tbuckley/cabot-search huggingface dataset:
Human immunodeficiency virus, hepatitis C and hepatitis B infections among blood donors in Germany 2000-2002: risk of virus transmission and the impact of nucleic acid amplification testing
Authors: Ruth Offergeld, D Faensen, S Ritter, O Hamouda
Journal: Eurosurveillance (2005)

Blood and plasma donations in Germany are collected by several institutions, namely the German Red Cross, community and hospital-based blood services, private blood centres, commercial plasma donation sites and transfusion services of the army. All blood donation centres are required to report quarterly data on infection markers to the Robert Koch Institute, thus providing current and accurate epidemiological data. The prevalence and incidence of relevant viral infections are low in the blood donor population in Germany, with a decreasing trend for hepatitis C infections in new and repeat donors since 1997. The implementation of mandatory nucleic acid amplification technique (NAT) testing for hepatitis C virus (HCV) in 1999 has markedly improved transfusion safety. HIV-NAT became mandatory in 2004 but was done voluntarily by the majority of the blood donation services before then. The potential benefit of hepatitis B virus (HBV) minipool NAT is not as clear because chronic HBV carriers with very low virus levels might donate unidentified. The residual risk of an infectious window period donation inadvertently entering the blood supply can be estimated using a mathematic model which multiplies the incidence rate by the number of days during which an infection may be present but not detectable, i.e. the length of the window period. The risk of an undetected infection without NAT testing was estimated to be 1 in 2 770 000 for HIV, 1 in 670 000 for HCV and 1 in 230 000 for HBV in 2001/2002. This contrasts with 1 in 5 540 000 for HIV, 1 in 4 400 000 for HCV and 1 in 620 000 for HBV with minipool NAT testing. This demonstrates that NAT testing can further reduce the already very small risk of infectious donations entering the blood supply.
Asthma in children with sickle cell disease and its association with acute chest syndrome
Authors: J M Knight-Madden
Journal: Thorax (2005)

<b>Background:</b> Pulmonary complications are a major cause of morbidity and mortality in sickle cell disease (SCD). The relationship of asthma with SCD and acute chest syndrome (ACS) remains uncertain. A study was undertaken to test the hypotheses that asthma and bronchial hyperreactivity (BHR) are more common in children with SCD than in ethnic matched controls and that SCD children with atopic asthma are more likely to have recurrent episodes of ACS. <b>Methods:</b> A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was administered and skin prick tests undertaken in 80 children with SCD and 80 ethnic matched controls aged 5–10 years. BHR was assessed by measurement of forced expiratory volume in 1 second before and after a bronchodilator (albuterol 200 μg) or an exercise challenge. <b>Results:</b> Asthma (48% <i>v</i> 22%, p = 0.002) and BHR (p = 0.02) but not atopy were more common in children with SCD than in controls. Atopy (66.6% <i>v</i> 29%, p = 0.007) and asthma (80% <i>v</i> 40%, p = 0.005), particularly atopic asthma (53% <i>v</i> 12%, p&lt;0.001), were more common in children with SCD who had suffered recurrent episodes of ACS than in those who had suffered a single or no episode. <b>Conclusions:</b> Asthma and BHR are more common in children with SCD than in ethnic matched controls, and atopic asthma appears to be associated with recurrent ACS. Early and effective anti-asthma therapy might reduce the pulmonary morbidity associated with SCD.
Inhibition of Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Is Not Sufficient to Account for Indole-3-Carbinol–Induced Apoptosis in Some Breast and Prostate Tumor Cells
Authors: Lynne M. Howells, E. Ann Hudson, Margaret M. Manson
Journal: Clinical Cancer Research (2005)

