tbuckley/cabot-search huggingface dataset:
Interleukin-8. A mitogen and chemoattractant for vascular smooth muscle cells.
Authors: T L Yue, X Wang, C P Sung, B Olson, P J McKenna, J L Gu, G Z Feuerstein
Journal: Circulation Research (1994)

Interleukin-8 (IL-8) is a chemokine produced by a variety of cell types involved in atherogenesis and is chemotactic for neutrophils and lymphocytes. A recent study has shown that IL-8 is angiogenic and induces proliferation and chemotaxis of endothelial cells. The present study was undertaken to find out whether IL-8 is also mitogenic and chemotactic for vascular smooth muscle cells. IL-8 induced a concentration-dependent (0.1 to 10 nmol/L) stimulation of DNA synthesis and cell proliferation in both human and rat aortic smooth muscle cells. In addition, IL-8 stimulated smooth muscle cells to produce prostaglandin E2, which can inhibit IL-8-induced smooth muscle cell proliferation. In the presence of indomethacin (5 mumol/L), IL-8 (1 nmol/L) stimulated an increase in human and rat aortic smooth muscle cell number during a 3-day period of incubation by 61 +/- 16% and 59 +/- 7% (n = 4), respectively. IL-8 also increased DNA synthesis in human and rat aortic smooth muscle cells by 98 +/- 10% and 151 +/- 27% (n = 5), respectively. Moreover, IL-8 stimulated rat aortic smooth muscle cell migration by 20-fold over the control value, with an EC50 value of 0.83 nmol/L; this chemotactic activity of IL-8 was also potentiated by indomethacin. Exposure of smooth muscle cells to IL-8 caused rapid and transient expression of the immediate-early genes c-fos and zif268 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
PDZ-Binding Kinase/T-LAK Cell-Originated Protein Kinase, a Putative Cancer/Testis Antigen with an Oncogenic Activity in Breast Cancer
Authors: Jae-Hyun Park, Meng-Lay Lin, Toshihiko Nishidate, Yusuke Nakamura, Toyomasa Katagiri
Journal: Cancer Research (2006)

Breast cancer is one of the most common cancers among women. To discover molecular targets that are applicable for development of novel breast cancer therapy, we previously did genome-wide expression profile analysis of 81 breast cancers and found dozens of genes that were highly and commonly up-regulated in breast cancer cells. Among them, we here focused on one gene that encodes PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), including a kinase domain. Northern blot analyses using mRNAs of normal human organs, breast cancer tissues, and cancer cell lines indicated this molecule to be a novel cancer/testis antigen. Reduction of PBK/TOPK expression by small interfering RNA resulted in significant suppression of cell growth probably due to dysfunction in the cytokinetic process. Immunocytochemical analysis with anti-PBK/TOPK antibody implicated a critical role of PBK/TOPK in an early step of mitosis. PBK/TOPK could phosphorylate histone H3 at Ser10 in vitro and in vivo, and mediated its growth-promoting effect through histone H3 modification. Because PBK/TOPK is the cancer/testis antigen and its kinase function is likely to be related to its oncogenic activity, we suggest PBK/TOPK to be a promising molecular target for breast cancer therapy.
Dialectical Behaviour Therapy for Post-traumatic Stress Disorder after Childhood Sexual Abuse in Patients with and without Borderline Personality Disorder: A Randomised Controlled Trial
Authors: Martin Bohus, Anne S. Dyer, Kathlen Priebe, Antje Krüger, Nikolaus Kleindienst, Christian Schmahl, Inga Niedtfeld, Regina Steil
Journal: Psychotherapy and Psychosomatics (2013)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Post-traumatic stress disorder (PTSD) with co-occurring severe psychopathology such as borderline personality disorder (BPD) is a frequent sequel of childhood sexual abuse (CSA). CSA-related PTSD has been effectively treated through cognitive-behavioural treatments, but it remains unclear whether success can be achieved in patients with co-occurring BPD. The aim of the present study was to determine the efficacy of a newly developed modular treatment programme (DBT-PTSD) that combines principles of dialectical behaviour therapy (DBT) and trauma-focused interventions. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Female patients (n = 74) with CSA-related PTSD were randomised to either a 12-week residential DBT-PTSD programme or a treatment-as-usual wait list. About half of the participants met the criteria for co-occurring BPD. Individuals with ongoing self-harm were not excluded. The primary outcomes were reduction of PTSD symptoms as assessed by the Clinician-Administered PTSD Scale (CAPS) and by the Posttraumatic Stress Diagnostic Scale (PDS). Hierarchical linear models were used to compare improvements across treatment groups. Assessments were carried out by blinded raters at admission, at end of treatment, and at 6 and 12 weeks post-treatment. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Under DBT-PTSD the mean change was significantly greater than in the control group on both the CAPS (33.16 vs. 2.08) and the PDS (0.70 vs. 0.14). Between-group effect sizes were large and highly significant. Neither a diagnosis of BPD nor the severity or the number of BPD symptoms was significantly related to treatment outcome. Safety analyses indicated no increase in dysfunctional behaviours during the trial. &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;DBT-PTSD is an efficacious treatment of CSA-related PTSD, even in the presence of severe co-occurring psychopathology such as BPD.
Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial
Authors: Stig-Frederik Trojahn Kølle, Anne Fischer-Nielsen, Anders Bruun Mathiasen, Jens Jørgen Elberg, Roberto S Oliveri, Peter V Glovinski, Jens Kastrup, Maria Kirchhoff, Bo Sonnich Rasmussen, Maj-Lis Møller Talman, Carsten Thomsen, Ebbe Dickmeiss, Krzysztof Tadeusz Drzewiecki
Journal: The Lancet (2013)
Methotrexate side-effects
Authors: H. ZACHARIAE
Journal: British Journal of Dermatology (1990)

