tbuckley/cabot-search huggingface dataset:
Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure
Authors: Ashley G. Henderson, Camille Ehre, Brian Button, Lubna H. Abdullah, Li-Heng Cai, Margaret W. Leigh, Genevieve C. DeMaria, Hiro Matsui, Scott H. Donaldson, C. William Davis, John K. Sheehan, Richard C. Boucher, Mehmet Kesimer
Journal: Journal of Clinical Investigation (2014)

The pathogenesis of mucoinfective lung disease in cystic fibrosis (CF) patients likely involves poor mucus clearance. A recent model of mucus clearance predicts that mucus flow depends on the relative mucin concentration of the mucus layer compared with that of the periciliary layer; however, mucin concentrations have been difficult to measure in CF secretions. Here, we have shown that the concentration of mucin in CF sputum is low when measured by immunologically based techniques, and mass spectrometric analyses of CF mucins revealed mucin cleavage at antibody recognition sites. Using physical size exclusion chromatography/differential refractometry (SEC/dRI) techniques, we determined that mucin concentrations in CF secretions were higher than those in normal secretions. Measurements of partial osmotic pressures revealed that the partial osmotic pressure of CF sputum and the retained mucus in excised CF lungs were substantially greater than the partial osmotic pressure of normal secretions. Our data reveal that mucin concentration cannot be accurately measured immunologically in proteolytically active CF secretions; mucins are hyperconcentrated in CF secretions; and CF secretion osmotic pressures predict mucus layer-dependent osmotic compression of the periciliary liquid layer in CF lungs. Consequently, mucin hypersecretion likely produces mucus stasis, which contributes to key infectious and inflammatory components of CF lung disease.
Is postural control affected by expertise in alpine skiing?
Authors: F Noé, T Paillard
Journal: British Journal of Sports Medicine (2005)

This study examined the postural performance of two groups of male skiers competing at different levels and the consequences on postural control of the suppression of visual afferences by eye closure.Seven national level (NAT) skiers and 7 regional level (REG) skiers were asked to stand as still as possible on a force platform with eyes opened and closed and while wearing or not wearing their ski boots in a stable posture and in two unstable postures (in the sagittal or frontal plane). Postural performance was assessed with centre of foot pressure measurements.REG and NAT skiers were similarly influenced by the absence of visual information and presented similar postural performance when tests were performed with ski boots. However, without ski boots, REG skiers displayed better postural performance than NAT skiers.The inferior postural performance of NAT skiers without ski boots could be a long term effect of repetitive wearing of ski boots, which impairs postural performance by restricting the range of motion of the ankle-foot complex. Since individuals with decreased postural performance are believed to be more susceptible to ankle injury than those with finer postural control, NAT skiers should benefit from specific training aimed at improving postural ability and preventing ankle injury.
Hemodynamic effects of nitroprusside and hydralazine in experimental cardiac tamponade.
Authors: N O Fowler, M Gabel, J C Holmes
Journal: Circulation (1978)

Cardiac tamponade is associated with decreased cardiac output and increased systemic vascular resistance. Thus, vasodilator drugs might lower systemic resistance and increase cardiac output. Three groups of dogs were studied during tamponade. Group I received nitroprusside only; group II received blood transfusion and then nitroprusside; group III received hydralazine. In group I, nitroprusside lowered right artrial pressure and systemic resistance; cardiac output was unchanged. In group II, transfusion raised right atrial pressure but not cardiac output. Then nitroprusside raised cardiac output significantly. Hydralazine decreased right atrial pressure less than nitroprusside but decreased vascular resistance and raised cardiac output. Both nitroprusside and hydralazine decreased systemic vascular resistance during tamponade, but only hydralazine raised cardiac output probably because of its lesser effect upon the capacitance vessels. Nitroprusside maintained cardiac output during tamponade despite lowered right atrial pressure but increased cardiac output only after transfusion.
Daily versus As-Needed Corticosteroids for Mild Persistent Asthma
Authors: Homer A. Boushey, Christine A. Sorkness, Tonya S. King, Sean D. Sullivan, John V. Fahy, Stephen C. Lazarus, Vernon M. Chinchilli, Timothy J. Craig, Emily A. Dimango, Aaron Deykin, Joanne K. Fagan, James E. Fish, Jean G. Ford, Monica Kraft, Robert F. Lemanske, Frank T. Leone, Richard J. Martin, Elizabeth A. Mauger, Gene R. Pesola, Stephen P. Peters, Nancy J. Rollings, Stanley J. Szefler, Michael E. Wechsler, Elliot Israel
Journal: New England Journal of Medicine (2005)

