tbuckley/cabot-search huggingface dataset:
Oxygen Is a Master Regulator of the Immunogenicity of Primary Human Glioma Cells
Authors: Michael R. Olin, Brian M. Andersen, Adam J. Litterman, Patrick T. Grogan, Aaron L. Sarver, Paul T. Robertson, Xueqing Liang, Wei Chen, Ian F. Parney, Matthew A. Hunt, Bruce R. Blazar, John R. Ohlfest
Journal: Cancer Research (2011)

Abstract With recent approval of the first dendritic cell (DC) vaccine for patient use, many other DC vaccine approaches are now being tested in clinical trials. Many of these DC vaccines employ tumor cell lysates (TL) generated from cells cultured in atmospheric oxygen (∼20% O2) that greatly exceeds levels found in tumors in situ. In this study, we tested the hypothesis that TLs generated from tumor cells cultured under physiologic oxygen (∼5% O2) would be more effective as a source for DC antigens. Gene expression patterns in primary glioma cultures established at 5% O2 more closely paralleled patient tumors in situ and known immunogenic antigens were more highly expressed. DCs treated with TLs generated from primary tumor cells maintained in 5% O2 took up and presented antigens to CD8 T cells more efficiently. Moreover, CD8 T cells primed in this manner exhibited superior tumoricidal activity against target cells cultured in either atmospheric 20% O2 or physiologic 5% O2. Together, these results establish a simple method to greatly improve the effectiveness of DC vaccines in stimulating the production of tumoricidal T cells, with broad implications for many of the DC-based cancer vaccines being developed for clinical application. Cancer Res; 71(21); 6583–9. ©2011 AACR.
Supplemental oxygen and quality of sleep in patients with chronic obstructive lung disease.
Authors: J L McKeon, K Murree-Allen, N A Saunders
Journal: Thorax (1989)

The hypothesis that supplemental oxygen could improve the quality of sleep was tested in 23 consecutive patients (14 male, nine female; age 42-74 years) with chronic obstructive lung disease (mean (SD) FEV1 0.81 (0.32) litre, FEV1/FVC 37% (12%). Patients breathed compressed air or supplemental oxygen via nasal cannulas on consecutive nights in a randomised, double blind, crossover trial. Quality of sleep was assessed by questionnaire and by electroencephalographic sleep staging. The study had a power of 80% to detect, at the 0.05 level, a 20% improvement in total sleep time. Seventeen patients slept for two nights in the laboratory. Oxygenation during sleep was improved by oxygen administration, but there was no improvement in quality of sleep. There was an acclimatisation effect with better sleep on the second night. Six patients spent an additional acclimatisation night in the laboratory as well as the two study nights. There was no difference in sleep quality between the second and third nights or between the compressed air and the oxygen nights in these patients. Subgroups of patients with an arterial carbon dioxide tension of over 43 mm Hg (5.7 kPa) (n = 12) and arterial oxygen saturation of less than 90% (n = 11) while awake did not show any improvement in quality of sleep on the oxygen night. It is concluded that supplemental oxygen improves nocturnal oxygenation but does not immediately improve the quality of sleep in the laboratory in patients with chronic obstructive lung disease.
Highly Expressed and Slowly Evolving Proteins Share Compositional Properties with Thermophilic Proteins
Authors: J. L. Cherry
Journal: Molecular Biology and Evolution (2009)

