tbuckley/cabot-search huggingface dataset:
Advanced Breast Cancer and Breast Cancer Mortality in Randomized Controlled Trials on Mammography Screening
Authors: Philippe Autier, Clarisse Héry, Jari Haukka, Mathieu Boniol, Graham Byrnes
Journal: Journal of Clinical Oncology (2009)

We assessed changes in advanced cancer incidence and cancer mortality in eight randomized trials of breast cancer screening.Depending on published data, advanced cancer was defined as cancer > or = 20 mm in size (four trials), stage II+ (four trials), and > or = one positive lymph node (one trial). For each trial, we obtained the estimated relative risk (RR) and 95% CI between the intervention and control groups, for both breast cancer mortality and diagnosis of advanced breast cancer. Using a meta-regression approach, log(RR-mortality) was regressed on log(RR-advanced cancer), weighting each trial by the reciprocal of the square of the standard error of log(RR) for mortality.RR for advanced breast cancer ranged from 0.69 (95% CI, 0.61 to 0.78) in the Swedish Two-County Trial to 0.97 (95% CI, 0.97 to 1.25) in the Canadian National Breast Screening Study-1 (NBSS-1) trial. Log(RR)s for advanced cancer were highly predictive of log(RR)s for mortality (R(2) = 0.95; P < .0001), and the linear regression curve had a slope of 1.00 (95% CI, 0.76 to 1.25) after fixing the intercept to zero. The slope changed only slightly after excluding the Two-County Trial and the Canadian NBSS-1 and NBSS-2 trials.In trials on breast cancer screening, for each unit decrease in incidence of advanced breast cancer, there was an equal decrease in breast cancer mortality. Monitoring of incidence of advanced breast cancer may provide information on the current impact of screening on breast cancer mortality in the general population.
Plasma Apolipoprotein L1 Levels Do Not Correlate with CKD
Authors: Leslie A. Bruggeman, John F. O'Toole, Michael D. Ross, Sethu M. Madhavan, Marlene Smurzynski, Kunling Wu, Ronald J. Bosch, Samir Gupta, Martin R. Pollak, John R. Sedor, Robert C. Kalayjian
Journal: Journal of the American Society of Nephrology (2013)

Polymorphisms in APOL1 are associated with CKD, including HIV-related CKD, in individuals of African ancestry. The apolipoprotein L1 (APOL1) protein circulates and is localized in kidney cells, but the contribution of APOL1 location to CKD pathogenesis is unclear. We examined associations of plasma APOL1 levels with plasma cytokine levels, dyslipidemia, and APOL1 genotype in a nested case-control study (n=270) of HIV-infected African Americans enrolled in a multicenter prospective observational study. Patients were designated as having CKD when estimated GFR (eGFR) decreased to <60 ml/min per 1.73 m(2) (eGFR<60 cohort) or protein-to-creatinine ratios became >3.5 g/g (nephrotic proteinuria cohort). Circulating APOL1 levels did not associate with APOL1 genotype, CKD status, or levels of proinflammatory cytokines, but did correlate with fasting cholesterol, LDL cholesterol, and triglyceride levels. At ascertainment, CKD-associated polymorphisms (risk variants) in APOL1 associated with the eGFR<60 cohort, but not the nephrotic-range proteinuria cohort. Of note, in both the eGFR<60 and nephrotic proteinuria cohorts, CKD cases with two APOL1 risk variants had significant declines in eGFR over a median of 4 years compared with individuals with one or no risk variants. APOL1 risk genotype was not associated with changes in proteinuria. Higher circulating proinflammatory cytokine levels were independently associated with CKD but not APOL1 genotype. In conclusion, the function of variant APOL1 proteins derived from circulation or synthesized in the kidney, but not the level of circulating APOL1, probably mediates APOL1-associated kidney disease in HIV-infected African Americans.
Mandibular advancement and obstructive sleep apnoea: a method for determining effective mandibular protrusion
Authors: L. C. Dort, E. Hadjuk, J. E. Remmers
Journal: European Respiratory Journal (2006)

