tbuckley/cabot-search huggingface dataset:
Association of locomotor complaints and disability in the Rotterdam study.
Authors: E Odding, H A Valkenburg, D Algra, F A Vandenouweland, D E Grobbee, A Hofman
Journal: Annals of the Rheumatic Diseases (1995)

To determine the association between joint complaints and locomotor disability.During a home interview survey 1901 men and 3135 women aged 55 years and over (the Rotterdam Study) were asked about joint pain and morning stiffness in the past month, and locomotor disability was assessed by six questions from the Health Assessment Questionnaire (HAQ).The prevalence of locomotor disability was 24.5% for men and 40.5% for women. The prevalence of joint pain in men was 0.7% for pain in the hips, knees, and feet simultaneously, 3.7% for pain at two joint sites, 16.0% for pain at one joint site, and 20.4% for pain in the hips and/or knees and/or feet (any joint site); the corresponding estimates for women were 1.9%, 9.0%, 23.7%, and 34.5%, respectively. The prevalence of generalised morning stiffness was 4.9% for men and 10.4% for women. The age adjusted odds ratios for locomotor disability in men ranged from 2.4 of pain at one joint site to 8.8 of pain at all three joint sites; for women these odds ratios varied between 2.5 and 5.7, respectively. The age adjusted odds ratios of generalised morning stiffness were 8.0 for men and 7.3 for women.There is a strong and independent association between locomotor disability and age, joint pain, and generalised morning stiffness in people aged 55 years and over. The odds for locomotor disability increase onefold for every year increase in age, while the presence of generalised morning stiffness is of greater influence than the presence of joint pain.
Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women
Authors: Sylvia Wassertheil-Smoller, Susan Hendrix, Marian Limacher, Gerardo Heiss, Charles Kooperberg, Alison Baird, Theodore Kotchen, J. David Curb, Henry Black, Jacques E. Rossouw, Aaron Aragaki, Monika Safford, Evan Stein, Somchai Laowattana, W. Jerry Mysiw, None for the WHI Investigators
Journal: JAMA (2003)

TROKE IS A MAJOR HEALTH issue for women. 1,2Cerebrovascular diseases are the third leading cause of death in the United States 3 and are the leading cause of adult disability.The Women's Health Initiative (WHI), beginning in the early 1990s was designed to examine a number of factors affecting the health of postmenopausal women. 4Recently 1 arm of the WHI, the clinical trial of estrogen plus progestin, was terminated 3 years before its planned completion date because its harmful effects outweighed its benefits.The overall results in this randomized double-blind clinical trial indicated that women in the estrogen plus progestin group had a 41% increase in locally adjudicated strokes over 5.2 years compared with women in the placebo group. 5Our report provides results over an additional 4 months (average follow-up 5.6 years) on subtypes of stroke, based on central adjudication of stroke events by neurologists, additional data on the effects of estro-
ATRA activates and PDGF-BB represses the SM22α promoter through KLF4 binding to, or dissociating from, its cis-DNA elements
Authors: Kun Yu, Bin Zheng, Mei Han, Jin-kun Wen
Journal: Cardiovascular Research (2011)

AimsKrüppel-like factor 4 (KLF4) is implicated in all-trans retinoic acid (ATRA)-induced and platelet-derived growth factor-BB (PDGF-BB)-repressed SM22α expression in vascular smooth muscle cells (VSMCs). However, its exact mechanism of action remains unclear. We determined how KLF4 plays different roles in ATRA- and PDGF-BB-dependent regulation of the SM22α gene.
Health status has improved more in women than in men with rheumatoid arthritis from 1994 to 2009: results from the Oslo rheumatoid arthritis register
Authors: C Austad, T K Kvien, I C Olsen, T Uhlig
Journal: Annals of the Rheumatic Diseases (2013)