Abstract Purpose and Experimental Design: Indole-3-carbinol has been proposed to induce apoptosis via a mechanism involving inhibition of protein kinase B (PKB) signaling in breast and prostate tumor cell lines. However, no functional data exist, and the effect of indole-3-carbinol on viability is known to be highly cell type specific. Here, we examine any requirement for PKB inhibition in induction of apoptosis by indole-3-carbinol in the MDA MB468 cell line using in vitro kinase assays, transfection, Western blotting, and flow cytometry. Comparison is also made with MCF10CA1 breast and PC3 prostate tumor cells. Results: Indole-3-carbinol directly inhibited activity of phosphatidylinositol 3-kinase (PI3K) immunoprecipitated from HBL100 or MDA MB468 cells in vitro. Nonetheless, we present three lines of evidence that inhibition of PI3K/PKB signaling is not required for induction of apoptosis by indole-3-carbinol. First, 50% inhibition of PKB phosphorylation by LY294002 resulted in only 15% apoptosis after 72 hours, whereas similar PKB inhibition by indole-3-carbinol coincided with 30% apoptosis after only 24 hours. Second, induction of phospho-PKB (p-PKB) levels following stimulation with epidermal growth factor did not prevent indole-3-carbinol–induced apoptosis. Third, overexpression of active PKBα did not prevent induction of apoptosis by indole-3-carbinol. Inhibition of PKB phosphorylation by LY294002 in the PC3 and MCF10CA1 tumor cell lines similarly failed to result in a significant increase in apoptosis. Conclusions: Our results show that inhibition of PI3K/PKB signaling by indole-3-carbinol or LY294002 is not directly correlated with induction of apoptosis in several breast or prostate cell lines.
A Role for ADAM12 in Breast Tumor Progression and Stromal Cell Apoptosis
Authors: Marie Kveiborg, Camilla Fröhlich, Reidar Albrechtsen, Verena Tischler, Nikolaj Dietrich, Peter Holck, Pauliina Kronqvist, Fritz Rank, Arthur M. Mercurio, Ulla M. Wewer
Journal: Cancer Research (2005)

Abstract As in developmental and regenerative processes, cell survival is of fundamental importance in cancer. Thus, a tremendous effort has been devoted to dissecting the molecular mechanisms involved in understanding the resistance of tumor cells to programmed cell death. Recently, the importance of stromal fibroblasts in tumor initiation and progression has been elucidated. Here, we show that stromal cell apoptosis occurs in human breast carcinoma but is only rarely seen in nonmalignant breast lesions. Furthermore, we show that ADAM12, a disintegrin and metalloprotease up-regulated in human breast cancer, accelerates tumor progression in a mouse breast cancer model. ADAM12 does not influence tumor cell proliferation but rather confers both decreased tumor cell apoptosis and increased stromal cell apoptosis. This dual role of ADAM12 in governing cell survival is underscored by the finding that ADAM12 increases the apoptotic sensitivity of nonneoplastic cells in vitro while rendering tumor cells more resistant to apoptosis. Together, these results show that the ability of ADAM12 to influence apoptosis may contribute to tumor progression.
Nurse-led palliative care for HIV-positive patients taking antiretroviral therapy in Kenya: a randomised controlled trial
Authors: Keira Lowther, Lucy Selman, Victoria Simms, Nancy Gikaara, Aabid Ahmed, Zipporah Ali, Hellen Kariuki, Lorraine Sherr, Irene J Higginson, Richard Harding
Journal: The Lancet HIV (2015)
Absence of Caspase 8 and High Expression of PED Protect Primitive Neural Cells from Cell Death
Authors: Lucia Ricci-Vitiani, Francesca Pedini, Cristiana Mollinari, Gerolama Condorelli, Désirée Bonci, Alessandra Bez, Augusto Colombo, Eugenio Parati, Cesare Peschle, Ruggero De Maria
Journal: The Journal of Experimental Medicine (2004)

The mechanisms that control neural stem and progenitor cell survival are unknown. In several pathological conditions, death receptor (DR) ligands and inflammatory cytokines exert a deleterious effect on neurons, whereas primitive neural cells migrate and survive in the site of lesion. Here, we show that even in the presence of inflammatory cytokines, DRs are unable to generate death signals in primitive neural cells. Neural stem and progenitor cells did not express caspase 8, the presence of which is required for initiating the caspase cascade. However, exogenous or cytokine-mediated expression of caspase 8 was not sufficient to restore their DR sensitivity. Searching for molecules potentially able to block DR death-inducing signaling complex (DISC), we found that primitive neural cells expressed high levels of the death effector domain-containing protein PED (also known as PEA-15). PED localized in the DISC and prevented caspase 8 recruitment and activation. Moreover, lentiviral-mediated delivery of PED antisense DNA resulted in dramatic down-regulation of the endogenous gene expression and sensitization of primitive neural cells to apoptosis mediated by inflammatory cytokines and DRs. Thus, absence of caspase 8 and high expression of PED constitute two levels of protection from apoptosis induced by DRs and inflammatory cytokines in neural stem and progenitor cells.
Anchorage-independent growth of synoviocytes from arthritic and normal joints. Stimulation by exogenous platelet-derived growth factor and inhibition by transforming growth factor-beta and retinoids.
Authors: R Lafyatis, E F Remmers, A B Roberts, D E Yocum, M B Sporn, R L Wilder
Journal: Journal of Clinical Investigation (1989)

