tbuckley/cabot-search huggingface dataset:
Human Apolipoprotein A-I Gene Transfer Reduces the Development of Experimental Diabetic Cardiomyopathy
Authors: Sophie Van Linthout, Frank Spillmann, Alexander Riad, Christiane Trimpert, Joke Lievens, Marco Meloni, Felicitas Escher, Elena Filenberg, Okan Demir, Jun Li, Mehdi Shakibaei, Ingolf Schimke, Alexander Staudt, Stephan B. Felix, Heinz-Peter Schultheiss, Bart De Geest, Carsten Tschöpe
Journal: Circulation (2008)

The hallmarks of diabetic cardiomyopathy are cardiac oxidative stress, intramyocardial inflammation, cardiac fibrosis, and cardiac apoptosis. Given the antioxidative, antiinflammatory, and antiapoptotic potential of high-density lipoprotein (HDL), we evaluated the hypothesis that increased HDL via gene transfer (GT) with human apolipoprotein (apo) A-I, the principal apolipoprotein of HDL, may reduce the development of diabetic cardiomyopathy.Intravenous GT with 3x10(12) particles/kg of the E1E3E4-deleted vector Ad.hapoA-I, expressing human apoA-I, or Ad.Null, containing no expression cassette, was performed 5 days after streptozotocin (STZ) injection. Six weeks after apoA-I GT, HDL cholesterol levels were increased by 1.6-fold (P<0.001) compared with diabetic controls injected with the Ad.Null vector (STZ-Ad.Null). ApoA-I GT and HDL improved LV contractility in vivo and cardiomyocyte contractility ex vivo, respectively. Moreover, apoA-I GT was associated with decreased cardiac oxidative stress and reduced intramyocardial inflammation. In addition, compared with STZ-Ad.Null rats, cardiac fibrosis and glycogen accumulation were reduced by 1.7-fold and 3.1-fold, respectively (P<0.05). Caspase 3/7 activity was decreased 1.2-fold (P<0.05), and the ratio of Bcl-2 to Bax was upregulated 1.9-fold (P<0.005), translating to 2.1-fold (P<0.05) reduced total number of cardiomyocytes with apoptotic characteristics and 3.0-fold (P<0.005) reduced damaged endothelial cells compared with STZ-Ad.Null rats. HDL supplementation ex vivo reduced hyperglycemia-induced cardiomyocyte apoptosis by 3.4-fold (P<0.005). The apoA-I GT-mediated protection was associated with a 1.6-, 1.6-, and 2.4-fold induction of diabetes-downregulated phospho to Akt, endothelial nitric oxide synthase, and glycogen synthase kinase ratio, respectively (P<0.005).ApoA-I GT reduced the development of streptozotocin-induced diabetic cardiomyopathy.
The Effects of Parathyroid Hormone and Alendronate Alone or in Combination in Postmenopausal Osteoporosis
Authors: Dennis M. Black, Susan L. Greenspan, Kristine E. Ensrud, Lisa Palermo, Joan A. McGowan, Thomas F. Lang, Patrick Garnero, Mary L. Bouxsein, John P. Bilezikian, Clifford J. Rosen
Journal: New England Journal of Medicine (2003)

Parathyroid hormone increases bone strength primarily by stimulating bone formation, whereas antiresorptive drugs reduce bone resorption. We conducted a randomized, double-blind clinical study of parathyroid hormone and alendronate to test the hypothesis that the concurrent administration of the two agents would increase bone density more than the use of either one alone.
Review of Neil C. Manson and Onora O'Neill, Rethinking Informed Consent in Bioethics<sup>1</sup>
Authors: Lisa S. Parker
Journal: The American Journal of Bioethics (2008)

Much of the thinking in Neil Manson and Onora O'Neill's 2007 volume is insightful, provocative, and illuminating—especially their analysis of information and privacy. Surprisingly, however, much of...
Physiological profiles and sport specific fitness of Asian elite squash players.
Authors: M K Chin, K Steininger, R C So, C R Clark, A S Wong
Journal: British Journal of Sports Medicine (1995)

There is a scarcity of descriptive data on the physiological characteristics of elite Asian squash players. The purpose of this study was to evaluate the physiological profile and sports specific fitness of Hong Kong elite squash players. It was conducted before the selection of the Hong Kong national squash team for the 1992 Asian Squash Championship. Ten elite squash players were selected as subjects for the study. Maximum oxygen uptake was measured using a continuous treadmill running test. A sports specific field test was performed in a squash court. The following means (s.d.) were observed: height 172.6(4.3) cm; weight 67.7(6.9) kg; body fat 7.4(3.4)%; forced vital capacity (FVC) 5.13(0.26) litres; maximum oxygen uptake (VO2max) 61.7(3.4) ml.kg-1.min-1; anaerobic threshold (AT) 80.2(3.3)% of VO2max; alactic power index 15.5(1.8) W.kg-1; lactic work index 323.5(29.4) J.kg-1, peak isokinetic dominant knee extensor and flexor strengths 3.11(0.29) Nm.kg-1 and 1.87(0.18) Nm.kg-1. The results show that the Hong Kong squash players have relatively high cardiorespiratory sports specific fitness and muscle strength which may be one of the key factors that contributed to the success of the Hong Kong team in the Asian Championship.
Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home
Authors: PJ Wijkstra, R Van Altena, J Kraan, V Otten, DS Postma, GH Koeter
Journal: European Respiratory Journal (1994)

We have developed a rehabilitation programme at home and have investigated its effects on quality of life (QOL), lung function, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). We studied 43 patients with severe airflow obstruction: forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 l (mean +/- SD), FEV1/inspiratory vital capacity (IVC) 37 +/- 7.9%. After stratification, 28 patients were randomly allocated in a home rehabilitation programme for 12 weeks. Fifteen patients in a control group received no rehabilitation. The rehabilitation group received physiotherapy by the local physiotherapist, and supervision by a nurse and a general practitioner. Quality of life was assessed by the four dimensions of the Chronic Respiratory Questionnaire (CRQ). We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea, emotion, and mastery. Lung function showed no changes in the rehabilitation group. The exercise tolerance improved significantly in the rehabilitation group compared to the control group. The improvement in quality of life was not correlated with the improvement in exercise tolerance. Rehabilitation of COPD patients at home may improve quality of life; this improvement is not correlated with an improvement in lung function and exercise tolerance.
Selective Inhibition of Fatty Acid Synthase for Lung Cancer Treatment
Authors: Hajime Orita, Jonathan Coulter, Colleen Lemmon, Ellen Tully, Aravinda Vadlamudi, Susan M. Medghalchi, Francis P. Kuhajda, Edward Gabrielson
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. However, in vitro use of previous generations of FAS inhibitors has been limited by severe, but reversible, anorexia in treated animals, which is thought to be related to a parallel stimulation of fatty acid oxidation by these agents. This study investigated pharmacologic inhibition of FAS using C93, a rationally designed molecule that inhibits FAS activity without affecting fatty acid oxidation in preclinical models of lung cancer. Experimental Design: Activity of C93 on FAS and fatty acid oxidation was evaluated in cultured non–small cell lung cancer (NSCLC) cells. Antineoplastic activity of the compound, given orally or by i.p. injection, was evaluated in s.c. and orthotopic NSCLC xenografts. Results: Our experiments confirm that C93 effectively inhibits FAS without stimulating fatty acid oxidation in lung cancer cells. More importantly, C93 significantly inhibits the growth of both s.c. and orthotopic xenograft tumors from human NSCLC cell lines without causing anorexia and weight loss in the treated animals. Conclusions: We conclude that inhibition of FAS can be achieved without parallel stimulation of fatty acid oxidation and that inhibition of tumor growth in vivo can be achieved without anorexia and weight loss. Thus, this therapeutic strategy holds promise for clinical treatment of cancers, including non–small cell lung cancer, the leading cause of cancer mortality in the United States and Europe.
Gene Expression Profiling in Non-Small Cell Lung Cancer
Authors: Russell D. Petty, Marianne C. Nicolson, Keith M. Kerr, Elaina Collie-Duguid, Graeme I. Murray
Journal: Clinical Cancer Research (2004)

Abstract Non-small cell lung cancer (NSCLC) is the most common cause of premature death from malignant disease in western countries. A better understanding of the molecular mechanisms underlying NSCLC etiology, pathogenesis, and therapeutics will lead to improved clinical outcomes. Recent technological advances in gene expression profiling (in particular, with cDNA and oligonucleotide microarrays) allow the simultaneous analysis of the expression of thousands of genes. In this review, the technology of global gene expression profiling is discussed, and the progress made thus far with it in NSCLC is reviewed. A new molecular classification of NSCLC has been developed, which has provided important insights into etiology and pathogenesis. Other studies have found potential biomarkers for NSCLC that may be of use in diagnosis, screening, and assessing the effectiveness of therapy. Finally, advances have been made in the understanding of the molecular mechanisms of NSCLC progression and the molecular mechanisms of action of currently used cytotoxic drugs. This may facilitate the improvement of current therapeutics and the identification of novel targets. Taken together, these advances hold the promise of an improved understanding of the molecular biology of NSCLC and its treatment, which in turn will lead to improved outcomes for this deadly disease.
The ketamine model for schizophrenia
Authors: Murray Alpert, Burt Angrist
Journal: Behavioral and Brain Sciences (2003)

Abstract This commentary compares clinical aspects of ketamine with the amphetamine model of schizophrenia. Hallucinations and loss of insight, associated with amphetamine, seem more schizophrenia-like. Flat affect encountered with ketamine is closer to the clinical presentation in schizophrenia. We argue that flat affect is not a sign of schizophrenia, but rather, a risk factor for chronic schizophrenia.
Geminin Functions Downstream of p53 in <i>K-ras</i>–Induced Gene Amplification of Dihydrofolate Reductase
Authors: Ling Shen, Takashi Nishioka, Jinjin Guo, Changyan Chen
Journal: Cancer Research (2012)

DNA strand breakage and perturbation of cell-cycle progression contribute to gene amplification events that can drive cancer. In cells lacking p53, DNA damage does not trigger an effective cell-cycle arrest and in this setting promotes gene amplification. This is also increased in cells harboring oncogenic Ras, in which cell-cycle arrest is perturbed and ROS levels that cause DNA single strand breaks are elevated. This study focused on the effects of v-K-ras and p53 on Methotrexate (MTX)-mediated DHFR amplification. Rat lung epithelial cells expressing v-K-ras or murine lung cancer LKR cells harboring active K-ras continued cell-cycle progression when treated with MTX. However, upon loss of p53, amplification of DHFR and formation of MTX-resistant colonies occurred. Expression levels of cyclin A, Geminin, and Cdt1 were increased in v-K-ras transfectants. Geminin was sufficient to prevent the occurrence of multiple replications via interaction with Cdt1 after MTX treatment, and DHFR amplification proceeded in v-K-ras transfectants that possess a functional p53 in the absence of geminin. Taken together, our findings indicate that p53 not only regulates cell-cycle progression, but also functions through geminin to prevent DHFR amplification and protect genomic integrity.
Effects of dietary intervention and quadriceps strengthening exercises on pain and function in overweight people with knee pain: randomised controlled trial
Authors: C. M Jenkinson, M. Doherty, A. J Avery, A. Read, M. A Taylor, T. H Sach, P. Silcocks, K. R Muir
Journal: BMJ (2009)

<b>Objective</b> To determine whether dietary intervention or knee strengthening exercise, or both, can reduce knee pain and improve knee function in overweight and obese adults in the community. <b>Design</b> Pragmatic factorial randomised controlled trial. <b>Setting</b> Five general practices in Nottingham. <b>Participants</b> 389 men and women aged 45 and over with a body mass index (BMI) of ≥28.0 and self reported knee pain. <b>Interventions</b> Participants were randomised to dietary intervention plus quadriceps strengthening exercises; dietary intervention alone; quadriceps strengthening exercises alone; advice leaflet only (control group). Dietary intervention consisted of individualised healthy eating advice that would reduce normal intake by 2.5 MJ (600 kcal) a day. Interventions were delivered at home visits over a two year period. <b>Main outcome measures</b> The primary outcome was severity of knee pain scored with the Western Ontario McMaster (WOMAC) osteoarthritis index at 6, 12, and 24 months. Secondary outcomes (all at 24 months) included WOMAC knee physical function and stiffness scores and selected domains on the SF-36 and the hospital anxiety and depression index. <b>Results</b> 289 (74%) participants completed the trial. There was a significant reduction in knee pain in the knee exercise groups compared with those in the non-exercise groups at 24 months (percentage risk difference 11.61, 95% confidence interval 1.81% to 21.41%). The absolute effect size (0.25) was moderate. The number needed to treat to benefit from a ≥30% improvement in knee pain at 24 months was 9 (5 to 55). In those randomised to knee exercise improvement in function was evident at 24 months (mean difference −3.64, −6.01 to −1.27). The mean difference in weight loss at 24 months in the dietary intervention group compared with no dietary intervention was 2.95 kg (1.44 to 4.46); for exercise versus no exercise the difference was 0.43 kg (−0.82 to 1.68). This difference in weight loss was not associated with improvement in knee pain or function but was associated with a reduction in depression (absolute effect size 0.19). <b>Conclusions</b> A home based, self managed programme of simple knee strengthening exercises over a two year period can significantly reduce knee pain and improve knee function in overweight and obese people with knee pain. A moderate sustained weight loss is achievable with dietary intervention and is associated with reduced depression but is without apparent influence on pain or function. <b>Trial registration</b> Current Controlled Trials ISRCTN 93206785.
Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study
Authors: Henrik Hasle, Todd A. Alonzo, Anne Auvrignon, Catherine Behar, Myron Chang, Ursula Creutzig, Alexandra Fischer, Erik Forestier, Alcira Fynn, Oskar A. Haas, Jochen Harbott, Christine J. Harrison, Nyla A. Heerema, Marry M. van den Heuvel-Eibrink, Gertjan J. L. Kaspers, Franco Locatelli, Peter Noellke, Sophia Polychronopoulou, Yaddanapudi Ravindranath, Bassem Razzouk, Dirk Reinhardt, Natalia N. Savva, Batia Stark, Stefan Suciu, Ichiro Tsukimoto, David K. Webb, Dorora Wojcik, William G. Woods, Martin Zimmermann, Charlotte M. Niemeyer, Susana C. Raimondi
Journal: Blood (2007)
Examination of the follicular lymphoma international prognostic index (FLIPI) in the National LymphoCare study (NLCS): a prospective US patient cohort treated predominantly in community practices
Authors: A.K. Nooka, C. Nabhan, X. Zhou, M.D. Taylor, M. Byrtek, T.P. Miller, J.W. Friedberg, A.D. Zelenetz, B.K. Link, J.R. Cerhan, H. Dillon, R. Sinha, P.J. Shenoy, D. Levy, K. Dawson, J.H. Hirata, C.R. Flowers
Journal: Annals of Oncology (2012)
Euglycemic Hyperinsulinemia Alters the Response to Orthostatic Stress in Older Adults With Type 2 Diabetes
Authors: Kenneth M. Madden, Gale Tedder, Chris Lockhart, Graydon S. Meneilly
Journal: Diabetes Care (2008)

Insulin has opposing influences on blood pressure by simultaneously increasing adrenergic activity and vasodilatating peripheral blood vessels. In this study, we sought to determine whether hyperinsulinemia affects tilt table responses in older adults with type 2 diabetes not complicated by orthostatic hypotension.Twenty-two older adults (mean age 71.7 +/- 1.1) with diet-controlled or oral hypoglycemic drug-controlled type 2 diabetes were recruited. All subjects with orthostatic hypotension, diabetic nephropathy, and sensory neuropathy were excluded. Subjects underwent euglycemic-hyperinsulinemic clamp and placebo "sham clamp" sessions. Sequential euglycemic-hyperinsulinemic clamps were performed for 2 h at 40 mU x m(-2) x min(-1) (low dose) and 2 h at 80 mU x m(-2) x min(-1) (high dose), and each was followed by a head-up tilt table test at 70 degrees C for 10 min.There were no incidents of presyncope during the sham clamp, whereas there were four presyncopal events during both the low-dose and high-dose tilts. Although the low-dose clamp showed no difference in the response between sessions (two-way ANOVA), subjects demonstrated a significantly larger decrease in mean arterial pressure (P = 0.005) and diastolic blood pressure (P = 0.08) during the high-dose tilt. Doppler measures of middle cerebral artery velocity were no different between the two sessions at either dose.The vasodilatory response to insulin can unmask orthostatic intolerance in older adults with type 2 diabetes, resulting in presyncopal symptoms. This could contribute to orthostatic hypotension in combination with other factors such as hyperthermia, hypovolemia, and adverse effects from medications.
Effect of Corticosteroid on Lung Parenchyma Remodeling at an Early Phase of Acute Lung Injury
Authors: Patricia R. M. Rocco, Alba B. Souza, Debora S. Faffe, Caroline P. Pássaro, Flávia B. Santos, Elnara M. Negri, Januário G. M. Lima, Renata S. Contador, Vera L. Capelozzi, Walter A. Zin
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

