tbuckley/cabot-search huggingface dataset:
Neither questions nor answers, just original data
Authors: E. Prats, J. Dorca, F. Manresa
Journal: European Respiratory Journal (2003)

BACKGROUND: The uptake of influenza vaccination among older people is suboptimal. Contact with a doctor or nurse is associated with older people deciding to accept influenza vaccination. AIM: To compare different forms of approach in improving uptake of influenza vaccination among patients aged 75 years and over in primary care. DESIGN OF STUDY: Randomised controlled trial. SETTING: One large rural general practice serving the town and surrounding area of Melton Mowbray, Leicestershire. METHOD: All 2,052 patients aged 75 years and over, registered with the practice and not living in nursing/residential homes or sheltered accommodation, were included in the study. One-third of patients were randomised to receive an offer of influenza vaccination as part of an over-75 health check administered by a practice nurse in the patient9s home, and two-thirds of patients were randomised to receive a personal letter of invitation to attend an influenza vaccination clinic held at the surgery. The main outcome measure was uptake of influenza vaccination. RESULTS: Six hundred and eighty patients were randomised to the health check arm of the trial and 1,372 were randomised to receive a personal letter. Of those randomised to the health check arm, 468 received the health check from the nurse. Overall, the difference in influenza vaccination uptake was 6.4% (95% confidence interval [CI] = 2.2% to 10.4%) with 67.9% (n = 932) of those who were sent a personal letter actually receiving the vaccine, compared with 74.3% (n = 505) of those offered a combined health check and influenza vaccination (P = 0.003). CONCLUSION: Combining home-based over- 75 health checks with influenza vaccination can improve uptake among older patients. However this intervention is likely to be costly and its effect on influenza vaccination rates is modest. The difference in uptake is greater among those who do not routinely comeforwardfor vaccination and a more viable option may be to target these patients.
Colour-cognition is more universal than colour-language
Authors: I. R. L. Davies
Journal: Behavioral and Brain Sciences (1997)

We acknowledge that empirical support for universal colour categories in colour cognition is insufficient: it relies too heavily on Rosch-Heider's work with the Dani. We offer new evidence supporting universal perceptual-cognitive colour categories. The same data also support language modulating colour-cognition: Universal structures are fine-tuned by language.
Methotrexate in Crohn's disease
Authors: D S Rampton
Journal: Gut (2001)

A minority of patients with Crohn's have disease refractory to or dependent on corticosteroids who are inappropriate for surgery; most will also have failed to respond to aminosalicylates, antibiotics, and/or a liquid formula diet. Firstline immunomodulatory therapy, given to initiate and maintain remission and allow tapering of steroid therapy, is usually azathioprine or 6-mercaptopurine. Unfortunately, approximately 20% of patients are resistant to or intolerant of thiopurines, and their management provides a difficult therapeutic challenge. The possible benefits of mycophenolate mofetil are unconfirmed, while infliximab is expensive and unproved in its long term efficacy and safety.#### Key points

Methotrexate is of proven value in psoriasis and rheumatoid arthritis.1 2 Since its effects in Crohn's disease were first reported …
Young v adult cirrhotics: a prospective, comparative analysis of the clinical profile, natural course and survival.
Authors: S K Sarin, S Chari, K R Sundaram, R K Ahuja, B S Anand, S L Broor
Journal: Gut (1988)

