tbuckley/cabot-search huggingface dataset:
Myocardial Adaptation During and After Sustained, Demand-Induced Ischemia
Authors: Mark Berman, Alan J. Fischman, James Southern, Edward Carter, Francis Mirecki, H. William Strauss, Adrian Nunn, Henry Gewirtz
Journal: Circulation (1996)

Background We tested the hypotheses that prolonged, demand-induced myocardial ischemia plateaus and that on relief of stress, myocardial function remains depressed, with proportionate reductions in blood flow and oxygen consumption indicative of hibernation. Methods and Results Closed-chest swine (n=20) were prepared with an 80% coronary stenosis. Hemodynamics, myocardial blood flow, oxygen, and lactate metabolism were measured in group 1 (n=9) (1) at baseline, (2) at 10 and 30 minutes of atrial pacing plus intravenous norepinephrine infusion, and (3) in 5 of 9 (group 1a) at ≈50 minutes after stress. Group 1a had ischemia assessed with 99m Tc-labeled BMS 181321. In group 2 (n=11), myocardial function was determined with radionuclide ventriculography (n=8), and myocardial necrosis was looked for with trichlorotetrazolium chloride staining (n=7), histology (n=10), and myocardial creatine kinase concentration (n=4). Baseline stenotic-zone endocardial blood flow was reduced versus the normal zone (0.94±0.33 versus 1.38±0.27 mL·min −1 ·g −1 , mean±SD; P &lt;.05), whereas epicardial flows were comparable (1.15±0.36 versus 1.16±0.26 mL·min −1 ·g −1 ). Stenotic-zone endocardial flow was unchanged versus baseline at 10 and 30 minutes of stress, whereas epicardial flow increased (1.62±0.53 mL·min −1 ·g −1 at 10 minutes and 1.44±0.51 mL·min −1 ·g −1 at 30 minutes, both P &lt;.05). Myocardial oxygen consumption increased versus baseline (10.8±2.9 mL·min −1 ·100 g −1 ) at 10 and 30 minutes of stress (14.9±5.2 and 13.9±4.5 mL·min −1 ·100 g −1 , both P &lt;.05). After stress, stenotic-zone blood flow and oxygen consumption were reduced ≈30% ( P &lt;.01) versus baseline. In group 2, stenotic-zone contraction with stress declined versus baseline and remained depressed throughout recovery. Histological and biochemical evidence of myocardial necrosis was absent in group 2. Conclusions Myocardial ischemia induced by a sustained increase in oxygen demand may not progress to necrosis but may instead plateau. After relief of stress, myocardial function remains depressed, with a proportionate reduction in blood flow and oxygen consumption consistent with myocardial hibernation.
The role of the sympathetic nervous system in intestinal inflammation
Authors: R H Straub, R Wiest, U G Strauch, P Harle, J Scholmerich
Journal: Gut (2006)

The nervous system in the intestine controls motility, secretion, sensory perception, and immune function.Peptidergic neurones with neurotransmitters such as substance P and nerve growth factors have been the main focus of neuroimmunomodulation research in the gut.This review summarises the present knowledge concerning the role of the sympathetic nervous system (SNS) in modulating intestinal inflammation.The role of the SNS for gut inflammation is compared with its role in rheumatoid arthritis which demonstrates notable similarities.Nerve fibres of the SNS not only enter the enteric plexuses but also innervate the mucosa and gut associated lymphoid tissue (GALT).The SNS has pro-and anti-inflammatory functions.Neurotransmitters such as norepinephrine, adenosine, and others can evoke remarkably different opposing effects depending on concentration (presence of sympathetic nerve fibres and extent of neurotransmitter release), receptor affinity at different receptor subtypes, expression of adrenoceptors, availability of cotransmitters, and timing of SNS activity in relation to the inflammatory course.This review attempts to integrate the different perspectives of the pro-and anti-inflammatory effects of the SNS on inflammatory disease of the gut.
Idiotype‐pulsed antigen presenting cells following autologous transplantation for multiple myeloma may be associated with prolonged survival
Authors: Martha Q. Lacy, Sumithra Mandrekar, Angela Dispenzieri, Suzanne Hayman, Shaji Kumar, Francis Buadi, David Dingli, Mark Litzow, Peter Wettstein, Douglas Padley, Brian Kabat, Dennis Gastineau, S. Vincent Rajkumar, Morie A. Gertz
Journal: American Journal of Hematology (2009)

