tbuckley/cabot-search huggingface dataset:
Load responsiveness of protein synthesis in adult mammalian myocardium: role of cardiac deformation linked to sodium influx.
Authors: R L Kent, J K Hoober, G Cooper
Journal: Circulation Research (1989)

Exposure of adult mammalian myocardium to increased hemodynamic loads augments cardiac protein synthesis, ultimately leading to hypertrophy of the affected chamber. This established relationship between loading conditions and protein synthesis was examined in terms of two questions. First, is there a basic difference between the anabolic effect of a passive load imposed on diastolic myocardium and that of an active load generated by systolic myocardium? This issue was addressed by measuring [3H]phenylalanine incorporation into muscle protein in either quiescent or contracting ferret papillary muscles, set at known isometric lengths. Myocardial protein synthesis increased in proportion to total muscle tension in each case, with an equivalent relation describing both quiescent and contracting muscles. Synthesis of two contractile proteins, actin and myosin heavy chain, were enhanced by muscle loading. Thus, a quantitative rather than qualitative difference between the anabolic effects of diastolic and systolic loading was demonstrated. Second, since increased sodium influx is an initial cellular response requisite to the growth-inducing activity of many substances, and since sodium entry through stretch-activated ion channels is stimulated by deformation of the sarcolemma, does cardiac deformation during increased loading promote sodium influx as a signal to increase anabolic activity? In either quiescent or contracting papillary muscles, the rate of 24Na+ uptake was found to increase with load. Streptomycin, a cationic blocker of the mechanotransducer ion channels, was without effect on protein synthesis in stimulated but slack muscles; however, it inhibited, in a dose-related manner, the augmented protein synthesis otherwise observed in contracting muscles developing tension. At 500 microM, streptomycin did not reduce active tension, but it did reduce the synthesis of both actin and myosin heavy chain. In a second pharmacologic approach, inotropic agents were chosen which uniformly increased muscle tension development but which had contrasting effects on sodium influx. Protein synthesis increased in the presence of Na+ influx enhancers, monensin or veratridine; however, protein synthesis decreased in the presence of amiloride, a sodium influx inhibitor. Thus, myocardial protein synthesis varied directly with sodium influx despite the positive inotropic effect observed with each of these agents. In addition, inhibition of protein synthesis by ouabain demonstrated that activation of the Na+ pump is required for the anabolic effect of load.(ABSTRACT TRUNCATED AT 400 WORDS)
Development of a new radiographic scoring system using digital image analysis.
Authors: J E Dacre, J S Coppock, K E Herbert, D Perrett, E C Huskisson
Journal: Annals of the Rheumatic Diseases (1989)

A scoring system using computerised analysis of digital stored images of knee radiographs has been developed. Measurement is based on the assessment of joint space size. It is sensitive, rapid, and reproducible. Plain radiographs are positioned on an acetate grid; a computer generated grid is superimposed on a digital image of the radiograph viewed on a closed circuit television monitor and the joint space measured automatically. Area and distance have been assessed; area measurements are more reproducible. Application of microcomputer based digital image analysis to radiological scoring systems is an important step in understanding the nature and progression of arthritis.
Impact of Diabetes on Employment and Income in Manitoba, Canada
Authors: A. Kraut, R. Walld, R. Tate, C. Mustard
Journal: Diabetes Care (2001)

To compare employment and income of working-age (18-64 years) people with and without diabetes.We conducted a prospective population-based cohort study based in Manitoba, Canada, consisting of 25,554 individuals without diabetes and 608 with diabetes, of whom 242 had a complication of the disease. Adjusted odds ratios (ORs) of employment and income variables were determined.Diabetic individuals with complications were twice as likely not to be in the labor force (OR 2.07 [95% CI 1.49-2.87]) than nondiabetic individuals. This difference was not evident for diabetic individuals without complications (OR 1.20 [0.93-1.56]). Diabetic individuals without complications had incomes similar to those of nondiabetic individuals. The total income of diabetic individuals with complications was 72% of the income of nondiabetic individuals. When the analysis was limited to only those in the labor force, diabetic workers with complications still had only 85% the employment income of nondiabetic people. Diabetic individuals with complications received 58% more social support income. In a separate analysis of aboriginal individuals, complicated diabetes was not associated with an increased likelihood of not working or a decrease in employment income.In general, complications of diabetes and the absence of the disease affect the ability to earn income in Manitoba, Canada. This effect was not identified in the aboriginal population of the province.
Sputum eosinophil count in a large population of patients with mild to moderate steroid‐naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness
Authors: R. Louis, J. Sele, M. Henket, D. Cataldo, J. Bettiol, L. Seiden, P. Bartsch
Journal: Allergy (2002)