In order to assess the frequency and profile of cirrhosis in the young, 169 consecutive patients with cirrhosis were studied. Sixty three (37%) patients of less than or equal to 35 years age were defined as young and the remaining 106 (63%) patients (greater than 35 years) as adult cirrhotics. Men predominated significantly (p less than 0.01) in the young cirrhotic group. The aetiology, the frequency of positive hepatitis B markers and initial clinical presentation were similar in the two groups. During the follow up period (30.6 +/- 29.7 months for the young and 25.8 +/- 21.7 months for the adult group), except for abdominal distension and pedal oedema which occurred significantly more often in the adult compared with the young cirrhotics, no difference was noted in the two groups. Twenty seven (39.7%) deaths (40% as a result of hepatic failure and 52% due to variceal bleeding) occurred in the young and 47 (44.3%) deaths (63.8% because of hepatic failure and 26% because of variceal bleeding) occurred in the adult cirrhotics during the follow up (difference NS). The five year survival (61.9% v 55.7%) and the probability of survival within the same Child9s grade of liver disease were comparable. In both the groups, however, the probability of survival was significantly higher in Child9s A compared with Child9s B and C and in Child9s B compared with Child9s C grade of liver disease. Survival was not influenced by sex of the patient and aetiology of cirrhosis. Results of this prospective study indicate that cirrhosis is not uncommon in young adults. The aetiology, clinical presentation, natural history of the disease and the survival rates in young cirrhotics do not differ significantly from adult cirrhotics.
Predictors of Adverse Outcome Among Patients With Hypertension and Coronary Artery Disease
Authors: Carl J. Pepine, Peter R. Kowey, Stuart Kupfer, Rainer E. Kolloch, Athanase Benetos, Giuseppe Mancia, Antonio Coca, Rhonda M. Cooper-DeHoff, Eileen Handberg, Efrain Gaxiola, Peter Sleight, C. Richard Conti, Ann C. Hewkin, Luigi Tavazzi
Journal: Journal of the American College of Cardiology (2006)
Detecting Ancient Admixture and Estimating Demographic Parameters in Multiple Human Populations
Authors: Jeffrey D. Wall, Kirk E. Lohmueller, Vincent Plagnol
Journal: Molecular Biology and Evolution (2009)

We analyze patterns of genetic variation in extant human polymorphism data from the National Institute of Environmental Health Sciences single nucleotide polymorphism project to estimate human demographic parameters. We update our previous work by considering a larger data set (more genes and more populations) and by explicitly estimating the amount of putative admixture between modern humans and archaic human groups (e.g., Neandertals, Homo erectus, and Homo floresiensis). We find evidence for this ancient admixture in European, East Asian, and West African samples, suggesting that admixture between diverged hominin groups may be a general feature of recent human evolution.
Neutrophils Recruited by IL-22 in Peripheral Tissues Function as TRAIL-Dependent Antiviral Effectors against MCMV
Authors: Maria A. Stacey, Morgan Marsden, Tu Anh Pham N, Simon Clare, Garry Dolton, Gabrielle Stack, Emma Jones, Paul Klenerman, Awen M. Gallimore, Philip R. Taylor, Robert J. Snelgrove, Trevor D. Lawley, Gordon Dougan, Chris A. Benedict, Simon A. Jones, Gavin W.G. Wilkinson, Ian R. Humphreys
Journal: Cell Host & Microbe (2014)

Highlights•Neutrophils are critical antiviral effector cells during MCMV virus infection•Neutrophils directly inhibit virus replication in a TRAIL-dependent manner•IL-22 inhibits virus replication in peripheral but not secondary lymphoid tissues•IL-22 orchestrates CXCL1-dependent neutrophil recruitmentSummaryDuring primary infection, murine cytomegalovirus (MCMV) spreads systemically, resulting in virus replication and pathology in multiple organs. This disseminated infection is ultimately controlled, but the underlying immune defense mechanisms are unclear. Investigating the role of the cytokine IL-22 in MCMV infection, we discovered an unanticipated function for neutrophils as potent antiviral effector cells that restrict viral replication and associated pathogenesis in peripheral organs. NK-, NKT-, and T cell-secreted IL-22 orchestrated antiviral neutrophil-mediated responses via induction in stromal nonhematopoietic tissue of the neutrophil-recruiting chemokine CXCL1. The antiviral effector properties of infiltrating neutrophils were directly linked to the expression of TNF-related apoptosis-inducing ligand (TRAIL). Our data identify a role for neutrophils in antiviral defense, and establish a functional link between IL-22 and the control of antiviral neutrophil responses that prevents pathogenic herpesvirus infection in peripheral organs.Graphical abstract
Genetic Structure of Pastoral and Farmer Populations in the African Sahel
Authors: Viktor Černý, Luísa Pereira, Eliška Musilová, Martina Kujanová, Alžběta Vašíková, Paola Blasi, Luisa Garofalo, Pedro Soares, Issa Diallo, Radim Brdička, Andrea Novelletto
Journal: Molecular Biology and Evolution (2011)