Journal Article Methotrexate side‐effects Get access H. ZACHARIAE H. ZACHARIAE Department of Dermatology, Marselisborg Hospital, University of Aarhus, Aarhus, Denmark Professor H.Zachariae, Department of Dermatology, Marselisborg Hospital, P.P. Orumsgade II, DK‐8000 Aarhus C, Denmark. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue s36, 1 June 1990, Pages 127–133, https://doi.org/10.1111/j.1365-2133.1990.tb02890.x Published: 01 June 1990
Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells
Authors: Takashi Yahata, Shizu Yumino, Yin Seng, Hiroko Miyatake, Tomoko Uno, Yukari Muguruma, Mamoru Ito, Hiroyuki Miyoshi, Shunichi Kato, Tomomitsu Hotta, Kiyoshi Ando
Journal: Blood (2006)
The effects of exercise on cognition in Parkinson’s disease: a systematic review
Authors: Danielle K Murray, Matthew A Sacheli, Janice J Eng, A Jon Stoessl
Journal: Translational Neurodegeneration (2014)

Cognitive impairments are highly prevalent in Parkinson’s disease (PD) and can substantially affect a patient’s quality of life. These impairments remain difficult to manage with current clinical therapies, but exercise has been identified as a possible treatment. The objective of this systematic review was to accumulate and analyze evidence for the effects of exercise on cognition in both animal models of PD and human disease. This systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Fourteen original reports were identified, including six pre-clinical animal studies and eight human clinical studies. These studies used various exercise interventions and evaluated many different outcome measures; therefore, only a qualitative synthesis was performed. The evidence from animal studies supports the role of exercise to improve cognition in humans through the promotion of neuronal proliferation, neuroprotection and neurogenesis. These findings warrant more research to determine what roles these neural mechanisms play in clinical populations. The reports on cognitive changes in clinical studies demonstrate that a range of exercise programs can improve cognition in humans. While each clinical study demonstrated improvements in a marker of cognition, there were limitations in each study, including non-randomized designs and risk of bias. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used and the quality of the evidence for human studies were rated from “low” to “moderate” and the strength of the recommendations were rated from “weak” to “strong”. Studies that assessed executive function, compared to general cognitive abilities, received a higher GRADE rating. Overall, this systematic review found that in animal models exercise results in behavioral and corresponding neurobiological changes in the basal ganglia related to cognition. The clinical studies showed that various types of exercise, including aerobic, resistance and dance can improve cognitive function, although the optimal type, amount, mechanisms, and duration of exercise are unclear. With growing support for exercise to improve not only motor symptoms, but also cognitive impairments in PD, health care providers and policy makers should recommend exercise as part of routine management and neurorehabilitation for this disorder.
Maternal blood pressure in pregnancy, birth weight, and perinatal mortality in first births: prospective study
Authors: Philip J Steer, Mark P Little, Tina Kold-Jensen, Jean Chapple, Paul Elliott
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To investigate the relation of diastolic blood pressure in pregnancy with birth weight and perinatal mortality. <b>Design</b> Prospective study. <b>Setting</b> 15 maternity units in one London health region, 1988-2000. <b>Participants</b> 210 814 first singleton births of babies weighing more than 200 g among mothers with no hypertension before 20 weeks9 gestation and without proteinuria, delivering between 24 and 43 weeks9 gestation. <b>Main outcome measures</b> Birth weight and perinatal mortality. <b>Results</b> The mean (SD) birth weight of babies born to mothers with no hypertension before 20 weeks9 gestation or proteinuria was 3282 g (545 g) and there were 1335 perinatal deaths, compared with 94 perinatal deaths among women with proteinuria or a history of hypertension. Diastolic blood pressure at booking for antenatal checks was progressively higher from weeks 34 to 40 of gestation. The birth weight of babies being delivered after 34 weeks was highest for highest recorded maternal diastolic blood pressures of between 70 and 80 mm Hg and lower for blood pressures outside this range. Both low and high diastolic blood pressures were associated with statistically significantly higher perinatal mortality. Using a linear quadratic model, 94 of 825 (11.4%) perinatal deaths could be attributed to mothers having blood pressure differing from the optimal blood pressure (82.7 mm Hg) predicted by the fitted model. Most of these excess deaths occurred with blood pressures below the optimal value. <b>Conclusions</b> Both low and high diastolic blood pressures in women during pregnancy are associated with small babies and high perinatal mortality.
Changes in Timing and kinematics of goal directed eye-hand movements in early-stage Parkinson’s disease
Authors: Danya Muilwijk, Simone Verheij, Johan JM Pel, Agnita JW Boon, Johannes van der Steen
Journal: Translational Neurodegeneration (2013)

