tbuckley/cabot-search huggingface dataset:
Roles of Circadian Rhythmicity and Sleep in Human Glucose Regulation*
Authors: Eve Van Cauter, Kenneth S. Polonsky, André J. Scheen
Journal: Endocrine Reviews (1997)

Causal Mechanisms of 24-h Rhythms of Glucose Regulation in Normal Young Subjects A. 24-h variations in glucose tolerance B. Causal mechanisms III.Alterations of 24-h Rhythms of Glucose Regulation in Normal Aging A. Daytime variations in glucose tolerance B. Nighttime variations in glucose tolerance C. Respective roles of sleep and time of day D. Significance and clinical implications IV.Diurnal Variations of Glucose Regulation in Obesity A. Daytime variations in glucose tolerance B. Nighttime variations in glucose tolerance C. Significance and clinical implications V. Alterations in 24-h Rhythmicity of Glucose Regulation in Non-Insulin-Dependent Diabetes Mellitus (NIDDM) A. Alterations in daytime variations in glucose tolerance B. Alterations in nighttime variations in glucose levels during fasting C. Significance and clinical implications VI
Five Hundred Cases of Myalgia in the British Army
Authors: M. Good
Journal: Annals of the Rheumatic Diseases (1942)

JUDGING by textbooks muscular diseases are very uncommon, but this is hardly in harmony with the fact that the musculature -the active locomotor apparatus-is the largest organ of the body.According to Sir Colin Mackenzie (1930) the animal body contains not less than 434 muscles, which constitute about 45 per cent. of the total weight, and the musculature con- tains about one-third of the total blood (R.J. S. McDowall, 1938).Further, one has to bear in mind that the muscles are subject for the greater part of the day to wear and tear, and from a purely theoretical point of view the muscles may be expected to be very liable to disease.Muscular diseases are very frequent indeed, but their recognition has been delayed probably owing to the fact that they give rise to referred or heterotopic (D.Waterston) pain.This fundamental fact regarding muscle physiology has been studied very recently-experimentally (Sir Thomas Lewis and I. H. Kellgren, 1938) and clinically (Good, 1938).The commonest muscular disease is myalgia, and is present in and responsible for pain complained of by the vast majority of people suffering from what is generally called rheumatism, and in a number of other minor diseases.Myalgia is a disease, the cardinal symptom of which is pain associated with more or less disturbance of function.Since the disturbance of function- e.g., locomotion-is solely due to pain, which is aggravated by contraction of the affected muscle or muscles, myalgia may be looked upon as the prototype of the disease of pain (La maladie de la douleur, R. Leriche, 1932).In.such conditions pain is the outstanding symptom, but it is a subjective phenomenon; local tenderness, too, is solely sub- jective.Experience has shown that there exist normosensitive, hypersensitive-and hyposensitive individuals or patients with regard to pain, indicating that the threshold of pain differs individually.In the case of myalgia the diagnosis can be based on objective phenomena.DErinmoN.-Myalgia is a muscular disease localised in well- definable parts of a muscle and in its appendages-tendon, 118 by copyright.
Acquired Resistance of Non–Small Cell Lung Cancer Cells to MET Kinase Inhibition Is Mediated by a Switch to Epidermal Growth Factor Receptor Dependency
Authors: Ultan McDermott, Raju V. Pusapati, James G. Christensen, Nathanael S. Gray, Jeff Settleman
Journal: Cancer Research (2010)

Abstract Cancer cells harboring MET amplification display striking sensitivity to selective small molecule inhibitors of MET kinase, prompting their clinical evaluation. Similar to the experience with traditional therapeutics, most patients responding to treatment with such molecular targeted therapeutics ultimately relapse with drug-resistant disease. In this study we modeled acquired resistance to experimental MET kinase inhibitor PF2341066 in MET-amplified non–small cell lung carcinoma (NSCLC) cell lines to identify drug resistance mechanisms that may arise in clinic. We found that activation of the epidermal growth factor receptor (EGFR) pathway emerges as a resistance mechanism in MET-amplified cells after prolonged exposure to PF2341066. Whereas combined inhibition of MET and EGFR kinases in MET-dependent NSCLC cells did not enhance their initial sensitivity to PF2341066, this combination dramatically suppressed the eventual emergence of drug-resistant clones after prolonged drug exposure. Conversely, activation of the EGFR pathway increased the yield of PF2341066-resistant clones, confirming the significance of this pathway in conferring resistance. Our findings support an intimate relationship between the EGFR and MET signaling pathways in NSCLC, and they suggest that combination treatment with MET and EGFR kinase inhibitors may be beneficial in MET-amplified NSCLC by reducing selection for drug resistant clones. Cancer Res; 70(4); 1625–34
Imaging of tophaceous gout: computed tomography provides specific images compared with magnetic resonance imaging and ultrasonography
Authors: J C Gerster
Journal: Annals of the Rheumatic Diseases (2002)

<h3>Abstract</h3> The SARS-CoV-2 Omicron/BA.1 lineage emerged in late 2021 and rapidly displaced the Delta variant before being overtaken itself globally by, the Omicron/BA.2 lineage in early 2022. Here, we describe how Omicron BA.1 and BA.2 show a lower severity phenotype in a hamster model of pathogenicity which maps specifically to the spike gene. We further show that Omicron is attenuated in a lung cell line but replicates more rapidly, albeit to lower peak titres, in human primary nasal cells. This replication phenotype also maps to the spike gene. Omicron spike (including the emerging Omicron lineage BA.4) shows attenuated fusogenicity and a preference for cell entry via the endosomal route. We map the altered Omicron spike entry route and partially map the lower fusogenicity to the S2 domain, particularly the substitution N969K. Finally, we show that pseudovirus with Omicron spike, engineered in the S2 domain to confer a more Delta-like cell entry route retains the antigenic properties of Omicron. This shows a distinct separation between the genetic determinants of these two key Omicron phenotypes, raising the concerning possibility that future variants with large antigenic distance from currently circulating and vaccine strains will not necessarily display the lower intrinsic severity seen during Omicron infection.
Possible Mechanism(s) of Arachidonic Acid–Induced Intracellular Acidosis in Rat Cardiac Myocytes
Authors: Mei-Lin Wu, Chih-Chiang Chan, Ming-Ja Su
Journal: Circulation Research (2000)

Abstract —Arachidonic acid (AA) and other nonesterified fatty acids (FAs) have been shown to exert harmful effects during cardiac ischemia. By continuously measuring intracellular pH (pH i ) changes in neonatal and adult cardiac myocytes, we have found, for the first time, that 10 μmol/L AA induces a substantial intracellular acidosis (0.3 to 0.4 pH units). We have ruled out the possibilities that the AA-induced acidosis is caused by (1) inhibition or stimulation of the pH i regulators, (2) protein kinase C activation or the generation of AA metabolites or free radicals, or (3) activation of NADPH oxidase or an inward H + current. The AA-induced acidosis fits to a simple diffusion mechanism, as proposed by Kamp and Hamilton (flip-flop model) for artificial phospholipid bilayers. The important properties found in the cardiac myocyte are that (1) the initial rate of acid flux (J H ) increases with the AA concentration (2 to 50 μmol/L), (2) FAs with a − COOH group (eg, AA, oleic acid, and linoleic acid) induce intracellular acidification, but FAs with a − COOCH 3 group (eg, AA methyl ester) have little effect on the pH i , (3) tetradecylamine (FA amine) induces intracellular alkalosis, and, most importantly, (4) both the AA- and tetradecylamine-induced pH i changes can be reversed by 0.3% BSA. Because a low concentration of AA (10 μmol/L) can induce a substantial acidosis, the possible involvement of the FA-evoked acidosis in the negative inotropic effect during cardiac ischemia is discussed. The full text of this article is available at http://www.circresaha.org.
Observations on THE TREATMENT OF SCOLIOSIS
Authors: D. M. Aitken
Journal: BMJ (1929)

TlE; treatmient of scoliosis is; the subject ot ouir discuvssion to-day.I should have pi-eferred tlhie title to be the lpitictilAes of treatmenit," :and r-popose to (ilate rather oil thlis aspect, leaving otitel-to 6,fill iii gaps;.scoliosis hlas beenl olle of tlte most difficldt problems in ortolpaedic ptactice; fromii the beginning.Different authoritiCs proclaimi the mierits of their own imetlhods, anid 1 feat-voltt Will say I amii nio better taunt the others.I canotit, lioeti C-er, honestly set tlhe subje(t before this imeet- ilug uiless I endea-otur to l)roseltt it as I .see it anid, as I have (iseoveted it for muvself in p)ractice. 1trustn, Ihowever, th,at I shall be able to slhowv tlha:t all (leplendIs oni followingo tieftitite funiidamental principles based 01I soustind anid estab- lislhed rules of anatomy ain(t physiology.If sounld basic llricpil)les can be estalblisc(led, any treatlnel ti0hich is in agreement wiitlh tlhemii cannl]ot be fiar wrono-g, and any tr'eat- Imlenit w-hiielh clashes wi-itlh thIeimi calls for a revision eitlier of
Metabolic vasodilation in the human forearm is preserved in hypercholesterolemia despite impairment of endothelium-dependent and independent vasodilation
Authors: S Duffy
Journal: Cardiovascular Research (1999)

Objective: Hypercholesterolemia has been shown to impair endothelium-mediated, nitric oxide (NO)-dependent responses to acetylcholine (ACh), serotonin, substance P and flow-mediated dilation. We have recently shown that NO contributes to metabolic vasodilation in the human forearm. We sought to determine whether metabolic vasodilation is impaired in healthy subjects with hypercholesterolemia. Methods: We compared the forearm blood flow (FBF) responses to isotonic exercise, ACh and the endothelium-independent vasodilator sodium nitroprusside in young, otherwise healthy volunteers with hypercholesterolemia and controls before and after the NO inhibitor NG-monomethyl-l-arginine (l-NMMA). FBF was measured using venous occlusion plethysmography. Hypercholesterolemic (n=20) and control (n=20) subjects were age- and gender-matched. Results: Total cholesterol (6.9±0.3 vs. 4.6±0.1 mmol/l, P<0.0001), low density lipoprotein (4.9±0.4 vs. 2.7±0.1 mmol/l, P<0.001) and triglyceride (1.3±0.2 vs. 0.8±0.1 mmol/l, P=0.005) levels were higher in the hypercholesterolemic group. Basal FBF and resistance were similar in the two groups. Hypercholesterolemia impaired the peak FBF response to ACh (11.1±1.9 vs. 17.6±2.2 ml/100 ml/min, P=0.03), and reduced the peak response to sodium nitroprusside (6.0±0.4 vs. 8.1±0.6 ml/100 ml/min, P<0.01). However, hypercholesterolemia did not affect peak hyperemic FBF (13.1±1.0 vs. 13.2±1.0 ml/100 ml/min, P=1.0) or the FBF volume repayment during the 1 or 5 min after exercise. Resting FBF was reduced by l-NMMA to a similar degree (by 33% vs. 40%, P=0.17) in both groups. Although l-NMMA reduced peak hyperemic FBF (by 16% vs. 17%, P=0.93) and the volume repaid after exercise in both groups, there were no differences between the two groups. Conclusions: Exercise-induced metabolic vasodilation is in part dependent on NO release. Hypercholesterolemia impairs NO-mediated vasodilation, but is not associated with a reduction in exercise-induced hyperemia. This may indicate that multiple compensatory mechanisms are operative in skeletal muscle metabolic vasodilation.
Comparative Analysis of Plant and Animal Calcium Signal Transduction Element Using Plant Full-Length cDNA Data
Authors: Toshifumi Nagata, Shigemi Iizumi, Kouji Satoh, Hisako Ooka, Jun Kawai, Piero Carninci, Yoshihide Hayashizaki, Yasuhiro Otomo, Kazuo Murakami, Kenichi Matsubara, Shoshi Kikuchi
Journal: Molecular Biology and Evolution (2004)