Objective To examine changes in patient reported outcome measures (PROs) over 15 years in a representative population of patients with rheumatoid arthritis (RA), with a particular focus on gender differences. Patients and methods Patients in the Oslo RA register filled in questionnaires including the Modified Health Assessment Questionnaire (MHAQ), the Short-Form 36 (SF-36) with physical (PCS) and mental component summaries and derived utility (SF-6D), visual analogue scales (VAS) for pain, patient global assessment of disease (PtGA) and fatigue, and checklists of medication commonly used in the treatment of RA. Data were collected at five time points during a 15-year period from 1994. Mixed model analyses were used to analyse longitudinal changes in PROs from 1994 to 1996, 2001, 2004 and 2009. Results Data were available from 829–1025 RA patients at each time point. PROs were statistically significantly improved from 1994 to 2009 (MHAQ, SF-36 PCS, SF-6D, pain VAS, PtGA VAS and fatigue VAS; all p&lt;0.001), and also with clinically important improvement. Men reported significantly better health status than women in 1994, but women improved significantly more than men over 15 years with a reduction of the gender gap in 2009. Antirheumatic medication was increasingly used over 15 years with no gender differences. Conclusions RA patients reported statistically significantly improved health status for most PROs from 1994 to 2009. Women improved most, and although they still reported higher disease impact than men, the gender differences were small at the final data collection in 2009.
A DOUBLE-BLIND COMPARISON OF WY-3498, DIAZEPAM AND PLACEBO IN PSYCHIATRIC OUTPATIENTS
Authors: WM NESSELHOF, D. M. GALLANT, M. P. BISHOP
Journal: American Journal of Psychiatry (1965)

Concerning diazepam, the results of this study are in apparent disagreement with the findings of certain other investigators(2-4). In an activity study of diazepam, good or excellent results were reported in 95% of 103 patients; 50% in a group of 60 patients in the same study subsequently placed on placebo for 1 month showed worsening of symptoms(2 The author appraised the effect of diazepam "as good or excellent if it exerted a positive effect upon symptomatology, as compared with previous agents." In our double-blind study, each of 3 groups of 14 psychoneurotic patients whose predominant symptom was anxiety received either WY-3498, diazepam, or placebo for a period of 6 weeks. Each patient's condition during and at the termination of medication was judged solely against his condition prior to medication, with no attempt to evaluate the patient's response to diazepam as compared with previous agents. In addition, adjunctive drugs and conventional psychotherapy were not used in this experiment. With this procedural approach, neither diazepam nor WY-3498 had a significantly greater therapeutic effect than placebo, not only in the global ratings of improvement but in the Overall and Gorham BPRS as well.
Hedgehog signalling and LSEC capillarisation: stopping this one in its tracks
Authors: Heather Francis, Jennifer Bohanan, Gianfranco Alpini
Journal: Gut (2012)

Liver sinusoidal endothelial cells (LSECs) display a unique phenotype and function as the exchange vessels of the liver.1 ,2 When successful, LSECs serve as the most powerful scavenger system in the body, however, during capillarisation (which induces a change in the phenotype of LSECs to a vascular type—vasculogenesis) defenestration and the formation of an organised basement membrane occur, resulting in unhealthy LSECs.2 Capillarisation is an event that precedes most liver diseases such as fibrosis, hepatitis and alcoholic liver injury as well as increases naturally with age (pseudocapillarisation).2

Hedgehog (Hh) signalling is an important component in the regulation of vasculogenesis, which increases during liver injury and influences the function of liver cells including cholangiocytes, hepatocytes, hepatic stellate cells (HSCs) and LSECs.3 ,4 LSECs produce Hh ligands and during vascular development Hh ligands (Sonic hedgehog, Indian hedgehog and Desert hedgehog) are activated, thus influencing the transmembrane receptor Patched which prevents the repression of Smoothened (SMO).3 ,5 This process affects the Gli family of transcription factors (Gli1, Gli2, Gli3) which regulates the transcription of the Hh genes.3 ,5 This autocrine mechanism influences cell viability, production and differentiation. …
A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation
Authors: M. van der Burg
Journal: Journal of Clinical Investigation (2005)

