tbuckley/cabot-search huggingface dataset:
Inflammatory disease and its control in rheumatic disorders.
Authors: F D Hart
Journal: BMJ (1975)

Inflammation is a central and essential component in most forms of arthritis-for instance, rheumatoid arthritis, acute gout, Reiter's disease, and even osteoarthrosis.The inflammatory changes are different in these various disorders.The underlying pathological processes produce entirely different changes in the body and the resulting clinical syndromes are entirely dissimilar.It follows that attempts to control the inflamnmatory changes have different effects on the different rheumatic disorders.Let us take four different rheumatic disorders-gout, ankylosing spondylitis, rheumatoid arthritis, and polymyalgia arteritica-and discuss what part inflammation plays in their symptomatology.In none does inflammation seem to have any useful function.With all due respect to mother nature the inflammatory process she puts there, presumably to perform some useful function initially, is now the disease itself in greater or lesser degree.It is inflammation that causes the local joint pain, tenderness, swelling, and stiffness and also the systemic illness that goes with it.In attempting to suppress this inflamma- tion we are doing nothing but good unless bacteria are present in the tissues.So had we a perfect non-toxic and highly effective anti-inflammatory agent, by suppressing inflammatory change we would eliminate much of the pain, swelling, stiffness, tenderness, and disability in many rheumatic disorders, even if we did not cure the disease. GoutThere is general agreement today that the intense discomfort of acute gout is due to deposition of crystals of monosodium urate in the tissues, which sets up an intense and acute inflammatory reaction.Seegmiller and Howell' suggested that three requirements were necessary for an acute attack of gout: (a) deposition in the tissues of crystals of monosodium urate; (b) development of an inflammatory
A molecular compendium of genes expressed in multiple myeloma
Authors: Jaime O. Claudio, Esther Masih-Khan, Hongchang Tang, Jason Gonçalves, Michael Voralia, Zhi Hua Li, Vincent Nadeem, Eva Cukerman, Ofelia Francisco-Pabalan, Choong Chin Liew, James R. Woodgett, A. Keith Stewart
Journal: Blood (2002)
Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways
Authors: Ivan G. Gomez, Deidre A. MacKenna, Bryce G. Johnson, Vivek Kaimal, Allie M. Roach, Shuyu Ren, Naoki Nakagawa, Cuiyan Xin, Rick Newitt, Shweta Pandya, Tai-He Xia, Xueqing Liu, Dorin-Bogdan Borza, Monica Grafals, Stuart J. Shankland, Jonathan Himmelfarb, Didier Portilla, Shiguang Liu, B. Nelson Chau, Jeremy S. Duffield
Journal: Journal of Clinical Investigation (2014)

MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously and evaluated the therapeutic potential of these anti-miR-21 oligonucleotides in chronic kidney disease. In a murine model of Alport nephropathy, miR-21 silencing did not produce any adverse effects and resulted in substantially milder kidney disease, with minimal albuminuria and dysfunction, compared with vehicle-treated mice. miR-21 silencing dramatically improved survival of Alport mice and reduced histological end points, including glomerulosclerosis, interstitial fibrosis, tubular injury, and inflammation. Anti-miR-21 enhanced PPARα/retinoid X receptor (PPARα/RXR) activity and downstream signaling pathways in glomerular, tubular, and interstitial cells. Moreover, miR-21 silencing enhanced mitochondrial function, which reduced mitochondrial ROS production and thus preserved tubular functions. Inhibition of miR-21 was protective against TGF-β-induced fibrogenesis and inflammation in glomerular and interstitial cells, likely as the result of enhanced PPARα/RXR activity and improved mitochondrial function. Together, these results demonstrate that inhibition of miR-21 represents a potential therapeutic strategy for chronic kidney diseases including Alport nephropathy.
Short Telomeres: A Novel Potential Predictor of Relapse in Ewing Sarcoma
Authors: Smadar Avigad, Inna Naumov, Anat Ohali, Marta Jeison, Gili Halevy Berco, Jacques Mardoukh, Batia Stark, Shifra Ash, Ian J. Cohen, Isaac Meller, Yehuda Kollender, Josephine Issakov, Isaac Yaniv
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Despite advances in therapy, &amp;gt;50% of patients with Ewing sarcoma will relapse. The current prognostic factors are not optimal for risk prediction. Studies have shown that telomere length could predict outcome in different malignancies. Our aim was to evaluate whether telomere length could be a better prognostic factor in Ewing sarcoma and correlate the results with clinical variables, outcome, and chromosomal instability. Experimental Design: Telomere length was determined in the primary tumor and peripheral blood of 32 patients with Ewing sarcoma. Chromosomal instability was evaluated by combining classical cytogenetics, comparative genomic hybridization and random aneuploidy. Telomere length was correlated to clinical variables, chromosomal instability, and outcome. Results: In 75% of the tumors, changes in telomere length, when compared with the corresponding peripheral blood lymphocytes, were noted. The majority of changes consisted of a reduction in telomere length. Patients harboring shorter telomeres had a significantly adverse outcome (P = 0.015). Chromosomal instability was identified in 65% of tumors, significantly correlating with short telomeres (P = 0.0094). Using multivariate analysis, telomere length remained the only significant prognostic variable (P = 0.034). Patients with short telomeres had a 5.3-fold risk of relapse as compared to those with unchanged or longer telomeres. Conclusion: We have shown that tumors with telomere length reduction result in genomic instability. In addition, telomere length reduction was the only significant predictor of outcome. We suggest that reduction of telomere length in tumor cells at diagnosis could serve as a prognostic marker in Ewing sarcoma.
Insulin-like Growth Factor-1 but Not Growth Hormone Augments Mammalian Myocardial Contractility by Sensitizing the Myofilament to Ca <sup>2+</sup> Through a Wortmannin-Sensitive Pathway
Authors: Antonio Cittadini, Yoshiki Ishiguro, Hinrik Strömer, Matthias Spindler, Alan C. Moses, Ross Clark, Pamela S. Douglas, Joanne S. Ingwall, James P. Morgan
Journal: Circulation Research (1998)

