tbuckley/cabot-search huggingface dataset:
Dissociation between contractile function and oxidative metabolism in postischemic myocardium. Attenuation by ruthenium red administered during reperfusion.
Authors: R H Benzi, R Lerch
Journal: Circulation Research (1992)

The oxidative metabolic rate may be disproportionately high compared with contractile function in postischemic reperfused myocardium. To study the potential involvement of intracellular calcium transport in high energy expenditure after reperfusion, we determined in isolated rat hearts the effect of ruthenium red, an inhibitor of mitochondrial calcium transport, on recovery of contractile function and oxidative metabolic rate. Hearts subjected to 60 minutes of no-flow ischemia exhibited, at 15 minutes after the onset of reperfusion, poor recovery of left ventricular pressure development to only 7% of the corresponding value measured in control hearts (p less than 0.01). However, myocardial oxygen consumption was recovered to 84% of control (p = NS). The ratio of isovolumic contractile performance (expressed as the product of heart rate and left ventricular pressure development) to myocardial oxygen consumption was severely depressed to 6% of control (p less than 0.01). Supplementation of the perfusate with 6 microM ruthenium red during the initial 40 minutes of reperfusion resulted in a reduction of myocardial oxygen consumption to 65% of the value measured after 15 minutes of reperfusion in hearts reperfused without ruthenium red (p less than 0.01), despite a threefold increase of left ventricular pressure development (p less than 0.05). Oxidation of both palmitate and glucose was reduced to a comparable extent by ruthenium red. The ratio of contractile performance to myocardial oxygen consumption increased progressively during infusion of ruthenium red and did not differ further from control hearts after 30 minutes of reperfusion. Cumulative myocardial release of creatine kinase was reduced by 47% (p less than 0.05) in hearts reperfused with ruthenium red-containing medium. The results provide circumstantial evidence for the hypothesis suggesting that enhanced energy expenditure by intracellular calcium transport may be involved in the mechanisms underlying the dissociation between left ventricular performance and myocardial oxidative metabolic rate early after postischemic reperfusion.
MELANOSIS AFTER ARSENOBENZOL..
Authors: W. J. O'DONOVAN
Journal: British Journal of Dermatology (1925)

Journal Article MELANOSIS AFTER ARSENOBENZOL.: (Case Record.) Get access W. J. O'DONOVAN, M.D., M.R.C.P. W. J. O'DONOVAN, M.D., M.R.C.P. First Asst., Derm. and Syph. Department, London Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 2, 1 February 1925, Pages 87–91, https://doi.org/10.1111/j.1365-2133.1925.tb09929.x Published: 01 February 1925
Association Between Iron Deficiency and A1C Levels Among Adults Without Diabetes in the National Health and Nutrition Examination Survey, 1999–2006
Authors: Catherine Kim, Kai McKeever Bullard, William H. Herman, Gloria L. Beckles
Journal: Diabetes Care (2010)

OBJECTIVE Iron deficiency has been reported to elevate A1C levels apart from glycemia. We examined the influence of iron deficiency on A1C distribution among adults without diabetes. RESEARCH DESIGN AND METHODS Participants included adults without self-reported diabetes or chronic kidney disease in the National Health and Nutrition Examination Survey 1999–2006 who were aged ≥18 years of age and had complete blood counts, iron studies, and A1C levels. Iron deficiency was defined as at least two abnormalities including free erythrocyte protoporphyrin &amp;gt;70 μg/dl erythrocytes, transferrin saturation &amp;lt;16%, or serum ferritin ≤15 μg/l. Anemia was defined as hemoglobin &amp;lt;13.5 g/dl in men and &amp;lt;12.0 g/dl in women. RESULTS Among women (n = 6,666), 13.7% had iron deficiency and 4.0% had iron deficiency anemia. Whereas 316 women with iron deficiency had A1C ≥5.5%, only 32 women with iron deficiency had A1C ≥6.5%. Among men (n = 3,869), only 13 had iron deficiency and A1C ≥5.5%, and only 1 had iron deficiency and A1C ≥6.5%. Among women, iron deficiency was associated with a greater odds of A1C ≥5.5% (odds ratio 1.39 [95% CI 1.11–1.73]) after adjustment for age, race/ethnicity, and waist circumference but not with a greater odds of A1C ≥6.5% (0.79 [0.33–1.85]). CONCLUSIONS Iron deficiency is common among women and is associated with shifts in A1C distribution from &amp;lt;5.5 to ≥5.5%. Further research is needed to examine whether iron deficiency is associated with shifts at higher A1C levels.
Psychiatric Status After Hysterectomy
Authors: Ronald L. Martin
Journal: JAMA (1980)

