tbuckley/cabot-search huggingface dataset:
Development of a health index in patients with ankylosing spondylitis (ASAS HI): final result of a global initiative based on the ICF guided by ASAS
Authors: U Kiltz, D van der Heijde, A Boonen, A Cieza, G Stucki, M A Khan, W P Maksymowych, H Marzo-Ortega, J Reveille, S Stebbings, C Bostan, J Braun
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The burden of disease in patients with ankylosing spondylitis (AS) can be considerable. However, no agreement has been reached among expert members of Assessment of SpondyloArthritis International Society (ASAS) to define severity of AS. Based on the International Classification of Functioning, Disability and Health (ICF), a core set of items for AS has been selected to represent the entire spectrum of possible problems in functioning. Based on this, the objective of this study was to develop a tool to quantify health in AS, the ASAS Health Index. <h3>Methods</h3> First, based on a literature search, experts' and patients' opinion, a large item pool covering the categories of the ICF core set was generated. In several steps this item pool was reduced based on reliability, Rasch analysis and consensus building after two cross-sectional surveys to come up with the best fitting items representing most categories of the ICF core set for AS. <h3>Results</h3> After the first survey with 1754 patients, the item pool of 251 items was reduced to 82. After selection by an expert committee, 50 items remained which were tested in a second cross-sectional survey. The results were used to reduce the number of items to a final set of 17 items. This selection showed the best reliability and fit to the Rasch model, no residual correlation, and absence of consistent differential item function and a Person Separation Index of 0.82. <h3>Conclusions</h3> In this long sequential study, 17 items which cover most of the ICF core set were identified that showed the best representation of the health status of patients with AS. The ASAS Health Index is a linear composite measure which differs from other measures in the public domain.
Reactive oxygen species induce apoptosis in cultured human mesangial cells.
Authors: H Sugiyama, N Kashihara, H Makino, Y Yamasaki, Z Ota
Journal: Journal of the American Society of Nephrology (1996)

Apoptosis is a distinct form of cell death that is observed under various physiologic and pathologic conditions, and it is thought to be important in regulating the number of glomerular cells. This study investigated the possible role of reactive oxygen species in the induction of apoptosis in cultured human mesangial cells. Fragmented nuclei with condensed chromatin, a morphologic characteristic of apoptosis, were observed by electron microscopy in mesangial cells exposed to 0.02 mM hydrogen peroxide for 4 h. Nuclear DNA extracted from mesangial cells that had been incubated with hydrogen peroxide (2 to 20 mM) or with xanthine (0.05 mM) and xanthine oxidase (5 to 100 mU/mL) showed the ladder pattern on electrophoresis that is a biochemical marker for apoptosis. Hydrogen peroxide (0.02 to 20 mM) decreased the number of viable cells, as determined by trypan blue exclusion, in a dose-dependent manner. Hydrogen peroxide or xanthine and xanthine oxidase increased the lactate dehydrogenase release from mesangial cells in a dose- and time-dependent manners. The release of lactate dehydrogenase was prevented by treatment with a free radical scavenger, catalase. Hydrogen peroxide (2 mM) also significantly increased the number of mesangial cells with fragmented DNA as detected by in situ nick end-labeling Results indicate that reactive oxygen species induce apoptosis in cultured human mesangial cells. Furthermore, apoptosis of mesangial cells induced by reactive oxygen species may contribute to the loss of such cells observed in glomerular disease.
The Bisphosphonate YM529 Inhibits Osteolytic and Osteoblastic Changes and CXCR-4–Induced Invasion in Prostate Cancer
Authors: Sotaro Miwa, Atsushi Mizokami, Evan T. Keller, Russell Taichman, Jian Zhang, Mikio Namiki
Journal: Cancer Research (2005)