Background: Although airway eosinophilia is seen as a cardinal feature of asthma, data eosinophilia are still lacking on the proportion of the asthma group exhibiting raised airway eosinophilia. This study aimed to assess the distribution of sputum eosinophil count and its relationship with methacholine bronchial hyperresponsiveness in mild to moderate steroid‐naive asthmatic people. Methods: Sputum was induced by inhalation of hypertonic saline (NaCl 4.5%) in 118 mild to moderate steroid‐naive asthmatic people consecutively recruited from our outpatient clinic, and in 44 healthy people. The asthma group was selected on the basis of an forced expiratory volume in 1 s (FEV 1 ) of ≥ 70% predicted, and a provocative methacholine concentration causing a fall of 20% in FEV 1 (PC 20 methacholine; PC 20 M) ≤ 16 mg/ml. Results: In the asthma group, the median (range) of the percentage and the absolute values of sputum eosinophils were 4.8% (0–75) and 38 10 3 /g (0–14 191), respectively, vs 0% (0–2.3) ( P &lt; 0.001) and 0 10 3 /g (0–53) ( P &lt; 0.001) in healthy participants. Based on the 95% percentile for normal values calculated from our healthy group, 69% of the asthma group had significantly raised sputum eosinophil count (that is &gt; 2%). In the asthma group, multiple regression analysis followed by a stepwise procedure revealed that sputum eosinophil count was significantly and inversely associated with PC 20 M accounting for 16% of its total variance ( P &lt; 0.001) while neutrophil counts positively related to PC 20 M accounting for 4% of total variance ( P &lt; 0.05). By contrast, no significant relationship was found between either eosinophil or neutrophil counts and the slope of forced vital capacity (FVC) vs FEV 1 from the methacholine challenge. Conclusions: We conclude that two‐thirds of people in the mild to moderate asthma group had increased sputum eosinophilia, which plays a limited role in determining the degree of methacholine airway hyperresponsiveness.
Physiological Testosterone Replacement Therapy Attenuates Fatty Streak Formation and Improves High-Density Lipoprotein Cholesterol in the Tfm Mouse
Authors: Joanne E. Nettleship, T. Hugh Jones, Kevin S. Channer, Richard D. Jones
Journal: Circulation (2007)

Background— Research supports a beneficial effect of physiological testosterone on cardiovascular disease. The mechanisms by which testosterone produces these effects have yet to be elucidated. The testicular feminized (Tfm) mouse exhibits a nonfunctional androgen receptor and low circulating testosterone concentrations. We used the Tfm mouse to determine whether testosterone modulates atheroma formation via its classic signaling pathway involving the nuclear androgen receptor, conversion to 17β-estradiol, or an alternative signaling pathway. Methods and Results— Tfm mice (n=31) and XY littermates (n=8) were separated into 5 experimental groups. Each group received saline (Tfm, n=8; XY littermates, n=8), physiological testosterone alone (Tfm, n=8), physiological testosterone in conjunction with the estrogen receptor α antagonist fulvestrant (Tfm, n=8), or physiological testosterone in conjunction with the aromatase inhibitor anastrazole (Tfm, n=7). All groups were fed a cholesterol-enriched diet for 28 weeks. Serial sections from the aortic root were examined for fatty streak formation. Blood was collected for measurement of total cholesterol, high-density lipoprotein cholesterol (HDLC), non-HDLC, testosterone, and 17β-estradiol. Physiological testosterone replacement significantly reduced fatty streak formation in Tfm mice compared with placebo-treated controls (0.37±0.07% versus 2.86±0.39%, respectively; P ≤0.0001). HDLC concentrations also were significantly raised in Tfm mice receiving physiological testosterone replacement compared with those receiving placebo (2.81±0.30 versus 2.08±0.09 mmol/L, respectively; P =0.05). Cotreatment with either fulvestrant or anastrazole completely abolished the improvement in HDLC. Conclusion— Physiological testosterone replacement inhibited fatty streak formation in the Tfm mouse, an effect that was independent of the androgen receptor. The observed increase in HDLC is consistent with conversion to 17β-estradiol.
Mite allergens during 18 months of intervention
Authors: M. Wickman, S. L. Nordvall, G. Pershagen, J. Korsgaard, N. Johansen, J. Sundell
Journal: Allergy (1994)