Exuberant tumor-like synovial cell proliferation with invasion of periarticular bone is a feature of rheumatoid arthritis in humans and of streptococcal cell wall (SCW)-induced arthritis in rats. These histologic observations prompted us to examine synoviocytes from arthritic joints for phenotypic characteristics of transformed cells. The capacity to grow in vitro under anchorage-independent conditions is a characteristic that correlates closely with potential in vivo tumorigenicity. In medium supplemented with 20% serum or in basal media supplemented with platelet-derived growth factor (PDGF), early passage synoviocytes from both SCW-induced and rheumatoid arthritic joints formed colonies in soft agarose. Epidermal growth factor (EGF), interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and transforming growth factor-beta (TGF-beta) did not support growth, although EGF enhanced PDGF-dependent growth. On the other hand, TGF-beta, as well as all-trans-retinoic acid, inhibited colony growth. Early passage normal rat and human synoviocytes also grew under the same conditions, but lung, skin, and late-gestation embryonic fibroblast-like cells did not. Considered in the context of other published data our findings provide cogent evidence that synoviocytes, but not other types of fibroblast-like cells, readily acquire phenotypic characteristics commonly associated with transformed cells. Expression of the transformed phenotype in the inflammatory site is likely regulated by paracrine growth factors, such as PDGF and TGF-beta.
Changes in fatigue index during an 8 week quadriceps resistance training programme for patients with COPD & healthy controls
Authors: Linzy Houchen, Samantha Harrison, Carolyn Sandland, Manoj Menon, Mike Morgan, Sally Singh, Mick Steiner
Journal: European Respiratory Journal (2012)

Introduction:  Fatigue index (FI) measures the reduction in muscle force during muscle testing/training & can be altered by resistance training (RT). FI is seldom reported in patients with COPD. In isokinetic testing 2 variables are of interest: peak torque (PT) & total work (TWor).   Aim:  To evaluate changes in FI for PT & TWor during 8weeks of RT in patients & healthy controls.   Methods:  70 patients [mean (SD) age 68.6 (9.1)yr, FEV 1 44.8(15.2)% pr, 42 men] & 22 controls [age 66.6 (5.1)yr, FEV 1 103.4(15.9)% pr, 12 men] completed quadriceps RT for 8weeks. RT was 5x30 knee extensions; 3times/week on a cybex dynamometer (speed=180°/sec). PT (Newton-metres:Nm) & TWor (Joules:J) were recorded for each set & FI was calculated as: set5/set1x100 for the right leg (weekly average). A high FI=less fatigue.   Results:  There were no significant differences between/within-groups for PT FI over 8weeks (FI approx 90% in both groups for all weeks).  TWor FI in the COPD group did not significantly change over 8weeks. Control subjects displayed improvements in TWor FI & the difference in FI at week8 was significant compared to baseline & week4. However there were no significant differences between the 2 groups for TWor FI (fig.1).   Conclusions:  Healthy controls experienced less fatigue in TWor as RT progressed. This did not occur in the COPD group & may be related to muscle dysfunction. TWor seems a more sensitive measure than PT.
Comorbidity in patients with branch retinal vein occlusion: case-control study
Authors: M. Bertelsen, A. Linneberg, T. Rosenberg, N. Christoffersen, H. Vorum, E. Gade, M. Larsen
Journal: BMJ (2012)

