tbuckley/cabot-search huggingface dataset:
Sex-linked differences in pulse oxymetry
Authors: A Ricart, T Pages, G Viscor, C Leal, J L Ventura
Journal: British Journal of Sports Medicine (2007)

The difference between genders has generated increasing interest in recent years. It is well known that women and men show differences in their respiratory system: different red blood cell counts, haemoglobin and 2,3-diphosphoglycerate plasma concentrations. Recently, further differences have been found in the ventilatory response to hypoxia and exercise and the evolution of some respiratory illnesses. In this study it was found that during rest at sea level, the haemoglobin oxygen saturation, as measured by pulse oxymetry, is slightly higher in women than in men (98.6 (SD 1.1)% versus 97.9 (SD 0.9)%; p = 0.001). These findings are consistent with other studies, which found gender differences in the transcutaneous or tissue PaO(2). The difference in oxygen saturation is not related to differences in ventilation. The disparity is modest and does not seem to produce great differences in the oxygen content of arterial blood, but combined with the different affinity of haemoglobin for oxygen or different metabolic rate, may play a role in the course of elite competition sports, high altitude ascents or the evaluation of critically ill patients. Further studies are needed to establish the degree, extent and clinical importance of these differences in the saturation of haemoglobin.
Prognostic Role of a Multigene Reverse Transcriptase-PCR Assay in Patients with Node-Negative Breast Cancer Not Receiving Adjuvant Systemic Therapy
Authors: Francisco J. Esteva, Aysegul A. Sahin, Massimo Cristofanilli, Kevin Coombes, Sang-Joon Lee, Joffre Baker, Maureen Cronin, Michael Walker, Drew Watson, Steven Shak, Gabriel N. Hortobagyi
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To test the ability of a reverse transcriptase-PCR (RT-PCR) assay, based on gene expression profiles, to accurately determine the risk of recurrence in patients with node-negative breast cancer who did not receive systemic therapy using formalin-fixed, paraffin-embedded tissue. A secondary objective was to determine whether the quantitative RT-PCR data correlated with immunohistochemistry assay data regarding estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. Patients and Methods: We obtained archival paraffin-embedded tissue from patients with invasive breast cancer but no axillary lymph node involvement who had received no adjuvant systemic therapy and been followed for at least 5 years. RNA was extracted from three 10-μm-thick sections. The expression of 16 cancer-related genes and 5 reference genes was quantified using RT-PCR. A gene expression algorithm was used to calculate a recurrence score for each patient. We then assessed the ability of the test to accurately predict distant recurrence-free survival in this population. Results: We identified 149 eligible patients. Median age at diagnosis was 59 years; mean tumor diameter was 2 cm; and 69% of tumors were estrogen receptor positive. Median follow-up was 18 years. The 5-year disease-free survival rate for the group was 80%. The 21 gene-based recurrence score was not predictive of distant disease recurrence. However, a high concordance between RT-PCR and immunohistochemical assays for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status was noted. Conclusions: RT-PCR can be done on paraffin-embedded tissue to validate the large numbers of genes associated with breast cancer recurrence. However, further work needs to be done to develop an assay to identify the likelihood of recurrent disease in patients with node-negative breast cancer who do not receive adjuvant tamoxifen or chemotherapy.
HBx Sensitizes Cells to Oxidative Stress-induced Apoptosis by Accelerating the Loss of Mcl-1 Protein via Caspase-3 Cascade
Authors: Liang Hu, Lei Chen, GuangZhen Yang, Liang Li, HanYong Sun, YanXin Chang, QianQian Tu, MengChao Wu, HongYang Wang
Journal: Molecular Cancer (2011)