V(D)J recombination of Ig and TCR loci is a stepwise process during which site-specific DNA double-strand breaks (DSBs) are made by RAG1/RAG2, followed by DSB repair by nonhomologous end joining. Defects in V(D)J recombination result in SCID characterized by absence of mature B and T cells. A subset of T–B–NK+ SCID patients is sensitive to ionizing radiation, and the majority of these patients have mutations in Artemis. We present a patient with a new type of radiosensitive T–B–NK+ SCID with a defect in DNA ligase IV (LIG4). To date, LIG4 mutations have only been described in a radiosensitive leukemia patient and in 4 patients with a designated LIG4 syndrome, which is associated with chromosomal instability, pancytopenia, and developmental and growth delay. The patient described here shows that a LIG4 mutation can also cause T–B–NK+ SCID without developmental defects. The LIG4-deficient SCID patient had an incomplete but severe block in precursor B cell differentiation, resulting in extremely low levels of blood B cells. The residual DH-JH junctions showed extensive nucleotide deletions, apparently caused by prolonged exonuclease activity during the delayed DH-JH ligation process. In conclusion, different LIG4 mutations can result in either a developmental defect with minor immunological abnormalities or a SCID picture with normal development.
Opportunities for Improving the Care of Patients with Chronic Renal Insufficiency
Authors: ALLEN R. NISSENSON, ALLAN J. COLLINS, JUDITH HURLEY, HANS PETERSEN, BRIAN J. G. PEREIRA, EARL P. STEINBERG
Journal: Journal of the American Society of Nephrology (2001)

There are between 2 and 13 million Americans with chronic kidney disease (CKD). Recent reports suggest that their treatment is currently suboptimal. To further investigate this issue, patterns of practice for the treatment of patients with CKD who were enrolled in a large health maintenance organization in New Mexico were analyzed. Among the >200,000 patients who were enrolled in the health maintenance organization between 1994 and 1997, a cohort of 1658 patients who exhibited at least two gender-specific, elevated creatinine concentrations (Cr), separated by at least 90 d, were identified. The proportions of patients with Cr values of <2.0, 2.0 to 2.9, 3.0 to 3.9, and > or =4.0 mg/dl were 73, 17, 3, and 7%, respectively. The majority of patients were treated by a primary care physician until Cr values reached 3.0 mg/dl, at which time a nephrologist was consulted. Care tended to be transferred to the nephrologist when the Cr reached 4.0 mg/dl. Only 7.4% of patients received erythropoietin (EPO). Use of EPO increased as Cr increased. EPO was unlikely to be prescribed unless the patient had visited a nephrologist. Fewer than one half of all patients with CKD and fewer than 20% of patients with CKD with Cr values of > or =4.0 mg/dl received an angiotensin-converting enzyme inhibitor (ACEI). Nephrologists were not more likely to prescribe ACEI than were primary care physicians. Diabetic patients were more likely to receive ACEI than were nondiabetic patients, but ACEI use was quite low even among diabetic patients with CKD. The average number of hospitalizations per patient-year increased as Cr increased and was more than twice as high for patients with Cr values of > or =4.0 mg/dl, compared with those with Cr values of <2.0 mg/dl. The reasons for hospitalization were more likely to be related to comorbidities than to CKD itself, however. There are many opportunities to improve the care of patients with CKD. Better adherence to practices known to be of clinical benefit for patients with CKD not only will improve patient outcomes but also may reduce the costs of care. Providers, policy-makers, and payers should view CKD as a major public health problem and initiate innovative programs to address this growing patient population.
Detection of MRD may predict the outcome of patients with Philadelphia chromosome–positive ALL treated with tyrosine kinase inhibitors plus chemotherapy
Authors: Farhad Ravandi, Jeffrey L. Jorgensen, Deborah A. Thomas, Susan O’Brien, Rebecca Garris, Stefan Faderl, Xuelin Huang, Sijin Wen, Jan A. Burger, Alessandra Ferrajoli, Partow Kebriaei, Richard E. Champlin, Zeev Estrov, Pramoda Challagundla, Sa A. Wang, Rajyalakshmi Luthra, Jorge E. Cortes, Hagop M. Kantarjian
Journal: Blood (2013)
A Public Ethos of Enhancement Across Asia
Authors: Darryl Macer
Journal: The American Journal of Bioethics (2014)

Click to increase image sizeClick to decrease image size NotesWolf, A., and D. R. J. Macer article under preparation; results are available at: http://www.unescobkk.org/rushsap/philosophical-reflection-and-the/philosophyteaching
CONTROL OF CENTRAL SYNAPTIC SPECIFICITY IN INSECT SENSORY NEURONS
Authors: Jonathan M. Blagburn, Jonathan P. Bacon
Journal: Annual Review of Neuroscience (2004)