Vaccines are attractive as consolidation therapy after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We report the results of a phase II trial of the immunotherapeutic, APC8020 (Mylovenge), given after ASCT for MM. We compared the results with that of other patients with MM who underwent ASCT at Mayo Clinic during the same time period. Twenty-seven patients were enrolled on the trial between July, 1998 and June, 2001, and the outcomes were compared to that of 124 consecutive patients transplanted during the same period, but not enrolled on the trial. The median (range) follow-up for patients still alive from the vaccine trial is 6.5 (2.9-8 years), and 7.1 (6-8 years) in the control group. The median age was 57.4 range (36.1-71.3) in the DB group and 56.4 (range, 30-69) in the trial group. Known prognostic factors including PCLI, B2M, and CRP were comparable between the groups. The median overall survival for the trial patients was 5.3 years (95% CI: 4.0 years-N/A) compared to 3.4 years (95% CI: 2.7-4.6 years) for the DB group (P = 0.02). The median time to progression and progression-free survival for the trial group was similar to the DB group. Although not a controlled trial, the vaccines given after ASCT appear to be associated with improved overall survival compared to historical controls. This approach warrants further investigation to confirm this and define the role of vaccine therapy in myeloma.
Total parenteral nutrition in the hospital and at home
Authors: E. C G Lee
Journal: Gut (1984)

Immunological studies in inflammatory bowel disease SIR,-The leading article by Ferguson (Gut 1983; 24: 687-91) on immunological studies in inflammatory bowel disease, and the paper by Fiocchi et al (pp.692-701) prompted us to refer our data on T function in Crohn's disease.While studying T rosette serum inhibitory factors in chronic active liver disease,' we also tested, as a disease control group, 14 sera from coeliac disease untreated patients.Rosette inhibitory factors were detected in 36% coeliac disease sera and they were associated with immunoglobulin factors reacting in immunofluorescence with purified T lymphocyte.Furthermore, inhibitory activity was abolished by treatment of sera with (NH4I2S02, which precipi- tates gammaglobulin fraction.We conclude that in some coeliac disease cases serum immunoglobulin factors, which can interfere with T lymphocyte functions, are present.We agree that direct studies on intestinal lymphoid system are likely to be the best way to detect immunological abnormalities underlying these diseases, but we would like to point out that also at this level results are rather conflicting.In fact, other authors2 have reported reduced suppressor cell activity in intestinal lymphocytes from patients with coeliac disease.Furthermore, our data would suggest that systemic factors also may be relevant in modulating immune reactions in these conditions.
New amber mutation in a beta-thalassemic gene with nonmeasurable levels of mutant messenger RNA in vivo.
Authors: G F Atweh, H E Brickner, X X Zhu, H H Kazazian, B G Forget
Journal: Journal of Clinical Investigation (1988)

We have identified a beta-thalassemia gene that carries a novel nonsense mutation in a Chinese patient. This mutation, a G to T substitution at the first position of codon 43, changes the glutamic acid coding triplet (GAG) to a terminator codon (TAG). Based on oligonucleotide hybridization studies of 78 Chinese and Southeast Asian beta-thalassemia chromosomes, we estimate that this mutation accounts for a small minority of the beta-thalassemia mutations in that population. Study of the expression of this cloned gene in a transient expression system demonstrated a 65% decrease in levels of normally spliced mutant beta-globin mRNA. However, the study of reticulocyte RNA isolated from an individual heterozygous for this mutation demonstrated a total absence of this mutant mRNA in vivo. The basis for this big discrepancy between the level of accumulated mRNA in vivo and in vitro is probably the result of differences in the stabilities of the mutant mRNA in erythroid cells.
Evaluation of the Ultraviolet Index: Media reactions and public response
Authors: Alan C. Geller, Drusilla Hufford, Donald R. Miller, Ting Sun, Stephen W. Wyatt, Barbara Reilley, Barbara Bewerse, John Lisco, Daniel Brooks, John Grupenhoff, Peyton Weary, Robert A. Lew, Howard K. Koh
Journal: Journal of the American Academy of Dermatology (1997)

