 carriers. The polymorphism does not decrease expression efficiency of C4BP. p.Arg240His is equally efficient as the wild type in binding and supporting degradation of C4BP but its ability to bind C3b and act as cofactor to its degradation both in fluid phase and on surfaces is impaired. This observation supports the hypothesis that dysregulation of the alternative pathway of complement is pivotal for aHUS. Three of the patients carry also mutations in membrane cofactor protein and factor H strengthening the hypothesis that individuals may carry multiple susceptibility factors with an additive effect on the risk of developing aHUS.
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| 18. |
- Brotonsc, Carlos, et al.
(författare)
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Prevention and health promotion in clinical practice: the views of general practitioners in Europe.
- 2005
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Ingår i: Preventive medicine. - : Elsevier BV. - 0091-7435. ; 40:5, s. 595-601
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Disease prevention and health promotion are important tasks in the daily practice of all general practitioners (GPs). The objective of this study was to explore the knowledge and attitudes of European GPs in implementing evidence-based health promotion and disease prevention recommendations in primary care, to describe GPs' perceived barriers to implementing these recommendations and to assess how GPs' own health behaviors affect their work with their patients. METHODS: A postal multinational survey was carried out from June to December 2000 in a random sample of GPs listed from national colleges of each country. RESULTS: Eleven European countries participated in the study, giving a total of 2082 GPs. Although GPs believe they should advise preventive and health promotion activities, in practice, they are less likely to do so. About 56.02% of the GPs answered that carrying-out prevention and health promotion activities are difficult. The two most important barriers reported were heavy workload/lack of time and no reimbursement. Associations between personal health behaviour and attitudes to health promotion or activities in prevention were found. GPs who smoked felt less effective in helping patients to reduce tobacco consumption than non-smoking GPs (39.34% versus 48.18%, P < 0.01). GPs who exercised felt that they were more effective in helping patients to practice regular physical exercise than sedentary GPs (59.14% versus 49.70%, P < 0.01). CONCLUSIONS: Significant gaps between GP's knowledge and practices persist in the use of evidence-based recommendations for health promotion and disease prevention in primary care.
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| 19. |
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| 20. |
- Hill, Deirdre A., et al.
(författare)
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Breast cancer risk following radiotherapy for Hodgkin lymphoma : modification by other risk factors
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 106:10, s. 3358-65
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Tidskriftsartikel (refereegranskat)abstract
- The importance of genetic and other risk factors in the development of breast cancer after radiotherapy (RT) for Hodgkin lymphoma (HL) has not been determined. We analyzed data from a breast cancer case-control study (105 patients, 266 control subjects) conducted among 3 817 survivors of HL diagnosed at age 30 years or younger in 6 population-based cancer registries. Odds ratios (ORs) and excess relative risks (ERRs) were calculated using conditional regression. Women who received RT exposure (> or = 5 Gy radiation dose to the breast) had a 2.7-fold increased breast cancer risk (95% confidence interval (CI) 1.4-5.2), compared with those given less than 5 Gy. RT exposure (> or = 5 Gy) was associated with an OR of 0.8 (95% CI, 0.2-3.4) among women with a first- or second-degree family history of breast or ovarian cancer, and 5.8 (95% CI, 2.1-16.3) among all other women (interaction P = .03). History of a live birth appeared to increase the breast cancer risk associated with RT among women not treated with ovarian-damaging therapies. Breast cancer risk following RT varied little according to other factors. The additional increased relative risk of breast cancer after RT for HL is unlikely to be larger among women with a family history of breast or ovarian cancer than among other women.
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| 21. |
- Jaarsma, Tiny, et al.
(författare)
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Palliative care in heart failure: a position statement from the palliative care workshop of the Heart Failure Association of the European Society of Cardiology.
- 2009
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Ingår i: European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology. - : Wiley. - 1388-9842 .- 1879-0844. ; 11:5, s. 433-43
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure is a serious condition and equivalent to malignant disease in terms of symptom burden and mortality. At this moment only a comparatively small number of heart failure patients receive specialist palliative care. Heart failure patients may have generic palliative care needs, such as refractory multifaceted symptoms, communication and decision making issues and the requirement for family support. The Advanced Heart Failure Study Group of the Heart Failure Association of the European Society of Cardiology organized a workshop to address the issue of palliative care in heart failure to increase awareness of the need for palliative care. Additional objectives included improving the accessibility and quality of palliative care for heart failure patients and promoting the development of heart failure-orientated palliative care services across Europe. This document represents a synthesis of the presentations and discussion during the workshop and describes recommendations in the area of delivery of quality care to patients and families, education, treatment coordination, research and policy.