Abstract Background Oxidative stress has been implicated in the pathogenesis of a wide spectrum of human diseases, including Hepatitis B virus (HBV)-related liver disease. Hepatitis B virus X protein (HBx) is a key regulator of HBV that exerts pleiotropic activity on cellular functions. Recent studies showed that HBx alters mitochondrial membrane potential, thereby sensitizing cells to pro-apoptotic signals. However, it remains largely unknown whether susceptibility of hepatocytes could be disturbed by HBx under oxidative stress conditions. The purpose of this study is to determine the apoptotic susceptibility of HBx-expressing hepatocytes upon exposure to pro-oxidant stimuli in vitro and in vivo and explore its underlying mechanism. Results Although expression of HBx itself did not activate apoptotic signaling, it significantly enhanced oxidative stress-induced cell death both in vitro and in vivo . Interestingly, this phenomenon was associated with a pronounced reduction of protein levels of Mcl-1, but not other anti-apoptotic Bcl-2 members. Importantly, enforced expression of Mcl-1 prevented HBx-triggered cell apoptosis; conversely, specific knockdown of Mcl-1 exacerbated HBx-induced apoptosis upon exposure to oxidative stress. Furthermore, inhibition of caspase-3 not only abrogated HBx-triggered apoptotic killing but also blocked HBx-induced Mcl-1 loss. Additionally, expression of HBx and Mcl-1 was found to be inversely correlated in HBV-related hepatocellular carcinogenesis (HCC) tissues. Conclusions Our findings indicate that HBx exerts pro-apoptotic effect upon exposure to oxidative stress probably through accelerating the loss of Mcl-1 protein via caspase-3 cascade, which may shed a new light on the molecular mechanism of HBV-related hepatocarcinogenesis.
Alterations in regional myocardial metabolism, perfusion, and wall motion in Duchenne muscular dystrophy studied by radionuclide imaging.
Authors: J K Perloff, E Henze, H R Schelbert
Journal: Circulation (1984)

Studies at necropsy have shown that the cardiomyopathy of Duchenne muscular dystrophy selects the posterobasal and contiguous lateral left ventricular (LV) walls as initial and primary sites of myocardial dystrophy in the absence of small-vessel coronary artery disease in these areas. The present investigation was designed chiefly to determine whether a myocardial metabolic abnormality could be identified in these same areas during a patient's life. Positron emission computed tomography was used to study regional LV metabolism with 18F 2-fluorodeoxyglucose, and metabolism and/or perfusion was studied with 13NH3. In addition, all subjects had the following performed: thallium-201 scans, technetium-99m multiple-gated equilibrium blood pool imaging, electrocardiograms, vectorcardiograms, and M mode and two-dimensional echocardiograms. 18F 2-fluorodeoxyglucose activity was selectively increased in the posterobasal and posterolateral walls of the left ventricle in 11 of 12 patients with technically adequate images, indicating accelerated regional exogenous glucose utilization. 13NH3 activity was selectively decreased in the same areas in 13 of 15 patients, indicating either a regional metabolic alteration in uptake and trapping, a reduction in regional blood flow, or both. These data identify a myocardial metabolic abnormality concentrated in specific segments of the LV free wall in living patients with Duchenne dystrophy.
Breast Conservation After Neoadjuvant Chemotherapy: The M.D. Anderson Cancer Center Experience
Authors: Allen M. Chen, Funda Meric-Bernstam, Kelly K. Hunt, Howard D. Thames, Mary Jane Oswald, Elesyia D. Outlaw, Eric A. Strom, Marsha D. McNeese, Henry M. Kuerer, Merrick I. Ross, S. Eva Singletary, Fredrick C. Ames, Barry W. Feig, Aysegul A. Sahin, George H. Perkins, Naomi R. Schechter, Gabriel N. Hortobagyi, Thomas A. Buchholz
Journal: Journal of Clinical Oncology (2004)

Purpose To determine patterns of local-regional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) among patients treated with breast conservation therapy after neoadjuvant chemotherapy. Patients and Methods Between 1987 and 2000, 340 cases of breast cancer were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy. Clinical stage at diagnosis (according to the 2003 American Joint Committee on Cancer system) was I in 4%, II in 58%, and III in 38% of patients. Only 4% had positive surgical margins. Results At a median follow-up period of 60 months (range, 10 to 180 months), 29 patients had developed LRR, 16 of which were IBTRs. Five-year actuarial rates of IBTR-free and LRR-free survival were 95% and 91%, respectively. Variables that positively correlated with IBTR and LRR were clinical N2 or N3 disease, pathologic residual tumor larger than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The presence of any one of these factors was associated with 5-year actuarial IBTR-free and LRR-free survival rates of 87% to 91% and 77% to 84%, respectively. Initial T category (T1–2 v T3–4) correlated with LRR but did not correlate with IBTR (5-year IBTR-free rates of 96% v 92%, respectively, P = .19). Conclusion Breast conservation therapy after neoadjuvant chemotherapy results in acceptably low rates of LRR and IBTR in appropriately selected patients, even those with T3 or T4 disease. Advanced nodal involvement at diagnosis, residual tumor larger than 2 cm, multifocal residual disease, and lymphovascular space invasion predict higher rates of LRR and IBTR.
Predicting height from ulna length in 2-6 year olds
Authors: Leanne Gauld, Lucy Keeling, Peter Sly, Claire Shakleton
Journal: European Respiratory Journal (2013)