Abstract —A growing body of evidence has been accumulated recently suggesting that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) affect cardiac function, but their mechanism(s) of action is unclear. In the present study, GH and IGF-1 were administered to isolated isovolumic aequorin-loaded rat whole hearts and ferret papillary muscles. Although GH had no effect on the indices of cardiac function, IGF-1 increased isovolumic developed pressure by 24% above baseline. The aequorin transients were abbreviated and demonstrated decreased amplitude. The positive inotropic effects of IGF-1 were not associated with increased intracellular Ca 2+ availability to the contractile machinery but to a significant increase of myofilament Ca 2+ sensitivity. Accordingly, the Ca 2+ -force relationship obtained under steady-state conditions in tetanized muscle was shifted significantly to the left (EC 50 , 0.44±0.02 versus 0.52±0.03 μmol/L with and without IGF-1 in the perfusate, respectively; P &lt;0.05); maximal Ca 2+ -activated tetanic pressure was increased significantly by 12% (211±3 versus 235±2 mm Hg in controls and IGF-1–treated hearts, respectively; P &lt;0.01). The positive inotropic actions of IGF-1 were not associated with changes in either pH i or high-energy phosphate content, as assessed by 31 P nuclear magnetic resonance spectroscopy, and were blocked by the phosphatidylinositol 3-kinase inhibitor wortmannin. Concomitant administration of IGF binding protein-3 blocked IGF-1–positive inotropic action in ferret papillary muscles. In conclusion, IGF-1 is an endogenous peptide that through a wortmannin-sensitive pathway displays distinct positive inotropic properties by sensitizing the myofilaments to Ca 2+ without increasing myocyte [Ca 2+ ] i .
Evolution of Percutaneous Coronary Intervention in Patients with Diabetes
Authors: Jamal S. Rana, Lakshmi Venkitachalam, Faith Selzer, Suresh R. Mulukutla, Oscar C. Marroquin, Warren K. Laskey, Elizabeth M. Holper, Vankeepuram S. Srinivas, Kevin E. Kip, Sheryl F. Kelsey, Richard W. Nesto
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate the association of successive percutaneous coronary intervention (PCI) modalities with balloon angioplasty (BA), bare-metal stent (BMS), drug-eluting stents (DES), and pharmacotherapy over the last 3 decades with outcomes among patients with diabetes in routine clinical practice. RESEARCH DESIGN AND METHODS We examined outcomes in 1,846 patients with diabetes undergoing de novo PCI in the multicenter, National Heart, Lung, and Blood Institute–sponsored 1985–1986 Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry and 1997–2006 Dynamic Registry. Multivariable Cox regression models were used to estimate the adjusted risk of events (death/myocardial infarction [MI], repeat revascularization) over 1 year. RESULTS Cumulative event rates for postdischarge (31–365 days) death/MI were 8% by BA, 7% by BMS, and 7% by DES use (P = 0.76) and for repeat revascularization were 19, 13, and 9% (P &amp;lt; 0.001), respectively. Multivariable analysis showed a significantly lower risk of repeat revascularization with DES use when compared with the use of BA (hazard ratio [HR] 0.41 [95% CI 0.29–0.58]) and BMS (HR 0.55 [95% CI 0.39–0.76]). After further adjustment for discharge medications, the lower risk for death/MI was not statistically significant for DES when compared with BA. CONCLUSIONS In patients with diabetes undergoing PCI, the use of DES is associated with a reduced need for repeat revascularization when compared with BA or BMS use. The associated death/MI benefit observed with the DES versus the BA group may well be due to greater use of pharmacotherapy.
Long‐term prognosis of medically treated patients with functional mitral regurgitation and left ventricular dysfunction
Authors: Eustachio Agricola, Alfonso Ielasi, Michele Oppizzi, Pompilio Faggiano, Luca Ferri, Alice Calabrese, Enrico Vizzardi, Ottavio Alfieri, Alberto Margonato
Journal: European Journal of Heart Failure (2009)
Vasopeptidase Inhibition Affords Greater Renoprotection than Angiotensin-Converting Enzyme Inhibition Alone
Authors: MAARTEN W. TAAL, VESSELIN D. NENOV, WAICHI WONG, SHARAD R. SATYAL, OLGA SAKHAROVA, JEONG HOON CHOI, JULIA L. TROY, BARRY M. BRENNER
Journal: Journal of the American Society of Nephrology (2001)

The renoprotective efficacy of the vasopeptidase inhibitor omapatrilat (OMA) was compared with that of enalapril (ENA) in male Munich-Wistar rats subjected to 5/6 nephrectomy. ENA and OMA administered beginning on day 2 after surgery were equally effective in normalizing systolic BP (SBP) and preventing glomerulosclerosis (GS) for 12 wk. Micropuncture studies of rats performed using a similar treatment protocol demonstrated greater reduction of glomerular capillary hydraulic pressure with OMA than with ENA, at similar mean arterial pressures. To investigate whether these glomerular hemodynamic differences might be associated with differences in chronic renoprotective efficacy, additional rats were included in a protocol in which treatment was delayed until 4 wk after surgery (after the onset of hypertension and proteinuria) and continued for a longer period. Both treatments normalized SBP, but OMA resulted in more sustained reduction of proteinuria than did ENA. At week 20, OMA- and ENA-treated rats exhibited less GS than did untreated (control) rats at week 12, but only the difference in control versus OMA values was statistically significant [GS scores: control (12 wk), 36 ± 4%; ENA (20 wk), 22 ± 6%; OMA (20 wk), 14 ± 2%]. The remaining ENA-treated rats were euthanized at 32 wk because of rapidly increasing proteinuria, whereas the remaining OMA-treated rats demonstrated a substantially slower increase in proteinuria until euthanasia at 50 wk. At this extremely late time point, OMA-treated rats exhibited GS scores similar to those of ENA-treated rats at 32 wk and control rats at 12 wk [GS scores: ENA (32 wk), 34 ± 5%; OMA (50 wk), 38 ± 8%]. It is concluded that, in this model, OMA affords greater long-term renoprotection than ENA when doses are adjusted to yield equivalent control of SBP.
Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production
Authors: Gail M. Gauvreau, Jeffrey M. Harris, Louis-Philippe Boulet, Heleen Scheerens, J. Mark Fitzgerald, Wendy S. Putnam, Donald W. Cockcroft, Beth E. Davis, Richard Leigh, Yanan Zheng, Barbro Dahlén, Yehong Wang, Romeo Maciuca, Irvin Mayers, X. Charlene Liao, Lawren C. Wu, John G. Matthews, Paul M. O’Byrne
Journal: Science Translational Medicine (2014)

A humanized monoclonal antibody that targets the membrane IgE B cell receptor was associated with improvements in asthmatic airway responses.
ELECTRON MICROSCOPY OF THE RENAL LESIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS.
Authors: M. S. SABOUR
Journal: British Journal of Dermatology (1966)