▪ Abstract Synaptic specificity is the culmination of several processes, beginning with the establishment of neuronal subtype identity, followed by navigation of the axon to the correct subdivision of neuropil, and finally, the cell-cell recognition of appropriate synaptic partners. In this review we summarize the work on sensory neurons in crickets, cockroaches, moths, and fruit flies that establishes some of the principles and molecular mechanisms involved in the control of synaptic specificity. The identity of a sensory neuron is controlled by combinatorial expression of transcription factors, the products of patterning and proneural genes. In the nervous system, sensory axon projections are anatomically segregated according to modality, stimulus quality, and cell-body position. A variety of cell-surface and intracellular signaling molecules are used to achieve this. Synaptic target recognition is also controlled by transcription factors such as Engrailed and may be, in part, mediated by cadherin-like molecules.
Opportunities and Challenges in the Era of Molecularly Targeted Agents and Radiation Therapy
Authors: Steven H. Lin, Thomas J. George, Edgar Ben-Josef, Jeffrey Bradley, Kevin S. Choe, Martin J. Edelman, Chandan Guha, Sunil Krishnan, Theodore S. Lawrence, Quynh-Thu Le, Bo Lu, Minesh Mehta, David Peereboom, Jann Sarkaria, Jinsil Seong, Dian Wang, Meng X. Welliver, C. Norman Coleman, Bhadrasain Vikram, Stephen Yoo, Christine H. Chung
Journal: JNCI Journal of the National Cancer Institute (2013)

The first annual workshop for preclinical and clinical development of radiosensitizers took place at the National Cancer Institute on August 8-9, 2012. Radiotherapy is one of the most commonly applied and effective oncologic treatments for solid tumors. It is well recognized that improved clinical efficacy of radiotherapy would make a substantive impact in clinical practice and patient outcomes. Advances in genomic technologies and high-throughput drug discovery platforms have brought a revolution in cancer treatment by providing molecularly targeted agents for various cancers. Development of predictive biomarkers directed toward specific subsets of cancers has ushered in a new era of personalized therapeutics. The field of radiation oncology stands to gain substantial benefit from these advances given the concerted effort to integrate this progress into radiation therapy. This workshop brought together expert clinicians and scientists working in various disease sites to identify the exciting opportunities and expected challenges in the development of molecularly targeted agents in combination with radiation therapy.
Circulating high-molecular-weight RAGE ligands activate pathways implicated in the development of diabetic nephropathy
Authors: Sally A. Penfold, Melinda T. Coughlan, Sheila K. Patel, Piyush M. Srivastava, Karly C. Sourris, David Steer, Diane E. Webster, Merlin C. Thomas, Richard J. MacIsaac, George Jerums, Louise M. Burrell, Mark E. Cooper, Josephine M. Forbes
Journal: Kidney International (2010)
Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E2 synthesis
Authors: R Bartoli
Journal: Gut (2000)

Animal model studies have shown that the colon tumour promoting effect of dietary fat depends not only on the amount but on its fatty acid composition. With respect to this, the effect of n9 fatty acids, present in olive oil, on colon carcinogenesis has been scarcely investigated.To assess the effect of an n9 fat diet on precancer events, carcinoma development, and changes in mucosal fatty acid composition and prostaglandin (PG)E(2) formation in male Sprague-Dawley rats with azoxymethane induced colon cancer.Rats were divided into three groups to receive isocaloric diets (5% of the energy as fat) rich in n9, n3, or n6 fat, and were administered azoxymethane subcutaneously once a week for 11 weeks at a dose rate of 7.4 mg/kg body weight. Vehicle treated groups received an equal volume of normal saline. Groups of animals were colectomised at weeks 12 and 19 after the first dose of azoxymethane or saline. Mucosal fatty acids were assessed at 12 and 19 weeks. Aberrant crypt foci and the in vivo intracolonic release of PGE(2) were assessed at week 12, and tumour formation at week 19.Rats on the n6 diet were found to have colonic aberrant crypt foci and adenocarcinomas more often than those consuming either the n9 or n3 diet. There were no differences between the rats on the n9 and n3 diets. On the other hand, administration of both n9 and n3 diets was associated with a decrease in mucosal arachidonate concentrations as compared with the n6 diet. Carcinogen treatment induced an appreciable increase in PGE(2) formation in rats fed the n6 diet, but not in those fed the n3 and n9 diets.Dietary olive oil prevented the development of aberrant crypt foci and colon carcinomas in rats, suggesting that olive oil may have chemopreventive activity against colon carcinogenesis. These effects may be partly due to modulation of arachidonic acid metabolism and local PGE(2) synthesis.
The vasopressor response to centrally administered ouabain.
Authors: R W Caldwell, E Songu-Mize, S L Bealer
Journal: Circulation Research (1984)

