tbuckley/cabot-search huggingface dataset:
The assessment of postural control and the influence of a secondary task in people with anterior cruciate ligament reconstructed knees using a Nintendo Wii Balance Board
Authors: Brooke E Howells, Ross A Clark, Clare L Ardern, Adam L Bryant, Julian A Feller, Timothy S Whitehead, Kate E Webster
Journal: British Journal of Sports Medicine (2012)

Background Postural control impairments may persist following anterior cruciate ligament (ACL) reconstruction. The effect of a secondary task on postural control has, however, not been determined. The purpose of this case–control study was to compare postural control in patients following ACL reconstruction with healthy individuals with and without a secondary task. Participants 45 patients (30 men and 15 women) participated at least 6 months following primary ACL reconstruction surgery. Participants were individually matched by age, gender and sports activity to healthy controls. Materials Postural control was measured using a Nintendo Wii Balance Board and customised software during static single-leg stance and with the addition of a secondary task. The secondary task required participants to match the movement of an oscillating marker by adducting and abducting their arm. Main outcome measures Centre of pressure (CoP) path length in both medial-lateral and anterior–posterior directions, and CoP total path length. Results When compared with the control group, the anterior–posterior path length significantly increased in the ACL reconstruction patients' operated (12.3%, p=0.02) and non-operated limbs (12.8%, p=0.02) for the single-task condition, and the non-operated limb (11.5%, p=0.006) for the secondary task condition. The addition of a secondary task significantly increased CoP path lengths in all measures (p&lt;0.001), although the magnitude of the increase was similar in both the ACL reconstruction and control groups. Discussion ACL reconstruction patients showed a reduced ability in both limbs to control the movement of the body in the anterior–posterior direction. The secondary task affected postural control by comparable amounts in patients after ACL reconstruction and healthy controls. Devices for the objective measurement of postural control, such as the one used in this study, may help clinicians to more accurately identify patients with deficits who may benefit from targeted neuromuscular training programs.
The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells
Authors: Jenna Kahn, Thomas J. Hayman, Muhammad Jamal, Barbara H. Rath, Tamalee Kramp, Kevin Camphausen, Philip J. Tofilon
Journal: Neuro-Oncology (2013)

The mammalian target of rapamycin (mTOR) has been suggested as a target for radiosensitization. Given that radiotherapy is a primary treatment modality for glioblastoma (GBM) and that mTOR is often dysregulated in GBM, the goal of this study was to determine the effects of AZD2014, a dual mTORC1/2 inhibitor, on the radiosensitivity of GBM stem-like cells (GSCs). mTORC1 and mTORC2 activities were defined by immunoblot analysis. The effects of this mTOR inhibitor on the in vitro radiosensitivity of GSCs were determined using a clonogenic assay. DNA double strand breaks were evaluated according to γH2AX foci. Orthotopic xenografts initiated from GSCs were used to define the in vivo response to AZD2014 and radiation. Exposure of GSCs to AZD2014 resulted in the inhibition of mTORC1 and 2 activities. Based on clonogenic survival analysis, addition of AZD2014 to culture media 1 hour before irradiation enhanced the radiosensitivity of CD133+ and CD15+ GSC cell lines. Whereas AZD2014 treatment had no effect on the initial level of γH2AX foci, the dispersal of radiation-induced γH2AX foci was significantly delayed. Finally, the combination of AZD2014 and radiation delivered to mice bearing GSC-initiated orthotopic xenografts significantly prolonged survival as compared with the individual treatments. These data indicate that AZD2014 enhances the radiosensitivity of GSCs both in vitro and under orthotopic in vivo conditions and suggest that this effect involves an inhibition of DNA repair. Moreover, these results suggest that this dual mTORC1/2 inhibitor may be a radiosensitizer applicable to GBM therapy.
Congenital acute megakaryoblastic leukemia
Authors: Barbara J Bain, Subarna Chakravorty, Philip Ancliff
Journal: American Journal of Hematology (2015)