<b>Objectives</b> To evaluate comorbidity before and after the diagnosis of branch retinal vein occlusion to determine whether it is a consequence of arterial thickening and therefore could serve as a diagnostic marker for other comorbidities and to evaluate the risk factors for the development of such occlusion. <b>Design</b> Case-control study with prospective follow-up data from Danish national registries. <b>Setting</b> Four secondary referral centres covering about 80% of the Danish population (4.4 million). <b>Participants</b> 1168 patients with photographically verified branch retinal vein occlusion and 116 800 controls alive and aged ≥40 when the occlusion was diagnosed in the corresponding case. <b>Main outcome measures</b> The risk of comorbidity 10 years and 1 year before the diagnosis of branch retinal vein occlusion and the incident comorbidity in a mean period of seven years after the diagnosis, with odds ratios and incidence rate ratios adjusted for age, sex, and year of diagnosis. <b>Results</b> Risk factors present 10 years and 1 year before the diagnosis of branch retinal vein occlusion included peripheral artery disease (odds ratio 1.83, 95% confidence interval 1.14 to 2.95), diabetes (1.74, 1.40 to 2.17) and arterial hypertension (2.16, 1.86 to 2.51). After the diagnosis, patients had an increased risk of developing arterial hypertension (incidence rate ratio 1.37, 95% confidence interval 1.15 to 1.57), diabetes (1.51, 1.17 to 2.04), congestive heart failure (1.41, 1.12 to 1.68), and cerebrovascular disease (1.49, 1.27 to 1.76). <b>Conclusion</b> Diabetes, hypertension, and peripheral artery disease are associated with an increased risk of developing branch retinal vein occlusion up to a decade later. Branch retinal vein occlusion was associated with an increased risk of subsequently developing hypertension, diabetes, congestive heart failure, and cerebrovascular disease, emphasising the importance of preventive initiatives. These results fit the assumption that branch retinal vein occlusion is a consequence of arterial thickening and that the arteriovenous crossing signs that precede it are hallmarks of arterial disease.
Low Dose Nesiritide and the Preservation of Renal Function in Patients With Renal Dysfunction Undergoing Cardiopulmonary-Bypass Surgery
Authors: Horng H. Chen, Thoralf M. Sundt, David J. Cook, Denise M. Heublein, John C Burnett
Journal: Circulation (2007)

Background— Renal insufficiency is associated with increased morbidity and mortality after cardiopulmonary bypass cardiac surgery. B-type natriuretic peptide is a cardiac hormone that enhances glomerular filtration rate and inhibits aldosterone. Cystatin has been shown to be a better endogenous marker of renal function than creatinine. Methods and Results— We performed a double-blinded placebo-controlled proof of concept pilot study in patients (n=40) with renal insufficiency preoperatively (defined as an estimated creatinine clearance of &lt;60 mL/min determined by the Cockroft-Gault formula), undergoing cardiopulmonary bypass cardiac surgery. Patients were randomized to placebo (n=20) or IV low dose nesiritide (n=20; 0.005 μg/Kg/min) for 24 hours started after the induction of anesthesia and before cardiopulmonary bypass. Patients in the nesiritide group had an increase of plasma B-type natriuretic peptide and its second messenger cGMP with a decrease in plasma cystatin levels at the end of the 24-hour infusion. These changes were not observed in the placebo group. There was a significant activation of aldosterone in the placebo group at the end of the 24-hour infusion, but not in the nesiritide group. At 48 and 72 hours, there was a decrease in estimated creatinine clearance and an increase in plasma cystatin as compared with end of the 24-hour infusion in the placebo group. In contrast, renal function was preserved in the nesiritide group with no significant change in estimated creatinine clearance and a trend for plasma cystatin to increase as compared with end of the 24-hour infusion. Conclusion— This proof of concept pilot study supports the conclusion that perioperative administration of low dose nesiritide is biologically active and decreases plasma cystatin in patients with renal insufficiency undergoing cardiopulmonary bypass cardiac surgery. Further studies are warranted to determine whether these physiological observations can be translated into improved clinical outcomes.
Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor.
Authors: N G McElvaney, H Nakamura, P Birrer, C A Hébert, W L Wong, M Alphonso, J B Baker, M A Catalano, R G Crystal
Journal: Journal of Clinical Investigation (1992)