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| 22. |
- Larsson, Maria U., et al.
(författare)
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Phonemic fluency deficits in asymptomatic gene carriers for Huntington's disease
- 2008
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Ingår i: Neuropsychology. - : American Psychological Association (APA). - 0894-4105 .- 1931-1559. ; 22:5, s. 596-605
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate verbal fluency in preclinical Huntington's disease (HD). Phonemic and semantic fluency and the rate of word production over time were assessed for 29 asymptomatic gene carriers and 34 noncarriers of HD. The relationship between fluency tasks and other cognitive domains was investigated. Compared to noncarriers, carriers produced fewer words and produced them more slowly in the phonemic fluency task but not in the semantic fluency task. When the carrier group was divided on the basis of Predicted-Years-To-Onset (PYTO), only carriers with <12 PYTO performed worse than noncarriers on both fluency tasks. Correlational analyses revealed that phonemic fluency was associated with cognitive speed and working memory, while semantic fluency was linked with crystallized abilities. The difference between carriers and noncarriers in phonemic fluency and a difference between the two carrier groups (<12 PYTO and ≥12 PYTO) in semantic fluency, but not in phonemic fluency, suggest that frontostriatal deficits may precede temporal involvement in preclinical HD.
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| 23. |
- O'Donnell, Deborah A, et al.
(författare)
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The mediating role of alienation in the development of maladjustment in youth exposed to community violence.
- 2006
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Ingår i: Development and psychopathology (Print). - 0954-5794 .- 1469-2198. ; 18:1, s. 215-32
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Tidskriftsartikel (refereegranskat)abstract
- A study was conducted to determine predictors of high risk/delinquent behavior and psychoemotional maladjustment in 1,478 sixth and eighth graders who took part in a survey of high-risk and adaptive behaviors. The first goal was to determine the extent to which two distinct dimensions of alienation, normlessness, and isolation/self-estrangement mediated the emergence of maladjustment in youth exposed to community violence. The second goal was to distinguish between violence witnessing and violence victimization, and determine whether these subtypes of violence exposure may differentially affect the proposed mediational factors. The results indicated that normlessness partially mediated the relationship between violence exposure and high-risk/delinquent behavior and between violence exposure and psychoemotional maladjustment. Isolation/self-estrangement partially mediated the relation between violence exposure and psychoemotional maladjustment. Although witnessing of, and victimization by, violence were both significant predictors of normlessness, only violent victimization was significantly linked to isolation/self-estrangement. These results elucidate the mechanisms by which community violence exposure may exert negative influences on youth and suggest that there are distinct patterns of risk associated with different forms of exposure.
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| 24. |
- Ozsahin, Hulya, et al.
(författare)
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Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation.
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:1, s. 439-45
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Tidskriftsartikel (refereegranskat)abstract
- Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in long-term follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies.
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| 25. |
- Pasquini, Ricardo, et al.
(författare)
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HLA-matched sibling hematopoietic stem cell transplantation for fanconi anemia: comparison of irradiation and nonirradiation containing conditioning regimens.
- 2008
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Ingår i: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 14:10, s. 1141-7
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Tidskriftsartikel (refereegranskat)abstract
- Related to the underlying DNA repair defect that is the hallmark of Fanconi anemia (FA), preparatory regimen-related toxicities have been obstacles to hematopoietic cell transplantation (HCT). In an attempt to decrease the risk and severity of regimen-related toxicities, nonirradiation regimens have been explored. The aim of this study is to compare outcomes after irradiation and nonirradiation regimens in 148 FA patients and identify risk factors impacting upon HCT outcomes. Hematopoietic recovery, acute and chronic graft-versus-host disease (aGVHD, GVHD), and mortality were similar after irradiation and nonirradiation regimens. In both groups of recipients aged >10 years, prior use of androgens and cytomegalovirus seropositivity in either the donor or recipient were associated with higher mortality. With median follow-ups >5 years, the 5-year probability of overall survival, adjusted for factors impacting overall mortality was 78% and 81% after irradiation and nonirradiation regimens, P = .61. In view of the high risk of cancer and other radiation-related effects on growth and development, these results support the use of nonirradiation preparatory regimens. As the peak time for developing solid tumors after HCT is 8 to 9 years, longer follow-up is required before definitive statements can be made regarding the impact of nonirradiation regimens on cancer risk.