Traditional pastoralists survive in few places in the world. They can still be encountered in the African Sahel, where annual alternations of dry and wet seasons force them to continual mobility. Little is known about the genetic structure of these populations. We present here the population distribution of 312 hypervariable segment I mitochondrial DNA (mtDNA) and 364 Y-short tandem repeat haplotypes in both farmer and pastoralist groups from the Lake Chad Basin and the West African Sahel. We show that the majority of pastoral populations (represented in the African Sahel by the Fulani nomads) fail to show significant departure from neutrality for mtDNA as evidenced by Fu's Fs statistics and exhibit lower levels of intrapopulation diversity measures for mtDNA when contrasted with farmers. These differences were not observed for the Y chromosome. Furthermore, analyses of molecular variance and population distributions of the mtDNA haplotypes show more heterogeneity in the sedentary groups than in the pastoralists. On the other hand, pastoralists retain a signature of a wide phylogenetic distance contributing to their male gene pool, whereas in at least some of the farmer populations, a founder effect and/or drift might have led to the presence of a single major lineage. Interestingly, these observations are in contrast with those recorded in Central Asia, where similar comparisons of farmer and pastoral groups have recently been carried out. We can conclude that in Africa, there have been no substantial mating exchanges between the Fulani pastoralists coming to the Lake Chad Basin from the West African Sahel and their farmer neighbors. At the same time, we suggest that the emergence of pastoralism might be an earlier and/or a demographically more important event than the introduction of sedentary agriculture, at least in this part of Africa.
Efficient SIVcpz replication in human lymphoid tissue requires viral matrix protein adaptation
Authors: Frederic Bibollet-Ruche, Anke Heigele, Brandon F. Keele, Juliet L. Easlick, Julie M. Decker, Jun Takehisa, Gerald Learn, Paul M. Sharp, Beatrice H. Hahn, Frank Kirchhoff
Journal: Journal of Clinical Investigation (2012)

SIVs infecting wild-living apes in west central Africa have crossed the species barrier to humans on at least four different occasions, one of which spawned the AIDS pandemic. Although the chimpanzee precursor of pandemic HIV-1 strains must have been able to infect humans, the capacity of SIVcpz strains to replicate in human lymphoid tissues (HLTs) is not known. Here, we show that SIVcpz strains from two chimpanzee subspecies are capable of replicating in human tonsillary explant cultures, albeit only at low titers. However, SIVcpz replication in HLT was significantly improved after introduction of a previously identified human-specific adaptation at position 30 in the viral Gag matrix protein. An Arg or Lys at this position significantly increased SIVcpz replication in HLT, while the same mutation reduced viral replication in chimpanzee-derived CD4(+) T cells. Thus, naturally occurring SIVcpz strains are capable of infecting HLTs, the major site of HIV-1 replication in vivo. However, efficient replication requires the acquisition of a host-specific adaptation in the viral matrix protein. These results identify Gag matrix as a major determinant of SIVcpz replication fitness in humans and suggest a critical role in the emergence of HIV/AIDS.
Sym004: A Novel Synergistic Anti–Epidermal Growth Factor Receptor Antibody Mixture with Superior Anticancer Efficacy
Authors: Mikkel Wandahl Pedersen, Helle Jane Jacobsen, Klaus Koefoed, Adam Hey, Charles Pyke, John Sørensen Haurum, Michael Kragh
Journal: Cancer Research (2010)

Epidermal growth factor receptor (EGFR) is a validated therapeutic target in cancer and EGFR antagonists with greater effectiveness than existing clinical agents remain of interest. Here, we report a novel approach based on Sym004, a mixture of two anti-EGFR monoclonal antibodies directed against distinct nonoverlapping epitopes in EGFR extracellular domain III. Like anti-EGFR monoclonal antibodies in current clinical use, Sym004 inhibits cancer cell growth and survival by blocking ligand-binding receptor activation and phosphorylation and downstream receptor signaling. However, unlike the other antibodies, Sym004 induces rapid and efficient removal of the receptor from the cancer cell surface by triggering EGFR internalization and degradation. Compared with reference anti-EGFR monoclonal antibodies, Sym004 exhibited more pronounced growth inhibition in vitro and superior efficacy in vivo. Together, these findings illustrate a strategy to target EGFR more effectively than existing clinical antibodies.
A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease.
Authors: M C Sneller, S E Straus, E S Jaffe, J S Jaffe, T A Fleisher, M Stetler-Stevenson, W Strober
Journal: Journal of Clinical Investigation (1992)