We obtained 32K full-length cDNA sequence data from the rice full-length cDNA project and performed a homology search against NCBI GenBank data. We have also searched homologs of Arabidopsis and other plants' genes with the databases. Comparative analysis of calcium ion transport proteins revealed that the genes specific for muscle and nerve calcium signal transduction systems (VDCC, IP3 receptor, ryanodine receptor) are very different in animals and plants. In contrast, Ca elements with basic functions in cell responses (CNGC, iGlu receptor, Ca2+ATPase, Ca2+/Na+ -K+ ion exchanger) are basically conserved between plants and animals. We also performed comparative analyses of calcium ion binding and/or controlling signal transduction proteins. Many genes specific for muscle and nerve tissue do not exist in plants. However, calcium ion signal transduction genes of basic functions of cell homeostasis and responses were well conserved; plants have developed a calcium ion interacting system that is more direct than in animals. Many species of plants have specifically modified calcium ion binding proteins (CPK, CRK), Ca2+/phospholipid-binding domains, and calcium storage proteins.
Is the <i>tidal wave</i> necessary? Is it likely?
Authors: Martin Garwicz, Gert Andersson
Journal: Behavioral and Brain Sciences (1997)

The main assumptions on which the tidal wave hypothesis rests will be questioned. First, since focal synchronous mossy fibre input is sufficient to ensure spread of activity along the parallel fibres, the tidal wave is redundant. Second, spatial and temporal characteristics of mossy fibre input make spatio-temporal sequences appropriate for setting up a tidal wave unlikely in the behaving animal.
Development of fetal thymocytes in organ cultures. Effect of interleukin 2.
Authors: M Skinner, G Le Gros, J Marbrook, J D Watson
Journal: The Journal of Experimental Medicine (1987)

Most fetal thymocytes from 14-d mouse embryos are Thy-1+, L3T4-, Ly-2-, and express the receptor for interleukin 2 (IL-2). The development of thymocytes has been followed in fetal thymus organ cultures. When fetal thymus from 14-d embryos were cultured for a 6-d period, thymocytes increased in number 20-40-fold, and 95% became Thy-1+, L3T4+, Ly-2+. The addition of IL-2 to organ cultures of 14-d fetal thymus inhibited, in a dose-dependent manner, cell proliferation and the appearance of Thy-1+, L3T4+, Ly-2+ thymocytes. The addition of IL-2 also resulted in the appearance of a population of cells that were cytotoxic for syngeneic and allogeneic fetal thymocytes and syngeneic tumour targets. While the events that lead to the expression of the IL-2 receptor on 14-d fetal thymocytes are unknown, IL-2 in fetal thymus organ cultures inhibits the normal maturation of fetal thymocytes and raises the question of whether the cytotoxic cells that appear reflect selection through an alternative pathway of development.
Reduced larger von Willebrand factor multimers at dawn in OSA plasmas reflect severity of apnoeic episodes
Authors: Noriko Koyama, Masanori Matsumoto, Shinji Tamaki, Masanori Yoshikawa, Yoshihiro Fujimura, Hiroshi Kimura
Journal: European Respiratory Journal (2012)