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| 26. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 27. |
- Ruchkin, Vladislav, et al.
(författare)
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Depressive symptoms and associated psychopathology in urban adolescents : a cross-cultural study of three countries.
- 2006
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Ingår i: Journal of Nervous and Mental Disease. - : Ovid Technologies (Wolters Kluwer Health). - 0022-3018 .- 1539-736X. ; 194:2, s. 106-13
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to compare cross-cultural trends of comorbid internalizing and externalizing psychopathology, prosocial beliefs, and perceptions of risk in adolescents with and without clinical levels of self-reported depressive symptoms. The Social and Health Assessment, a self-report survey, was conducted in a representative sample of 3309 adolescents 14 to 17 years old from urban communities in the United States (N = 1343), Belgium (N = 946), and Russia (N = 1009). In all three countries, girls reported higher levels of depressive symptoms than boys. The findings also demonstrate that in both genders, depressive symptoms were associated with increased levels of internalizing and externalizing problems, as well as lower levels of prosocial beliefs and low perceptions of harm from risk-taking behavior. Depressed boys had relatively higher levels of externalizing problems than depressed girls. Greater levels of internalizing problems observed in depressed youth, as compared with their nondepressed counterparts, were not gender-specific. Current findings suggest that the relationships between depression and comorbid psychopathology are not culture-specific and have similar patterns in different populations.
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| 28. |
- Rönnberg, Jerker, et al.
(författare)
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Cognitive Hearing Science: The role of a working memory system for speech understanding in old age
- 2009
-
Ingår i: <em>Hearing care for adults</em>. - Stäfa : Phonak.
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Many older adults with hearing impairment continue to have substantial communication difficulties after being fitted with hearing aids, and many do not choose to wear hearing aids. Two group communication education programs aimed at such older people are described. The 'Keep on Talking' program has a health promotion focus, and is aimed at maintaining communication for older adults living in the community. An experimental group (n = 120) attended the program, and a control group (n = 130) received a communication assessment but no intervention. Significant improvements were found in the experimental participants in terms of knowledge about communication changes with age and about strategies to maintain communication skills. At the follow-up evaluation at 1 year, 45% of the experimental group, compared to 10% of the control group, had acted to improve their communication skills. The 'Active Communication Education' program focuses on the development of problem-solving strategies to improve communication in everyday life situations. Preliminary outcomes have been assessed on a small scale (n = 14) to date. It is concluded that communication programs represent an important adjunct to, or supplement for, the traditional approach that focuses on hearing aid fitting.
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| 29. |
- Salim, Sa'ad, et al.
(författare)
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CD83(+)CCR7(-) Dendritic Cells Accumulate in the Subepithelial Dome and Internalize Translocated Escherichia coli HB101 in the Peyers Patches of Heal Crohns Disease
- 2009
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 174:1, s. 82-90
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Tidskriftsartikel (refereegranskat)abstract
- Recurrent Crohns disease originates with small erosions in the follicle-associated epithelium overlying the Peyers patches. Animal studies have illustrated mucosal immune regulation by dendritic cells located in the subepithelial dome. The aim of this study was to characterize the dendritic cells at this specific site in patients with Crohns disease. Heal tissues were obtained after surgery performed on Crohns patients; ileal samples from noninflammatory bowel disease and ulcerative colitis served as standard and inflammatory controls, respectively. Flow cytometry of isolated intestinal mononuclear cells showed a larger subset of dendritic cells in Crohns samples compared with controls. This finding was corroborated by confocal microscopy, showing enhanced infiltrates of cells positive for the dendritic cell markers, DC-SIGN(+) and CD83(+), in the subepithelial dome. Moreover, the CD83(+) cells in Crohns tissues showed reduced expression of the lymph node migratory receptor, CCR7, possibly contributing to the high numbers of dendritic cells. After exposure to nonpathogenic Escherichia coli in Ussing chambers, dendritic cells in the subepithelial dome of Crohns disease demonstrated increased co-localization with translocated bacteria. Immunohistochemical results revealed that DC-SIGN(+) cells in Crohns tissues were found to express toll-like receptor 4 and produce tumor necrosis factor-a. In conclusion, nonmigrating dendritic cells that accumulate in the subepithelial dome and internalize nonpathogenic bacteria may be important for the onset and perpetuation of mucosal inflammation in Crohns disease.
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| 30. |
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| 31. |
- Siles, Rogelio, et al.
(författare)
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Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents
- 2008
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 71:3, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2',3'-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human cancer cell lines in vitro (average GI(50) = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC50 = 2.8 mu M). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents.
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| 32. |
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| 33. |
- Tam, Miguel A., 1976, et al.
(författare)
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Differential expansion, activation and effector functions of conventional and plasmacytoid dendritic cells in mouse tissues transiently infected with Listeria monocytogenes.
- 2006
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Ingår i: Cellular microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 8:7, s. 1172-87
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DC) are crucial in generating immunity to infection. Here we characterize changes in DC in terms of number, activation and effector functions, focusing on conventional DC (cDC) and plasmacytoid DC (pDC), in Listeria-infected mice. Kinetic studies showed a subset- and tissue-specific expansion of cDC and upregulation of CD80 and CD86 on splenic and mesenteric lymph node (MLN) cDC after intragastric infection. Expansion of pDC was more prolonged than cDC, and pDC upregulated CD86 and MHC-II, but not CD80, in both the spleen and MLN. cDC were an important source of IL-12 but not TNF-alpha during infection, while pDC made neither of these cytokines. Instead other CD11c(int) cells produced these cytokines. Using five-colour flow cytometry and double intracellular cytokine staining, we detected phenotypically similar CD11c(int)CD11b(+)Gr1(+) cells with distinct capacities to produce TNF-alpha/IL-12 or TNF-alpha/iNOS (inducible nitric oxide synthase) in Listeria-infected tissues. IL-12p70 was also produced by sorted CD11c(hi) and CD11c(int)CD11b(+)Gr1(+) cells. Furthermore, production of TNF-alpha, iNOS and IL-12 was differentially dependent on cellular localization of the bacteria. Cytosol-restricted bacteria induced TNF-alpha and iNOS-producing cells, albeit at lower frequency than wild-type bacteria. In contrast, IL-12 was induced only with wild-type bacteria. These data provide new insight into the relative abundance and function of distinct CD11c-expressing populations during the early stage of Listeria infection.
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| 34. |
- Tam, Miguel A., 1976, et al.
(författare)
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Early cellular responses to Salmonella infection: dendritic cells, monocytes, and more.
- 2008
-
Ingår i: Immunological reviews. - 1600-065X. ; 225, s. 140-62
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Forskningsöversikt (refereegranskat)abstract
- SUMMARY: Dendritic cells (DCs), monocytes, macrophages, and neutrophils are myeloid-derived phagocytes critical to controlling bacterial infections, and these cells have complementary functions to ensure host survival. Recent data have shed light on the dynamics and function of myeloid cells at the early stage of infection. In particular, murine infection models with Salmonella enterica serovar Typhimurium have been useful for understanding the host response required to develop immunity to systemic salmonellosis. This review summarizes the early cellular responses in the intestinal lymphoid tissues to Salmonella and discusses Peyer's patch-dependent and -independent penetration of bacteria through the intestinal epithelium. Once Salmonella accesses host tissue, phagocytes respond by recruitment, redistribution, and activation in intestinal tissues. Recruited monocytes are specialized in controlling bacterial replication by producing anti-microbial molecules but are poor antigen-presenting cells. In contrast, DCs undergo maturation by direct (bacteria-mediated) and indirect (cytokine-mediated) pathways in vivo to optimize their antigen presentation capacity, and directly matured DCs have unique mechanisms to ensure T-cell stimulation. Toll-like receptor signaling is critical to DC maturation and myeloid cell recruitment during Salmonella infection, and the role of myeloid differentiation factor 88 (MyD88)-dependent and MyD88-independent pathways as well as proinflammatory cytokines and type 1 interferons in these processes are discussed.
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| 35. |
- Tam, Miguel A., 1976, et al.
(författare)
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MyD88 and IFN-alphabeta differentially control maturation of bystander but not Salmonella-associated dendritic cells or CD11cintCD11b+ cells during infection.