A newborn baby girl, born to non-consanguineous Northern European parents, presented with an epistaxis at 10 days of age. She was found to have hepatosplenomegaly. There were no clinical features of Down syndrome. Her full blood count showed: white blood cell count 36 × 109/l, hemoglobin concentration 133 g/l, and platelet count 74 × 109/l. Her peripheral blood film (images) showed numerous blast cells with distinctive features. They had a high nucleocytoplasmic ratio and small indistinct nucleoli. The scanty cytoplasm varied from weakly to moderately basophilic and extended into irregular basophilic blebs and fronds. There were also some giant platelets. The cytological features were those of acute megakaryoblastic leukemia. Bone marrow aspiration was difficult. The hemodilute, aparticulate aspirate showed 18% blast cells. Cytogenetic analysis of aspirated bone marrow showed t(1;22)(p13;q13). This subtype of acute myeloid leukemia is associated with an RBM15-MKL1 fusion gene. It usually presents within the first 6 months of life and at least four congenital cases have been reported previously, in addition to a previous brief report of this case 1-3. Occurrence in identical twins at the age of two months provides further evidence of an intrauterine origin 4. The bone marrow blast cell percentage may be below 20%. Following several courses of combination chemotherapy, remission was achieved but the bone marrow remained hypocellular with low peripheral blood counts. Following sibling hematopoietic stem cell transplantation, she achieved long-term relapse-free survival.
Inhibition of cytotoxic T lymphocyte-induced target cell DNA fragmentation, but not lysis, by inhibitors of DNA topoisomerases I and II.
Authors: W K Nishioka, R M Welsh
Journal: The Journal of Experimental Medicine (1992)

Cytotoxic T lymphocytes (CTL) kill their target cells via a contact-dependent mechanism that results in the perturbation of the target cell's plasma membrane and the fragmentation of the target cell's DNA into nucleosomal particles. The membrane disruption is presumed to be due to the action of perforin, while the DNA fragmentation is thought to be by the activation of an endogenous nuclease(s). DNA topoisomerases I and II are nuclear enzymes with inherent endonuclease activities. We have investigated their role in the CTL-induced DNA fragmentation process. We report that in CTL killing assays, the treatment of target cells with topoisomerase I and II inhibitors blocks the CTL-induced DNA fragmentation process, but not the lysis of the target cell.
The War and Winter-Stations for Invalids
Authors: C. T. Williams
Journal: BMJ (1870)

LNov. 5, I870.is also given an excellent resum6 of the researches of previous German and French Anatomists into the distribution of the par vagum in the abdomen.The account of the liver-nerves by Kollmann appears to be more in accordance with what might be expected from analogy, and from pathological observation and inference, than the descriptions of the other authors.But the vagueness and unsatisfactory state of our knowledge on the above subject must now be evident.Besides, although some anatomists mention anterior and posterior hepatic plexuses, yet only few, as John Reid, Swan, and Valentin, ap- pear to have distinguished plexuses or nerves of the right from plexuses or nerves of the left lobe, and we know little as to the ultimate destination of the nerves in the interior of the liver.As to this ultimate distribution, the substance of the knowledge we appear to possess is as follows.The combined sympathetic and pneu- mogastric branches "enter the liver supported by the hepatic artery and its branches, along which they may be traced a considerable way in the portal canals, but their ultimate distribution is not known.""The gall-bladder receives nerves along the hepatic artery from the cceliac plexus."(Quain's Anatomy, 7th Edition, I867, vol.ii, pp.867 and 868.)Ellis (Demonstrations of Anatomy, 3rd Edition, i852) says, "the hepatic plexus is continued on the vena portae, hepatic artery, and bile- duct, to the transverse fissure, where it enters the liver and ramifies on the vessels."Cruveilhier says that the hepatic plexus of the sympathetic (which comprises the pneumogastric hepatic nerves) "gains the transverse fissure of the liver, divides like the vena portae and hepatic artery, and may be traced for some distance in the capsule of Glisson."(Anatomy,
Addiction is not as puzzling as it seems
Authors: Jim Orford
Journal: Behavioral and Brain Sciences (1996)