In response to the increasing rate of skin cancer, particularly melanoma in the United States, the Environmental Protection Agency, the National Weather Service, the Centers for Disease Control and Prevention, National Association of Physicians for the Environment, and the American Academy of Dermatology, developed the Ultraviolet Index (UVI) to inform the public of the strength of the sun's rays and advise on methods for sun protection.Our purpose was to evaluate the extent to which television stations and newspapers reported the UVI and assess the public's response to it.To evaluate the effect of this effort, we surveyed television weather forecasters at 185 stations and examined weather pages in 54 newspapers in 58 cities that received the UVI reports. We also conducted a population probability telephone survey of 700 white adults (18 years of age and older) in these 58 cities.Seventy-one percent of the 169 stations that provided survey data for both 1994 and 1995 broadcast the UVI; 61% of newspapers reported the UVI. Nearly 64% of the 700 respondents (n = 445) had heard of the UVI. Of these respondents, 38% (n = 170) stated that they or their family changed their sun protection practices as a result of the UVI.The majority of television weather forecasters and newspapers reported the UVI. Most of the public was aware of the UVI, causing some to change sun protection practices. Further evaluation is required to maximize the effect of the UVI on sun protection practices.
Risk of cervical injuries in mixed martial arts
Authors: T Kochhar, D L Back, B Mann, J Skinner
Journal: British Journal of Sports Medicine (2005)

Background: Mixed martial arts have rapidly succeeded boxing as the world’s most popular full contact sport, and the incidence of injury is recognised to be high. Objective: To assess qualitatively and quantitatively the potential risk for participants to sustain cervical spine and associated soft tissue injuries. Methods: Four commonly performed manoeuvres with possible risks to the cervical spine were analysed with respect to their kinematics, and biomechanical models were constructed. Results: Motion analysis of two manoeuvres revealed strong correlations with rear end motor vehicle impact injuries, and kinematics of the remaining two suggested a strong risk of injury. Mathematical models of the biomechanics showed that the forces involved are of the same order as those involved in whiplash injuries and of the same magnitude as compression injuries of the cervical spine. Conclusions: This study shows that there is a significant risk of whiplash injuries in this sport, and there are no safety regulations to address these concerns.
The Phadiatop® test compared with RAST, with the CAP system; proposal for a third Phadiatop outcome: “inconclusive”
Authors: M. J. J. S. Crobach, A. A. Kaptein, J. A. Kramps, J. Hermans, J. Ridderikhoff, J. D. Mulder
Journal: Allergy (1994)

In 19 general practices, blood samples were obtained from 361 patients aged 12 years or older with chronic nasal symptoms. The Phadiatop test and a panel of RASTs to common inhalant allergens were performed on all sera with the recently introduced Pharmacia CAP system. The RAST panel was accepted as the standard. The sensitivity of the Phadiatop was 94% (95% confidence interval (CI): 89–97%), the specificity 98% (95% CI: 95–99%), the positive predictive value 97% (95% CI: 94–99%), and the negative predictive value 95% (95% CI: 91–98%). It is noteworthy that these values are very similar to those found in hospital outpatient departments. It was possible to reduce further the small percentage of false outcomes by replacing the cutoff point of the Phadiatop ratio of 1.00 by the two cutoff points 0.75 and 1.15. This resulted in three possible outcomes: a highly predictive positive outcome, a highly predictive negative outcome, and an “inconclusive” outcome. Alternatively, the cutoff point of 1.00 may be maintained while attaching the annotation “borderline” to all positive or negative Phadiatop outcomes where the Phadiatop ratio is between 0.75 and 1.15. By this simple method, physicians are alerted to the possibility of a false outcome; on the basis of the case history and other clinical findings, they can then decide whether further testing should be done.
Endothelial Function Predicts Progression of Carotid Intima-Media Thickness
Authors: Julian P.J. Halcox, Ann E. Donald, Elizabeth Ellins, Daniel R. Witte, Martin J. Shipley, Eric J. Brunner, Michael G. Marmot, John E. Deanfield
Journal: Circulation (2009)