Abstract Bisphosphonates are useful for the treatment of prostate cancer bone metastasis. However, the role of bisphosphonate on the development of the osteoblastic component of prostate cancer bone metastases is not defined. In the present study, the third-generation bisphosphonate, YM529 (minodoronate), was tested for its effects on the osteolytic PC-3 and novel osteoblastic LNCaP-SF cell lines. YM529 inhibited both osteolytic and osteoblastic changes in an intratibial tumor injection murine model. In vitro, YM529 inhibited both the proliferation and the invasion of both prostate cancer cell lines. The stromal cell–derived factor-1 (or CXCL12)/CXCR-4 pathway is believed to play an important role in the development of prostate cancer bone metastases. Thus, we determined if YM529 affected this pathway. YM529 suppressed CXCR-4 expression in PC-3 and LNCaP-SF in vitro and in vivo and this was associated with decreased in vitro invasion. These results suggest that YM529 may inhibit cancer cell invasion into the bone matrix by repressing the expression of CXCR-4 in bone metastasis lesions.
Oral rapamycin to inhibit restenosis after stenting of de novo coronary lesions
Authors: Ron Waksman, Andrew E. Ajani, Augusto D. Pichard, Rebecca Torguson, Ellen Pinnow, Daniel Canos, Lowell F. Satler, Kenneth M. Kent, Pramod Kuchulakanti, Chrysoula Pappas, Louise Gambone, Neil Weissman, Maureen C. Abbott, Joseph Lindsay
Journal: Journal of the American College of Cardiology (2004)
Adrenaline increases the rate of cycling of crossbridges in rat cardiac muscle as measured by pseudo-random binary noise-modulated perturbation analysis.
Authors: J F Hoh, G H Rossmanith, L J Kwan, A M Hamilton
Journal: Circulation Research (1988)

The mechanism of action of adrenaline on cardiac contractility in rat papillary muscles containing V1 and V3 isomyosins was analyzed during barium-activated contractures at 25 degrees C by frequency domain analysis using pseudo-random binary noise-modulated perturbations. The analysis characterizes a frequency (fmin) at which dynamic stiffness of a muscle is a minimum, a parameter that reflects the rate of cycling of crossbridges. We have previously shown that fmin for V1- and V3-containing papillary muscles were 2.1 +/- 0.2 Hz (mean +/- SD) (n = 10) and 1.1 +/- 0.2 Hz (n = 8), respectively, and that these values were independent of the level of activation. The present study's goal was to determine whether the inotropic action of adrenaline was associated with an increased rate of crossbridge cycling. The results show that a saturating dose of adrenaline increased fmin in V1 hearts by 49 +/- 2% (n = 11). The action on V3 hearts was significantly less; the increase in fmin was 26 +/- 2% (n = 6). The increase in fmin for V1 hearts was shown to be sensitive to the beta-blocking agent propranolol. These results suggest that adrenaline significantly increases the rate of crossbridge cycling by a beta-receptor-mediated mechanism. We conclude that the increased contractility of the heart in the presence of adrenaline arises not only from more complete activation of the contractile proteins but also from the increased rate at which each crossbridge can transduce energy.
An induction dose of epoetin α of 40 000 IU daily for three consecutive days increases and maintains hemoglobin levels in anemic cancer patients undergoing chemotherapy
Authors: G. Mustacchi, R. Ceccherini, C. Dellach, S. Foladore, S. Milani, M. Leita, M. Sisto
Journal: Annals of Oncology (2006)
Prognostic indices for COPD patient management: how many do we need?
Authors: W.D. van Dijk, T.R.J. Schermer, C. van Weel
Journal: European Respiratory Journal (2011)

Prognostic indices for COPD patient management: how many do we need?To the Editors:Prognostic indices represent clinicians' and scientists' best intentions to improve the care of patients.Implicit in the development of indices is that they will allow a better understanding of patients' needs in relation to an underlying disease.Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition with a high impact on patients' wellbeing, health care utilisation and mortality [1].To date, 15 prognostic indices for COPD patients have been reported since the publication of the BODE (body mass index, obstruction, dyspnoea and exercise) index in 2004 [2-14].All indices except one were developed or enhanced for clinical use.However, in current COPD guidelines, airflow obstruction is still the only structured measure that guides clinicians on treatment decisions, along with information on patients' subjective wellbeing at the time of their visit.ESTEBAN et al. [15] developed a potentially useful prognostic instrument for COPD patients to predict their mortality: COPD classification and analysis tree (CART).Their validation method was fairly good due to the use of a separate validation cohort, analysing both COPD-CART's discriminative potency and accuracy, and comparing COPD-CART with some previously reported indices (BODE, HADO (health, activity, dyspnoea and obstruction) and ADO (age, dyspnoea and obstruction)) [16].However, in order to value its added predictive quality, we wonder how this new index compares to the classic standard measurement, i.e. obstruction, in their validation cohort.Above all, it is essential to justify the utilisation of indices before recommending that practitioners use them.Since COPD-CART was developed for clinical utilisation and claims to be of better use than existing indices, our most important question does not concern its validity but whether this instrument will indeed affect patient care.The British Medical Journal has previously published a series on prognosis studies, with an emphasis on the need for impact studies that demonstrate improvement of decision making and patient outcome when using an index to guide patient management [17].Despite various validation methods of the still growing number of COPD prognostic indices, none of these indices has revealed its impact in daily practice yet.The proof of the pudding is in the eating: good intentions could turn out to have less impact than anticipated, or may even do more harm than good.
Surgery in the treatment of cervical and thoracic disc protrusions.
Authors: A Naylor
Journal: BMJ (1977)