The objectives of the study were to test the hypotheses that it is possible, during routine polysomnography (PSG), to prospectively identify favourable candidates for mandibular repositioning appliance (MRA) therapy in the treatment of obstructive sleep apnoea (OSA) and to accurately estimate an optimal protrusive distance at which to fabricate the MRA. A series of subjects underwent a remotely controlled mandibular positioner (RCMP) test during PSG monitoring. The ability of the RCMP test to eliminate OSA and the target protrusion at which that occurred was compared with the success of a custom oral MRA in the 33 subjects who completed the protocol. The RCMP test was a success in 15 subjects and a failure in 18 subjects. Appliance therapy was initiated in 38 subjects and completed in 33. MRA therapy was successful at target protrusion in 80% of subjects who had a successful RCMP test and failed in 78% of those who failed the RCMP test. In conclusion the remotely controlled mandibular positioner test outcome demonstrated a statistically significant association with mandibular repositioning appliance outcome. The target protrusion determined during the remotely controlled mandibular positioner test was the effective therapeutic protrusion in subjects with a successful remotely controlled mandibular positioner test.
High prevalence of low affinity peptide–MHC II tetramer–negative effectors during polyclonal CD4+ T cell responses
Authors: Joseph J. Sabatino, Jun Huang, Cheng Zhu, Brian D. Evavold
Journal: The Journal of Experimental Medicine (2011)

T cell affinity for antigen initiates adaptive immunity. However, the contribution of low affinity cells to a response is unknown as it has not been possible to assess the entire affinity range of a polyclonal T cell repertoire. In this study, we used a highly sensitive two-dimensional binding assay to identify low affinity cells in polyclonal autoreactive and pathogen-reactive CD4+ T cell populations specific for myelin oligodendrocyte glycoprotein (MOG) and lymphocytic choriomeningitis virus (LCMV) antigens, respectively. Low affinity CD4+ T cells, below detection with peptide–major histocompatibility complex class II tetramers, were at least as frequent as high affinity responders and contributed significant effector cytokines in both primary antigen–specific responses. We further demonstrated that MOG- and LCMV-specific CD4+ T cells possessed similarly broad ranges in their affinities (&amp;gt;100-fold wide), only differing in the frequencies of low and high affinity cells. Thus, low as well as high affinity CD4+ T cells are critical effectors in autoimmune and pathogen-specific responses.
Renal and Cardiovascular Protection in Type 2 Diabetes Mellitus
Authors: Giacomo Deferrari, Maura Ravera, Luca Deferrari, Simone Vettoretti, Elena Ratto, Denise Parodi
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, and target BP less than 130/85 or 130/80 mmHg are now recommended. Inhibition of renin angiotensin aldosterone system (RAAS) plays an essential role in the treatment of hypertension and diabetes-related complications. Studies focusing on renal end-points suggest that angiotensin-converting enzyme inhibitors (ACE-I) are more effective than other traditional agents in reducing the onset of clinical proteinuria in both type 1 and type 2 diabetic patients with incipient nephropathy, mainly in normotensive ones (secondary prevention). However, several small trials in type 2 diabetic patients with overt nephropathy (tertiary prevention) failed to demonstrate a specific renoprotective role for ACE-I, at variance with type 1 diabetes. Three recent large trials address the question of whether angiotensin II receptor blockers (ARB) prevent the development of clinical proteinuria or delay the progression of nephropathy in type 2 diabetes. The IRMA study showed that irbesartan is more effective than conventional therapy in preventing the development of clinical proteinuria and in favoring the regression to normoalbuminuria for comparable BP control in patients with incipient nephropathy. The IDNT and RENAAL trials showed that ARB are more effective than traditional antihypertensive therapies in reducing progression toward end-stage renal failure (ESRF) in type 2 diabetic patients with overt nephropathy independently of changes in BP. Moreover, a reduction in hospitalizations for heart failure was demonstrated for ARB-treated patients compared with placebo. Furthermore, the LIFE study showed that losartan is more effective than conventional therapy in reducing cardiovascular morbidity and mortality in a cohort of diabetic patients with hypertension and left ventricular hypertrophy. In conclusion, ARB seem to be effective in both preventing renal damage and reducing progression toward ESRF in type 2 diabetic patients. Thus, the guidelines for the prevention and treatment of diabetic nephropathy are now changed. In type 1 diabetes ACE-I are the first-choice drug; in type 2 diabetes, ARB are considered first-choice drugs in secondary prevention as well as ACE-I and have been now elected the unique first-choice drug in tertiary prevention of ESRF. Finally, ARB should be considered as the first-choice drug in cardiovascular prevention too, as well as ACE-I. E-mail: [email protected]
Detached Pieces of Articular Cartilage Forming Loose Bodies in both Knee-Joints
Authors: W. A. Lane
Journal: BMJ (1893)