The sequences of proteins encoded by a genome evolve at different rates. A correlate of a protein's evolutionary rate is its expression level: highly expressed proteins tend to evolve slowly. Some explanations of rate variation and the correlation between rate and expression predict that more slowly evolving and more highly expressed proteins have more favorable equilibrium constants for folding. Proteins from thermophiles generally have more stable folds than proteins from mesophiles, and it is known that there are systematic differences in amino acid content between thermophilic and mesophilic proteins. I examined whether there are analogous correlations of amino acid frequencies with evolutionary rate and expression level within genomes. In most of the organisms analyzed, there is a striking tendency for more slowly evolving proteins to be more thermophile-like in their amino acid compositions when adjustments are made for variation in GC content. More highly expressed proteins also tend to be more thermophile-like by the same criteria. These results suggest that part of the evolutionary rate variation among proteins is due to variation in the strength of selection for stability of the folded state. They also suggest that increasing strength of this selective force with expression level plays a role in the correlation between evolutionary rate and expression level.
EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 2: Exploring decision rules for clinical utility
Authors: P. Conaghan, M. A. D'Agostino, P. Ravaud, G. Baron, M. Le Bars, W. Grassi, E. Martin-Mola, R. Wakefield, J.-L. Brasseur, A. So, M. Backhaus, Michel Malaise, G. Burmester, N. Schmidely, P. Emery, M. Dougados
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Synovial inflammation (as defined by hypertrophy and effusion) is common in osteoarthritis (OA) and may be important in both pain and structural progression. <b>Objective:</b> To determine if decision rules can be devised from clinical findings and ultrasonography (US) to allow recognition of synovial inflammation in patients with painful knee OA. <b>Methods:</b> A EULAR-ESCISIT cross sectional, multicentre study enrolled subjects with painful OA knee who had clinical, radiographic, and US evaluations. A classification and regression tree (CART) analysis was performed to find combinations of predictor variables that would provide high sensitivity and specificity for clinically detecting synovitis and effusion in individual subjects. A range of definitions for the two key US variables, synovitis and effusion (using different combinations of synovial thickness, depth, and appearance), were also included in exploratory analyses. <b>Results:</b> 600 patients with knee OA were included in the analysis. For both knee synovitis and joint effusion, the sensitivity and specificity were poor, yielding unsatisfactory likelihood ratios (75% sensitivity, 45% specificity, and positive LR of 1.36 for knee synovitis; 71.6% sensitivity, 43.2% specificity, and positive LR of 1.26 for joint effusion). The exploratory analyses did not improve the sensitivity and specificity (demonstrating positive LRs of between 1.26 and 1.57). <b>Conclusion:</b> Although it is possible to determine clinical and radiological predictors of OA inflammation in populations, CART analysis could not be used to devise useful clinical decision rules for an individual subject. Thus sensitive imaging techniques such as US remain the most useful tool for demonstrating synovial inflammation of the knee at the individual level.
Contralateral pulmonary metastases in lung cancer
Authors: W. I. B. Onuigbo
Journal: Thorax (1974)

<b>Onuigbo, W. I. B. (1974).</b><i>Thorax</i>, <b>29</b>, 132-133. <b>Contralateral pulmonary metastases in lung cancer.</b> It has long been known that lung cancer may attack many organs and yet spare the opposite lung. In 100 cases of this tumour studied at necropsy, only 22 showed contralateral pulmonary spread. Contralateral deposits are generally small and may be related to damaged tissues. Although tissue unsuitability is supposed to underlie the limitation of metastases in recipient organs, this does not apply to the contralateral lung. Since lung tissue is readily accessible to bloodborne cancer cells, research should be directed towards explaining the paradoxical paucity of the metastases.
Lymph Node–Targeted Immunotherapy Mediates Potent Immunity Resulting in Regression of Isolated or Metastatic Human Papillomavirus–Transformed Tumors
Authors: Kent A. Smith, Brenna L. Meisenburg, Victor L. Tam, Robb R. Pagarigan, Raymond Wong, Diljeet K. Joea, Liz Lantzy, Mayra A. Carrillo, Todd M. Gross, Uriel M. Malyankar, Chih-Sheng Chiang, Diane M. Da Silva, Thomas M. Kündig, W. Martin Kast, Zhiyong Qiu, Adrian Bot
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The goal of this study was to investigate the therapeutic potential of a novel immunotherapy strategy resulting in immunity to localized or metastatic human papillomavirus 16–transformed murine tumors. Experimental Design: Animals bearing E7-expressing tumors were coimmunized by lymph node injection with E7 49-57 antigen and TLR3-ligand (synthetic dsRNA). Immune responses were measured by flow cytometry and antitumor efficacy was evaluated by tumor size and survival. In situ cytotoxicity assays and identification of tumor-infiltrating lymphocytes and T regulatory cells were used to assess the mechanisms of treatment resistance in bulky disease. Chemotherapy with cyclophosphamide was explored to augment immunotherapy in late-stage disease. Results: In therapeutic and prophylactic settings, immunization resulted in a considerable expansion of E7 49-57 antigen–specific T lymphocytes in the range of 1/10 CD8+ T cells. The resulting immunity was effective in suppressing disease progression and mortality in a pulmonary metastatic disease model. Therapeutic immunization resulted in control of isolated tumors up to a certain volume, and correlated with antitumor immune responses measured in blood. In situ analysis showed that within bulky tumors, T-cell function was affected by negative regulatory mechanisms linked to an increase in T regulatory cells and could be overcome by cyclophosphamide treatment in conjunction with immunization. Conclusions: This study highlights a novel cancer immunotherapy platform with potential for translatability to the clinic and suggests its potential usefulness for controlling metastatic disease, solid tumors of limited size, or larger tumors when combined with cytotoxic agents that reduce the number of tumor-infiltrating T regulatory cells. (Clin Cancer Res 2009;15(19):6167–76)
A lesson learnt: My brother's keeper?
Authors: M. Ahmed
Journal: BMJ (1997)