Abstract Objective Many daily activities involve intrinsic or extrinsic goal-directed eye and hand movements. An extensive visuomotor coordination network including nigro-striatal pathways is required for efficient timing and positioning of eyes and hands. The aim of this study was to investigate how Parkinson’s disease (PD) affects eye-hand coordination in tasks with different cognitive complexity. Methods We used a touch screen, an eye-tracking device and a motion capturing system to quantify changes in eye-hand coordination in early-stage PD patients (H&amp;Y &lt; 2.5) and age-matched controls. Timing and kinematics of eye and hand were quantified in four eye-hand coordination tasks (pro-tapping, dual planning, anti-tapping and spatial memory task). Results In the pro-tapping task, saccade initiation towards extrinsic goals was not impaired. However, in the dual planning and anti-tapping task initiation of saccades towards intrinsic goals was faster in PD patients. Hand movements were differently affected: initiation of the hand movement was only delayed in the pro-tapping and dual planning task. Overall, hand movements in PD patients were slower executed compared to controls. Interpretation Whereas initiation of saccades in an extrinsic goal-directed task (pro-tapping task) is not affected, early stage PD patients have difficulty in suppressing reflexive saccades towards extrinsic goals in tasks where the endpoint is an intrinsic goal (e.g. dual planning and anti-tapping task). This is specific for eye movements, as hand movements have delayed responses in the pro-tapping and dual planning task. This suggests that reported impairment of the dorsolateral prefrontal cortex in early-stage PD patients affects only inhibition of eye movements. We conclude that timing and kinematics of eye and hand movements in visuomotor tasks are affected in PD patients. This result may have clinical significance by providing a behavioral marker for the early diagnosis of PD.
Class of Multiple Sequence Alignment Algorithm Affects Genomic Analysis
Authors: B. P. Blackburne, S. Whelan
Journal: Molecular Biology and Evolution (2012)