Based on the knowledge that neutrophil elastase (NE) in cystic fibrosis (CF) epithelial lining fluid (ELF) can induce human bronchial epithelial cells to express the gene for interleukin 8 (IL-8), an 8.5-kD neutrophil chemoattractant, we have evaluated CF ELF for the presence of IL-8, and investigated the ability of aerosolized recombinant secretory leukoprotease inhibitor (rSLPI) to suppress NE, and hence IL-8, levels on the respiratory epithelial surface in CF. Enzyme-linked immunoassay revealed 21.9 +/- 4.8 nM IL-8 in CF ELF compared with none in normals. Active NE was detectable in ELF of all individuals with CF and was significantly decreased (P < 0.03) after aerosolization of rSLPI. Human bronchial epithelial cells exposed to CF ELF recovered before rSLPI therapy expressed IL-8 mRNA transcripts, but ELF recovered after rSLPI therapy induced far less bronchial epithelial cell IL-8 gene expression. Consistent with this, rSLPI aerosol therapy caused a marked reduction in CF ELF IL-8 levels (P < 0.05) and neutrophil number (P < 0.02). There was also a clear association between CF ELF active NE and IL-8 levels (r = 0.94). These data suggest that rSLPI therapy not only suppresses respiratory epithelial NE levels, but also breaks a cycle of inflammation on the CF epithelial surface.
Exercise and the prevention of back pain disability
Authors: Martin R Underwood
Journal: British Journal of Sports Medicine (2000)

Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.
Evolutionary history of the hybridogenetic hybrid frog Rana esculenta as deduced from mtDNA analyses.
Authors: C Spolsky, T Uzzell
Journal: Molecular Biology and Evolution (1986)

mtDNA of the hybridogenetic hybrid frog Rana esculenta from Switzerland, Austria, and Poland was compared to mtDNA of the parental species R. ridibunda and R. lessonae using electrophoretic analysis of restriction enzyme fragments. Two mtDNA phenotypes, with 3.4% sequence divergence, are present in R. lessonae: type C is found in Poland, and type D is found in Switzerland. Rana ridibunda from Poland has either of two mtDNA phenotypes: type A is the typical ridibunda mtDNA, and type B is a lessonae mitochondrial genome, introgressed into R. ridibunda, that differs from type C mtDNA of R. lessonae by only 0.3%. Each of the three lessonae genomes differs from A, the typical ridibunda mtDNA, by approximately 8%. All four types of mtDNA (A and B of R. ridibunda, C and D of R. lessonae) are found in R. esculenta. Of 62 R. esculenta from Poland, 58 had type C, three had type A, and one had type B mtDNA. All nine R. esculenta from Switzerland had type D mtDNA. All three R. esculenta from Austria, from a population in which males of R. esculenta are rare, had ridibunda mtDNA, two having type B and one having type A. Both field observations and studies of mating preference indicate that the primary hybridizations that produce R. esculenta are between R. ridibunda females and R. lessonae males; thereafter, R. esculenta lineages are usually maintained by matings of R. esculenta females with R. lessonae males. The presence of ridibunda mtDNA in the three R. esculenta sampled from Austria, its occasional presence in R. esculenta populations in Poland, and its absence from R. esculenta in Switzerland support both the direction of the original hybridization and the rarity of formation of new R. esculenta lineages. The preponderance of R. esculenta individuals with lessonae mtDNA in our samples from central Europe suggests that most lineages have gone through at least one mating between an R. lessonae female and an R. esculenta male. This reveals a greater reproductive role for R. esculenta males than their partial sterility and infrequent matings would suggest.
Differential Evolution of the 13 Atlantic Salmon Hox Clusters
Authors: S. Mungpakdee, H.-C. Seo, A. R. Angotzi, X. Dong, A. Akalin, D. Chourrout
Journal: Molecular Biology and Evolution (2008)

Hox cluster organization represents a valuable marker to study the effects of recent genome duplication in salmonid fish (25–100 Mya). Using polymerase chain reaction amplification of cDNAs, BAC library screening, and genome walking, we reconstructed 13 Hox clusters in the Atlantic salmon containing 118 Hox genes including 8 pseudogenes. Hox paralogs resulting from the genome duplication preceding the radiation of ray-finned fish have been much better preserved in salmon than in other model teleosts. The last genome duplication in the salmon lineage has been followed by the loss of 1 of the 4 HoxA clusters. Four rounds of genome duplication after the vertebrate ancestor salmon Hox clusters display the main organizational features of vertebrate Hox clusters, with Hox genes exclusively that are densely packed in the same orientation. Recently, duplicated Hox clusters have engaged a process of divergence, with several cases of pseudogenization or asymmetrical evolution of Hox gene duplicates, and a marked erosion of identity in noncoding sequences. Strikingly, the level of divergence attained strongly depends on the Hox cluster pairs rather than on the Hox genes within each cluster. It is particularly high between both HoxBb clusters and both HoxDa clusters, whereas both HoxBa clusters remained virtually identical. Positive selection on the Hox protein–coding sequences could not be detected.