Wickman M, Nordvall SL, Pershagen G, Korsgaard J, Johansen N, Sundell J. Mite allergens during 18 months of intervention. In Stockholm, Sweden, 17 children with newly diagnosed sensitization to house‐dust mites (HDM) and 11 children with previously diagnosed HDM‐sensitization were included in a study of HDM‐allergen avoidance. Mattress dust was collected on repeated occasions during 18 months and assayed for concentration of major HDM allergens. During the first 12 months, the parents of the intervention group were instructed to intensify cleaning and airing of the child's bedroom. During the last 6 months of the study, the mattresses and pillows of seven children in the intervention group and sibling controls were encased in semipermeable polyurethane covers. The homes exhibited a high absolute indoor humidity throughout the year, and even during the winter the mean levels exceeded 7 g/kg. No mite allergen reduction was seen in the intervention group during the first year. However, among the newly diagnosed HDM‐sensitized children, there was a mean reduction of the mattress mite allergen concentration of 83% ( P = 0.02), and this was most pronounced in the homes with low humidity. At the end of the mattress encasement period, an average difference of 98% ( P &lt; 0.001) was found between the vacuumed amount of mite allergen on top of the covers and that underneath.
Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor
Authors: Francesco De Marchis, Domenico Ribatti, Claudia Giampietri, Alessandro Lentini, Debora Faraone, Marco Scoccianti, Maurizio C. Capogrossi, Antonio Facchiano
Journal: Blood (2002)
The Evolution of Melanoma Resistance Reveals Therapeutic Opportunities
Authors: Meghna Das Thakur, Darrin D. Stuart
Journal: Cancer Research (2013)

The RAS-RAF-MEK-ERK pathway is a key driver of proliferation and survival signals in tumor cells and has been the focus of intense drug development efforts over the past 20 years. The recent regulatory approval of RAF inhibitors and a MAP-ERK kinase (MEK) inhibitor for metastatic melanoma provides clinical validation of tumor dependency on this pathway. Unfortunately, the therapeutic benefit of these agents is often short lived and resistance develops within a matter of months. Preclinical models of resistance to vemurafenib have provided critical insights into predicting, validating, and characterizing potential mechanisms. A key observation has been that vemurafenib-resistant tumor cells suffer a fitness deficit in the absence of drug treatment and this led to the predication that modulating the selective pressure of drug treatment through intermittent dosing could delay or prevent the emergence of resistant tumors. Most importantly, the preclinical data are supported by observations in vemurafenib-treated patients with melanoma providing a strong rationale for clinical testing of alternative dosing regimens.
Meat Consumption and Its Association With C-Reactive Protein and Incident Type 2 Diabetes
Authors: Geertruida J. van Woudenbergh, Anneleen Kuijsten, Basia Tigcheler, Eric J.G. Sijbrands, Frank J.A. van Rooij, Albert Hofman, Jacqueline C.M. Witteman, Edith J.M. Feskens
Journal: Diabetes Care (2012)