1 IUich, I, Medical Nemesis. London, Calder and Boyars, 1974. 2 Journal of Medical Ethics, 1975, 1, 78-80. 3 Campbell, A V, Moral Dilemma in Medicine, 2nd edn. Edinburgh/London, Churchill Livingstone, 1975. 4 Maxwell, R, Health Care: The Growing Dilemma. New York, McKinsey and Co, 1974. 5 Cochrane, A L, Effectiveness and Efficiency. London, Nuffield Hospitals Trust, 1972. 6 Berlin, I, in Political Philosophy, ed A Quinton, Oxford University Press, 1967. 7 Titmuss, R M, The Gift Relationship. London, Allen and Unwin, 1970. 8 Abel-Smith, B, Value for Money in Health Services, p 191. London, Heinemann, 1976. 9 Office of Health Economies, Health Care in Developing Countries, p 206. London, OHE, 1972. 10 Mill, J S, in Utilitarianism, ed M Warnock. London, Fontana, 1962. 11 Abel-Smith, B, Value for Money in Health Services, p 135. London, Heinemann, 1976. 12 Hart, J T, Lancet, 1971, 1, 405. 13 DHSS, Priorities for Health and Personal Social Services in England. London, DHSS, 1976. 14 Scottish Home and Health Department, The Health Service in Scotland: The Way Ahead. Edinburgh, HMSO, 1976. 15 DHSS, Sharing Resources for Health in England: Report of the Resource Allocation Working Party, London, DHSS, 1976. 16 British Medical Journal, 1976, 1, 787. 17 Abel-Smith, B, Value for Money in Health Services, London, Heinemann, 1976.
Practice injury rates in collegiate sports
Authors: J Agel, J Schisel
Journal: British Journal of Sports Medicine (2011)

Background Published data has demonstrated that collegiate athletes sustain significantly higher game than practice injury rates (13.8 vs 4.0 injuries per 1000 A-Es). Review of this data demonstrates disparities within the practice injury rates with pre-season practice injury rates being significantly higher than in-season and post-season practice rates. Objective Our a priori primary hypothesis was that Fall sports would show the largest differential in pre-season compared to in-season practice injury rates. Our secondary hypothesis was that Division I would report higher rates of pre-season practice injury rates compared to Divisions II and III. Setting National Collegiate Athletic Association (NCAA). Participants 250 NCAA Injury Surveillance System participating schools with 182 000 injuries with 1 300 000 exposures. Assessment of risk factors The dependent variables are sport, season and division. Main outcome measure The independent variable is injury; defined as time loss of 1 day or more from a scheduled athletic activity. Results Pre-season practice consistently resulted in the highest injury rates across all Divisions regardless of season. Men's football (Fall) had the highest rate ratio of pre-season to in-season practice injury (3.47 (3.40, 3.54)). Men's and Women's soccer (Fall) were next (3.28 (3.11, 3.45), 3.27 (3.09, 3.45). Women's Division 1 soccer, had the greatest differential between pre-season and in-season practice injury as well as the highest pre-season practice injury rate for all sports except Division 1 men's wrestling (Winter). There was no consistent injury pattern demonstrated across season when sports were analyzed by Division. Conclusion Pre-season practices are responsible for a disproportionate share of practice injuries. Fall sports demonstrate the highest within sport practice injury rates. Attention should be paid to this finding in order to ensure that practices are conducted in a safe manner for the athletes and all potential injury prevention options taken advantage of.
Circulating Half-Life of PEGylated Recombinant Methioninase Holoenzyme Is Highly Dose Dependent on Cofactor Pyridoxal-5′-Phosphate
Authors: Zhijian Yang, Xinghua Sun, Shukuan Li, Yuying Tan, Xiaoen Wang, Nan Zhang, Shigeo Yagi, Tomoaki Takakura, Yoshinao Kobayashi, Akio Takimoto, Takayuki Yoshioka, Akinori Suginaka, Eugene P. Frenkel, Robert M. Hoffman
Journal: Cancer Research (2004)