Abstract Heyman's target article seeks to resolve the apparent paradox surrounding the issue of control in relation to addictive behaviour. The present commentary argues that addiction is in fact less paradoxical and more easily understandable than Heyman supposes. A fully satisfactory model of addiction, however, requires a more multifaceted approach than that provided by the type of behavioural choice theory favoured by Heyman.
Response to Letter Regarding Article, “Risk of Acute Myocardial Infarction After the Death of a Significant Person in One's Life: The Determinants of Myocardial Infarction Onset Study”
Authors: Elizabeth Mostofsky, Jane B. Sherwood, Murray A. Mittleman, Malcolm Maclure, Geoffrey H. Tofler, James E. Muller
Journal: Circulation (2012)
Microsatellite instability and the clinicopathological features of sporadic colorectal cancer
Authors: R Ward, A Meagher, I Tomlinson, T O'Connor, M Norrie, R Wu, N Hawkins
Journal: Gut (2001)

BACKGROUND AND AIMS In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice. METHODS DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53. RESULTS Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%. CONCLUSIONS We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.
Phosphoinositide 3-kinase inhibitor suppresses interleukin-17 expression in a murine asthma model
Authors: S.J. Park, K.S. Lee, S.R. Kim, K.H. Min, H. Moon, M.H. Lee, C.R. Chung, H.J. Han, K.D. Puri, Y.C. Lee
Journal: European Respiratory Journal (2010)

Phosphoinositide 3-kinases (PI3Ks) contribute to the pathogenesis of asthma by regulating the activation of inflammatory mediators, inflammatory cell recruitment and immune cell function. Recent findings have indicated that PI3Ks also regulate the expression of interleukin (IL)-17, which has been recognised as an important cytokine involved in airway inflammation. In the present study, we investigated a role of PI3Kδ in the regulation of IL-17 expression in allergic airway disease using a murine model of asthma. After ovalbumin inhalation, administration of a selective p110δ inhibitor, IC87114, significantly attenuated airway infiltration of total cells, lymphocytes, neutrophils and eosinophils, as well as airway hyperresponsiveness, and attenuated the increase in IL-17 protein and mRNA expression. Moreover, IC87114 reduced levels of IL-4, -5 and -13, expression of keratinocyte chemoattractant protein and mRNA, and nuclear factor (NF)-κB activity. In addition, a NF-κB inhibitor, BAY 11-7085 substantially reduced the increase in IL-17 protein levels. Our results also showed that inhibition of IL-17 activity with an anti-IL-17 antibody remarkably reduced airway inflammation and hyperresponsiveness. These findings suggest that inhibition of the p110δ signalling pathway suppresses IL-17 expression through regulation of NF-κB activity and, thus, has therapeutic potential in asthma.
Modest Levels of Physical Activity Are Associated With a Lower Incidence of Diabetes in a Population With a High Rate of Obesity
Authors: Amanda M. Fretts, Barbara V. Howard, Barbara McKnight, Glen E. Duncan, Shirley A.A. Beresford, Darren Calhoun, Andrea M. Kriska, Kristi L. Storti, David S. Siscovick
Journal: Diabetes Care (2012)

OBJECTIVE To examine the association of objectively measured participation in low levels of physical activity with incident type 2 diabetes. RESEARCH DESIGN AND METHODS The study population included participants free of diabetes and cardiovascular disease at baseline (n = 1,826) who participated in a follow-up examination. Generalized estimating equations were used to examine the association of steps per day with incident diabetes. RESULTS During 5 years of follow-up, 243 incident cases of diabetes were identified. When compared with participants in the lowest quartile of steps per day (&amp;lt;3,500 steps), participants in the upper three quartiles of steps per day had lower odds for diabetes, consistent with a threshold effect. Contrasting the three upper quartiles with the lowest quartile, the odds ratio of diabetes was 0.71 (95% CI 0.51–0.98). CONCLUSIONS Modest levels of physical activity are associated with a lower risk of incident diabetes, compared with lower levels of activity.
Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratios
Authors: Jörn-Hendrik Weitkamp, Tatsuki Koyama, Michael T Rock, Hernan Correa, Jeremy A Goettel, Pranathi Matta, Kyra Oswald-Richter, Michael J Rosen, Brian G Engelhardt, Daniel J Moore, D Brent Polk
Journal: Gut (2012)