In mice, the two distinct autosomal recessive genes lpr and gld can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8- T cell population in peripheral lymphoid tissue. This phenotype does not precisely mirror any human disease. In this report we describe two patients with a progressive lymphoproliferative disorder associated with autoimmunity. The peripheral blood and lymph nodes of these patients contained large numbers of an unusual CD4-CD8- T cell population. These CD4-CD8- T cells express surface markers characteristic of mature peripheral blood T cells (CD3, CD2, CD5), express the alpha/beta form of the T cell receptor, and do not express surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16, CD56). Functionally, these cells exhibited deficient proliferation and lymphokine production upon stimulation with mitogenic antibodies to CD3 or CD2. Both proliferation and lymphokine production could be augmented by co-stimulation with an antibody directed at the CD28 determinant. The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice.
Comparison of Two Ultrasmall Superparamagnetic Iron Oxides on Cytotoxicity and MR Imaging of Tumors
Authors: Mulan Li, Hoe Suk Kim, Lianji Tian, Mi Kyung Yu, Sangyong Jon, Woo Kyung Moon
Journal: Theranostics (2012)

This study was performed to compare the cytotoxicity and magnetic resonance (MR) contrast in diverse cultured cells and xenograft tumors models of two ultra-small superparamagnetic iron oxides (USPIOs), thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and monocrystalline iron oxide nanoparticles (MION-47).Transmission electron microscopy (TEM) images and R(2) relaxivity values of the TCL-SPION and MION-47 were obtained and the cell viability and cell growth velocity of treated and untreated human fibroblasts and human umbilical vein endothelial cells (HUVEC) were evaluated. The effect of TCL-SPION and MION-47 on the secretion of interlukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), the production of nitric oxides and the mitochondrial membrane potentials in murine macrophage cells (RAW264.7) was compared. Human hepatocellular carcinoma cells (HepG2, 5x10(5)) were subcutaneously injected into nude mice (BALB/c) and in vivo MR imaging of tumors before and after injection with TCL-SPION or MION-47 (12.5 mg Fe/kg) was performed on a 1.5 Tesla MRI scanner.On TEM images, the average core diameter of TCL-SPION was 9 nm whereas that of MION-47 was 5 nm. TCL- SPION (345.0 ± 6.2 mM(-1)sec(-1)) had higher relaxivity (R(2)) than MION-47 (130.7 ± 1.1 mM(-1)sec(-1)). Significant changes in cell viability and growth were not found in human fibroblasts and HUVEC exposed to TCL-SPION and MION-47. However, IL-6 and TNF-α secretions increased dose-dependently and significantly in the macrophages treated with MION-47 or TCL-SPION. TCL-SPION had a lower stimulatory effect on IL-6 secretions than did MION-47 (P <0.05) and nitric oxides were produced in the macrophages by MION-47 but not TCL-SPION. A change in the mitochondrial membrane potential of the macrophages was observed 24 hours after the exposure, and MION-47 induced more collapses of the mitochondrial membrane potential than did TCL-SPION. In the in vivo MR imaging, 33.0 ± 1.3% and 7.5 ± 0.4% signal intensity decrease on T(2)*-weighted images was observed in the tumors injected with TCL-SPION and MION-47, respectively.Due to the modified surface properties and larger core size of its iron oxide nanoparticles, TCL-SPION achieves lower cytotoxicity and better tumor MR contrast than MION-47. Our study suggests that TCL-SPION may be used as a new platform for tumor imaging and therapy monitoring.
Vitamin D3 Enhances the Apoptotic Response of Epithelial Tumors to Aminolevulinate-Based Photodynamic Therapy
Authors: Sanjay Anand, Clara Wilson, Tayyaba Hasan, Edward V. Maytin
Journal: Cancer Research (2011)