Abstract Recombinant methioninase (rMETase) has been shown to target the elevated methionine (MET) dependence of tumor cells and arrest their growth as well as make tumors more sensitive to standard chemotherapy agents. Polyethylene glycol (PEG)-modified rMETase (PEG-rMETase) has reduced antigenicity compared with unmodified rMETase. However, PEG-rMETase has a limited active circulating half-life due to rapid in vivo dissociation of its cofactor pyridoxal-5′-phosphate (PLP), a surprising finding, because PLP is tightly bound to PEG-rMETase in buffer. The question asked in the current study was on the effect of increasing doses of PLP to extend the circulating half-life of active PEG-rMETase holoenzyme in vivo. rMETase was conjugated with methoxypolyethylene glycol succinimidyl glutarate 5000 (MEGC-PEG). Miniosmotic pumps containing various concentrations of PLP were implanted in BALB-C mice. PLP-infused mice were then injected with a single dose of 4000 or 8000 units/kg PEG-rMETase. Mice infused with 5, 50, 100, 200, and 500 mg/ml PLP-containing miniosmotic pumps increased plasma PLP to 7, 24, 34, 60, and 95 μm, respectively, from the PLP baseline of 0.3 μm. PLP increased the half-life of MEGC-PEG-rMETase holoenzyme in a dose-dependent manner. Pumps containing 500 mg/ml PLP increased the half-life of MEGC-PEG-rMETase holoenzyme 4.5-fold from 1.5 to 7 h. Infused PLP did not extend the half-life of MEGC-PEG-rMETase apoenzyme. With a dose of 4000 units/kg MEGC-PEG-rMETase in the mice infused with 5, 50, 200, and 500 mg/ml PLP, plasma MET was depleted from 50 μm to ≤5 μm for 8, 24, 72, and 72 h, respectively. Thus, PLP infusion could extend the period of MET depletion by MEGC-PEG-rMETase by ∼10-fold in a dose-dependent manner. The mice given 8000 units/kg MEGC-PEG-rMETase showed a similar plasma MET depletion time course, indicating that the limiting factor for MEGC-PEG-rMETase-mediated MET depletion in vivo was PLP. The extended time of MET depletion by MEGC-PEG-rMETase was due to the maintenance of active MEGC-PEG-rMETase holoenzyme by infused PLP. The infused PLP either bound to apo-MEGC-PEG-rMETase and/or inhibited dissociation of PLP from holo-PEG-rMETase, thereby maintaining the holoenzyme form of MEGC-PEG-rMETase in vivo. The combination of MEGC-PEG-rMETase treatment with PLP infusion suggests an effective clinical strategy for long-term MET depletion to arrest cancer growth.
Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-β signaling
Authors: Seung-Beom Hong, HyoungBin Oh, Vladimir A Valera, Jaime Stull, Duy-Tan Ngo, Masaya Baba, Maria J Merino, W Marston Linehan, Laura S Schmidt
Journal: Molecular Cancer (2010)