Forty-four randomly selected women who received noncancer hysterectomy were evaluated preoperatively and at one-year follow-up. The findings did not support the hypothesis that the hysterectomy procedure is followed by an excess of psychiatric symptoms. The group, in fact, was less symptomatic at follow-up than presurgically. On the whole, women manifesting psychiatric symptoms during the follow-up had had similar problems before surgery. Many of the symptoms were associated with a presurgical diagnosis of hysteria (Briquet's somatization syndrome), found at a striking excess in the sample (27% vs the 1% or 2% expected). The authors suggest that when hysteria is diagnosed, therapeutic decisions regarding hysterectomy should be based on objective findings rather than on complaints, in that women with hysteria may be placed at risk of hysterectomy on the basis of psychiatric rather than gynecologic illness. (<i>JAMA</i>244:350-353, 1980)
A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis
Authors: Maria B. Arvelo, Jeffrey T. Cooper, Christopher Longo, Soizic Daniel, Shane T. Grey, Jerome Mahiou, Eva Czismadia, Graziella Abu-Jawdeh, Christiane Ferran
Journal: Hepatology (2002)

Apoptosis of hepatocytes is a seminal feature of fulminant hepatic failure. We show that the anti-apoptotic protein A20 is upregulated in hepatocytes by pro-inflammatory stimuli and functions to protect from apoptosis and limit inflammation by inhibiting NF-κB. Adenoviral mediated hepatic expression of A20 in BALB/c mice yields an 85% survival rate in the D-galactosamine (D-gal)/lipolysaccharide (LPS) model of acute toxic hepatitis compared with 15% to 20 % in control mice. Expression of A20 preserves normal liver function as assessed by prothrombin time. The protective effect of A20 is independent of tumor necrosis factor (TNF) inhibition. Maintaining high circulating TNF levels may be advantageous for liver regeneration. Our data supports this hypothesis as evidenced by increased proliferating cell nuclear antigen (PCNA) expression in the livers of mice expressing A20 compared with a dominant negative mutant of the TNF receptor (TNF-R), 6 hours following D-gal/LPS administration. In conclusion, these results qualify A20 as part of a physiologic, protective response of hepatocytes to injury and a promising gene therapy candidate for clinical applications aimed at preventing and treating viral and toxic fulminant hepatic failure.
Lung function indices for predicting mortality in COPD
Authors: Afroditi K. Boutou, Dinesh Shrikrishna, Rebecca J. Tanner, Cayley Smith, Julia L. Kelly, Simon P. Ward, Michael I. Polkey, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2013)

Chronic obstructive pulmonary disease (COPD) is characterised by high morbidity and mortality. It remains unknown which aspect of lung function carries the most prognostic information and if simple spirometry is sufficient. Survival was assessed in COPD outpatients whose data had been added prospectively to a clinical audit database from the point of first full lung function testing including spirometry, lung volumes, gas transfer and arterial blood gases. Variables univariately associated with survival were entered into a multivariate Cox proportional hazard model. 604 patients were included (mean ± SD age 61.9 ± 9.7 years; forced expiratory volume in 1 s 37 ± 18.1% predicted; 62.9% males); 229 (37.9%) died during a median follow-up of 83 months. Median survival was 91.9 (95% CI 80.8-103) months with survival rates at 3 and 5 years 0.83 and 0.66, respectively. Carbon monoxide transfer factor % pred quartiles (best quartile (>51%): HR 0.33, 95% CI 0.172-0.639; and second quartile (51-37.3%): HR 0.52, 95% CI 0.322-0.825; versus lowest quartile (<27.9%)), age (HR 1.04, 95% CI 1.02-1.06) and arterial oxygen partial pressure (HR 0.85, 95% CI 0.77-0.94) were the only parameters independently associated with mortality. Measurement of gas transfer provides additional prognostic information compared to spirometry in patients under hospital follow-up and could be considered routinely.
Tumor Cells Upregulate Normoxic HIF-1α in Response to Doxorubicin
Authors: Yiting Cao, Joseph M. Eble, Ejung Moon, Hong Yuan, Douglas H. Weitzel, Chelsea D. Landon, Charleen Yu-Chih Nien, Gabi Hanna, Jeremy N. Rich, James M. Provenzale, Mark W. Dewhirst
Journal: Cancer Research (2013)

Abstract Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that controls cellular homeostasis. Although its activation benefits normal tissue, HIF-1 activation in tumors is a major risk factor for angiogenesis, therapeutic resistance, and poor prognosis. HIF-1 activity is usually suppressed under normoxic conditions because of rapid oxygen-dependent degradation of HIF-1α. Here, we show that, under normoxic conditions, HIF-1α is upregulated in tumor cells in response to doxorubicin, a chemotherapeutic agent used to treat many cancers. In addition, doxorubicin enhanced VEGF secretion by normoxic tumor cells and stimulated tumor angiogenesis. Doxorubicin-induced accumulation of HIF-1α in normoxic cells was caused by increased expression and activation of STAT1, the activation of which stimulated expression of iNOS and its synthesis of nitric oxide (NO) in tumor cells. Mechanistic investigations established that blocking NO synthesis or STAT1 activation was sufficient to attenuate the HIF-1α accumulation induced by doxorubicin in normoxic cancer cells. To our knowledge, this is the first report that a chemotherapeutic drug can induce HIF-1α accumulation in normoxic cells, an efficacy-limiting activity. Our results argue that HIF-1α-targeting strategies may enhance doxorubicin efficacy. More generally, they suggest a broader perspective on the design of combination chemotherapy approaches with immediate clinical impact. Cancer Res; 73(20); 6230–42. ©2013 AACR.
The Evolutionary Origin of Peroxisomes: An ER-Peroxisome Connection
Authors: Agatha Schlüter, Stéphane Fourcade, Raymond Ripp, Jean Louis Mandel, Olivier Poch, Aurora Pujol
Journal: Molecular Biology and Evolution (2006)

The peroxisome is an essential eukaryotic organelle, crucial for lipid metabolism and free radical detoxification, development, differentiation, and morphogenesis from yeasts to humans. Loss of peroxisomes invariably leads to fatal peroxisome biogenesis disorders in man. The evolutionary origin of peroxisomes remains unsolved; proposals for either a symbiogenetic or cellular membrane invagination event are unconclusive. To address this question, we have probed with a peroxisomal proteome, an "ensemble" of 19 representative eukaryotic complete genomes. Molecular phylogenetic and sequence comparison tools allowed us to identify four proteins as peroxisomal markers for unequivocal in silico peroxisome detection. We have then detected the Apicomplexa phylum as the first group of organisms devoid of peroxisomes, in the presence of mitochondria. Finally, we deliver evidence against a prokaryotic ancestor of peroxisomes: (1) the peroxisomal membrane is composed of purely eukaryotic bricks and is thus useful to trace the eukaryotes in their evolutionary paths and (2) the peroxisomal matrix protein import system shares mechanistic similarities with the endoplasmic reticulum/proteasome degradation process, indicating a common evolutionary history.
Smoking assessment & treatment in hospital: Are we providing “right care” and/or missing cannabis-smoking?
Authors: Louise Restrick, Erin Cumbus, Oliver Thomas, Myra Stern
Journal: European Respiratory Journal (2011)

Introduction:  Hospital admission provides opportunities for quit-smoking advice/support. Some inpatients also smoke cannabis, which causes bullous-emphysema, but prevalence is unknown. The study aimed to determine inpatient cannabis-smoking and to measure effectiveness of our quit-smoking service   Methods:  Trainees/medical students carried out a single-day cross-sectional survey of adult inpatients, using standardised anonymous questionnaires, hospital notes and medication charts. Data was compared with previous surveys over five years.   Results:  184/223 inpatients were interviewed. Cigarette-smoking prevalence was 33/184 (18%); cannabis-smoking 12/184 (6.5%). 10/33 (30%) cigarette-smokers smoked cannabis. 544 patients were interviewed over 5 years:  Inpatient smoking prevalence and advice to stop smoking did not change (16±2% and 57±4% respectively). NRT prescription and cessation plan documentation increased to 44% and 35% respectively.   Conclusions:  1/5 inpatients smoke but
Efficacy of natural cycle IVF: a review of the literature
Authors: M. J. Pelinck
Journal: Human Reproduction Update (2002)

Since the introduction of IVF treatments, natural cycle IVF has been largely replaced by IVF with ovarian stimulation. However, natural cycle IVF has several advantages. It is associated with a close to zero multiple pregnancy rate, and a zero risk of ovarian hyperstimulation syndrome. Per cycle, natural cycle IVF is less time consuming, physically and emotionally less demanding for patients, and cheaper than stimulated IVF, but also less effective. This systematic literature review addresses the issue of effectiveness of natural cycle IVF. Herein, 20 studies describing natural cycle IVF are presented; 12 case series and eight in which a comparison was made between natural cycle IVF and IVF with ovarian stimulation. Good-quality randomized controlled trials and formal cost-effectiveness analyses are lacking. The 20 selected studies comprised a total of 1800 cycles of natural cycle IVF, resulting in 819 embryo transfers (45.5% per cycle) and 129 ongoing pregnancies (7.2% per cycle and 15.8% per embryo transfer). Efficacy of natural cycle IVF is hampered by high cancellation rates because of premature LH rise and premature ovulations. It is concluded that natural cycle IVF is a low-risk, low-cost and patient-friendly procedure. A randomized controlled trial comparing natural cycle IVF with current standard treatment strategies is warranted.
Cumulative Effect of Risk Alleles in CFH, ARMS2, and VEGFA on the Response to Ranibizumab Treatment in Age-related Macular Degeneration
Authors: Dzenita Smailhodzic, Philipp S. Muether, John Chen, Angela Kwestro, Alice Yang Zhang, Amer Omar, Johannes P.H. Van de Ven, Jan E.E. Keunen, Bernd Kirchhof, Carel B. Hoyng, B. Jeroen Klevering, Robert K. Koenekoop, Sascha Fauser, Anneke I. den Hollander
Journal: Ophthalmology (2012)
The Mammalian Target of Rapamycin Signaling Pathway: Twists and Turns in the Road to Cancer Therapy
Authors: Robert T. Abraham, James J. Gibbons
Journal: Clinical Cancer Research (2007)

The immunosuppressive drug rapamycin played a key role in the functional characterization of mammalian target of rapamycin (mTOR), an unusual protein kinase that coordinates growth factor and nutrient availability with cell growth and proliferation. Several rapamycin-related compounds are now in various stages of clinical development as anticancer agents. This article highlights recent advances in our understanding of the mTOR signaling pathway and the implications of these findings for the clinical application of mTOR inhibitors in cancer patients.
Evolutionary and Population Genomics of the Cavity Causing Bacteria Streptococcus mutans
Authors: Omar E. Cornejo, Tristan Lefébure, Paulina D. Pavinski Bitar, Ping Lang, Vincent P. Richards, Kirsten Eilertson, Thuy Do, David Beighton, Lin Zeng, Sang-Joon Ahn, Robert A. Burne, Adam Siepel, Carlos D. Bustamante, Michael J. Stanhope
Journal: Molecular Biology and Evolution (2012)

Streptococcus mutans is widely recognized as one of the key etiological agents of human dental caries. Despite its role in this important disease, our present knowledge of gene content variability across the species and its relationship to adaptation is minimal. Estimates of its demographic history are not available. In this study, we generated genome sequences of 57 S. mutans isolates, as well as representative strains of the most closely related species to S. mutans (S. ratti, S. macaccae, and S. criceti), to identify the overall structure and potential adaptive features of the dispensable and core components of the genome. We also performed population genetic analyses on the core genome of the species aimed at understanding the demographic history, and impact of selection shaping its genetic variation. The maximum gene content divergence among strains was approximately 23%, with the majority of strains diverging by 5–15%. The core genome consisted of 1,490 genes and the pan-genome approximately 3,296. Maximum likelihood analysis of the synonymous site frequency spectrum (SFS) suggested that the S. mutans population started expanding exponentially approximately 10,000 years ago (95% confidence interval [CI]: 3,268–14,344 years ago), coincidental with the onset of human agriculture. Analysis of the replacement SFS indicated that a majority of these substitutions are under strong negative selection, and the remainder evolved neutrally. A set of 14 genes was identified as being under positive selection, most of which were involved in either sugar metabolism or acid tolerance. Analysis of the core genome suggested that among 73 genes present in all isolates of S. mutans but absent in other species of the mutans taxonomic group, the majority can be associated with metabolic processes that could have contributed to the successful adaptation of S. mutans to its new niche, the human mouth, and with the dietary changes that accompanied the origin of agriculture.
How long should we talk to patients? A study in doctor-patient communication.
Authors: V Wright, R Hopkins, K Burton
Journal: Annals of the Rheumatic Diseases (1982)

