tbuckley/cabot-search huggingface dataset:
GSK3β Phosphorylates Newly Identified Site in the Proline-Alanine–Rich Region of Cardiac Myosin–Binding Protein C and Alters Cross-Bridge Cycling Kinetics in Human
Authors: Diederik W. D. Kuster, Vasco Sequeira, Aref Najafi, Nicky M. Boontje, Paul J. M. Wijnker, E. Rosalie Witjas-Paalberends, Steven B. Marston, Cristobal G. dos Remedios, Lucie Carrier, Jeroen A. A. Demmers, Charles Redwood, Sakthivel Sadayappan, Jolanda van der Velden
Journal: Circulation Research (2013)

Cardiac myosin-binding protein C (cMyBP-C) regulates cross-bridge cycling kinetics and, thereby, fine-tunes the rate of cardiac muscle contraction and relaxation. Its effects on cardiac kinetics are modified by phosphorylation. Three phosphorylation sites (Ser275, Ser284, and Ser304) have been identified in vivo, all located in the cardiac-specific M-domain of cMyBP-C. However, recent work has shown that up to 4 phosphate groups are present in human cMyBP-C.To identify and characterize additional phosphorylation sites in human cMyBP-C.Cardiac MyBP-C was semipurified from human heart tissue. Tandem mass spectrometry analysis identified a novel phosphorylation site on serine 133 in the proline-alanine-rich linker sequence between the C0 and C1 domains of cMyBP-C. Unlike the known sites, Ser133 was not a target of protein kinase A. In silico kinase prediction revealed glycogen synthase kinase 3β (GSK3β) as the most likely kinase to phosphorylate Ser133. In vitro incubation of the C0C2 fragment of cMyBP-C with GSK3β showed phosphorylation on Ser133. In addition, GSK3β phosphorylated Ser304, although the degree of phosphorylation was less compared with protein kinase A-induced phosphorylation at Ser304. GSK3β treatment of single membrane-permeabilized human cardiomyocytes significantly enhanced the maximal rate of tension redevelopment.GSK3β phosphorylates cMyBP-C on a novel site, which is positioned in the proline-alanine-rich region and increases kinetics of force development, suggesting a noncanonical role for GSK3β at the sarcomere level. Phosphorylation of Ser133 in the linker domain of cMyBP-C may be a novel mechanism to regulate sarcomere kinetics.
The feature of BCG complications in children
Authors: Stela Kulcitkaia
Journal: European Respiratory Journal (2013)

Background: The problem of adverse events following BCG immunization remains actual and hasn’t been definitively resolved.

Aim: To study frequency, clinical picture, diagnosis, treatment and prevention of BCG complications in children.

Materials and methods: There were supervised 611 children with BCG complications during 10 years in Moldova.

Results: The increase of BCG complications, both at vaccination and revaccination, occurred due to changing the vaccine preparation (from 2.1 to 78.1 cases per 100 000 children). According to the classification of BCG complications by WHO’s European Bureau, the most frequently diagnosed complications referred to the first category: regional lymphadenitis (63.5%), cool abscesses (18.9%) and ulcers (12.8%). In the 2nd category of complications there were included ostitis (3.1%) and uveitis (0.7%). Generalized processes of the 3rd category didn’t occur. From the 4th category, cutaneous rashes (0.2%) and cheloid scars (0.8%) were observed. BCG osteitis in children diagnosing was based on: bones destruction, local few pronounced changes, sufficient general state and biopsy hotbed data. Children with ulcer had allergic reactions manifested due to the high specific cellular sensitivity to tuberculin, having got the least quantity of antibodies. The patients with abscess, with predominant toxic reactions because of the lowest sensitivity to tuberculin, had the biggest quantity of tuberculosis antibodies. The most well-balanced report of specific cellular and humoral sensitivity was observed in patients with regional lymphadenitis.