To investigate whether intake of different types of meat is associated with circulating C-reactive protein (CRP) and risk of type 2 diabetes in a prospective cohort study.Our analysis included 4,366 Dutch participants who did not have diabetes at baseline. During a median follow-up period of 12.4 years, 456 diabetes cases were confirmed. Intake of red meat, processed meat, and poultry was derived from a food frequency questionnaire, and their association with serum high-sensitivity CRP was examined cross-sectionally using linear regression models. Their association with risk of type 2 diabetes was examined using multivariate Cox proportional hazards model, including age, sex, family history of diabetes, and lifestyle and dietary factors.An increment of 50 g of processed meat was associated with increased CRP concentration (β(processed meat) = 0.12; P = 0.01), whereas intake of red meat and poultry was not. When comparing the highest to the lowest category of meat intake with respect to diabetes incidence, the adjusted relative risks were as follows: for red meat (1.42 [95% CI 1.06-1.91]), for processed meat (1.87 [1.26-2.78]), and for poultry (0.95 [0.74-1.22]). Additional analysis showed that the associations were not affected appreciably after inclusion of CRP into the model. After adjustment for BMI, however, the association for red meat attenuated to 1.18 (0.88-1.59).Intake of processed meat is associated with higher risk of type 2 diabetes. It appears unlikely that CRP mediates this association.
Risk of invasive pneumococcal infections among working age adults with asthma
Authors: P. Klemets, O. Lyytikainen, P. Ruutu, J. Ollgren, T. Kaijalainen, M. Leinonen, J. Pekka Nuorti
Journal: Thorax (2010)

Information about the risk of invasive pneumococcal infection (IPI) among adults with asthma is limited and inconsistent. To evaluate this association, a population-based case-control study was conducted.Cases of IPI (Streptococcus pneumoniae isolated from blood or cerebrospinal fluid) were identified through national, population-based laboratory surveillance during 1995-2002. To maximise exclusion of chronic obstructive pulmonary disease, the analysis was limited to patients aged 18-49 years and 10 selected age-, sex- and health district-matched controls for each case from the Population Information System. Information on underlying medical conditions was obtained through linking surveillance data to other national health registries. Asthma requiring > or =1 hospitalisation in the past 12 months was defined as high risk asthma (HRA); low risk asthma (LRA) was defined as entitlement to prescription drug benefits and no hospitalisation for asthma in the past 12 months.1282 patients with IPI and 12 785 control subjects were identified. Overall, 7.1% of cases and 2.5% of controls had asthma (6.0% and 2.4% had LRA whereas 1.1% and 0.1% had HRA, respectively. After adjustment for other independent risk factors in a conditional logistic regression model, IPI was associated with both LRA (matched OR (mOR) 2.8; 95% CI 2.1 to 3.6) and HRA (mOR, 12.3; 95% CI 5.4 to 28.0). The adjusted population-attributable risk was 0.039 (95% CI 0.023 to 0.055) for LRA and 0.01 (95% CI 0.0035 to 0.017) for HRA.Working age adults with asthma are at increased risk of IPI. In this population, approximately 5% of disease burden could be attributed to asthma. These findings support adding medicated asthma in adults to the list of indications for pneumococcal vaccination.
Relationship between lymphovascular invasion (LVI) and prognostic markers in different subtypes of breast cancer
Authors: C. G. Panopoulos, C. Tzavara, K. Papadimitriou, N. Pistalmatzian, G. Lypas, V. Barbounis, S. Demiri, G. Koumakis, N. Apostolikas, A. Efremidis
Journal: Journal of Clinical Oncology (2009)

e22109 Background: Prognostic and predictive factors for invasive breast cancer (BC) are well established. LVI was added to the list of prognostic factors for node negative patients (St.Gallen 2006). The aim of this study was to investigate the relationship of LVI with known prognostic markers and its role on different subtypes of breast cancer. Methods: 367 patients with primary BC were evaluated in this study. Tumoral and peritumoral breast tissue was examined for LVI. The patient's age, menopausal status, tumor histology, tumor size, histologic grade, lymph node (LN) involvement, hormone receptor (HR) status and HER-2 status were determined as markers of prognosis. The association of LVI with the aforementioned markers was evaluated using multiple logistic regression analysis. Results: The distribution of the patients was as follows: 40.9% were HR + and HER-2 - (luminal type), (32.4%) were triple negative, 26.7% were HER-2 Positive (9.5% of them were HER-2 + and HR -, while 17.2% were HER-2 + and HR+). Almost half of the patients (48.8%) had one or more positive nodes. Multiple analysis revealed that histologic grade, LN involvement and HER-2 positivity were independently associated with LVI. Patients with histologic grade II and III had 5.31 (95% CI: 1.14–24.75) and 7.03 (95% CI: 1.47- 33.53) times greater odds for LVI respectively compared to those with grade I. Patients with one or more than three nodes involved had 3.95 (95% CI: 2.13–7.33) and 6.29 (95% CI: 3.14–12.63) times greater odds for LVI respectively compared with node negative tumors. Furthermore, HER-2 positive patients had almost twofold likelihood for LVI (OR=1.80, 95% CI: 1.02–3.16). The effect of HER-2 positivity on LVI was independent of HR status. Age, menopausal status, tumor histology, tumor size and HR status were not significantly associated with LVI. Conclusions: LVI shows a close relationship with known markers of poor prognosis as histologic grade, and LN invasion. More aggressive tumors as HER-2 + tumors have a significantly higher probability of LVI, which may be used as an indicator of more aggressive behavior of the primary tumor. No significant financial relationships to disclose.
The dramaturgy of dreams in Pleistocene minds and our own
Authors: Keith Gunderson
Journal: Behavioral and Brain Sciences (2000)