LOOSE IODIES IN BOTHI KNEE-JOINTS.r= namL 12u7 form the chorda tympani nor the nerve to the stapedius were involved, thiat is to say, the swelliing of the nerves was sliglht, only sufficient to cause their coinpression at the stylo-mastoid foramina.It may be inferred thiat the compression was just enough to interfere withi the nerves as conductors of impres- sioIns from their nuclear centres, but not enoughl to produce degenerative changes.Dr. Gowers says: " Fallopian neuritis scarcely ever occurs on bothl sides simultaneously, althlouglh I lhave more than once known a second attack on the othler side to occur withliii a few months of the first."The same authlor says that it
Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis
Authors: N.G. Koulouris, S. Retsou, E. Kosmas, K. Dimakou, K. Malagari, G. Mantzikopoulos, A. Koutsoukou, J. Milic-Emili, J. Jordanoglou
Journal: European Respiratory Journal (2003)

In this study the authors investigated whether expiratory flow limitation (FL) is present during tidal breathing in patients with bilateral bronchiectasis (BB) and whether it is related to the severity of chronic dyspnoea (Medical Research Council (MRC) dyspnoea scale), exercise capacity (maximal mechanical power output ( WR max )) and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring. Lung function, MRC dyspnoea, HRCT score, WR max and FL were assessed in 23 stable caucasian patients (six males) aged 56±17 yrs. FL was assessed at rest both in seated and supine positions. To detect FL, the negative expiratory pressure (NEP) technique was used. The degree of FL was rated using a five-point FL score. WR max was measured using a cyclo-ergometer. According to the NEP technique, five patients were FL during resting breathing when supine but not seated, four were FL both seated and supine, and 14 were NFL both seated and supine. Furthermore, it was shown that: 1) in stable BB patients FL during resting breathing is common, especially in the supine position; 2) the degree of MRC dyspnoea is closely related to the five-point FL score; 3) WR max (% pred) is more closely correlated with the MRC dyspnoea score than with the five-point FL score; and 4) HRCT score is closely related to forced expiratory volume in one second % pred but not five-point FL score. In conclusion, flow limitation is common at rest in sitting and supine positions in patients with bilateral bronchiectasis. Flow limitation and reduced exercise capacity are both associated with more severe dyspnoea. Finally, high-resolution computed tomography scoring correlates best with forced expiratory volume in one second.
Is Endoscopic Balloon Dilation for Removal of Bile Duct Stones Associated with an Increased Risk for Pancreatitis or a Higher Rate of Hyperamylasemia?
Authors: J. J. Bergman, A.-M. van Berkel, M. J. Bruno, P. Fockens, E. A. Rauws, J. G. Tijssen, G. N. Tytgat, K. Huibregtse
Journal: Endoscopy (2001)

Background and Study Aims: We studied the rate of pancreatitis and asymptomatic hyperamylasemia after endoscopic balloon dilation (EBD) and endoscopic sphincterotomy (EST) for removal of bile duct stones.
Hemodynamic Consequences of Induced Changes in Blood Volume
Authors: James Conway, Miklos Gellai
Journal: Circulation Research (1966)