Conclusion: The causes of BCG complications development consisted of technical errors, vaccine’s biological properties, and the complicated evolution of the vaccinal process.
How to interpret changes in the London chest activity of daily living scale in patients with COPD
Authors: Gianna W. Bisca, Mahara Proença, Alexandre Salomão, Nidia A. Hernandes, Fabio Pitta
Journal: European Respiratory Journal (2013)

Background: Dyspnea and fatigue frequently impair the ability to perform activities of daily living (ADL) in patients with chronic obstructive pulmonary disease (COPD). Several questionnaires and scales have been used to assess limitations in ADL before and after treatment in this population; among them, the London Chest Activity of Daily Living (LCADL) scale is responsive to intervention to a higher extent when compared to other tools. However, the minimal detectable change (MDC) for this scale remains unknown.

Objective: To determine the MDC for functional status improvement measured by the LCADL scale in patients with COPD.

Methods: Forty patients with COPD (20 male, 66±7 years, FEV1 44±16% predicted) participated in a 3-month high-intensity exercise program based on endurance and strength training (3x/week, 12 weeks). Before and after the protocol all participants responded to the LCADL scale and the Saint George Respiratory Questionnaire (SGRQ). In order to calculate the MDC (distribution-based estimates), we used the standard error of measurement and the effect size.

Results: There was improvement in the domains and total score of the LCADL after the program. The MDC estimated for the LCADL were 0.89, 2.60, 0.44, 0.58 and 3.88 points for self-care, domestic, physical and leisure domains and total score, respectively. Correlations between changes in LCADL and in SGRQ were weak (r<0.4 for all).

Conclusion: This study provided MDC for the domains and total score of the LCADL. A change of 4 points in the total score of the LCADL can be interpreted as a meaningful change.
Dietary Prevention and Treatment of Heart Disease.
Authors: Arthur L. Bloomfield
Journal: Annals of Internal Medicine (1960)

Dr. Gofman's work, especially on the amount and signifi- cance of the blood lipoproteins, is well known.In the open- ing chapters he sustains the thesis of the bad effect on the coronary arteries of increased quantities of certain lipo- protein fractions.These changes he thinks can be prevented or delayed by dietary regulation.At this point the dietitian (Dobbin) takes over the major burden of the discussion to which nearly two-thirds of the book are given over.Planning the diet and the preparation of foods are gone into in detail.
Anxiety and depression in tuberculosis hospitalized patients in comparison to healthy individuals
Authors: Ionela Iovan, Dorin Vancea, Zeno Fratila, Ovidiu Burlacu
Journal: European Respiratory Journal (2012)

Introduction: Very little is known about the psychiatric comorbidities in tuberculosis (TB), which must be recognized and managed in order to improve adherence to the treatment.

Aim: To assess the presence of depression and anxiety in TB patients, at the diagnostic and after 6 weeks of hospitalization, in comparison with healthy individuals.

Methods: 63 consecutive pulmonary TB patients (F/M:21/42) and 63 healthy individuals, completed the Hospital Anxiety and Depression Scale (HADS) and a respiratory symptoms questionnaire.

Results: In the 63 TB patients the rate of moderate/severe level of anxiety and depression (HAD anxiety/depression >11) was 65%, significantly higher than in healthy individuals (11%, p<0.05). Anxiety was detected in 27 (43%) and depression in 31 (49%) of the patients at diagnosis, with higher prevalence of anxiety in women (57%, p=0.177).

After 6 weeks of hospitalization the rate of patients presenting anxiety and depression didn't decrease (p=0.3). Their elevated HADS scores were associated with the persistence of respiratory symptoms and a poor clinical status.

Conclusions: The prevalence of anxiety and depression, which are independent predictors of poor treatment adherence, is very high in TB patients.

The results suggest that the TB control programs should include strategies of regular screening and treatment for depression, which can improve treatment adherence, patient management and disease outcomes.
Pancreatic Carcinogenesis: Effect of Secretin in the Hamster-Nitrosamine Model2
Authors: Allan G. Howatson, David C. Carter
Journal: JNCI Journal of the National Cancer Institute (1987)

Journal Article Pancreatic Carcinogenesis: Effect of Secretin in the Hamster-Nitrosamine Model Get access Allan G. Howatson, Allan G. Howatson Search for other works by this author on: Oxford Academic PubMed Google Scholar David C. Carter David C. Carter Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 78, Issue 1, January 1987, Pages 101–105, https://doi.org/10.1093/jnci/78.1.101 Published: 01 January 1987 Article history Received: 10 July 1985 Revision received: 09 July 1986 Accepted: 24 July 1986 Published: 01 January 1987
Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer.
Authors: A H Paterson, T J Powles, J A Kanis, E McCloskey, J Hanson, S Ashley
Journal: Journal of Clinical Oncology (1993)

PURPOSE Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer. PATIENTS AND METHODS We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients). RESULTS The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P &lt; .01), in the number of terminal hypercalcemic episodes (seven v 17; P &lt; .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P &lt; .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P &lt; .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P &lt; .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups. CONCLUSIONS These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases.
Oral Immunotherapy for Peanut Allergy
Authors: Katherine Anagnostou, Andrew Clark
Journal: Annual Review of Medicine (2015)

Peanut allergy is a common disease and the cause of severe, life-threatening allergic reactions and death. It is rarely outgrown; most pediatric patients carry the disease into adulthood. Peanut allergy poses a significant burden on the quality of life of sufferers and their families, which results mainly from the fear of accidental peanut ingestion but is also due to dietary and social restrictions. Current standard management involves avoidance advice, patient education, and provision of emergency rescue medication. Immunotherapy, commonly used to treat other allergic diseases, has shown promise as a disease-modifying therapy for peanut allergy. Results from studies of oral immunotherapy show high efficacy rates, improvement in quality of life, and a good safety profile. Treatment may result in sustained unresponsiveness in a proportion of patients, whereas others require ongoing treatment.
Cetuximab administered through pulmonary route in a mice model of lung tumor
Authors: Laurent Guilleminault, Flora Paul, Stephanie Lerondel, Valérie Schubnel, Jerome Montharu, Michèle De Monte, Alain Lepape, Etienne Lemarié, Nathalie Heuzé-Vourc'h
Journal: European Respiratory Journal (2013)

Introduction:  Emerging evidences indicate that monoclonal antibodies delivered through pulmonary route may be a promising treatment for lung diseases. We assessed the efficacy and tumor distribution of cetuximab, an anti-EGFR antibody, delivered through the pulmonary route in a murine model of lung tumor.   Methods:  A549-luc cells were orotracheally inoculated into lungs of Balb/C nude females to develop an orthotopic murine model of NSCLC sensitive to cetuximab. Nine days after inoculation, tumor were treated with cetuximab intraperitoneally (n=15), aerosol cetuximab (n=17) at a dose of 10 mg/kg or NaCl aerosol (n=16), once a week for three weeks. Bioluminescence imaging was used to homogenise group before treatment and to follow up tumor growth. For intratumoral biodistribution study, cetuximab was conjugated to a fluorophore and delivered in the orthotopic mouse model of NSCLC either through ip, iv or the pulmonary route. Three dimensional near-infrared fluorescence imaging (NIRF) was used to determine tumor uptake of cetuximab.   Results:  As shown by bioluminescence imaging, the growth of A549-luc tumors was statistically decreased by 40% in mice treated with aerosolized cetuximab and 24% in the group treated with ip cetuximab comparatively to the control group (p   Conclusion:  The pulmonary delivery of mAb, such as cetuximab, may be relevant for treating respiratory diseases, but further investigations are required to understand the molecular mechanisms associated with the therapeutic response.
Abstract 1879: Global Lv Strain Is An Accurate Measure For Scar Extent After Myocardial Infarct. A Comparison Of Longitudinal, Circumferential And Radial Strain Measurements
Authors: Trond Vartdal, Ola Gjesdal, Thomas Helle-Valle, Ketil Lunde, Einar Hopp, Hans-Jørgen Smith, Halfdan Ihlen, Thor Edvardsen
Journal: Circulation (2007)