Height predicts normal spirometry and Forced Oscillation Technique (FOT) values. Its measurement can be difficult with mobility or joint problems. Prediction equations from ulna length to height and spirometry exist for 7-18 year olds. 1  For young children, use of existing prediction equations have not been assessed.  Aim: To assess if published height prediction equations are appropriate in children 2-6 years, and develop new equations where appropriate.  Methods: Children (2-6 years) were recruited from childcare, excluding those with medical conditions. Height was measured with a Harpenden Stadiometer and ulna length with Harpenden callipers. Regression analysis devised prediction equations from ulna length to height. Student t test assessed differences between actual height, and the value predicted by the published prediction equation.  Results: 234 children were recruited, mean age: males 3.73 ±1.09, females 3.70 ±1.09 years. 34 (12.82%) were excluded. A linear relationship exists between ulna length and height 2-18 years. The prediction equation for males is: 4.629*ulna + 1.340*age +26.974 (R 2  0.97, RMSE 3.84); for females: 4.577*ulna + 1.343*age + 28.345 (R 2  0.96, RMSE 3.78). The published prediction equation overestimates height in males (mean +1.11cm ±1.72, p  Conclusion: In children aged 2-6 years in whom height measurement is difficult, new prediction equations for height from ulna length should be used as published prediction equations overestimate height in young children.  1. Gauld et al.  Devel Med Child Neurol  2004:46;475-480.
Time trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: multicentre observational study
Authors: David Dolling, Caroline Sabin, Valerie Delpech, Erasmus Smit, Anton Pozniak, David Asboe, Andrew Leigh Brown, Duncan Churchill, Ian Williams, Anna Maria Geretti, Andrew Phillips, Nicola Mackie, Gary Murphy, Hannah Castro, Deenan Pillay, Patricia Cane, David Dunn, David Dolling
Journal: BMJ (2012)