Although guidelines recommend daily therapy for patients with mild persistent asthma, prescription patterns suggest that most such patients use these so-called controller therapies intermittently. In patients with mild persistent asthma, we evaluated the efficacy of intermittent short-course corticosteroid treatment guided by a symptom-based action plan alone or in addition to daily treatment with either inhaled budesonide or oral zafirlukast over a one-year period.In a double-blind trial, 225 adults underwent randomization. The primary outcome was morning peak expiratory flow (PEF). Other outcomes included the forced expiratory volume in one second (FEV1) before and after bronchodilator treatment, the frequency of exacerbations, the degree of asthma control, the number of symptom-free days, and the quality of life.The three treatments produced similar increases in morning PEF (7.1 to 8.3 percent; approximately 32 liters per minute; P=0.90) and similar rates of asthma exacerbations (P=0.24), even though the intermittent-treatment group took budesonide, on average, for only 0.5 week of the year. As compared with intermittent therapy or daily zafirlukast therapy, daily budesonide therapy produced greater improvements in pre-bronchodilator FEV1 (P=0.005), bronchial reactivity (P<0.001), the percentage of eosinophils in sputum (P=0.007), exhaled nitric oxide levels (P=0.006), scores for asthma control (P<0.001), and the number of symptom-free days (P=0.03), but not in post-bronchodilator FEV1 (P=0.29) or in the quality of life (P=0.18). Daily zafirlukast therapy did not differ significantly from intermittent treatment in any outcome measured.It may be possible to treat mild persistent asthma with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen. Further studies are required to determine whether this novel approach to treatment should be recommended.
Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer.
Authors: D I Jodrell, M J Egorin, R M Canetta, P Langenberg, E P Goldbloom, J N Burroughs, J L Goodlow, S Tan, E Wiltshaw
Journal: Journal of Clinical Oncology (1992)

The study was undertaken to define the relationship between tumor response and carboplatin area under the curve (AUC) in patients with ovarian cancer; to study the relationship between carboplatin AUC and myelosuppression in the same population; to establish the true impact of carboplatin AUC, prior therapy, and pretreatment platelet and WBC counts on toxicity; and to define an optimal carboplatin exposure for treating patients with ovarian cancer.With the equation AUC = dose/(glomerular filtration rate [GFR]+25), carboplatin AUC (course 1) was calculated for 1,028 patients (450 previously untreated) who received single-agent carboplatin (40 to 1,000 mg/m2) for advanced ovarian cancer. GFR was measured (chromium-51-edathamil [51Cr-EDTA] or creatinine clearance) in all patients.Regression analysis showed that carboplatin AUC, prior treatment, and Eastern Cooperative Oncology Group grade performance status (PS) are predictors of tumor response, thrombocytopenia, and leukopenia. Pretreatment platelet and WBC counts are additional predictors of thrombocytopenia and leukopenia, respectively. Although the likelihood of tumor response increased with increasing carboplatin AUC, this relationship was nonlinear. In all patient subsets, the likelihood of complete response (CR) or overall response did not increase significantly above a carboplatin AUC of 5 to 7 mg/mL x minutes. At any given carboplatin AUC, thrombocytopenia occurred more frequently than leukopenia, although both approached 100% as carboplatin AUC increased. Both thrombocytopenia and leukopenia were more frequent in pretreated than in untreated patients regardless of pretreatment count. At any carboplatin AUC, the influence of PS on likelihood of response and toxicity was profound.Carboplatin dosing by AUC will lead to more predictable toxicity, and increasing carboplatin AUC above 5 to 7 mg/mL x minutes does not improve the likelihood of response but does increase myelotoxicity. Therefore, careful evaluation of high-dose carboplatin therapy in a prospective, randomized trial is needed before such treatment becomes accepted practice.
Evo-devo, modularity, and evolvability: Insights for cultural evolution
Authors: Simon M. Reader
Journal: Behavioral and Brain Sciences (2006)