In vivo (lung resistive and viscoelastic pressures and static elastance) and in vitro (tissue resistance, elastance, and hysteresivity) respiratory mechanics were analyzed 1 and 30 days after saline (control) or paraquat (P [10 and 25 mg/kg intraperitoneally]) injection in rats. Additionally, P10 and P25 were treated with methylprednisolone (2 mg/kg intravenously) at 1 or 6 hours after acute lung injury (ALI) induction. Collagen and elastic fibers were quantified. Lung resistive and viscoelastic pressures and static elastance were higher in P10 and P25 than in the control. Tissue elastance and resistance augmented from control to P10 (1 and 30 days) and P25. Hysteresivity increased in only P25. Methylprednisolone at 1 or 6 hours attenuated in vivo and in vitro mechanical changes in P25, whereas P10 parameters were similar to the control. Collagen increment was dose and time dependent. Elastic fibers increased in P25 and at 30 days in P10. Corticosteroid prevented collagen increment and avoided elastogenesis. In conclusion, methylprednisolone led to a complete maintenance of in vivo and in vitro respiratory mechanics in mild lesion, whereas it minimized the changes in tissue impedance and extracellular matrix in severe ALI. The beneficial effects of the early use of steroids in ALI remained unaltered at Day 30.
Revision Rates after Primary Hip and Knee Replacement in England between 2003 and 2006
Authors: Nokuthaba Sibanda, Lynn P Copley, Jim D Lewsey, Mick Borroff, Paul Gregg, Alex J MacGregor, Martin Pickford, Martyn Porter, Keith Tucker, Jan H van der Meulen
Journal: PLoS Medicine (2008)

Background Hip and knee replacement are some of the most frequently performed surgical procedures in the world. Resurfacing of the hip and unicondylar knee replacement are increasingly being used. There is relatively little evidence on their performance. To study performance of joint replacement in England, we investigated revision rates in the first 3 y after hip or knee replacement according to prosthesis type. Methods and Findings We linked records of the National Joint Registry for England and Wales and the Hospital Episode Statistics for patients with a primary hip or knee replacement in the National Health Service in England between April 2003 and September 2006. Hospital Episode Statistics records of succeeding admissions were used to identify revisions for any reason. 76,576 patients with a primary hip replacement and 80,697 with a primary knee replacement were included (51% of all primary hip and knee replacements done in the English National Health Service). In hip patients, 3-y revision rates were 0.9% (95% confidence interval [CI] 0.8%–1.1%) with cemented, 2.0% (1.7%–2.3%) with cementless, 1.5% (1.1%–2.0% CI) with "hybrid" prostheses, and 2.6% (2.1%–3.1%) with hip resurfacing (p < 0.0001). Revision rates after hip resurfacing were increased especially in women. In knee patients, 3-y revision rates were 1.4% (1.2%–1.5% CI) with cemented, 1.5% (1.1%–2.1% CI) with cementless, and 2.8% (1.8%–4.5% CI) with unicondylar prostheses (p < 0.0001). Revision rates after knee replacement strongly decreased with age. Interpretation Overall, about one in 75 patients needed a revision of their prosthesis within 3 y. On the basis of our data, consideration should be given to using hip resurfacing only in male patients and unicondylar knee replacement only in elderly patients.
Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome
Authors: Dong W. Chang, Shinichi Hayashi, Sina A. Gharib, Tomas Vaisar, S. Trevor King, Mitsuhiro Tsuchiya, John T. Ruzinski, David R. Park, Gustavo Matute-Bello, Mark M. Wurfel, Roger Bumgarner, Jay W. Heinecke, Thomas R. Martin
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment.The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS).Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis.An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks.Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.