<b>Objective</b> To evaluate whether the prevalence of HIV-1 transmitted drug resistance has continued to decline in infections probably acquired within the United Kingdom. <b>Design</b> Multicentre observational study. <b>Setting</b> All UK public laboratories conducting tests for genotypic HIV resistance as a part of routine care. <b>Participants</b> 14 584 patients infected with HIV-1 subtype B virus, who were first tested for resistance before receiving antiretroviral therapy between January 2002 and December 2009. <b>Main outcome measure</b> Prevalence of transmitted drug resistance, defined as one or more resistance mutations from the surveillance list recommended by the World Health Organization. <b>Results</b> 1654 (11.3%, 95% confidence interval 10.8% to 11.9%) patients had one or more mutations associated with transmitted HIV-1 drug resistance; prevalence was found to decline from 15.5% in 2002 to 9.6% in 2007, followed by a slight increase to 10.9% in 2009 (P=0.21). This later rise was mainly a result of increases in resistance to nucleos(t)ide reverse transcriptase inhibitors (from 5.4% in 2007 to 6.6% in 2009, P=0.24) and protease inhibitors (1.5% to 2.1%, P=0.12). Thymidine analogue mutations, including T215 revertants, remained the most frequent mutations associated with nucleos(t)ide reverse transcriptase inhibitors, despite a considerable fall in stavudine and zidovudine use between 2002 and 2009 (from 29.4% of drug regimens in 2002 to 0.8% in 2009, from 47.9% to 8.8%, respectively). <b>Conclusions</b> The previously observed decline in the prevalence of transmitted drug resistance in HIV-1 infections probably acquired in the UK seems to have stabilised. The continued high prevalence of thymidine analogue mutations suggests that the source of this resistance may be increasingly from patients who have not undergone antiretroviral therapy and who harbour resistant viruses. Testing of all newly diagnosed HIV-1 positive people should be continued.
Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis
Authors: Maša Umiċeviċ Mirkov, Jing Cui, Sita H Vermeulen, Eli A Stahl, Erik J M Toonen, Remco R Makkinje, Annette T Lee, Tom W J Huizinga, Renee Allaart, Anne Barton, Xavier Mariette, Corinne Richard Miceli, Lindsey A Criswell, Paul P Tak, Niek de Vries, Saedis Saevarsdottir, Leonid Padyukov, S Louis Bridges, Dirk-Jan van Schaardenburg, Tim L Jansen, Ellen A J Dutmer, Mart A F J van de Laar, Pilar Barrera, Timothy R D J Radstake, Piet L C M van Riel, Hans Scheffer, Barbara Franke, Han G Brunner, Robert M Plenge, Peter K Gregersen, Henk-Jan Guchelaar, Marieke J H Coenen
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment. This study was aimed at identifying genetic factors predicting anti-TNF treatment outcome in patients with RA using a genome-wide association approach. <h3>Methods</h3> We conducted a multistage, genome-wide association study with a primary analysis of 2 557 253 single-nucleotide polymorphisms (SNPs) in 882 patients with RA receiving anti-TNF therapy included through the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry and the database of Apotheekzorg. Linear regression analysis of changes in the Disease Activity Score in 28 joints after 14 weeks of treatment was performed using an additive model. Markers with p&lt;10<sup>−3</sup> were selected for replication in 1821 patients from three independent cohorts. Pathway analysis including all SNPs with p&lt;10<sup>−3</sup> was performed using Ingenuity. <h3>Results</h3> 772 markers showed evidence of association with treatment outcome in the initial stage. Eight genetic loci showed improved p value in the overall meta-analysis compared with the first stage, three of which (rs1568885, rs1813443 and rs4411591) showed directional consistency over all four cohorts studied. We were unable to replicate markers previously reported to be associated with anti-TNF outcome. Network analysis indicated strong involvement of biological processes underlying inflammatory response and cell morphology. <h3>Conclusions</h3> Using a multistage strategy, we have identified eight genetic loci associated with response to anti-TNF treatment. Further studies are required to validate these findings in additional patient collections.
Association of Dopamine Transporter Reduction With Psychomotor Impairment in Methamphetamine Abusers
Authors: Nora D. Volkow, Linda Chang, Gene-Jack Wang, Joanna S. Fowler, Maria Leonido-Yee, Dinko Franceschi, Mark J. Sedler, S. John Gatley, Robert Hitzemann, Yu-Shin Ding, Jean Logan, Christopher Wong, Eric N. Miller
Journal: American Journal of Psychiatry (2001)

Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant.Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function.Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment.These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.
Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol
Authors: Philippe Moreau, Cyrille Hullin, Frédéric Garban, Ibrahim Yakoub-Agha, Lotfi Benboubker, Michel Attal, Gérald Marit, Jean-Gabriel Fuzibet, Chantal Doyen, Laurent Voillat, Christian Berthou, Nicolas Ketterer, Philippe Casassus, Mathieu Monconduit, Mauricette Michallet, Albert Najman, Jean-Jacques Sotto, Régis Bataille, Jean-Luc Harousseau
Journal: Blood (2005)
The effect of lung transplantation on the neural drive to the diaphragm in patients with severe COPD
Authors: H Brath, H Lahrmann, T Wanke, W Wisser, M Wild, B Schlechta, H Zwick, W Klepetko, OC Burghuber
Journal: European Respiratory Journal (1997)