The 13 questions to which 173 rheumatic outpatients most frequently wished to know the answer were made the basis of a structured interview. Two lengths of interview were conducted in a controlled trial (short being of 2 minutes9 duration, long ranging from 4 to 11 minutes). Sixty patients referred directly from their general practitioners, and not being in any of the remedial professions, were randomly assigned to one of the 2 groups. They were tested by an independent observer immediately after interview, and one month later at their return appointment, by means of a questionnaire that covered the 13 items of information given to all the patients. The longer interview resulted in significantly more information being retained. Of individual questions only 3 scored significantly better with the longer interview--that about the reasons for x-rays immediately after interview, and the role of heredity and the place of rest at delayed recall.
Erratum. The Relative and Combined Ability of High-Sensitivity Cardiac Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide to Predict Cardiovascular Events and Death in Patients With Type 2 Diabetes. Diabetes Care 2014;37:295–303
Authors: Graham S. Hillis, Paul Welsh, John Chalmers, Vlado Perkovic, Clara K. Chow, Qiang Li, Min Jun, Bruce Neal, Sophia Zoungas, Neil Poulter, Giuseppe Mancia, Bryan Williams, Naveed Sattar, Mark Woodward
Journal: Diabetes Care (2015)
Primary virus-induced lymphomas evade T cell immunity by failure to express viral antigens.
Authors: W L Vasmel, E J Sijts, C J Leupers, E A Matthews, C J Melief
Journal: The Journal of Experimental Medicine (1989)

T lymphoma induction by the mink cell focus-inducing murine leukemia virus MCF 1233 in C57BL/10 and C57BL/6 mice is influenced by a strongly Th-dependent, H-2I-A-restricted antiviral immune response (25). We compared the MHC class I as well as viral env and gag antigenic cell surface profiles of frequent T lymphomas of H-2I-A nonresponder-type mice to that of rare T lymphomas of H-2I-A responder-type mice. Membrane immunofluorescence studies, with a panel of anti-env mAbs (reactive with the highly conserved gp70f epitope, the p15Ec epitope, and the gp70-p15E complex), a polyclonal anti-p30 serum, and anti-H-2 class I mAbs, showed that all 17 nonresponder tumors tested expressed high levels of both env and gag viral proteins, and 15 of these 17 nonresponder tumors expressed high levels of H-2 class I K and D antigens. In contrast, 10 of 11 responder lymphomas lacked env and/or gag determinants. The only responder lymphoma with both strong env and gag expression failed to express H-2K and -D antigens. Preferential loss of env or gag expression did not correlate with H-2 class I allelic specificities. Both responder and nonresponder T lymphoma DNA contained multiple, predominantly MCF-like, newly acquired proviral integrations. Differences in viral antigen cell surface expression were confirmed at cytoplasmic and RNA levels. The amounts of 8.2- and 3.2-kb viral RNA were greatly reduced in two responder lymphomas when compared with four nonresponder lymphomas. In both responder lymphomas, aberrantly sized viral RNA species were found. Upon in vivo passage of these responder lymphomas in either immunocompetent or T cell-deficient nu/nu mice, it was found that various molecular mechanisms may underlie the lack of viral antigen expression at the cell surface of these lymphomas. One lymphoma re-expressed viral antigens when transplanted with nu/nu mice, whereas the other remained stably gag negative. The combined findings indicate that an H-2I-A-regulated antiviral immune response not only strongly reduces T lymphoma incidence, but also forces T lymphomas that still arise to poorly express viral antigens, thus explaining their escape from immunosurveillance.