Evolutionary developmental biology (“evo-devo”) may provide insights and new methods for studies of cognition and cultural evolution. For example, I propose using cultural selection and individual learning to examine constraints on cultural evolution. Modularity, the idea that traits vary independently, can facilitate evolution (increase “evolvability”), because evolution can act on one trait without disrupting another. I explore links between cognitive modularity, evolutionary modularity, and cultural evolvability.
Metabolic Syndrome: Is Nlrp3 Inflammasome a Trigger or a Target of Insulin Resistance?
Authors: Marcelo A. Mori, Olivier Bezy, C. Ronald Kahn
Journal: Circulation Research (2011)

T he Nlrp3 inflammasome has recently been implicated in the development of the metabolic syndrome through the impairment of adipose tissue insulin sensitivity.Recent literature associates Nlrp3 activation with much pathology caused by prolonged insulin resistance state, therefore establishing Nlrp3 as a promising therapeutic target for type-2-diabetes treatment.More than 27% of the U.S. population suffers from the metabolic syndrome, 1 which includes several of our most common health problems, such as central obesity, glucose intolerance/type 2 diabetes, dyslipidemia with accelerated atherosclerosis, hypertension, nonalcoholic hepatosteatosis, and elevated uric acid with increased risk of gout. 2 Despite the varied clinical presentation, many of the components of the metabolic syndrome are driven by one single etiologic factor-insulin resistance. 3,4Indeed, mouse models with insulin resistance in various tissues have been shown to mimic many aspects of the metabolic syndrome. 5,6espite the growing body of evidence that demonstrates the importance of diet and obesity to the onset of insulin resistance and the metabolic syndrome, the molecular mechanisms underlying this phenomenon are not completely understood.Inflammation at the level of adipose tissue and liver, 7-9 oxidative stress, 10 and mitochondrial dysfunction 11 have all been shown to promote insulin resistance.However, how these act to give rise to the multifactorial pathophysiology of insulin resistance and how alterations in the energy balance can be sensed by cells of the organism and translated into signals that could affect insulin sensitivity are not known.In a recent report, Vandanmagsar et al 12 demonstrate that danger signals originating with obesity are sensed by the Nlrp3 class of cytosolic pattern recognition receptors, whichThe opinions expressed in this Commentary are not necessarily those of the editors or of the American Heart Association.
Mixed Tocopherols Prevent Mammary Tumorigenesis by Inhibiting Estrogen Action and Activating PPAR-γ
Authors: Hong Jin Lee, Jihyeung Ju, Shiby Paul, Jae-Young So, Andrew DeCastro, Amanda Smolarek, Mao-Jung Lee, Chung S. Yang, Harold L. Newmark, Nanjoo Suh
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Tocopherols are lipophilic antioxidants present in vegetable oils. Although the antioxidant and anticancer activities of α-tocopherol (vitamin E) have been studied for decades, recent intervention studies with α-tocopherol have been negative for protection from cancer in humans. The tocopherols consist of four isoforms, which are the α, β, γ, and δ variants, and recent attention is being given to other isoforms. In the present study, we investigated the inhibitory effect of a tocopherol mixture rich in γ- and δ-tocopherols against mammary tumorigenesis. Experimental Design: Female Sprague Dawley rats were treated with N-methyl-N-nitrosourea (NMU), and then fed diets containing 0.1%, 0.3%, or 0.5% mixed tocopherols rich in γ- and δ-tocopherols for 9 weeks. Tumor burden and multiplicity were determined, and the levels of markers of inflammation, proliferation, and apoptosis were evaluated in the serum and in mammary tumors. The regulation of nuclear receptor signaling by tocopherols was studied in mammary tumors and in breast cancer cells. Results: Dietary administration of 0.1%, 0.3%, or 0.5% mixed tocopherols suppressed mammary tumor growth by 38%, 50%, or 80%, respectively. Tumor multiplicity was also significantly reduced in all three mixed tocopherol groups. Mixed tocopherols increased the expression of p21, p27, caspase-3, and peroxisome proliferator activated receptor-γ, and inhibited AKT and estrogen signaling in mammary tumors. Our mechanistic study found that γ- and δ-tocopherols, but not α-tocopherol, activated peroxisome proliferator activated receptor-γ and antagonized estrogen action in breast cancer. Conclusion: The results suggest that γ- and δ-tocopherols may be effective agents for the prevention of breast cancer.
Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 3-Year Outcomes
Authors: Philip R. Schauer, Deepak L. Bhatt, John P. Kirwan, Kathy Wolski, Stacy A. Brethauer, Sankar D. Navaneethan, Ali Aminian, Claire E. Pothier, Esther S.H. Kim, Steven E. Nissen, Sangeeta R. Kashyap
Journal: New England Journal of Medicine (2014)

