tbuckley/cabot-search huggingface dataset:
The DosR Regulon Modulates Adaptive Immunity and Is Essential for <i>Mycobacterium tuberculosis</i> Persistence
Authors: Smriti Mehra, Taylor W. Foreman, Peter J. Didier, Muhammad H. Ahsan, Teresa A. Hudock, Ryan Kissee, Nadia A. Golden, Uma S. Gautam, Ann-Marie Johnson, Xavier Alvarez, Kasi E. Russell-Lodrigue, Lara A. Doyle, Chad J. Roy, Tianhua Niu, James L. Blanchard, Shabaana A. Khader, Andrew A. Lackner, David R. Sherman, Deepak Kaushal
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Hypoxia promotes dormancy by causing physiologic changes to actively replicating Mycobacterium tuberculosis. DosR controls the response of M. tuberculosis to hypoxia.To understand DosR's contribution in the persistence of M. tuberculosis, we compared the phenotype of various DosR regulon mutants and a complemented strain to M. tuberculosis in macaques, which faithfully model M. tuberculosis infection.We measured clinical and microbiologic correlates of infection with M. tuberculosis relative to mutant/complemented strains in the DosR regulon, studied lung pathology and hypoxia, and compared immune responses in lung using transcriptomics and flow cytometry.Despite being able to replicate initially, mutants in DosR regulon failed to persist or cause disease. On the contrary, M. tuberculosis and a complemented strain were able to establish infection and tuberculosis. The attenuation of pathogenesis in animals infected with the mutants coincided with the appearance of a Th1 response and organization of hypoxic lesions wherein M. tuberculosis expressed dosR. The lungs of animals infected with the mutants (but not the complemented strain) exhibited early transcriptional signatures of T-cell recruitment, activation, and proliferation associated with an increase of T cells expressing homing and proliferation markers.Delayed adaptive responses, a hallmark of M. tuberculosis infection, not only lead to persistence but also interfere with the development of effective antituberculosis vaccines. The DosR regulon therefore modulates both the magnitude and the timing of adaptive immune responses in response to hypoxia in vivo, resulting in persistent infection. Hence, DosR regulates key aspects of the M. tuberculosis life cycle and limits lung pathology.
Walking: common exercise for public and energy expenditure
Authors: G Shyam Mohan Reddy
Journal: British Journal of Sports Medicine (2010)

Everyone should have an aim. But do not forget that on the quality of your aim will depend the quality of your life style. Your aim should be high and wide, generous and disinterested; this will make your life precious to yourself and to all. To work for your perfection the first step is to become conscious of yourself, of the different parts of your being and their respective activities. In a short, the so-called scientific exercises are consistent with the law of exercises, that is, the appropriate exercises intensity which is suitable for each person's physical features and individual exercises expenditure patterns. For the public, walking is one of the most common exercise. The most efficient and appropriate form of exercises and reasonable exercises intensity can account for the balance between human meal and energy expenditure, which also can maintain and improve health and exercise ability. All of these need the control of energy expenditure, if we want to control it effectively, we should acquaint ourselves with the law of the energy expenditure and build energy expenditure models, where the personal energy expenditure models are particularly important. By getting the walking frequency we can have the statistical analysis with the energy expenditure. Then with the energy expenditure, we will get the carbohydrate and fat expenditure in a period of exercises.
Overexpression of Tropomysin-Related Kinase B in Metastatic Human Pancreatic Cancer Cells
Authors: Guido M. Sclabas, Shuichi Fujioka, Christian Schmidt, Zhongkui Li, Wayne A.I. Frederick, