tbuckley/cabot-search huggingface dataset:
Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation
Authors: Karl S Peggs, Ann Hunter, Rajesh Chopra, Anne Parker, Premini Mahendra, Donald Milligan, Charles Craddock, Ruth Pettengell, Ahmet Dogan, Kirsty J Thomson, Emma C Morris, Geoff Hale, Herman Waldmann, Anthony H Goldstone, David C Linch, Stephen Mackinnon
Journal: The Lancet (2005)
Decreased maximal aerobic capacity with use of a triphasic oral contraceptive in highly active women: a randomised controlled trial
Authors: C M Lebrun, M A Petit, D C McKenzie, J E Taunton, J C Prior
Journal: British Journal of Sports Medicine (2003)

Oral contraceptives are commonly used by women athletes. However, their effect on athletic performance is unclear.To examine the effects of a moderate dose, triphasic oral contraceptive on measures of athletic performance in highly trained women athletes.This is a double blind, placebo controlled trial in 14 women with ovulatory menstrual cycles and maximal aerobic capacity (VO(2)MAX) >/==" BORDER="0">50 ml/kg/min. Four measures of athletic performance were tested: VO(2)MAX, anaerobic capacity (anaerobic speed test), aerobic endurance (time to fatigue at 90% of VO(2)MAX), and isokinetic strength (Cybex II dynamometer). Height, weight, and six skinfold measurements were also recorded. All these observational tests were completed during both the follicular and mid-luteal phases of an ovulatory menstrual cycle. Cycle phases were confirmed by assaying plasma oestradiol and progesterone. Participants were subsequently randomly assigned to either a tricyclic oral contraceptive or placebo and retested in identical fashion (oral contraceptive phase).Absolute and relative changes in VO(2)MAX from follicular to oral contraceptive phase decreased in the oral contraceptive group by 4.7%, whereas the placebo group showed a slight increase (+1.5%) over the same time period. Two of the women taking oral contraceptive had decreases of 4 and 9 ml/kg/min. In contrast, most women in the placebo group improved or maintained VO(2)MAX. There was also a significant increase in the sum of skinfolds in women taking oral contraceptive compared with those taking placebo (p<0.01). There were no significant changes in other physiological variables (maximum ventilation, heart rate, respiratory exchange ratio, packed cell volume) or measures of performance (anaerobic speed test, aerobic endurance, isokinetic strength) as a function of oral contraceptive treatment.The decrease in VO(2)MAX that occurs when oral contraceptive is taken may influence elite sporting performance in some women. Further studies are required to determine the mechanisms of this change.
Creation of a Genetic Calcium Channel Blocker by Targeted Gem Gene Transfer in the Heart
Authors: Mitsushige Murata, Eugenio Cingolani, Amy D. McDonald, J. Kevin Donahue, Eduardo Marbán
Journal: Circulation Research (2004)

Calcium channel blockers are among the most commonly used therapeutic drugs. Nevertheless, the utility of calcium channel blockers for heart disease is limited because of the potent vasodilatory effect that causes hypotension, and other side effects attributable to blockade of noncardiac channels. Therefore, focal calcium channel blockade by gene transfer is highly desirable. With a view to creating a focally applicable genetic calcium channel blocker, we overexpressed the ras-related small G-protein Gem in the heart by somatic gene transfer. Adenovirus-mediated delivery of Gem markedly decreased L-type calcium current density in ventricular myocytes, resulting in the abbreviation of action potential duration. Furthermore, transduction of Gem resulted in a significant shortening of the electrocardiographic QTc interval and reduction of left ventricular systolic function. Focal delivery of Gem to the atrioventricular (AV) node significantly slowed AV nodal conduction (prolongation of PR and AH intervals), which was effective in the reduction of heart rate during atrial fibrillation. Thus, these results indicate that gene transfer of Gem functions as a genetic calcium channel blocker, the local application of which can effectively modulate cardiac electrical and contractile function.
The Associations of Fibroblast Growth Factor 23 and Uncarboxylated Matrix Gla Protein With Mortality in Coronary Artery Disease: The Heart and Soul Study
Authors: Benjamin D. Parker
Journal: Annals of Internal Medicine (2010)

Background: Fibroblast growth factor 23 (FGF23), uncarboxylated matrix Gla protein (ucMGP), and fetuin-A are regulators of mineral metabolism and inhibitors of vascular calcification. Whether circulating levels of each are associated with cardiovascular disease (CVD) events or mortality in populations without end-stage renal disease is unknown. Objective: To evaluate the associations of FGF23, ucMGP, and fetuin-A with mortality and CVD events. Design: Observational study. Setting: 12 outpatient clinics in the San Francisco Bay area. Patients: 833 outpatients with stable coronary artery disease (CAD), recruited from 11 September 2000 to 20 December 2002. Measurements: Fibroblast growth factor 23, ucMGP, and fetuin-A concentrations were measured at baseline. Participants were followed until 1 December 2008 for mortality and CVD events. Results: During a median follow-up of 6.0 years, 220 participants died and 182 had CVD events. Compared with participants with FGF-23 levels in the lowest tertile, those in the highest tertile had 2-fold greater risk for mortality (hazard ratio [HR], 2.15 [95% CI, 1.43 to 3.24]) and CVD events (HR, 1.83 [CI, 1.15 to 2.91]) after adjustment for traditional CVD risk factors, C-reactive protein levels, and kidney function. The highest ucMGP tertile was associated with lower mortality risk (HR, 0.48 [CI, 0.31 to 0.75]) and showed a nonsignificant trend toward lower CVD event risk by tertile analysis (HR, 0.65 [CI, 0.40 to 1.05])—an association that was significant when modeled continuously (P = 0.029). No significant association of fetuin-A with mortality (HR, 0.84 [CI, 0.55 to 1.27]) or CVD events (HR, 0.99 [CI, 0.64 to 1.55]) was observed. Limitation: Participants had prevalent CAD. Conclusion: In outpatients with stable CAD, higher FGF23 and lower ucMGP levels are independently associated with mortality and CVD events. Primary Funding Source: American Heart Association.
CIP2A Is Associated with Human Breast Cancer Aggressivity
Authors: Christophe Côme, Anni Laine, Maïa Chanrion, Henrik Edgren, Elina Mattila, Xiaoling Liu, Jos Jonkers, Johanna Ivaska, Jorma Isola, Jean-Marie Darbon, Olli Kallioniemi, Simon Thézenas, Jukka Westermarck
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To investigate the clinical relevance of the recently characterized human oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) in human breast cancer. Experimental Design: CIP2A expression (mRNA and protein) was measured in three different sets of human mammary tumors and compared with clinicopathologic variables. The functional role of CIP2A in breast cancer cells was evaluated by small interfering RNA–mediated depletion of the protein followed by an analysis of cell proliferation, migration, anchorage-independent growth, and xenograft growth. Results: CIP2A mRNA is overexpressed (n = 159) and correlates with higher Scarff-Bloom-Richardson grades (n = 251) in samples from two independent human breast cancer patients. CIP2A protein was found to be overexpressed in 39% of 33 human breast cancer samples. Furthermore, CIP2A mRNA expression positively correlated with lymph node positivity of the patients and with the expression of proliferation markers and p53 mutations in the tumor samples. Moreover, CIP2A protein expression was induced in breast cancer mouse models presenting mammary gland–specific depletion of p53 and either BRCA1 or BRCA2. Functionally, CIP2A depletion was shown to inhibit the expression of its target protein c-Myc. Loss of CIP2A also inhibited anchorage-independent growth in breast cancer cells. Finally, CIP2A was shown to support MDA-MB-231 xenograft growth in nude mice. Conclusions: Our data show that CIP2A is associated with clinical aggressivity in human breast cancer and promotes the malignant growth of breast cancer cells. Thus, these results validate the role of CIP2A as a clinically relevant human oncoprotein and warrant further investigation of CIP2A as a therapeutic target in breast cancer treatment. (Clin Cancer Res 2009;15(16):5092–100)
Feasibility of Eliminating Ocular &lt;EMPH TYPE="ITAL"&gt;Chlamydia trachomatis&lt;/EMPH&gt; With Repeat Mass Antibiotic Treatments
Authors: Muluken Melese
Journal: JAMA (2004)

ASS ANTIMICROBIAL ADministrations have been used in several control programs and have been contemplated for many others.2][3] Various forms of mass treatment have been used for bacterial diseases, including sexually transmitted chlamydia and syphilis. 4,5The World Health Organization (WHO) 6 and its partners are now using repeated mass azithromycin administrations to control the ocular strains of chlamydia that cause trachoma, the world's leading cause of infectious blindness. 7Trachoma meets the critical criteria for eradicability: there is an effective treatment for the ocular strains of Chlamydia trachomatis, and there is no known animal reservoir.Cur
Lack of Renal Dopamine D5 Receptors Promotes Hypertension
Authors: Laureano Asico, Xiaojie Zhang, Jifu Jiang, David Cabrera, Crisanto S. Escano, David R. Sibley, Xiaoyan Wang, Yu Yang, Roslyn Mannon, John E. Jones, Ines Armando, Pedro A. Jose
Journal: Journal of the American Society of Nephrology (2010)

Disruption of the dopamine D<sub>5</sub> receptor gene in mice increases BP and causes salt sensitivity. To determine the role of renal <i>versus</i> extrarenal D<sub>5</sub> receptors in BP regulation, we performed cross-renal transplantation experiments. BP was similar between wild-type mice and wild-type mice transplanted with wild-type kidneys, indicating that the transplantation procedure did not affect BP. BP was lower among D<sub>5</sub><sup>−/−</sup> mice transplanted with wild-type kidneys than D<sub>5</sub><sup>−/−</sup> kidneys, demonstrating that the renal D<sub>5</sub> receptors are important in BP control. BP was higher in wild-type mice transplanted with D<sub>5</sub><sup>−/−</sup> kidneys than wild-type kidneys but not significantly different from syngenic transplanted D<sub>5</sub><sup>−/−</sup> mice, indicating the importance of the kidney in the development of hypertension. On a high-salt diet, all mice with D<sub>5</sub><sup>−/−</sup> kidneys excreted less sodium than mice with wild-type kidneys. Transplantation of a wild-type kidney into a D<sub>5</sub><sup>−/−</sup> mouse decreased the renal expression of AT<sub>1</sub> receptors and Nox-2. Conversely, transplantation of a D<sub>5</sub><sup>−/−</sup> kidney into a wild-type mouse increased the expression of both, suggesting that both renal and extrarenal factors are important in the regulation of AT<sub>1</sub> receptor and Nox-2 expression. These results highlight the role of renal D<sub>5</sub> receptors in BP homeostasis and the pathogenesis of hypertension.
A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis
Authors: Paul J Rutgeerts, Richard N Fedorak, Daan W Hommes, Andreas Sturm, Daniel C Baumgart, Brian Bressler, Stefan Schreiber, John C Mansfield, Marna Williams, Meina Tang, Jennifer Visich, Xiaohui Wei, Mary Keir, Diana Luca, Dimitri Danilenko, Jackson Egen, Sharon O'Byrne
Journal: Gut (2012)

<h3>Objective</h3> Etrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC. <h3>Design</h3> In the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD). <h3>Results</h3> In the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively. <h3>Conclusion</h3> Etrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted.
Nutritional Aspects of Collagen Metabolism
Authors: R A Berg, J S Kerr
Journal: Annual Review of Nutrition (1992)