Abstract Photodynamic therapy, mediated by exogenously administered aminolevulinic acid (ALA-PDT), followed by exposure to a laser or broadband light source, is a promising modality for treatment of many types of cancers; however, it remains inadequate to treat large, deep, solid tumors. In this article, we report that calcitriol, the active form of vitamin D3, can be administered before ALA as a nontoxic preconditioning regimen to markedly increase the efficacy of ALA-PDT. Using mouse models of squamous cell skin cancer for preclinical proof of concept, we showed that calcitriol, delivered topically or intraperitoneally, increased tumoral accumulation of the PDT-activated ALA product protoporphyrin-IX (PpIX) up to 10-fold, mainly by altering expression of the porphyrin-synthesis enzymes coproporphyrinogen oxidase (increased) and ferrochelatase (decreased). Calcitriol-pretreated tumors underwent enhanced apoptotic cell death after ALA-based PDT. Mechanistic studies have documented activation of the extrinsic apoptotic pathway, with specific cleavage of caspase-8 and increased production of TNF-α in tumors preconditioned by calcitriol treatment before receiving ALA-PDT. Very low doses of calcitriol (0.1–1 μg/kg body weight) were sufficient to elicit tumor-selective enhancement to ALA-PDT efficacy, rendering toxicity concerns negligible. Our findings define a simple, nontoxic, and highly effective preconditioning regimen to enhance the response of epithelial tumors to ALA-PDT, possibly broadening its clinical applications by selectively enhancing accumulation of photosensitizer PpIX together with TNF-α in tumors. Cancer Res; 71(18); 6040–50. ©2011 AACR.
THE EFFECT OF HYPERTROPHIC CARTILAGE ON BONE MARROW GROWTH
Authors: Charles Huggins, Kenneth McLane Smith
Journal: The Journal of Experimental Medicine (1938)

Intravenous injections of colloidal thorium dioxide were made in rabbits and moderate amounts caused no significant changes in the cellular elements of venous blood. Thorium dioxide was held locally with great tenacity in the cells of the reticulo-endothelial system in the bone marrow and showed little tendency to migrate despite drastic stimuli to the marrow in the form of anemia and plethora. In recently injected rabbits, thorium-laden macrophages abutted each cartilage column in the direction of growth where the cartilage was being removed. In marrow which had formed subsequent to injection the macrophages were thorium-free, allowing recognition of the new tissue by x-ray and histological techniques as clear zones. The growth pattern of marrow could be detected in this way. The bone marrow increases in length principally in the region of hypertrophic cartilage at the metaphyses and it is evident that the increase is facilitated by the presence of macrophages whose primary function is the resolution of the wasted hypertrophic cartilage cells. Growth in thickness of bone marrow occurs at its circumference. In contrast to the zonal growth of bone marrow, growth of the reticuloendothelial system in liver and spleen is chiefly interstitial.
Akt2 Regulates All Akt Isoforms and Promotes Resistance to Hypoxia through Induction of miR-21 upon Oxygen Deprivation
Authors: Christos Polytarchou, Dimitrios Iliopoulos, Maria Hatziapostolou, Filippos Kottakis, Ioanna Maroulakou, Kevin Struhl, Philip N. Tsichlis
Journal: Cancer Research (2011)

The growth and survival of tumor cells in an unfavorable hypoxic environment depend upon their adaptability. Here, we show that both normal and tumor cells expressing the protein kinase Akt2 are more resistant to hypoxia than cells expressing Akt1 or Akt3. This is due to the differential regulation of microRNA (miR) 21, which is upregulated by hypoxia only in Akt2-expressing cells. By upregulating miR-21 upon oxygen deprivation, Akt2 downregulates PTEN and activates all three Akt isoforms. miR-21 also targets PDCD4 and Sprouty 1 (Spry1), and the combined downregulation of these proteins with PTEN is sufficient to confer resistance to hypoxia. Furthermore, the miR-21 induction by Akt2 during hypoxia depends upon the binding of NF-κB, cAMP responsive element-binding protein (CREB), and CBP/p300 to the miR-21 promoter, in addition to the regional acetylation of histone H3K9, all of which are under the control of Akt2. Analysis of the Akt2/miR-21 pathway in hypoxic MMTV-PyMT-induced mouse mammary adenocarcinomas and human ovarian carcinomas confirmed the activity of the pathway in vivo. Taken together, this study identifies a novel Akt2-dependent pathway that is activated by hypoxia and promotes tumor resistance via induction of miR-21.