Purpose: Recent progress by speckle tracking echocardiography (STE) provides the opportunity to assess left ventricular (LV) function in 3 dimensions. We studied LV longitudinal, circumferential and radial strain and calculated which strain parameter that correlated best to myocardial scar mass in patients with chronic ischemic heart disease. Methods: 40 patients (aged 58 ± 10 years, 9 women) were studied 8.5 ± 5.4 months after a first myocardial infarction. LV infarct mass was estimated by late enhancement MRI and compared to global LV strain. Global LV strain is calculated by averaging all segmental peak systolic strain values by STE in a 16 segment model. Longitudinal strain was assessed from 3 apical views, and circumferential- and radial strain from 3 short axis slices (apical, mid and basal). Results: In average, 7.9 ± 4.1 segments and a total of 34 ± 27g were infarcted. Transmural infarct (≥50% transmural) was found in 25 patients. All global strains correlated significantly with infarct mass (figure ). In a ROC analysis, longitudinal strain was superior to identify substantial (≥30g) myocardial infarcts (sensitivity = 0.80, specificity = 0.85). Circumferential strain was best to identify minor (≥5g) myocardial infarcts (sensitivity = 0.82, specificity = 0.86). Conclusion: Assessment of strain in all 3 major dimensions reflects decreased LV function due to ischemic myocardium. Global longitudinal- and circumferential- strains are excellent markers to identify patients with myocardial infarct. Figure: Correlation plots
Association of xenobiotic metabolizing gene polymorphisms and chronic obstructive pulmonary disease in Indian population
Authors: Naushad Khan, Mradul Daga, Nitish Kamble, Govind Mawari, Istaq Ahmed, S.A. Husain
Journal: European Respiratory Journal (2012)

Background and Aim: Genetic susceptibility to the development of chronic obstructive pulmonary disease might depend on variation in the activities of enzymes that detoxify cigarette smoke products. We studied the relationship of GSTP1, GSTM1, and GSTT1 gene polymorphisms with COPD risk in a case- control study of Indian patients and controls.  Material and methods: A total of 186 patients with COPD and 160 healthy controls were included in the study. The Frequencies of GSTP1, GSTM1 alleles was determined by using conventional Multiplex PCR and GSTP1 by polymerase chain reaction and restriction fragment length polymorphisms technique.  Results: A significant case –control difference was observed for the presence of null GSTM1, (61.8% Vs 55.0 %, P= 0.04). No difference was observed in the frequency of GSTT1 Null genotype and COPD susceptibility. (54.8% vs 50.6% OR: 1.26; CI: 0.87- 1.84; P value = 0.82) For GSTP1 polymorphism we found that Subjects homozygous variants Val/ Val were at increased risk of developing COPD (OR: 2.58; CI: 1.2- 4.8) as compared to heterozygote variants Ile/ Val (OR: 1.28 CI: 0.7-2.14) Also, the mutant allele frequency (Val) was significantly higher in patients as compared to controls and the difference was found to be statistically significant. (OR: 1.8 CI: 1.4- 4.2; P Value =0.001)  Conclusion: We propose that subjects with GSTM1 null allele and GST P1 homozygous isoleucine genotypes are at higher risk of COPD and are significant indicators of susceptibility to chronic obstructive pulmonary disease in Indian population.  Keywords: Chronic Obstructive Pulmonary Disease, Polymerase chain reaction, Gluthathione S- transferase.
Prediction of deterioration of bronchial asthma (BA) control after six months of basic anti-inflammatory therapy
Authors: Nelly M. Smirnova, Anna G. Prihodko, Juliy M. Perelman
Journal: European Respiratory Journal (2012)