Chronic Obstructive Pulmonary Disease (COPD) is characterised by complex inflammatory, neuronal and fibrotic changes. Brain-derived Neurotrophic Factor (BDNF) and Transforming Growth Factor-β1 (TGF-β1) are stored in alpha-granules of platelets. Serum BDNF and TGF-β1 are predominantly platelet-derived (released from platelets during serum preparation). BDNF is a key regulator of neuronal plasticity, whereas TGF-β1 is involved in tissue repair and emphysema pathogenesis. We have previously shown that serum BDNF but not TGF-β1 is elevated in asthma, correlating with disease severity. The present study aimed to investigate serum concentrations of BDNF and TGF-β1 in different stages of COPD compared to non-COPD controls. 63 patients with stable COPD (GOLD 2: n=22, GOLD 3: n=28, GOLD 4: n=13) and 17 age- and comorbidity-matched controls without COPD were enrolled. Serum levels of BDNF and TGF-β1 were measured using ELISA. Serum levels of BDNF and TGF-β1 were significantly elevated in all stages of COPD as compared to controls. Highest BDNF concentrations were found in GOLD stage 3 (with a trend towards a decrease in GOLD stage 4), whereas highest TGF-β1 serum levels were found in GOLD stage 4. In contrast to asthma, COPD appears to be characterised by increased concentrations of both BDNF and TGF-β1. Very severe COPD is associated with highest TGF-β1 concentrations, but relatively lower BDNF concentrations. We thus speculate that these findings might reflect a maximum of neuronal and inflammatory activity in GOLD stages 2 and 3, and a predominant activity of tissue remodeling factors in GOLD stage 4.
Does the surface tension make the lung inherently unstable?
Authors: Y C Fung
Journal: Circulation Research (1975)

Many authors regard the human lung as a collection of 300 million bubbles independently connected by cylindrical tubes. Under surface tension such a model is inherently unstable in the sense that the small alveoli would empty into the large ones so that the lung would consist only of collapses and hyperinflated alveoli. It has been demonstrated that this basic model is wrong. My observation is based on the well-known fact that both sides of each interalveolar septum are exposed to ventilated air. When the topological relationship between the alveolar septa is properly taken into account, it can be shown that each interalveolar septum is a minimal surface and that there is no problem of inherent instability in the sense mentioned earlier. However, the lung structure is flimsy and can become unstable in the same sense that an airplane structure or an Atlas rocket can become unstable. The clarification of lung inflation and atelectasis can proceed in a rational manner when the confusion of an erroneous model is removed.
Acquisition of Resistance to Butyrate Enhances Survival after Stress and Induces Malignancy of Human Colon Carcinoma Cells
Authors: Isabel López de Silanes, Nieves Olmo, Javier Turnay, Gonzalo González de Buitrago, Pablo Pérez-Ramos, Ana Guzmán-Aránguez, Marta García-Díez, Emilio Lecona, Myriam Gorospe, M. Antonia Lizarbe
Journal: Cancer Research (2004)