The notion of simulation in dreaming of threat recognition and avoidance faces difficulties deriving from (1) some typical characteristics of dream artifacts (some “surreal,” some not) and (2) metaphysical issues involving the need for some representation in the theory of a perspective subject making use of the artifact. [Hobson et al.; Revonsuo]
Epratuzumab, a Humanized Anti-CD22 Antibody, in Aggressive Non-Hodgkin’s Lymphoma
Authors: John P. Leonard, Morton Coleman, Jamie C. Ketas, Amy Chadburn, Richard Furman, Michael W. Schuster, Eric J. Feldman, Michelle Ashe, Stephen J. Schuster, William A. Wegener, Hans J. Hansen, Heather Ziccardi, Michael Eschenberg, Urte Gayko, Scott Z. Fields, Alessandra Cesano, David M. Goldenberg
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We conducted a single-center, dose-escalation study evaluating the safety, pharmacokinetics, and efficacy of epratuzumab, an anti-CD22 humanized monoclonal antibody, in patients with aggressive non-Hodgkin’s lymphoma. Experimental Design: Epratuzumab was administered once weekly for 4 weeks at 120-1000-mg/m2 doses to 56 patients [most (n = 35) with diffuse large B-cell lymphoma]. Results: Patients were heavily pretreated (median, 4 prior therapies), 25% received prior high-dose chemotherapy with stem cell transplant, and 84% had bulky disease (≥5 cm). Epratuzumab was well tolerated, with no dose-limiting toxicity. Most (95%) infusions were completed within 1 h. The mean serum half-life was 23.9 days. Across all dose levels and histologies, objective responses (ORs) were observed in five patients (10%; 95% confidence interval, 3–21%), including three complete responses. In patients with diffuse large B-cell lymphoma, 15% had ORs. Overall, 11 (20%) patients experienced some tumor mass reduction. Median duration of OR was 26.3 weeks, and median time to progression for responders was 35 weeks. Two responses are ongoing at ≥34 months, including one rituximab-refractory patient. Conclusions: These data demonstrate that epratuzumab has a good safety profile and exerts antitumor activity in aggressive non-Hodgkin’s lymphoma at doses of ≥240 mg/m2, thus warranting further evaluation in this clinical setting.
A Randomized Trial of Sugar-Sweetened Beverages and Adolescent Body Weight
Authors: Cara B. Ebbeling, Henry A. Feldman, Virginia R. Chomitz, Tracy A. Antonelli, Steven L. Gortmaker, Stavroula K. Osganian, David S. Ludwig
Journal: New England Journal of Medicine (2012)

Consumption of sugar-sweetened beverages may cause excessive weight gain. We aimed to assess the effect on weight gain of an intervention that included the provision of noncaloric beverages at home for overweight and obese adolescents.
Influence of thyroid status on the paradoxical growth hormone response to thyrotropin-releasing hormone in human obesity
Authors: V. Coiro, R. Volpi, L. Capretti, G. Speroni, C. Marchesi, P.P. Vescovi, G. Caffarri, R. Colla, G. Rossi, C. Davoli, P. Chiodera
Journal: Metabolism (1994)