The effects of transfusion or bleeding on cardiac output and blood pressure have been followed for periods of seven to ten hours in trained, conscious dogs. When blood volume is increased by transfusion of blood, supplemented by dextran to minimize the expected change in hematocrit, cardiac output and blood pressure increase initially. After one and one-half hours the cardiac output returns to the initial level but blood pressure remains elevated and calculated peripheral resistance increases. This state has been maintained for a period of ten hours by repeated transfusion. After bleeding, with replacement of packed cells, again to minimize the change in hematocrit, cardiac output decreases initially and peripheral resistance increases, but after three hours, output returns to its former level, and peripheral resistance falls below the control value. These changes become more prominent when a second hemorrhage is performed two hours after the first one. The reduction of resistance was then maintained for seven hours. These findings demonstrate that the effects of changes in blood volume are not limited to the acute changes in cardiac output and filling pressure. After periods of one to three hours, changes in peripheral resistance also become evident.
A UK NEQAS ring study evaluating observer variation in the diagnosis of HER2 amplification using the Kreatech™ HER2 FISH probe.
Authors: JM Bartlett, FM Campbell, M Ibrahim, J Thomas, P Wenyck, IO Ellis, E Kay, Y Connolly, A O'Grady, P Cunningham, S Barnett, J Starczynski, K Miller
Journal: Cancer Research (2009)

Abstract Abstract #3005 Background: Whilst HER2 testing is well established as a key requirement for all newly diagnosed breast cancers the quality and consistency of HER2 testing remains a point of controversy. Most countries use FISH or ISH based testing for HER2 gene amplification in equivocal (IHC 2+) cases. Data on reproducibility and portability of novel and even established HER2 methods is sparse. We report on a multicentre evaluation of intra and inter-observer/site variation in scoring HER2 results from 45 breast cancers measured in 8 laboratories using the Kreatech™ HER2 FISH probe.&amp;#x2028; Methods: A commercial tissue micro-array (TMA; Stretton Scientific UK) containing 2 replicate cores from 45 breast cancers was circulated to 8 laboratories with varying experience in FISH methodology. Five laboratories (1-5) were UK NEQAS reference labs, 3 further experienced routine diagnostic labs (A-C) participated in the scheme designed to test the site to site reproducibility of the Kreatech™ FISH probe. All laboratories FISHed a 90 core TMA and 7/8 reported results for all assessable cores, 1 lab reported 1 result per evaluable cases (as per the original study design). Results were collated centrally and analyzed for intra and inter-observer between both “reference” laboratories (labs 1-5) and non-reference laboratories (A-C).&amp;#x2028; Results: Overall 81% of cores (range 70-94%) were successfully analysed by Kreatech™ FISH. Intra-observer variation was lower than expected at 4.7% (range 3.5-8.4%) for HER2 ratio. Mean intersite variation in HER2:Chr 17 ratio was significantly lower (8.5%) for reference vs non-reference (13.4%) laboratories (p=0.0013). Of 546 reported cores only 7 (1.3%) were discordant (with 4 borderline). Analysis of site to site variation highlighted possible systematic differences in scoring approaches in 3/8 laboratories including a “reference laboratory”.&amp;#x2028; Conclusions: Intra- and inter-observer variation of absolute HER2 ratios appears to be tightly controlled across 8 laboratories using Kreatech™ HER2 FISH probes. Detailed comparisons of scoring results suggests some systematic differences between a few laboratories in the interpretation of FISH. However the majority of laboratories show extremely tight reproducibility of numeric HER2 FISH results. This study highlights the potential for extremely robust and quantitatively reproducible FISH results from both “diagnostic” and “reference” laboratories. However it also suggests continued quality assessments are essential to good performance. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3005.
Phase I/II Study of an Anti-CD30 Monoclonal Antibody (MDX-060) in Hodgkin's Lymphoma and Anaplastic Large-Cell Lymphoma
Authors: Stephen M. Ansell, Steven M. Horwitz, Andreas Engert, Khuda Dad Khan, Thomas Lin, Roger Strair, Tibor Keler, Robert Graziano, Diann Blanset, Michael Yellin, Steven Fischkoff, Albert Assad, Peter Borchmann
Journal: Journal of Clinical Oncology (2007)

MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1kappa monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed.In the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients--16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma--were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg.MDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment.MDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.
Abstract 5114: The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines
Authors: Ghada A. Abd Ellatif, Marianne Georges Tadros, Ashraf Bahey Eldin Abd El Naim, Amany Ibrahim Khalifa, Ahmad M. Alabd
Journal: Cancer Research (2014)