Abstract Acquired resistance to apoptosis by tumor cells remains a major obstacle for cancer treatment, and hence the analysis of resistance to apoptosis constitutes a major goal in the development of antitumoral drugs. We have established a butyrate-resistant human colon adenocarcinoma cell line (BCS-TC2.BR2) from nontumorigenic BCS-TC2 cells to analyze whether the acquisition of such phenotype confers resistance to apoptosis and stress. Although BCS-TC2.BR2 cells exhibited a more differentiated phenotype than the parental BCS-TC2 cells, higher butyrate concentrations remained capable of additionally enhancing their differentiation without inducing apoptosis. Survival rates of BCS-TC2.BR2 cells after glucose deprivation and heat shock were higher than those of parental cells, revealing a stress-resistant phenotype. These findings were accompanied by key differences between parental and butyrate-resistant cells in gene expression profiles and the acquisition of in vivo tumorigenicity. In conclusion, cells gaining resistance to an endogenous physiological modulator of growth, differentiation, and apoptosis concurrently acquired resistance to other agents that influence cell survival.
Experience with Community Mental Health Centers
Authors: LUCY D. OZARIN, SAUL FELDMAN, FRED E. SPANER
Journal: American Journal of Psychiatry (1971)

The authors report on the experiences gleaned from site visits to federally funded mental health centers that are now in operation. Their most important findings were: the formation of public and nonprofit corporations to serve as planning and fiscal agents facilitates the growth of local interagency networks of service, the organizational structure of a center program determines its capability to deliver services, citizen participation is vital for community support and program planning, and manpower utilization is enhanced by the use of auxiliary mental health workers.
Intestinal lymphangiectasia and reversible high liver stiffness
Authors: Laura Milazzo, Anna Maria Peri, Lucia Lodi, Guido Gubertini, Anna Lisa Ridolfo, Spinello Antinori
Journal: Hepatology (2014)

Primary intestinal lymphangiectasia (PIL) is a protein-losing enteropathy characterized by tortuous and dilated lymph channels of the small bowel. The main symptoms are bilateral lower limb edema, serosal effusions, and vitamin D malabsorption resulting in osteoporosis. We report here a case of long-lasting misdiagnosed PIL with a peculiar liver picture, characterized by a very high stiffness value at transient elastography, which decreased with clinical improvement. The complex interplay between lymphatic and hepatic circulatory system is discussed. (Hepatology 2014;60:759–761)
High and Rising Health Care Costs. Part 2: Technologic Innovation
Authors: Thomas Bodenheimer
Journal: Annals of Internal Medicine (2005)

Technologic innovation, in combination with weak cost-containment measures, is a major factor in high and rising health care costs. Evidence suggests that improved health care technologies generally increase rather than reduce health care expenditures. Greater availability of such technologies as magnetic resonance imaging, computed tomography, coronary artery bypass graft, angioplasty, cardiac and neonatal intensive care units, positron emission tomography, and radiation oncology facilities is associated with greater per capita use and higher spending on these services. Because the spread of new technologies is relatively unrestrained in the United States, many of these technologies are used to a greater extent than in other nations, and the United States thereby incurs higher health care costs. Nations with a greater degree of health system integration have relied on expenditure controls and global budgets to control costs. Although diffusion of technology takes place more slowly in more tightly budgeted systems, the use of innovative technologies in those systems tends to catch up over time.
Inhibition of Protein Synthesis in Cardiac Hypertrophy and its Relation to Myocardial Failure
Authors: Volker Zühlke, Wolfgang du Mesnil de Rochemont, Sigmundur Gudbjarnason, Richard J. Bing
Journal: Circulation Research (1966)