In short-term randomized trials (duration, 1 to 2 years), bariatric surgery has been associated with improvement in type 2 diabetes mellitus.We assessed outcomes 3 years after the randomization of 150 obese patients with uncontrolled type 2 diabetes to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary end point was a glycated hemoglobin level of 6.0% or less.The mean (±SD) age of the patients at baseline was 48±8 years, 68% were women, the mean baseline glycated hemoglobin level was 9.3±1.5%, and the mean baseline body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.0±3.5. A total of 91% of the patients completed 36 months of follow-up. At 3 years, the criterion for the primary end point was met by 5% of the patients in the medical-therapy group, as compared with 38% of those in the gastric-bypass group (P<0.001) and 24% of those in the sleeve-gastrectomy group (P=0.01). The use of glucose-lowering medications, including insulin, was lower in the surgical groups than in the medical-therapy group. Patients in the surgical groups had greater mean percentage reductions in weight from baseline, with reductions of 24.5±9.1% in the gastric-bypass group and 21.1±8.9% in the sleeve-gastrectomy group, as compared with a reduction of 4.2±8.3% in the medical-therapy group (P<0.001 for both comparisons). Quality-of-life measures were significantly better in the two surgical groups than in the medical-therapy group. There were no major late surgical complications.Among obese patients with uncontrolled type 2 diabetes, 3 years of intensive medical therapy plus bariatric surgery resulted in glycemic control in significantly more patients than did medical therapy alone. Analyses of secondary end points, including body weight, use of glucose-lowering medications, and quality of life, also showed favorable results at 3 years in the surgical groups, as compared with the group receiving medical therapy alone. (Funded by Ethicon and others; STAMPEDE ClinicalTrials.gov number, NCT00432809.).
Pharmacological modification of epidermal detoxification systems
Authors: D.R. BICKERS, M. DAS, H. MUKHTAR
Journal: British Journal of Dermatology (1986)