Background : Now it is accepted that the assessment of asthma control should include not only clinical manifestations, but also control of the expected future risk to the patients.  Aim:  To develop the way of prediction of uncontrolled BA after 6 months of basic anti-inflammatory therapy.  Methods : 84 patients with uncontrolled BA were examined. At the first examination the test of isocapnic hyperventilation with cold air (IHCA) was conducted; the collection of the exhaled breath condensate before and after the IHCA with the identification of hydrogen peroxide (H 2 O 2 ) was done. In 24 weeks of basic therapy there was the second clinical examination where the control level over BA symptoms was determined. Depending on the obtained data the patients retrospectively were divided into two groups: the 1 st  group included 48 patients with the partial or total BA control, the 2 nd  group consisted of 36 patients with uncontrolled BA.  Results:  It was established that high airway hyperresponsiveness and the degree of oxidative stress intensity are independent predictors of BA control. On this basis and with the help of discriminant analysis we made a discriminant equation that allows to predict an uncontrolled course of the disease: D=-0.502×FEV 1  (after IHCA)+8.062×H 2 O 2  (after IHCA). The boundary value of the discriminant function is 23.07. If D>23.07, an uncontrolled course of the disease after 6 months of basic therapy can be predicted with 91% probability.  Conclusion : The application of the developed method gives a possibility of a differentiated approach to the choice of BA basic therapy taking into account the risk of uncontrolled course of the disease.
Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation?
Authors: T Jansson, J E Westlin, H Ahlström, A Lilja, B Långström, J Bergh
Journal: Journal of Clinical Oncology (1995)

PURPOSE To investigate if sequential positron emission tomographic (PET) scans with the glucose analog 18F-2-fluoro-2-deoxy-D-glucose (18FDG) and/or L-methyl-11C-methionine (11C-methionine) in patients with breast cancer could provide early information on the efficacy of polychemotherapy. PATIENTS AND METHODS Sixteen patients with breast cancer (11 with locally advanced tumors, three with recurrent disease in the contralateral breast, two of them with distant and regional metastases, and two with distant metastases) underwent a baseline and two follow-up PET scans after the first and third/fourth polychemotherapy course. Tumor response was determined clinically/radiographically after three/four polychemotherapy courses. RESULTS Five patients were investigated with 18FDG, seven with both 11C-methionine and 18FDG, and four with only 11C-methionine before polychemotherapy. 11C-methionine presented a more distinct visualization of primary/contralateral breast cancers in five of seven patients when compared with 18FDG. Twelve of 16 patients demonstrated a response using conventional methods after the third/fourth course of polychemotherapy. Eight of these 12 clinical responders had a significant decrease in tracer uptake at the first PET scan performed 6 to 13 days after the first polychemotherapy course, and these reductions were further augmented after the third/fourth course and corresponded to the conventional therapy evaluation (clinical examination, computed tomography [CT], ultrasonography, and mammography). CONCLUSION Our data indicate that PET may be of clinical value in predicting response to chemotherapy in patients with locally advanced breast cancer and/or metastatic disease earlier than any other method used.
Ownership of written asthma action plans in a large Australian survey
Authors: Helen Reddel, Matthew Peters, Peter Everett, Paul Flood, Susan Sawyer
Journal: European Respiratory Journal (2013)

Background : Written asthma action plans (WAAP) are important in asthma self-management, but uptake is limited. This study examined factors associated with WAAP ownership in a large Australian survey.

Methods : People ≥16 years with current asthma (diagnosis, and symptoms/treatment in last year) completed an online survey, including Asthma Control Test (ACT) and WAAP ownership. Data were weighted to Australian asthma population by age, gender and state.

Results : WAAP data were available for 2610 participants, 57% female. WAAP ownership was higher for females and age 16-29, but did not vary by socioeconomic status.

View this table:

WAAP ownership





* Agreement on Likert scale 1-7; p<0.001 vs like rows; ♣ p<0.001 across columns

Conclusions : Overall rates of WAAP ownership in Australia are sub-optimal, although somewhat higher in at-risk patients. People with a WAAP are more likely to follow it if they are older, have higher health literacy, or feel that the action plan is practical, easy to understand, or personalised to themselves.