Plasma von Willebrand factor (VWF), produced in and released from vascular endothelial cells by various stimuli including hypoxia, induces platelet aggregation under high shear stress and plays dual pivotal roles in haemostasis and thrombosis within arterioles, which are regulated by the size of vWF multimers (VWFMs). Patients with obstructive sleep apnoea (OSA) have increased risk of thrombotic cardiovascular events, but the pathogenesis is unclear. We examined the relationship between VWF and OSA by measuring VWF antigen (VWF:Ag), VWFMs, VWF collagen binding activity (VWF:CB) and a disintegrin-like, metalloproteinase, and thrombospiondin type 1 motifs 13. A total of 58 OSA patients were enrolled. Blood samples were collected before sleep, after sleep, and after one night of nasal continuous positive airway pressure therapy. Based on VWFM analysis, OSA patients were classified into three groups; consistently normal VWFMs (group 1, n=29), increased high molecular weight (HMW)-VWFMs at 06:00 h (group 2, n=18), and decreased or absent HMW-VWFMs at 06:00 h (group 3, n=11). Patients in group 3 had significantly worse apnoea/hypopnoea index; VWF:CB followed a similar pattern. We observed a significant decrease in platelet count between 21:00 h and 06:00 h in OSA patients, potentially associated with reduced larger VWFMs together with decreased VWF:Ag levels. Severe OSA may contribute to an arterial pro-thrombotic state.
Role of the Increase in p21 in Cisplatin-Induced Acute Renal Failure in Rats
Authors: TAKEHIKO MIYAJI, AKIHIKO KATO, HIDEO YASUDA, YOSHIHIDE FUJIGAKI, AKIRA HISHIDA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The goal of this study was to clarify the role of p21, a cyclin-dependent kinase inhibitor, in acute renal failure (ARF). This was accomplished with the examination of the renal expression of p21 in cisplatin (CDDP)-induced ARF and in rechallenge injury with CDDP. The injection of CDDP (5 mg/kg) into rats induced increases in serum creatinine and tubular damage and the number of in situ DNA nick end labeling—positive cells, which peaked at day 5, followed by recovery to control levels by day 14. The rechallenge with the same dose of CDDP 14 d after the first dose of CDDP induced significantly less injury and no significant increase in in situ DNA nick end labeling—positive cells. The first CDDP dose significantly increased p53-positive nuclei at day 1, which disappeared by day 5, and the number of p21-positive nuclei, which had two peaks on days 3 and 9. The number of proliferating cell nuclear antigen (PCNA)-positive nuclei peaked at days 3 and 12. A significant increase in the incorporation of 5-bromo 2′-deoxyuridine (BrdU) was found at day 5 and peaked at day 7. The second injection of CDDP induced significant increases in the number of p21-, p53-, and PCNA-positive nuclei within 2 d but did not affect the incorporation of BrdU. These findings suggested that ( 1 ) CDDP induced two peaks of the increase in p21; ( 2 ) the first peak occurred shortly after CDDP and was accompanied by overexpression of p53 and PCNA but not with BrdU incorporation, possibly reflecting G1 arrest and DNA repair; ( 3 ) the second peak of p21 occurred through an p53-independent pathway and may contribute to cell differentiation; and ( 4 ) the overexpression of p21 and PCNA in rechallenge injury may contribute to acquired resistance in CDDP-induced ARF via enhanced DNA repair.
EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases
Authors: S van Assen, N Agmon-Levin, O Elkayam, R Cervera, M F Doran, M Dougados, P Emery, P Geborek, J P A Ioannidis, D R W Jayne, C G M Kallenberg, U Müller-Ladner, Y Shoenfeld, L Stojanovich, G Valesini, N M Wulffraat, M Bijl
Journal: Annals of the Rheumatic Diseases (2010)