<h3>Background</h3> Necrotising enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. Immaturity of gastrointestinal immune regulation may predispose preterm infants to NEC as FOXP3 T regulatory cells (Treg) are critical for intestinal immune homoeostasis. <h3>Objective</h3> To investigate the hypothesis that abnormal developmental regulation of lamina propria Treg would define premature infants with NEC. <h3>Design</h3> Lamina propria mononuclear cell populations from surgically resected ileum from 18 patients with NEC and 30 gestational age-matched non-NEC surgical controls were prospectively isolated. Polychromatic flow cytometry was performed to phenotype and analyse lamina propria T cell populations. The cytokine gene expression profile in NEC tissue was compared with that of non-NEC controls. <h3>Results</h3> The total number of Treg, CD4, or CD8 T cells in each ileum section was independent of gestational age, age or postmenstrual age and similar between patients with NEC and controls. In contrast, the ratio of Treg to CD4 T cells or Treg to CD8 T cells was significantly lower in NEC ileum than in infants without NEC (medians 2.9% vs 6.6%, p=0.001 and medians 6.6% vs 25.9%, p&lt;0.001, respectively). For any given number of CD4 or CD8 T cells, Treg were, on average, 60% lower in NEC ileum than in controls. NEC tissue cytokine gene expression profiles were characteristic of inhibited Treg development or function. Treg/CD4 and Treg/CD8 ratios recovered between initial resection for NEC and reanastomosis. <h3>Conclusion</h3> The proportion of lamina propria Treg is significantly reduced in the ileum of premature infants with NEC and may contribute to the excessive inflammatory state of this disease.
Next-Generation Sequencing Technology Reveals a Characteristic Pattern of Molecular Mutations in 72.8% of Chronic Myelomonocytic Leukemia by Detecting Frequent Alterations in <i>TET2</i>, <i>CBL</i>, <i>RAS</i>, and <i>RUNX1</i>
Authors: Alexander Kohlmann, Vera Grossmann, Hans-Ulrich Klein, Sonja Schindela, Tamara Weiss, Beray Kazak, Frank Dicker, Susanne Schnittger, Martin Dugas, Wolfgang Kern, Claudia Haferlach, Torsten Haferlach
Journal: Journal of Clinical Oncology (2010)

Purpose Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that is characterized by features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. Thus far, data on a comprehensive cytogenetic or molecular genetic characterization are limited. Patients and Methods Here, we analyzed 81 thoroughly characterized patients with CMML (CMML type 1, n = 45; CMML type 2, n = 36) by applying next-generation sequencing (NGS) technology to investigate CBL, JAK2, MPL, NRAS, and KRAS at known mutational hotspot regions. In addition, complete coding regions were analyzed for RUNX1 (β isoform) and TET2 aberrations. Results Cytogenetic aberrations were found in 18.2% of patients (14 of 77 patients). In contrast, at least one molecular mutation was observed in 72.8% of patients (59 of 81 patients). A mean of 1.6 mutations per patient was observed by this unprecedented screening. In total, 105 variances were detected by this comprehensive molecular screening. After excluding known polymorphisms or silent mutations, 82 distinct mutations remained (CBL, n = 15; JAK2V617F, n = 8; MPL, n = 0; NRAS, n = 10; KRAS, n = 12; RUNX1, n = 7; and TET2, n = 41). With respect to clinical data, a better outcome was seen for patients carrying TET2 mutations (P = .013). Conclusion The number of molecular markers used to categorize myeloid neoplasms is constantly increasing. Here, NGS screening has been demonstrated to support a comprehensive characterization of the molecular background in CMML. A pattern of molecular mutations translates into different biologic and prognostic categories of CMML.
Co-culture of naïve CD4+ T cells and vitamin D modulate – Th17 cells in young asthmatic children
Authors: Besma Hamdi, Wajih Kaabachi, Berraies Anissa, Ammar Jamel, Kamel Hamzaoui, Agnes Hamzaoui
Journal: European Respiratory Journal (2014)