The rate of myocardial protein synthesis was studied in hearts of rabbits with experimentally produced cardiac hypertrophy and treatment with actinomycin D and puromycin as well as in animals maintained on a protein-free diet. Actinomycin D and puromycin inhibited myocardial incorporation of glycine-2-C 14 only if protein synthesis was stimulated by means of aortic stenosis. Actinomycin D had no effect on the normal myocardium. Animals on protein-free diet also showed a decreased rate of glycine-2-C 14 uptake into heart muscle protein after production of aortic stenosis, but an increased incorporation into skeletal muscle protein. Inhibition of protein synthesis during the first stage of cardiac hypertrophy was associated with the development of heart failure, regardless of whether the inhibition occurred as a result of actinomycin D, of puromycin or of protein-free diet. As compared to animals maintained on a regular diet, myocardial protein turnover rate in unoperated animals was not altered significantly by protein-free diet.
Induction of Collecting Duct Morphogenesis In Vitro by Heparin-Binding Epidermal Growth Factor-Like Growth Factor
Authors: TSUKASA TAKEMURA, SATOSHI HINO, HIROAKI KUWAJIMA, HIDEHIKO YANAGIDA, MITSURU OKADA, MICHIO NAGATA, SEI SASAKI, JONATHAN BARASCH, RAYMOND C. HARRIS, KAZUO YOSHIOKA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the epidermal growth factor family of growth factors, is synthesized as a membrane-an-chored precursor (proHB-EGF) that is capable of stimulating adjacent cells in a juxtacrine manner. ProHB-EGF is cleaved in a protein kinase C-dependent process, to yield the soluble form. It was observed that HB-EGF acts as a morphogen for the collecting duct system in developing kidneys. HB-EGF protein was expressed in the ureteric bud of embryonic kidneys. Cultured mouse ureteric bud cells (UBC) produced HB-EGF via protein kinase C activation. After stimulation with phorbol ester (12- O -tetradecanoylphorbol-13-acetate) or recombinant soluble HB-EGF, UBC cultured in three-dimensional collagen gels formed short tubules with varied abundant branches. When proHB-EGF-transfected UBC were stimulated with 12- O -tetradecanoylphorbol-13-acetate and cultured in collagen gels, they exhibited linear growth, forming long tubular structures with few branches at the time of appearance of proHB-EGF on the cell surface. The structures exhibited a strong resemblance to the early branching ureteric bud of embryonic kidneys. When UBC were cultured in the presence of transforming growth factor-β and soluble HB-EGF, they formed long tubules and few branches, similar to the structures observed in proHB-EGF-transfected UBC. These cells exhibited apical-basolateral polarization and expression of the water channel aquaporin-2. These findings indicate that soluble HB-EGF and proHB-EGF induce branching tubulogenesis in UBC in different ways. Juxtacrine activation by proHB-EGF or the synergic action of soluble HB-EGF with transforming growth factor-β is important for well balanced morphogenesis of the collecting duct system.
Heart rate variability: Possible implications for management of pulmonary arterial hypertension patients
Authors: Khrystyna Semen, Lyubomyr Solovey, Marta Karapinka, Olha Yelisyeyeva
Journal: European Respiratory Journal (2012)

The aim: to study heart rate variability (HRV) and its relationships with pulmonary hemodynamics and level of NT-proBNP in pulmonary arterial hypertension (PAH) patients.  Material and methods. 6 patients with idiopathic PAH and 3 with congenital heart disease associated PAH with (mean age 31±12 years, 7 patients with FC II and 2 patients with FC III by NYHA/WHO) were enrolled. All subjects underwent right heart catheterization. Level of NT-proBNP was determined in blood. The short-time ECG records obtained in supine position and during orthostatic test were analyzed with Poly-Spectrum software (Neurosoft, Russia). Nine healthy subjects served as a control.  Results. Severe pulmonary hypertension was found in all patients with mean pulmonary arterial pressure 53±14 mmHg, resting pulmonary vascular resistance 1180±650 dyn •s•cm-5. Total power of PAH patients ranged from 150 ms2 to 2540 ms2 with the very low frequency and low frequency bands predominance in the spectral structure. The orthostatic test caused dramatic lowering in all HRV indexes in PAH subjects. Borderline values of NT-proBNP (up to 400 pg/ml) in PAH subjects were accompanied by some decrease in HRV. Simultaneously, significantly increased NT-proBNP levels (400-3200 pg/ml) were associated with marked HRV lowering both in supine position and during orthostatic test.  Conclusions. Patients with severe PAH were shown with individual various range of HRV parameters, correlating with the level of a neurohumoral activation marker NT-proBNP. HRV can be used in clinical practice to monitor progression of right-sided HF and, consequently, to determine prognosis in PAH patients.