INTRODUCTION  370 EXTRACELLULAR MATRIX  370 Collagen Types and Tissue Distribution. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . 370 Collagen Turnover. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .   372 AMINO ACID DEFICIENCy  374 Starvation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .   ......... 374 Nutritional Emphysema . . . . . . . . . . . . . . .. . .. . . . . . . . . . . . . .. . ..... . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . .. 376 CONTRIBUTION OF COLLAGEN TO NUTRITION  376 ROLE OF VITAMINS IN COLLAGEN METABOLISM ........ . .   .... ......... . . 377 Vitamin A. . . . . . . . . . ... . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. 377 Vitamin C .. ... . .. . ........   .. . . .. .. ...... ... . ... . ...   . . . . . . .. .... ........ . . 378 Vitamin D .........   ..... .   . .... .... .......   ......... . . 380 MINERAL BALANCE AND BONE HOMEOSTASIS AS RELATED TO COLLAGEN METABOLISM   ... ...   .. ..   .     381 Calcitonin . . . . . . . . . . .     381 Parathyroid Hormone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . 382 CONCLUSION  383
Long term follow up of changes in FEV1 and treatment intensity during Pseudomonas aeruginosa colonisation in patients with cystic fibrosis
Authors: M. Ballmann, P. Rabsch, H. von der Hardt
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Colonisation with <i>Pseudomonas aeruginosa </i>(PA) is a striking feature of lung involvement in cystic fibrosis. To identify the clinical consequences of the different steps of colonisation with PA under a defined therapeutic regime (no prophylactic antibiotic treatment as long as patients had no severe pulmonary disease), their influence on pulmonary function and on therapeutic intensity was examined. <h3>METHODS</h3> Forty patients with cystic fibrosis were followed from first detection of PA (PA1), chronic PA colonisation (PAc), first mucoid PA detection (PAm), to chronic mucoid PA colonisation (PAcm). Percentage predicted forced expiratory volume in one second (FEV<sub>1</sub>), the number of intravenous antibiotic treatment courses, and the percentage of patients on inhaled antibiotics were followed retrospectively and longitudinally in relation to the different steps of PA colonisation. The annual changes in FEV<sub>1</sub> and therapeutic intensity in the two years preceding each step were compared with the two years following each step. Changes in FEV<sub>1</sub> were related to therapeutic intensity. <h3>RESULTS</h3> The mean (SD) annual changes in FEV<sub>1</sub> (% predicted) worsened significantly only with the transition to the mucoid stages (PAm: 4.6 (13.2) versus –4.3 (8.1); PAcm: 7.3 (12.0) versus –4.8 (7.4)) with a mean difference (95% CI) between before and after the transition of 8.9 (2.6 to 15.2) for PAm and 12.1 (6.4 to 17.6) for PAcm. With non-mucoid PA stages the therapeutic intensity increased in the year of transition and with mucoid PA stages it increased in the years following transition. Therapeutic intensity was unrelated to changes in FEV<sub>1</sub>. <h3>CONCLUSION</h3> With the treatment regime used an accelerated decrease in FEV<sub>1</sub> was successfully prevented in the non-mucoid stages but not in the mucoid stages of PA colonisation.
New health funding allocation targets England's deprived areas
Authors: Rebecca Coombes
Journal: BMJ (2005)

Deprived areas in England will get proportionally larger increases in funds for primary health care in the next couple of years, the health secretary, John Reid, announced last week.

The funding increase—in which no trust will get less than an average of 8.1% more in 2006-7 and 2007-8 than in 2005-6—was greeted as a step in the right direction, although critics queried how much of the extra cash would be used up in new pay deals for staff.

Mr Reid said that a total of £135bn ($250bn; €200bn) had been allocated to primary care trusts for 2006-7 …
Primary Granulocyte Colony-Stimulating Factor Prophylaxis During the First Two Cycles Only or Throughout All Chemotherapy Cycles in Patients With Breast Cancer at Risk for Febrile Neutropenia
Authors: Maureen J. Aarts, Frank P. Peters, Caroline M. Mandigers, M. Wouter Dercksen, Jacqueline M. Stouthard, Hans J. Nortier, Hanneke W. van Laarhoven, Laurence J. van Warmerdam, Agnes J. van de Wouw, Esther M. Jacobs, Vera Mattijssen, Carin C. van der Rijt, Tineke J. Smilde, Annette W. van der Velden, Mehmet Temizkan, Erdogan Batman, Erik W. Muller, Saskia M. van Gastel, George F. Borm, Vivianne C.G. Tjan-Heijnen
Journal: Journal of Clinical Oncology (2013)

Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy.In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm.After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis).In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.
Radiofrequency Thermal Ablation of Hepatocellular Carcinoma Liver Nodules Can Activate and Enhance Tumor-Specific T-Cell Responses
Authors: Alessandro Zerbini, Massimo Pilli, Amalia Penna, Guido Pelosi, Claudia Schianchi, Atim Molinari, Simona Schivazappa, Carlo Zibera, Francesco F. Fagnoni, Carlo Ferrari, Gabriele Missale
Journal: Cancer Research (2006)

Abstract Radiofrequency thermal ablation (RFA) destroys tumoral tissue generating a local necrosis followed by marked inflammatory response with a dense T-cell infiltrate. In this study, we tested whether hepatocellular carcinoma thermal ablation can induce or enhance T-cell responses specific for hepatocellular carcinoma–associated antigens. Peripheral blood mononuclear cells derived from 20 patients with hepatocellular carcinoma were stimulated before and a month after RFA treatment with autologous hepatocellular carcinoma–derived protein lysates obtained before and immediately after RFA treatment. The effect of thermal ablation on memory T-cell responses to recall antigens [tetanus toxoid, protein purified derivative (PPD), Escherichia coli] was also assessed. T-cell reactivity was analyzed in an IFN-γ enzyme-linked immunospot assay and by intracellular IFN-γ staining. Treatment was followed by a significant increase of patients responsive either to tumor antigens derived from both the untreated hepatocellular carcinoma tissue (P &amp;lt; 0.05) and the necrotic tumor (P &amp;lt; 0.01) and by a higher frequency of circulating tumor-specific T cells. T-cell responses to recall antigens were also significantly augmented. Phenotypic analysis of circulating T and natural killer cells showed an increased expression of activation and cytotoxic surface markers. However, tumor-specific T-cell responses were not associated with protection from hepatocellular carcinoma relapse. Evidence of tumor immune escape was provided in one patient by the evidence that a new nodule of hepatocellular carcinoma recurrence was not recognized by T cells obtained at the time of RFA. In conclusion, RFA treatment generates the local conditions for activating the tumor-specific T-cell response. Although this effect is not sufficient for controlling hepatocellular carcinoma, it may represent the basis for the development of an adjuvant immunotherapy in patients undergoing RFA for primary and secondary liver tumors. (Cancer Res 2006; 66(2): 1139-46)
Additive antiproteinuric effect of converting enzyme inhibition and a low protein intake.
Authors: L M Ruilope, M C Casal, M Praga, J M Alcazar, G Decap, V Lahera, J L Rodicio
Journal: Journal of the American Society of Nephrology (1992)

The hypothesis that converting enzyme inhibition and a protein-restricted diet could have additive antiproteinuric effects has been tested. A group of 17 patients with proteinuria in excess of 3 g/24 h per 1.73 m2 of body surface area were submitted to a 3-wk period of study, after a 4-wk wash-out period during which protein intake was 1.0 g/kg per day and in the absence of any medication. During the first and second weeks of the study, protein intake was lowered to 0.3 g/kg per day, and in the third week, it returned to 1.0 g/kg per day. Enalapril (20 mg daily) was administered during the second and third weeks of the study. Initially and at the end of each week thereafter, we determined blood pressure, GFR (inulin clearance), RPF (para-aminohippurate clearance), plasma sodium and potassium, PRA and aldosterone, and the 24-h urine excretion of sodium potassium, protein, and urea. The low protein intake during the first week induced a significant fall of proteinuria (P < 0.01), GFR (P < 0.01), and RPF (P < 0.01) in the absence of changes in filtration fraction. The addition of enalapril induced a further decrease of proteinuria (P < 0.01) and a fall in filtration fraction (P < 0.05), whereas plasma potassium, PRA, GFR, and RPF values increased (P < 0.01). The rise in protein intake during the last week of the study induced a significant rise in proteinuria, GFR, and RPF (P < 0.01), although the first of these parameters attained values significantly lower (P < 0.05) than those observed initially.(ABSTRACT TRUNCATED AT 250 WORDS)