Background— Endothelial dysfunction develops early and has been shown to predict the development of clinical complications of atherosclerosis. However, the relationship between early endothelial dysfunction and the progression of arterial disease in the general population is unknown. We investigated endothelial dysfunction, risk factors, and progression of carotid intima-media thickness (cIMT) in late-middle-aged individuals at low to intermediate cardiovascular risk in a prospective study between 1997 and 2005. Methods and Results— Brachial artery flow-mediated dilatation and cIMT were measured in 213 nonsmoking British civil servants recruited from a prospective cohort (Whitehall II study). Participants (age, 45 to 66 years) were free of clinical cardiovascular disease and diabetes mellitus. Risk factors and Framingham Risk Score were determined at baseline. cIMT was repeated 6.2±0.4 years later. At baseline, age, blood pressure, low-density lipoprotein cholesterol, and Framingham Risk Score correlated with cIMT. However, only flow-mediated dilatation, not risk factors or Framingham Risk Score, was associated with average annual progression of cIMT. This relationship remained significant after adjustment for risk factors whether entered as separate variables or as Framingham Risk Score. Further adjustment for waist circumference, triglycerides, and employment grade had no significant effect. Conclusions— Systemic endothelial function was associated with progression of preclinical carotid arterial disease over a 6-year period and was more closely related to cIMT changes than conventional risk factors. Thus, the relationship between endothelial dysfunction and adverse outcome is likely to be due not only to destabilization of established disease in high-risk populations but also to its impact on the evolution of the atherosclerotic substrate. Flow-mediated dilatation testing provides an integrated vascular measure that may aid the prediction of structural disease evolution and represents a potential short- to intermediate-term outcome measure for evaluation of preventive treatment strategies.
MSH2–MSH6 stimulates DNA polymerase η, suggesting a role for A:T mutations in antibody genes
Authors: Teresa M. Wilson, Alexandra Vaisman, Stella A. Martomo, Patsa Sullivan, Li Lan, Fumio Hanaoka, Akira Yasui, Roger Woodgate, Patricia J. Gearhart
Journal: The Journal of Experimental Medicine (2005)

Activation-induced cytidine deaminase deaminates cytosine to uracil (dU) in DNA, which leads to mutations at C:G basepairs in immunoglobulin genes during somatic hypermutation. The mechanism that generates mutations at A:T basepairs, however, remains unclear. It appears to require the MSH2–MSH6 mismatch repair heterodimer and DNA polymerase (pol) η, as mutations of A:T are decreased in mice and humans lacking these proteins. Here, we demonstrate that these proteins interact physically and functionally. First, we show that MSH2–MSH6 binds to a U:G mismatch but not to other DNA intermediates produced during base excision repair of dUs, including an abasic site and a deoxyribose phosphate group. Second, MSH2 binds to pol η in solution, and endogenous MSH2 associates with the pol in cell extracts. Third, MSH2–MSH6 stimulates the catalytic activity of pol η in vitro. These observations suggest that the interaction between MSH2–MSH6 and DNA pol η stimulates synthesis of mutations at bases located downstream of the initial dU lesion, including A:T pairs.
Interleukin-1, immune activation pathways, and different mechanisms in osteoarthritis and rheumatoid arthritis.
Authors: B Kirkham
Journal: Annals of the Rheumatic Diseases (1991)

The properties of interleukin-1 suggest that it has a central role in the immunopathology of many arthritides (figure). This review of IL-1 covers recent in vitro findings together with data from in vivo studies and discusses the implications for rheumatoid arthritis and osteoarthritis
ON THE WHITE REACTION (WHITE LINE) IN DERMATOLOGY
Authors: ARTHUR WHITFIELD
Journal: British Journal of Dermatology (1938)

Journal Article ON THE WHITE REACTION (WHITE LINE) IN DERMATOLOGY Get access ARTHUR WHITFIELD ARTHUR WHITFIELD Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 50, Issue 2, 1 February 1938, Pages 71–82, https://doi.org/10.1111/j.1365-2133.1938.tb10475.x Published: 01 February 1938
Molecular Basis of Adaptive Shift in Body Size in Drosophila melanogaster: Functional and Sequence Analyses of the Dca Gene
Authors: S. F. Lee, Y. Chen, A. K. Varan, C. W. Wee, L. Rako, J. K. Axford, R. T. Good, M. J. Blacket, C. Reuter, L. Partridge, A. A. Hoffmann
Journal: Molecular Biology and Evolution (2011)

Latitudinal body size clines in animals conforming to Bergmann's rule occur on many continents but isolating their underlying genetic basis remains a challenge. In Drosophila melanogaster, the gene Dca accounts for approximately 5–10% of the natural wing size variation (McKechnie SW, Blacket MJ, Song SV, Rako L, Carroll X, Johnson TK, Jensen LT, Lee SF, Wee CW, Hoffmann AA. 2010. A clinally varying promoter polymorphism associated with adaptive variation in wing size in Drosophila. Mol Ecol. 19:775–784). We present here functional evidence that Dca is a negative regulator of wing size. A significant negative latitudinal cline of Dca gene expression was detected in synchronized third instar larvae. In addition, we clarified the evolutionary history of the three most common Dca promoter alleles (Dca237-1, Dca237-2, and Dca247) and showed that the insertion allele (Dca247), whose frequency increases with latitude, is associated with larger wing centroid size and higher average cell number in male flies. Finally, we showed that the overall linkage disequilibrium (LD) was low in the Dca promoter and that the insertion/deletion polymorphism that defines the Dca alleles was in strong LD with two other upstream sites. Our results provide strong support that Dca is a candidate for climatic adaptation in D. melanogaster.
Superficial Venous Thrombosis and Venous Thromboembolism
Authors: Hervé Decousus
Journal: Annals of Internal Medicine (2010)