Multiple sequence alignment (MSA) is the heart of comparative sequence analysis. Recent studies demonstrate that MSA algorithms can produce different outcomes when analyzing genomes, including phylogenetic tree inference and the detection of adaptive evolution. These studies also suggest that the difference between MSA algorithms is of a similar order to the uncertainty within an algorithm and suggest integrating across this uncertainty. In this study, we examine further the problem of disagreements between MSA algorithms and how they affect downstream analyses. We also investigate whether integrating across alignment uncertainty affects downstream analyses. We address these questions by analyzing 200 chordate gene families, with properties reflecting those used in large-scale genomic analyses. We find that newly developed distance metrics reveal two significantly different classes of MSA methods (MSAMs). The similarity-based class includes progressive aligners and consistency aligners, representing many methodological innovations for sequence alignment, whereas the evolution-based class includes phylogenetically aware alignment and statistical alignment. We proceed to show that the class of an MSAM has a substantial impact on downstream analyses. For phylogenetic inference, tree estimates and their branch lengths appear highly dependent on the class of aligner used. The number of families, and the sites within those families, inferred to have undergone adaptive evolution depend on the class of aligner used. Similarity-based aligners tend to identify more adaptive evolution. We also develop and test methods for incorporating MSA uncertainty when detecting adaptive evolution but find that although accounting for MSA uncertainty does affect downstream analyses, it appears less important than the class of aligner chosen. Our results demonstrate the critical role that MSA methodology has on downstream analysis, highlighting that the class of aligner chosen in an analysis has a demonstrable effect on its outcome.
Modulation of polymorphonuclear leukocyte microbicidal activity and oxidative metabolism by fibrinogen degradation products D and E.
Authors: J W Kazura, J D Wenger, R A Salata, A Z Budzynski, G H Goldsmith
Journal: Journal of Clinical Investigation (1989)

Fibrinogen degradation products (FDP) D and E are typically present in blood of patients with disseminated intravascular coagulation and related conditions in which granulocyte (PMN) defense against bacterial infection may be compromised. This study was intended to determine whether FDP modify PMN functions critical to their bactericidal activity. Incubation of human PMN and Escherichia coli with 50-100 micrograms/ml FDP did not affect phagocytosis, but reduced by greater than 90% the cells' ability to inhibit bacterial colony growth compared with control PMN incubated with albumin or fibrinogen. FDP (10-100 micrograms/ml) inhibited PMN O2- release and chemotaxis stimulated by FMLP by 17-50% (P less than 0.005) and 41% (P less than 0.01), respectively. Fragment E3, and not fragment D1, was primarily responsible for inhibition of FMLP-induced PMN O2- release. Phorbol myristate acetate (10 ng/ml), 1-oleoyl-2-acetylglycerol (10(-6) M), AA (4.2 x 10(-5) M), and zymosan-activated serum-stimulated PMN O2- release were also decreased 37-63% by FDP compared with control protein. There are at least two mechanisms by which FDP may impair PMN responses. With respect to FMLP, FDP (16-100 micrograms/ml) inhibited specific binding to the cell surface over a ligand concentration range of 1.4-85 nM [3H]FMLP. In contrast, FDP did not effect the extent of phorbol ester binding to PMN but blocked activation of protein kinase C. These data suggest that elevated plasma FDP inhibit several PMN functions critical to the bactericidal role of these inflammatory cells.
Risk factors for asthma in young adults. Spanish Group of the European Community Respiratory Health Survey
Authors: J Sunyer, JM Anto, M Kogevinas, MA Barcelo, JB Soriano, A Tobias, N Muniozguren, J Martinez-Moratalla, F Payo, JA Maldonado
Journal: European Respiratory Journal (1997)

We assessed the association of asthma prevalence in young adults with susceptibility factors and environmental exposures, taking into account the age at asthma onset. A random sample of the general population, aged 20-44 yrs, in five areas of Spain (Albacete, Barcelona, Galdakao, Huelva, and Oviedo) was selected in the frame of the European Community Respiratory Health Survey (ECRHS). Overall, 2,646 subjects (response rate = 60.9%) responded to a respiratory questionnaire and 1,797 (41.4%) finalized a bronchial challenge. Atopy to perennial (odds ratio (OR) = 10.2, 95% confidence interval 4.2-25) and seasonal allergens (11.5, 4.6-28), parental asthma (4.5, 2.5-8.4), and birth order (OR for no older siblings in comparison to having more than two = 3.2, 1.2-9.1) were associated with current asthma whatever the age of asthma onset. Past asthma was associated to a lesser extent with atopy (OR around 3.5 to both perennial and seasonal allergens). Lower respiratory tract infections before the age of 5 yrs (LRTI), having had a pet in childhood, and being born in a younger cohort were associated with asthma starting before the age of 15 yrs, but not after. Male gender was more frequent in childhood asthma and female gender in adulthood. In addition to the known risk factors of asthma (atopy to perennial allergens, parental asthma) we provide evidence for an association of asthma (whatever the age of onset) with sensitization to seasonal allergens, and having less than three older siblings; and for an association of childhood asthma with lower respiratory tract infections.
Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts.
Authors: B L Davidson, S A Tarlé, T D Palella, W N Kelley
Journal: Journal of Clinical Investigation (1989)