Ouabain (80 micrograms/kg) injected into the lateral cerebroventricles (ICV) of rats produced a prompt and sustained increase in arterial blood pressure. A diastolic blood pressure increase of about 40 mm Hg began within 10 minutes of injection and lasted at lest 1 hour. This dose of ouabain had no effect on arterial pressure when given intravenously. The vasopressor response to intracerebroventricularly administered ouabain was not blocked by prior intravenous administration of phentolamine (1 mg/kg) or hexamethonium (3 mg/kg). However, continuous intravenous infusion of saralasin (2 micrograms/kg per min) prevented the pressor response to intracerebroventricularly administered ouabain. In addition, bilateral nephrectomy, adrenalectomy, pretreatment with intravenously administered propranolol (2 mg/kg) or captopril (10 mg/kg) abolished the increase in blood pressure evoked by intracerebroventricularly administered ouabain. Plasma renin and epinephrine levels at the peak of the pressor response to intracerebroventricularly administered ouabain were respectively, about 2.5- and 2-fold higher than in control rats. Our data indicate that ouabain administered into the central nervous system produces a hypertensive effect which does not primarily involve peripheral alpha-adrenergic receptors, but appears to be due to angiotensin II produced by renin of renal origin. These data suggest that digitalis agents can interact with sites in the central nervous system to induce a release of renin from the kidney; this release appears to involve activation of beta-adrenergic receptors by catecholamines from the adrenal medulla, perhaps through a direct adrenal-kidney vascular network.
Helicobacter pylori and antibiotic resistance
Authors: F. Megraud
Journal: Gut (2007)

his is an introduction to the Gut tutorial ''Helicobacter pylori and antibiotic resistance'' hosted on BMJ Learning-the best available learning website for medical professionals from the BMJ Group.H pylori is a Gram-negative flagellated spiral bacteria.Infection with H pylori is mainly acquired in childhood.About 15% of infected people will develop a peptic ulcer and 1% will develop gastric cancer during their lifetime.Resistance to antibiotics is important as it leads to treatment failure.The prevalence of H pylori resistance to clarithromycin is ,5% for adults in northern Europe, but as high as 20% in southern Europe.Resistance to clarithromycin is caused by previous consumption of macrolides.Resistance is higher in children because prescriptions of these drugs, particularly for children, have increased during the past decade, mainly for respiratory tract infections.The prevalence of H pylori resistance to metronidazole varies from 20-40% in Europe and the USA to 50-80% in developing countries.Metronidazole is used extensively for treating parasitic diseases in tropical countries, which is probably why there is more resistance there.For patients needing a second course of eradication treatment, a regimen should be chosen that does not include antibiotics given previously.Once you successfully eradicate H pylori, adult reinfection rates are low at ,1% a year.To access the tutorial (Interactive Case History), click on BMJ Learning: Take this module on BMJ Learning from the content box at the top right and bottom left of the online article.For more information please go to: http://gut.bmj.
Mutant huntingtin impairs immune cell migration in Huntington disease
Authors: Wanda Kwan, Ulrike Träger, Dimitrios Davalos, Austin Chou, Jill Bouchard, Ralph Andre, Aaron Miller, Andreas Weiss, Flaviano Giorgini, Christine Cheah, Thomas Möller, Nephi Stella, Katerina Akassoglou, Sarah J. Tabrizi, Paul J. Muchowski
Journal: Journal of Clinical Investigation (2012)

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.