- 2008
-
Ingår i: Cellular microbiology. - : Hindawi Limited. - 1462-5822 .- 1462-5814. ; 10:7, s. 1517-29
-
Tidskriftsartikel (refereegranskat)abstract
- The interface between dendritic cells (DCs) and T cells is critical to elicit effective immunity against pathogens. The maturation state of DCs determines the quality of the interaction and governs the type of response. DCs can be matured directly through activating Toll-like receptors (TLRs) or indirectly by cytokines. We explore the role of the TLR adaptor MyD88 on DC maturation during Salmonella infection. Using Salmonella expressing GFP, we also examine the phenotype and function of bacteria-associated DCs matured in the absence of bacteria-mediated TLR signalling. MyD88 was required for upregulation of CD80 on DCs during infection, whereas CD86 and CD40 were upregulated independently of MyD88, although requiring a higher bacterial burden in the MLN. MyD88-independent upregulation was mediated by IFN-alphabeta produced during infection. In infected MyD88(-/-)IFN-alphabetaR(-/-) mice, which lack most bacteria-driven TLR signalling, indirect DC maturation was abolished. In contrast, DCs containing Salmonella upregulated co-stimulatory molecules independently of MyD88 and IFN-alphabeta, revealing a pathway of phenotypic maturation active in infected DCs. However, despite high co-stimulatory molecule expression, Salmonella-containing DCs from MyD88(-/-) or MyD88(-/-)IFN-alphabetaR(-/-) mice had a compromised capacity to activate T cells. Thus, bacterial stimulation of TLRs influences DC function at multiple levels that modulates their capacity to direct antibacterial immunity.
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| 36. |
- Tam, Miguel A., 1976, et al.
(författare)
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MyD88 and interferon-alpha/beta are differentially required for dendritic cell maturation but dispensable for development of protective memory against Listeria.
- 2009
-
Ingår i: Immunology. - : Wiley. - 1365-2567 .- 0019-2805. ; 128:3, s. 429-38
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Tidskriftsartikel (refereegranskat)abstract
- Signalling pathways mediated by MyD88 are important for sensing Toll-like receptor (TLR) ligands and directing an immune response. However, the influence of MyD88-derived cytokines and interferon (IFN)-alpha/beta, the latter being made by both MyD88-dependent and -independent pathways, in phenotypic and functional dendritic cell (DC) maturation during infection is poorly understood. Here we investigate the contribution of MyD88-dependent and -independent pathways to DC maturation, CD8 T-cell activation and the generation of protective memory against Listeria monocytogenes. We show that neither MyD88 deficiency alone nor MyD88/IFN-alphabetaR double deficiency alters Listeria-induced costimulatory molecule up-regulation on DCs in vivo. In contrast, DCs from infected IFN-alphabetaR(-/-) mice had higher CD80 and CD86 expression than wild-type DCs. We then examined the function of DCs matured in infected knockout mice. We found that DCs from Listeria-infected MyD88(-/-) and MyD88(-/-) IFN-alphabetaR(-/-) mice induced little or no IFN-gamma by CD8 T cells, respectively. In contrast, DCs from infected IFN-alphabetaR(-/-) mice had a greater capacity to induce IFN-gamma compared with DCs from infected wild-type mice. When the CD8 T-cell memory response was analysed, infected MyD88(-/-) and MyD88(-/- )IFN-alphabetaR(-/-) mice were found to have fewer bacteria-specific memory CD8 T cells than wild-type mice. However, the fraction of bacteria-specific CD8 T cells making IFN-gamma was similar in all mouse strains, and MyD88(-/-) and MyD88(-/- )IFN-alphabetaR(-/-) mice survived lethal challenge. Together the data suggest an inhibitory effect of IFN-alpha/beta on functional DC maturation during Listeria infection and reveal overlapping roles of MyD88-induced cytokines and IFN-alpha/beta in DC maturation and protective anti-Listeria immunity.
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| 37. |
- Thompson, Hilaire J., et al.
(författare)
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Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody
- 2006
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 24:11, s. 3063-3072
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Tidskriftsartikel (refereegranskat)abstract
- Axonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG-specific monoclonal antibody (mAb). Anesthetized rats (n = 102) were subjected to either lateral fluid percussion brain injury (n = 59) or sham injury (n = 43). In surviving animals, beginning at 1 h post-injury, 8.64 mu g anti-MAG mAb (n = 33 injured, n = 21 sham) or control IgG (n = 26 injured, n = 22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n = 14 sham, n = 11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post-injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post-injury. At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain-injured animals receiving anti-MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P < 0.01) post-injury when compared with brain-injured IgG-treated animals. Additionally, at 8 weeks post-injury, the anti-MAG mAb-treated brain-injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P < 0.05) when compared with their brain-injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.
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| 38. |
- Travis, Lois B., et al.