To develop evidence-based European League Against Rheumatism (EULAR) recommendations for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD).A EULAR task force was composed of experts representing 11 European countries, consisting of eight rheumatologists, four clinical immunologists, one rheumatologist/clinical immunologist, one infectious disease physician, one nephrologist, one paediatrician/rheumatologist and one clinical epidemiologist. Key questions were formulated and the eligible spectrum of AIIRD, immunosuppressive drugs and vaccines were defined in order to perform a systematic literature review. A search was made of Medline from 1966 to October 2009 as well as abstracts from the EULAR meetings of 2008 and 2009 and the American College of Rheumatology (ACR) meetings of 2007 and 2008. Evidence was graded in categories I-IV, the strength of recommendations was graded in categories A-D and Delphi voting was applied to determine the level of agreement between the experts of the task force.Eight key questions and 13 recommendations addressing vaccination in patients with AIIRD were formulated. The strength of each recommendation was determined. Delphi voting revealed a very high level of agreement with the recommendations among the experts of the task force. Finally, a research agenda was proposed.Recommendations for vaccination in patients with AIIRD based on the currently available evidence and expert opinion were formulated. More research is needed, particularly regarding the incidence of vaccine-preventable infectious diseases and the safety of vaccination in patients with AIIRD.
HSP90 inhibitor, celastrol, arrests human monocytic leukemia cell U937 at G0/G1 in thiol-containing agents reversible way
Authors: Bin Peng, Limin Xu, Fanfan Cao, Tingxuan Wei, Chunxin Yang, Georges Uzan, Denghai Zhang
Journal: Molecular Cancer (2010)

Abstract Background Because some of heat shock protein 90's (HSP90) clients are key cell cycle regulators, HSP90 inhibition can affect the cell cycle. Recently, celastrol is identified both as a novel inhibitor of HSP90 and as a potential anti-tumor agent. However, this agent's effects on the cell cycle are rarely investigated. In this study, we observed the effects of celastrol on the human monocytic leukemia cell line U937 cell cycle. Results Celastrol affected the proliferation of U937 in a dose-dependent way, arresting the cell cycle at G0/G1 with 400 nM doses and triggering cell death with doses above 1000 nM. Cell cycle arrest was accompanied by inhibition of HSP90 ATPase activity and elevation in HSP70 levels (a biochemical hallmark of HSP90 inhibition), a reduction in Cyclin D1, Cdk4 and Cdk6 levels, and a disruption of the HSP90/Cdc37/Cdk4 complex. The observed effects of celastrol on the U937 cell cycle were thiol-related, firstly because the effects could be countered by pre-loading thiol-containing agents and secondly because celastrol and thiol-containing agents could react with each other to form new compounds. Conclusions Our results disclose a novel action of celastrol-- causing cell cycle arrest at G0/G1 phase based upon thiol-related HSP90 inhibition. Our work suggests celastrol's potential in tumor and monocyte-related disease management.
Inferior capsular shift operation for multidirectional instability of the shoulder in players of contact sports
Authors: C-H Choi, D J Ogilvie-Harris
Journal: British Journal of Sports Medicine (2002)

To assess the results of inferior capsular shift for multidirectional instability of the shoulder in athletes.Multidirectional instability was surgically corrected in 53 shoulders in 47 athletes who engaged in contact sports. A history of major trauma was found in eight patients, the others having had minor episodes. Before surgery, all patients had complex combinations of instabilities. The surgical approach was selected according to the predominant direction of instability.Anterior inferior capsular shift was carried out in 37 shoulders, and anterior dislocation recurred in three. In one of these, it was anterior alone, one was anterior and inferior, and one was unstable in all three directions. After posterior inferior capsular shift in 16 shoulders, one dislocation occurred anteriorly and one posteriorly. With the anterior approach, four athletes could not return to sport. Two patients treated with the posterior approach could not return to sport. Of these six failures, five patients had had bilateral repairs. Successful repair based on the criteria of the American Shoulder and Elbow Association was achieved in 92% of anterior repairs and 81% of posterior repairs. Successful return to sport was noted in 82% of patients with anterior repairs, 75% with posterior repairs, and 17% with bilateral repairs. Overall, there were five subsequent dislocations, three in the anterior repair group (8%), and two in the posterior repair group (12%).Inferior capsular shift can successfully correct multidirectional instability in most players of contact sports, but the results in bilateral cases are poor.