Journal Article Pharmacological modification of epidermal detoxification systems Get access D.R. BICKERS, D.R. BICKERS Case Western Reserve University, Departments of Dermatology, University Hospitals of Cleveland and Veterans Administration Medical Center, 10701 East Boulevard, Cleveland, Ohio, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar M. DAS, M. DAS Case Western Reserve University, Departments of Dermatology, University Hospitals of Cleveland and Veterans Administration Medical Center, 10701 East Boulevard, Cleveland, Ohio, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar H. MUKHTAR H. MUKHTAR Case Western Reserve University, Departments of Dermatology, University Hospitals of Cleveland and Veterans Administration Medical Center, 10701 East Boulevard, Cleveland, Ohio, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s31, 1 August 1986, Pages 9–16, https://doi.org/10.1111/j.1365-2133.1986.tb02101.x Published: 01 August 1986
A New Lead From Genetic Studies in Depressed Siblings: Assessing Studies of Chromosome 3
Authors: Steven P. Hamilton
Journal: American Journal of Psychiatry (2011)

Studies by Breen et al. and Pergadia et al. find evidence for genetic linkage between major depressive disorder and the same region on chromosome 3. The linked region contains the gene GRM7, which encodes a protein for the metabotropic glutamate receptor 7 (mGluR7). Both studies used affected sibling pairs, and neither was able to replicate its finding using association studies in individuals from larger population-based studies. Other family-based studies have also failed to find a signal in this region. Furthermore, there are some differences in how the phenotype was classified, with Breen et al. finding evidence only in the most severely affected patients. Nonetheless, the finding is not without other substantive support. A meta-analysis of 3,957 case subjects with major depressive disorder and 3,428 control subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), Genetics of Recurrent Early-onset Depression (GenRED), and the Genetic Association Information Network–MDD (GAIN-MDD) data sets demonstrated a region of association for major depressive disorder within GRM7. Thus, the significance of this finding remains uncertain, although it points to a gene that might hold significant promise for further developments in studying the pathophysiology and treatment of major depressive disorder.
Developmental switch of intestinal antimicrobial peptide expression
Authors: Sandrine Ménard, Valentina Förster, Michael Lotz, Dominique Gütle, Claudia U. Duerr, Richard L. Gallo, Birgitta Henriques-Normark, Katrin Pütsep, Mats Andersson, Erik O. Glocker, Mathias W. Hornef
Journal: The Journal of Experimental Medicine (2008)

Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.
The effect of pulmonary rehabilitation on exercise recovery times in COPD
Authors: Daniel H. Toms, Sarah E. Jones, Samantha S.C. Kon, Jane L. Canavan, Claire M. Nolan, William D.-C. Man
Journal: European Respiratory Journal (2013)

Background The incremental shuttle walk (ISW) is an exercise outcome used in pulmonary rehabilitation (PR). The minimum clinically important difference (MID) for the ISW in COPD is 47.5 metres. Many COPD patients report improvement in exercise capacity following PR despite not achieving the MID for the ISW. We hypothesised that ISW recovery times improve in COPD patients who do not achieve the ISW MID with PR. Aim To determine whether heart rate (HR), BORG score and oxygen saturation (O2) recovery times improve with PR in patients who show limited or no improvement in ISW. Method We retrospectively analysed data from 156 consecutive COPD patients completing an 8 week PR program who showed a +/-47.5 metre change in ISW. HR, BORG and O2 were measured pre and post ISW prior to starting PR and at completion. Recovery times were calculated as the time taken for the HR, BORG and O2 to return to their baseline after the ISW. Values were normalised to ISW distance. Pre and post PR data was analysed using Wilcoxon Tests. Results Baseline characteristics are presented as median (25th, 75th percentiles). Age 71 years (65, 76), FEV1 % predicted 42.5 (28.0, 57.8), MRC 4 (3, 4) and ISW 190 (90, 270). The median pre-post change in ISW was 20 (0, 40). There were statistically significant improvements in normalised HR, BORG and O2 recovery times.

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Conclusion HR, BORG and O2 recovery times following ISW are responsive to change with PR. This may be an alternative method of showing physiological response to PR in COPD patients.