(författare)
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Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma
- 2005
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 97:19, s. 1428-37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many women develop breast cancer after treatment for Hodgkin lymphoma (HL) at a young age. We estimated this future risk, taking into account age and calendar year of HL diagnosis, HL treatment information, population breast cancer incidence rates, and competing causes of death. METHODS: Relative risks of breast cancer for categories defined by radiation dose to the chest (0, 20- < 40 Gy, or > or = 40 Gy) and use of alkylating agents (yes or no) were estimated from a case-control study conducted within an international population-based cohort of 3817 female 1-year survivors of HL diagnosed at age 30 years or younger from January 1, 1965, through December 31, 1994. To compute cumulative absolute risks of breast cancer, we used modified standardized incidence ratios to relate cohort breast cancer risks to those in the general population, enabling application of population-based breast cancer rates, and we allowed for competing risks by using population-based mortality rates in female HL survivors. RESULTS: Cumulative absolute risks of breast cancer increased with age at end of follow-up, time since HL diagnosis, and radiation dose. For an HL survivor who was treated at age 25 years with a chest radiation dose of at least 40 Gy without alkylating agents, estimated cumulative absolute risks of breast cancer by age 35, 45, and 55 years were 1.4% (95% confidence interval [CI] = 0.9% to 2.1%), 11.1% (95% CI = 7.4% to 16.3%), and 29.0% (95% CI = 20.2% to 40.1%), respectively. Cumulative absolute risks were lower in women treated with alkylating agents. CONCLUSIONS: Breast cancer projections varied considerably by type of HL therapy, time since HL diagnosis, and age at end of follow-up. These estimates are applicable to HL survivors treated with regimens of the past and can be used to counsel such patients and plan management and preventive strategies. Projections should be used with caution, however, in patients treated with more recent approaches, including limited-field radiotherapy and/or ovary-sparing chemotherapy.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Tully, Mary, et al.
(författare)
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Pharmacists' changing views of their supplementary prescribing authority.
- 2007
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Ingår i: Pharmacy World & Science. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 29:6, s. 628-634
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the views and experiences of pharmacists in England before and after they registered as supplementary prescribers. Method Eight pharmacists were recruited from training courses; seven from secondary care and one from primary care and interviewed during training and again after registration. In the first interviews, topics included previous experience, views on current roles, responsibilities and accountability for prescribing and how these might change. In the second interviews, the pharmacists discussed how these had actually changed after gaining supplementary prescribing authority, how their role worked in practice and how they saw it developing in the future. Main outcome measure Descriptions of anticipated and actual changes in their roles, responsibilities and accountability before and after registration as supplementary prescribers Results The pharmacists anticipated that training would legitimise their current ‘informal’ prescribing practices, with increased legal responsibility and accountability, but experienced many procedural delays in implementing their new role. Pharmacists who were already heavily involved with prescribing were more likely to work as prescribers, but not necessarily within the clinical management plan framework. The desire to maintain the efficiency of their existing clinical services impacted negatively on the pharmacists’ ability or willingness to prescribe in this legally approved manner. Conclusion Clear and realistic expectations need to be set by the pharmacists as to what is achievable and greater attention needs to be paid to minimising delays between the end of training and the beginning of practice, to minimise reduction in motivation and redeployment of staff.
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| 44. |
- van Kempen, Elise E.M.M., et al.
(författare)
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Children's annoyance reactions to aircraft and road traffic noise
- 2009
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America. - 0001-4966 .- 1520-8524. ; 125:2, s. 895-904
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Tidskriftsartikel (refereegranskat)abstract
- Since annoyance reactions of children to environmental noise have rarely been investigated, no source specific exposure-response relations are available. The aim of this paper is to investigate children’s reactions to aircraft and road traffic noise and to derive exposure-response relations. To this end, children’s annoyance reactions to aircraft and road traffic noise in both the home and the school setting were investigated using the data gathered in a cross-sectional multicenter study, carried out among 2844 children age 9–11 years attending 89 primary schools around three European airports. An exposure-response relation was demonstrated between exposure to aircraft noise at school LAeq, 7–23 h and severe annoyance in children: after adjustment for confounders, the percentage severely annoyed children was predicted to increase from about 5.1% at 50 dB to about 12.1% at 60 dB. The findings were consistent across the three samples. Aircraft noise at home LAeq,7–23 h demonstrated a similar relation with severe annoyance. Children attending schools with higher road traffic noise LAeq,7–23 h were more annoyed. Although children were less annoyed at levels above 55 dB, the shapes of the exposure-response relations found among children were comparable to those found in their parents.
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