Little is known about the effects of lung transplantation (LT) on the neural drive to the diaphragm and on the endurance of respiratory muscles in patients with severe chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate these effects of single-lung (SLT) and double-lung transplantation (DLT). The neural drive to the diaphragm was assessed during fatiguing inspiratory threshold loading manoeuvres in six SLT recipients, six DLT recipients and seven patients with severe COPD, by using diaphragmatic surface electromyograms. During threshold loading, the patients had to generate 80% of their maximal transdiaphragmatic pressure with each breath. The endurance of inspiratory muscles was defined as the time from the beginning of a resistive breathing trial until exhaustion (t lim). In DLT recipients and even in SLT recipients (on both sides), neural activation of the diaphragm was significantly lower than in COPD patients (p &lt; 0.05). However, no statistically significant difference in t lim was seen between LT recipients and COPD patients. The data suggest that single-lung and double-lung transplantations cause a significant decrease of the neural drive to the diaphragm, while the endurance of inspiratory muscles is well-preserved in patients with advanced chronic obstructive pulmonary disease. This may contribute to reduced sensation of inspiratory effort during ventilatory stress, thus improving the quality of life.
Potassium chloride preparations and fecal blood loss. A parallel study with a 10 percent solution and a non-enteric-coated waxy-matrix tablet
Authors: J. A. Rider
Journal: JAMA (1975)

Concentrated potassium chloride produces ulceration of the gastrointestinal mucosa. Dilute solutions are frequently not acceptable to the patient. A tablet containing potassium chloride crystals suspended in a waxy matrix has been developed to avoid these drawbacks. We measured fecal blood loss by a radioactive chromium technique on 20 subjects during five days while they were given potassium chloride, 40mEq/day; ten subjects took a 10% solution; the others the waxy-matrix tablet. Fecal blood loss did not differ significantly between these groups. Mean fecal blood losses in both groups were slightly increased during the potassium chloride administration but never exceeded acceptable normal limits.
Late appearance of the Philadelphia chromosome with monosomy 7 in a patient with de novo AML with trilineage myelodysplasia
Authors: Kosei Matsue, Toshihiro Miyamoto, Mami Ito, Koji Tsukuda
Journal: American Journal of Hematology (1995)

Abstract We report here a patient with de novo acute myelocytic leukemia with trilineage myelodysplasia (AML/TMDS) in whom cytogenetic analysis was normal at diagnosis and in whom Philadelphia chromosome (Ph1) with monosomy 7 emerged at the terminal stage of the disease. Reverse transcription polymerse chain reaction (RT‐PCTR) on the Ph1 positive specimen detected the mRNA encoding p190bcr/ab1 was not detected at diagnosis and or at relapse. These observations support the hypothesis that late‐appearing Phl and monosomy 7 might be the result of clonal evolution during the course of leukemia, and p190bcr/abl might play a role in the terminal transformation or progression of leukemia. © 1995 Wiley‐Liss, Inc.
Characterization of the molecular defect in infantile and adult acid alpha-glucosidase deficiency fibroblasts.
Authors: N G Beratis, G U LaBadie, K Hirschhorn
Journal: Journal of Clinical Investigation (1978)

Different clinical expressions of acid alpha-glucosidase deficiency have been described. The present study was undertaken to investigate the basic metabolic defect in the infantile and adult forms of the disease. Acid alpha-glucosidase (EC 3.2.1.20) was purified from normal and from adult acid alpha-glucosidase deficiency fibroblasts. The pH optimum; Michaelis constant; electrophoretic mobility in starch; thermal denaturation at pH 4.0 and 7.0; and inhibition by turanose, alpha-methylglucoside and trehalose were the same in purified enzyme from normal and mutant cells. Placental acid alpha-glucosidase was purified to, or near, homogeneity. Monospecific antibodies raised against the enzyme in each of three enzyme peaks obtained from the last purification step were found to cross-react with the enzyme of all three peaks, and with purified, normal fibroblast enzyme. Cross-reacting material (CRM) also was identified in fibroblast lysates from normal subjects and from both forms of acid alpha-glucosidase deficiency. The amount of CRM in the adult form appeared to be significantly less than in normal cells or cells from the infantile form. Enzyme activity was demonstrated in the immune complexes of the normal and adult acid alpha-glucosidase deficiency fibroblasts, but not of the infantile form. Competition for antibody binding sites was observed between normal and both types of mutant enzymes. The findings indicate that this case of infantile acid alpha-glucosidase deficiency is the result of a structural gene mutation which causes the synthesis of a catalytically inactive (CRM-positive) enzyme protein. It appears that in the adult form, the mutation causes a reduction in the amount of the enzyme protein present in the cells.