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an inborn error of purine metabolism. Mutant HPRT gene sequences from patients deficient in enzyme activity have previously been characterized by cDNA cloning or amino acid sequencing techniques. The presence of HPRT-specific mRNA in nearly all deficient subjects, as well as the small size of the HPRT mRNA (1,400 bp), make the polymerase chain reaction (PCR) an alternative for the identification of mutations at this locus. In this report we use the PCR to identify previously undetermined mutations in HPRT mRNA from B lymphoblasts derived from 10 deficient individuals. Six of these variants contain single point mutations, three contain deletions, and one contains a single nucleotide insertion. Several of these mutations map near previously identified HPRT variants, and are located in evolutionarily conserved regions of the molecule.
Alcohol as a Cause of Renal Disease
Authors: W. H. Dickinson
Journal: BMJ (1872)

IN my worhk on l/bzminziria, I ventured to bring forward some facts which seemed to show almost conclusively that alcohol is not so pro- lific a source of renal disease as has been thought.The degree, indeed, to which disease of this nature has been attributed to drink is so ex- travagant as to carry its own refutation.It was said by a distinguished niorthern physician-and the saying has been often approvingly quoted -that in Edinburglh three-fourths, or even four-fifths, of the cases of granular degeneration could be traced to intemperance.AXnd Dr. Roberts, whlo follows oni the same side, though less numerical, is still, as I think, extravagant in saying, "The abuse of spirituous liquors raniks high-probably higher than any other single circumstance-as a
ZEB1 transcriptionally regulated carbonic anhydrase 9 mediates the chemoresistance of tongue cancer via maintaining intracellular pH
Authors: Guopei Zheng, Cong Peng, Xiaoting Jia, Yixue Gu, Zhijie Zhang, Yingen Deng, Chengkun Wang, Nan Li, Jiang Yin, Xiaorong Liu, Minying Lu, Hailin Tang, Zhimin He
Journal: Molecular Cancer (2015)

Chemoresistance is a major obstacle in successfully treating cancers, and the mechanisms responsible for drug resistance are still far from understood. Carbonic anhydrase 9 (CA9) has been shown to be upregulated in the drug-resistant tongue cancer cell line Tca8113/PYM and to be associated with drug resistance. However, the mechanisms regulating CA9 expression and its role in drug resistance remain unclear. Bioinformatic and experimental analysis involving ChIP and luciferase reporter assays were used to validate Zinc finger E-box-binding homeobox 1 (ZEB1) as a transcriptional regulator of CA9. Gene expression and protein levels were evaluated by quantitative RT-PCR and western blotting, respectively. Sensitivity to chemotherapy was examined using the MTS assay and Hoechst staining and analysis caspase-3 activity to evaluate changes in apoptosis. Intracellular pH (pHi) was measured using fluorescent pH-indicator BCECF-AM. Protein expression in patient tissue samples was examined by immunohistochemistry and survival of tongue cancer patients from which these samples were derived was also analyzed. ZEB1 bound to the promoter of CA9 to positively regulate CA9 expression in tongue cancer cells. Knockdown of CA9 using short interfering RNA (siRNA) abolished the chemoresistance resulting from ZEB1 overexpression in Tca8113 and SCC-25 cells, and CA9 overexpression attenuated chemosensitivity induced by ZEB1 knockdown in Tca8113/PYM cells. CA9 knockdown also prevented maintenance of pHi mediated by overexpression of ZEB1 in Tca8113 and SCC-25 cells following chemotherapy, associated with increased apoptosis and caspase-3 activation. Conversely, ectopic expression of CA9 suppressed decrease in pHi mediated by ZEB1 knockdown in Tca8113/PYM cells following chemotherapy, accompanied by decreased apoptosis and caspase-3 activation. Importantly, a positive correlation was observed between ZEB1 and CA9 protein expression in tongue cancer tissues, and expression of these proteins associated with a poor prognosis for patients. Our finding that tumor cells regulate pHi in response to chemotherapy provides new insights into mechanisms of drug resistance during cancer treatment. Identification of the ZEB1–CA9 signaling axis as a biomarker of poor prognosis in tongue cancer will be valuable in future development of therapeutic strategies aimed at improving treatment efficacy, especially in terms of drug resistance associated with this disease.