Journal Article ELECTRON MICROSCOPY OF THE RENAL LESIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS. Get access M. S. SABOUR, Ph.D., D.M., M.R.C.P., M.R.C.P.E. M. S. SABOUR, Ph.D., D.M., M.R.C.P., M.R.C.P.E. The Fleming Memorial Electron Microscopy Unit for Renal Research, Department of Medicine, Ain‐Shams University, Cairo, Egypt, U.A.R Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 78, Issue 1, 1 January 1966, Pages 43–51, https://doi.org/10.1111/j.1365-2133.1966.tb12132.x Published: 01 January 1966
Apparent absence of BRCA2 protein in a proportion of acute myeloid leukemia cell lines
Authors: F Chen, A L Medhurst, J P de Winter, Q Waisfisz, M A Rooimans, A B Oostra, S Meyer, K J Zhang, B Xia, G Pals, F Arwert, C M Zwaan, H Joenje
Journal: Leukemia (2004)
Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis.
Authors: M Matsuda, H Fujiwara, T Onodera, M Tanaka, D J Wu, T Fujiwara, Y Hamashima, C Kawai
Journal: Circulation (1987)

To assess the importance of contraction band necrosis (CBN) in patients with acute myocardial infarction (AMI) treated with selective intracoronary thrombolysis, CBN, coagulation necrosis, and infarct size (expressed as CBN + coagulation necrosis) were analyzed quantitatively in 16 autopsied hearts. Intracoronary thrombolysis was performed from 2 to 6 hr after the onset of AMI, and the time from the onset of AMI to death was 7 to 168 hr. Cineangiography revealed no evidence of good collateral circulation in any of the patients. The 16 patients were classified into three groups: six patients with successful thrombolysis (100% to 99% stenosis, group I), five patients with unsuccessful thrombolysis (100% to 100%, group II), and five patients with 99% stenosis before thrombolysis (group III). Among the three groups, there were no significant differences in the time from the onset of AMI to thrombolysis, the time from the onset of AMI to death, the cause of death, or the degree of collateral circulation. The percentage of the risk area involved by the infarct in group I (82 +/- 6%) was similar to that in group II (80 +/- 11%). Infarct size was not reduced in group I because collateral circulation was not good and because the degree of recanalization after thrombolysis was 1%. However, the percentage of the infarct area with CBN was significantly higher in group I (20 +/- 9%) then in group II (3 +/- 3%). This finding shows that diffuse CBN occurred after reperfusion in patients with AMI treated with thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial
Authors: Michael Eddleston, Edmund Juszczak, Nick A Buckley, Lalith Senarathna, Fahim Mohamed, Wasantha Dissanayake, Ariyasena Hittarage, Shifa Azher, K Jeganathan, Shaluka Jayamanne, MH Rezvi Sheriff, David A Warrell
Journal: The Lancet (2008)
Hereditary hypotrichosis simplex of the scalp.
Authors: JAIME TORIBIO, PEDRO A. QUINONES
Journal: British Journal of Dermatology (1974)

A peculiar variety of hereditary hypotrichosis is described. The abnormality has affected a large family over the course of eight generations. This genealogy is the fullest so far known of hereditary hypotrichosis. The condition is a hypotrichosis limited to the scalp, which first manifests itself in the early school-years. Afterwards the loss of scalp hair gradually progresses to almost total alopecia. This terminal stage is reached between the ages of 20 and 25 years, and the condition affects males and females in a similar way. From the genetic point of view, the abnormality is transmitted with an autosomal dominant mode of inheritance with full penetrance.
Demonstration of macromolecular inhibitor(s) of calcification and nucleational factor(s) in fluid from calcifying sites in cartilage
Authors: David S. Howell, Julio C. Pita, Juan F. Marquez, Robert A. Gatter
Journal: Journal of Clinical Investigation (1969)

An extracellular fluid phase (C(f1)), aspirated by micropuncture techniques from the hypertrophic cell zone of calcifying epiphyseal certilage, has been characterized in a calcifying system in vitro in respect to the behavior of sedimenting and supernatant fractions after high speed ultracentrifugation. To perform these tests on the starting samples of 20 nl of C(f1), macroscopic analytical methods were scaled down for the identification of relevant organic components, including hexuronic acid and proteinpolysaccharides (PPL). The mineral accretion system was designed to simulate physiologic conditions in the calcifying cartilage septa of normal rats, and the mineral used for seeding was an immature calcium phosphate similar to native cartilage mineral. Normal C(f1) or its dilutions in synthetic lymph up to 1:4 completely prevented mineral accretion in vitro. The inhibitory action was localized to the sedimented fractions after ultracentrifugation and could be destroyed by incubation with trypsin or hyaluronidase. The sediment of C(f1) contained 2 mg of hexuronic acid per ml of C(f1) and gave a strong reaction of identification for a light fraction of PPL by fluorescent antibodies to rat PPL. PPL fractions were tested in the same mineral accretion systems as C(f1) and exhibited responses similar to those of C(f1). Also, there was evidence of a mineral phase in C(f1) of normal rats, in C(f1) of rats with healing rickets, but not in C(f1) of untreated rachitic rats. These results are interpreted to indicate that certain PPLs function as an inhibitor of crystal growth at extracellular sites premonitory to calcification. Evidence for a low density inhibitor of mineral accretion was found in normal serum but not in C(f1).
Aseptic Meningitis and High School Football Players
Authors: Melinda Moore, Roy C. Baron, Marc R. Filstein, John P. Lofgren, Diane L. Rowley, Lawrence B. Schonberger, Milford H. Hatch
Journal: JAMA (1983)