Abstract Background Germline mutations in the FLCN gene are responsible for the development of fibrofolliculomas, lung cysts and renal neoplasia in Birt-Hogg-Dube' (BHD) syndrome. The encoded protein folliculin (FLCN) is conserved across species but contains no classic motifs or domains and its function remains unknown. Somatic mutations or loss of heterozygosity in the remaining wild type copy of the FLCN gene have been found in renal tumors from BHD patients suggesting that FLCN is a classic tumor suppressor gene. Results To examine the tumor suppressor function of FLCN , wild-type or mutant FLCN (H255R) was stably expressed in a FLCN-null renal tumor cell line, UOK257, derived from a BHD patient. When these cells were injected into nude mice, tumor development was inversely dependent upon the level of wild-type FLCN expression. We identified genes that were differentially expressed in the cell lines with or without wild-type FLCN , many of which are involved in TGF-β signaling, including TGF-β2 ( TGFB2 ) , inhibin β A chain ( INHBA ) , thrombospondin 1 ( THBS1 ), gremlin ( GREM1 ), and SMAD3 . In support of the in vitro data, TGFB2 , INHBA , THBS1 and SMAD3 expression levels were significantly lower in BHD-associated renal tumors compared with normal kidney tissue. Although receptor mediated SMAD phosphorylation was not affected, basal and maximal TGF-β-induced levels of TGFB2 , INHBA and SMAD7 were dramatically reduced in FLCN-null cells compared with FLCN -restored cells. Secreted TGF-β2 and activin A (homo-dimer of INHBA) protein levels were also lower in FLCN-null cells compared with FLCN -restored cells. Consistent with a growth suppressive function, activin A (but not TGF-β2) completely suppressed anchorage-independent growth of FLCN-null UOK257 cells. Conclusions Our data demonstrate a role for FLCN in the regulation of key molecules in TGF-β signaling and confirm deregulation of their expression in BHD-associated renal tumors. Thus, deregulation of genes involved in TGF-β signaling by FLCN inactivation is likely to be an important step for tumorigenesis in BHD syndrome.
Increased endothelin-1 levels in athletes
Authors: I N Legakis, T Mantzouridis, T Mountokalakis
Journal: British Journal of Sports Medicine (2003)

Endothelin-1 (ET-1), a potential vasoconstrictor peptide, may contribute to the exercise induced redistribution of blood flow in muscles.1,2 On the other hand, the latter parameter in athletes may be expanded secondary to muscle volume and as a consequence of increased ET-1 production.3 In this study, we found a difference in basal serum …
The promoter activity of human Mfn2 depends on Sp1 in vascular smooth muscle cells
Authors: Eleonora Sorianello, Francesc X. Soriano, Sergio Fernández-Pascual, Ana Sancho, Deborah Naon, Marian Vila-Caballer, Herminia González-Navarro, José Portugal, Vicente Andrés, Manuel Palacín, Antonio Zorzano
Journal: Cardiovascular Research (2012)

Mitofusin-2 (Mfn2) expression is dysregulated in vascular proliferative disorders and its overexpression attenuates the proliferation of vascular smooth muscle cells (VSMCs) and neointimal lesion development after balloon angioplasty. We sought to gain insight into the mechanisms that control Mfn2 expression in VSMCs. We cloned and characterized 2 kb of the 5′-flanking region of the human Mfn2 gene. Its TATA-less promoter contains a CpG island. In keeping with this, 5′-rapid amplification of cDNA ends revealed six transcriptional start sites (TSSs), of which TSS2 and TSS5 were the most frequently used. The strong CpG island was found to be non-methylated under conditions characterized by large differences in Mfn2 gene expression. The proximal Mfn2 promoter contains six putative Sp1 motifs. Sp1 binds to the Mfn2 promoter and its overexpression activates the Mfn2 promoter in VSMCs. Chemical inhibition of Sp1 reduced Mfn2 expression, and Sp1 silencing reduced transcriptional activity of the Mfn2 promoter. In keeping with this view, Sp1 and Mfn2 mRNA levels were down-regulated in the aorta early after an atherogenic diet in apolipoprotein E-knockout mice or in VSMCs cultured in the presence of low serum. Sp1 is a key factor in maintaining basal Mfn2 transcription in VSMCs. Given the anti-proliferative actions of Mfn2, Sp1-induced Mfn2 transcription may represent a mechanism for prevention of VSMC proliferation and neointimal lesion and development.
RTOG 9804: A Prospective Randomized Trial for Good-Risk Ductal Carcinoma In Situ Comparing Radiotherapy With Observation
Authors: Beryl McCormick, Kathryn Winter, Clifford Hudis, Henry Mark Kuerer, Eileen Rakovitch, Barbara L. Smith, Nour Sneige, Jennifer Moughan, Amit Shah, Isabelle Germain, Alan C. Hartford, Afshin Rashtian, Eleanor M. Walker, Albert Yuen, Eric A. Strom, Jeannette L. Wilcox, Laura A. Vallow, William Small, Anthony T. Pu, Kevin Kerlin, Julia White
Journal: Journal of Clinical Oncology (2015)

The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation.This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method.Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients.In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.