1,25-Dihydroxyvitamin D3 (Vit D) deficiency has been associated with childhood asthma inflammatory pathways, however data are still lacking about the effect of vitamin D supplementation on immune regulation in asthmatic children. In this study, we investigated Vit D inhibitory effect on the immune response in young asthmatic patients and the possible mechanisms involved.  Peripheral blood CD4 +  T cells from 10 asthmatic patients with hypovitaminosis D and 10 healthy controls were cultured under Th17 polarizing conditions in the presence or absence of Vit D, and IL-17cytokines production was determined by ELISA and flow cytometry. mRNA expression of several factors related to Th17 cell function were determined by real-time PCR. The effect of Vit D-treated dendritic cells (DCs) on CD4 +  T cell response was determined by ELISA and flow cytometry.  Stimulation of naive CD4 +  T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in asthmatic patients than healthy controls. The addition of Vit D significantly inhibited Th17 cell differentiation both in patients[ P  ] and in normal controls [ P = 0.0001 ] in dose dependent way. Vit D was able to inhibit the gene expression of RORC, IL-17, IL-23R, and CCR6 differenciation. Vit D-treated DCs significantly inhibited IL-17 level [291.0 ± 83.59pg/ml  v.s.  452.0 ± 116.0 pg/ml;  P = 0.0022 ] and decreased the percentage of CD4 + IL-17 +  [4.35% ± 1.12%  v.s.  5.91% ± 1.17%; P = 0.0072 ] in young asthmatics.  The findings suggest that the inhibitory effect of VitD on the Th17 response was mediated via both T cells and DCs. DCs pathway is involved in the direct inhibition of VitD on Th17 cell differentiation in young asthmatics.
Cellular immune reaction in the pancreas is induced by constitutively active I B kinase-2
Authors: T. Aleksic, B. Baumann, M. Wagner, G. Adler, T. Wirth, C. K Weber
Journal: Gut (2006)

Activation of the nuclear factor kappaB (NF-kappaB) system is a major event in acute and chronic inflammatory processes. NF-kappaB cascades are comprised of IkappaB kinases, IkappaBs and NF-kappaB dimers. Little is known of the individual roles of these proteins in organ specific inflammation. The aim of the present study was to analyse the consequences of ectopic IkappaB kinase-2 (IKK2) activation in the pancreas of mice.Transgenic mice were generated using an inducible genetic system (tet system) to conditionally overexpress a gain of function mutant of IKK2 (tetO-IKK2-EE) in the pancreas. To achieve transgene expression in the pancreas, these animals were crossed with CMV-rtTA mice that are known to express the rtTA protein in the pancreas.In these double transgenic animals, doxycycline treatment induced expression of IKK2-EE (IKK2(CA)) in pancreatic acinar cells resulting in moderate activation of the IkappaB kinase complex, as measured by the immune complex kinase assay, and up to 200-fold activation of the transgene expression cassette, as detected by luciferase assay. IKK2(CA) expression in the pancreas had a mosaic appearance. Ectopic IKK2(CA) mostly activated the classical NF-kappaB pathway. The activation level of the NF-kappaB cascade induced by IKK2(CA) was considerably lower compared with that observed after supramaximal caerulein stimulation but still led to the formation of leucocyte infiltrates first observed after 4 weeks of doxycycline stimulation with a maximum after 8-12 weeks. The infiltrates were mainly composed of B lymphocytes and macrophages. Increased mRNA levels of tumour necrosis factor alpha and RANTES were detected in pancreatic acinar cells. However, only minor damage to pancreatic tissue was observed. A combination of supramaximal caerulein stimulation with induction of IKK2(CA) caused increased tissue damage compared with either IKK2(CA) or caerulein alone.Our observations suggest that the role of IKK2 activation in pancreatic acini is to induce leucocyte infiltration, but at a moderate level of activation it is not sufficient to induce pancreatic damage in mice. The IKK2(CA) induced infiltrations resemble those observed in autoimmune pancreatitis, indicating a role for IKK2/NF-kappaB in this disease. IKK2(CA) in pancreatic acinar cells increases tissue damage of secretagogue induced experimental pancreatitis underlining the proinflammatory role of the IKK/NF-kappaB pathway in this disease.