During 1978 and 1980, epidemiologists at the Centers for Disease Control investigated seven outbreaks of aseptic meningitis-like illness (AMLI) occurring in high school football players in four different states. One or more enterovirus types were isolated from affected students at all seven schools. Attack rates were highest among the varsity football teams (range, 21% to 68%), although junior varsity teams were also affected at most schools (range, 5% to 63%). Non-football athletes were relatively spared. The illness was also reported by nonathletes at all three schools where more extensive investigations were undertaken. At one school, the AMLI attack rate was higher among students who were close friends of football players than among students who were not close friends; at the other two schools, these rates were similar. Hospitalization was more likely for football players with AMLI than for affected nonfootball players. Transmission of enteroviruses among football players was probably from person to person, although there was additional evidence to implicate common vehicle transmission at two schools. We conclude that football players may or may not have been more likely to be exposed to the enteroviruses circulating in their communities, but once introduction of a virus into a team occurred, transmission potential may have been enhanced, resulting in a large number of AMLI cases in players.
Effects of Statin Therapy According to Plasma High-Sensitivity C-Reactive Protein Concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
Authors: John J.V. McMurray, John Kjekshus, Lars Gullestad, Peter Dunselman, Åke Hjalmarson, Hans Wedel, Magnus Lindberg, Finn Waagstein, Peer Grande, Jaromir Hradec, Gabriel Kamenský, Jerzy Korewicki, Timo Kuusi, François Mach, Naresh Ranjith, John Wikstrand
Journal: Circulation (2009)

We examined whether the antiinflammatory action of statins may be of benefit in heart failure, a state characterized by inflammation in which low cholesterol is associated with worse outcomes.We compared 10 mg rosuvastatin daily with placebo in patients with ischemic systolic heart failure according to baseline high sensitivity-C reactive protein (hs-CRP) <2.0 mg/L (placebo, n=779; rosuvastatin, n=777) or > or = 2.0 mg/L (placebo, n=1694; rosuvastatin, n=1711). The primary outcome was cardiovascular death, myocardial infarction, or stroke. Baseline low-density lipoprotein was the same, and rosuvastatin reduced low-density lipoprotein by 47% in both hs-CRP groups. Median hs-CRP was 1.10 mg/L in the lower and 5.60 mg/L in the higher hs-CRP group, with higher hs-CRP associated with worse outcomes. The change in hs-CRP with rosuvastatin from baseline to 3 months was -6% in the low hs-CRP group (27% with placebo) and -33.3% in the high hs-CRP group (-11.1% with placebo). In the high hs-CRP group, 548 placebo-treated (14.0 per 100 patient-years of follow-up) and 498 rosuvastatin-treated (12.2 per 100 patient-years of follow-up) patients had a primary end point (hazard ratio of placebo to rosuvastatin, 0.87; 95% confidence interval, 0.77 to 0.98; P=0.024). In the low hs-CRP group, 175 placebo-treated (8.9 per 100 patient-years of follow-up) and 188 rosuvastatin-treated (9.8 per 100 patient-years of follow-up) patients experienced this outcome (hazard ratio, 1.09; 95% confidence interval, 0.89 to 1.34; P>0.2; P for interaction=0.062). The numbers of deaths were as follows: 581 placebo-treated (14.1 per 100 patient-years of follow-up) and 532 rosuvastatin-treated (12.6 per 100 patient-years) patients in the high hs-CRP group (hazard ratio, 0.89; 95% confidence interval, 0.79 to 1.00; P=0.050) and 170 placebo-treated (8.3 per 100 patient-years) and 192 rosuvastatin-treated (9.7 per 100 patient-years) patients in the low hs-CRP group (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43; P=0.14; P for interaction=0.026).In this retrospective hypothesis-generating study, we found a significant interaction between hs-CRP and the effect of rosuvastatin for most end points whereby rosuvastatin treatment was associated with better outcomes in patients with hs-CRP > or = 2.0 mg/L.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.