Background: Superficial venous thrombosis (SVT) is perceived to have a benign prognosis. Objective: To assess the prevalence of venous thromboembolism in patients with SVT and to determine the 3-month incidence of thromboembolic complications. Design: National cross-sectional and prospective epidemiologic cohort study. (ClinicalTrials.gov registration number: NCT00818688) Setting: French office- and hospital-based vascular medicine specialists. Patients: 844 consecutive patients with symptomatic SVT of the lower limbs that was at least 5 cm on compression ultrasonography. Measurements: Incidence of venous thromboembolism and extension or recurrence of SVT in patients with isolated SVT at presentation. Results: Among 844 patients with SVT at inclusion (median age, 65 years; 547 women), 210 (24.9%) also had deep venous thrombosis (DVT) or symptomatic pulmonary embolism. Among 600 patients without DVT or pulmonary embolism at inclusion who were eligible for 3-month follow-up, 58 (10.2%) developed thromboembolic complications at 3 months (pulmonary embolism, 3 [0.5%]; DVT, 15 [2.8%]; extension of SVT, 18 [3.3%]; and recurrence of SVT, 10 [1.9%]), despite 540 patients (90.5%) having received anticoagulants. Risk factors for complications at 3 months were male sex, history of DVT or pulmonary embolism, previous cancer, and absence of varicose veins. Limitation: The findings are from a specialist referral setting, and the study was terminated before the target patient population was reached because of slow recruitment. Conclusion: A substantial number of patients with SVT exhibit venous thromboembolism at presentation, and some that do not can develop this complication in the subsequent 3 months. Primary Funding Source: GlaxoSmithKline, sanofi-aventis, and the Ministère Français de la Santé et des Sports (Programme Hospitalier de Recherche Clinique).
Genetics of Obesity in Humans
Authors: I. Sadaf Farooqi, Stephen O’Rahilly
Journal: Endocrine Reviews (2006)

Considerable attention has focused on deciphering the hypothalamic pathways that mediate the behavioral and metabolic effects of leptin. We and others have identified several single gene defects that disrupt the molecules in the leptin-melanocortin pathway causing severe obesity in humans. In this review, we consider these human monogenic obesity syndromes and discuss how far the characterization of these patients has informed our understanding of the physiological role of leptin and the melanocortins in the regulation of human body weight and neuroendocrine function.
Defibrillator Versus β-Blockers for Unexplained Death in Thailand (DEBUT)
Authors: Koonlawee Nademanee, Gumpanart Veerakul, Morton Mower, Khanchit Likittanasombat, Rungroj Krittayapong, Kiertijai Bhuripanyo, Surapun Sitthisook, Lertlak Chaothawee, Mei Ying Lai, Stanley P. Azen
Journal: Circulation (2003)

Sudden Unexplained Death Syndrome (SUDS) is the leading cause of death in young, healthy, Southeast Asian men. The role of an implantable cardioverter defibrillator (ICD) for mortality reduction in these patients remains unclear.The Defibrillator Versus beta-Blockers for Unexplained Death in Thailand (DEBUT) study is a randomized, clinical trial conducted in 2 phases (pilot study followed by the main trial) to compare the annual all-cause mortality rates among SUDS patients treated with beta-blockers versus that among those treated with an ICD. A total of 86 patients who were SUDS survivors and probable SUDS survivors were randomized to receive an ICD or propranolol (20 patients were in the pilot study and 66 were in the main trial). The primary end point was death from all causes. The secondary end point was recurrent ventricular tachycardia/ventricular fibrillation (VF) or cardiac arrest. During the 3-year follow-up period of the main trial, there were 4 deaths; all occurred in the beta-blocker group (P=0.02). Seven subjects in the ICD arm had recurrent VF, and all were effectively treated by the ICD. On the basis of the main trial results, the Data Safety Monitoring Board stopped the study. In total (both from the Pilot study and the main trial), there were 7 deaths (18%) in the beta-blocker group and no deaths in the ICD group, but there were a total of 12 ICD patients receiving ICD discharges due to recurrent VF.ICD treatment provides full protection from death related to primary VF in a SUDS population and is superior to beta-blockade treatment.