Abstract Herceptin is considered an essential treatment option for double negative breast cancer. Resveratrol and didox are known chemopreventive agents with potential anticancer properties. The aim of the current study is to investigate the influence of resveratrol and didox on the cytotoxicity profile of herceptin in her-2 receptor positive and her-2 receptor negative breast cancer cell lines. The IC50's of herceptin in T47D and MCF-7 were 0.126±0.01 ng/ml and 26.71±1.85 ng/ml respectively. Equitoxic combination of herceptin with resveratrol or didox in T47D significantly reduced the IC50 to 0.05±0.01 and 0.029±0.006 ng/ml, respectively and similar results were obtained in MCF-7. The gene expression of Bcl-xl was markedly decreased in T47D cells following treatment with herceptin/resveratrol compared to herceptin alone. Immunocytochemical staining of her-2 receptor in T47D cells showed a significant reduction after treatment with herceptin/resveratrol combination compared to herceptin alone. On the other hand, combination of herceptin and didox had no significant effect on her-2 receptor expression. Cell cycle analysis showed an arrest at G2/M phase for both cell lines following treatment with herceptin alone and in either combinations regimen. In conclusion the combination of herceptin with resveratrol and didox improved the cytotoxic profile of herceptin in T47D (her-2 receptor positive cell line) and to a lesser extent in MCF-7 (her-2 receptor negative cell line). Citation Format: Ghada A. Abd Ellatif, Marianne Georges Tadros, Ashraf Bahey Eldin Abd El Naim, Amany Ibrahim Khalifa, Ahmad M. Alabd. The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5114. doi:10.1158/1538-7445.AM2014-5114
Vaccine Mandates Are Justifiable Because We Are All in This Together
Authors: John D. Lantos, Mary Anne Jackson
Journal: The American Journal of Bioethics (2013)

Influenza is a deadly disease. Every year, in the United States, 200,000 people are hospitalized with influenza and 23,000–33,000 people die of the disease (Heron 2008). Unimmunized health care wor...
Functional Determinants of Temperature Adaptation in Enzymes of Cold- versus Warm-Adapted Mussels (Genus Mytilus)
Authors: B. L. Lockwood, G. N. Somero
Journal: Molecular Biology and Evolution (2012)

Temperature is a strong selective force on the evolution of proteins due to its effects on higher orders of protein structure and, thereby, on critical protein functions like ligand binding and catalysis. Comparisons among orthologous proteins from differently thermally adapted species show consistent patterns of adaptive variation in function, but few studies have examined functional adaptation among multiple structural families of proteins. Thus, with our present state of knowledge, it is difficult to predict what fraction of the proteome will exhibit adaptive variation in the face of temperature increases of a few to several degrees Celsius, that is, temperature increases of the magnitude predicted by models of global warming. Here, we compared orthologous enzymes of the warm-adapted Mediterranean mussel Mytilus galloprovincialis and the cold-adapted Mytilus trossulus, a native of the North Pacific Ocean, species whose physiologies exhibit significantly different responses to temperature. We measured the effects of temperature on the kinetics (Michaelis–Menten constant—Km) of five enzymes that are important for ATP generation and that represent distinct protein structural families. Among phosphoglucomutase (PGM), phosphoglucose isomerase (PGI), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (GTP) (PEPCK), and isocitrate dehydrogenase (NADP) (IDH), only IDH orthologs showed significantly different thermal responses of Km between the two species. The Km of isocitrate of M. galloprovincialis-IDH was intrinsically lower and more thermally stable than that of M. trossulus-IDH and thus had higher substrate affinity at high temperatures. Two amino acid substitutions account for the functional differences between IDH orthologs, one of which allows for more hydrogen bonds to form near the mobile region of the active site in M. galloprovincialis-IDH. Taken together, our findings cast light on the targets of adaptive evolution in the context of climate change; only a minority of proteins might adapt to small changes in temperature, and these adaptations may involve only small changes in sequence.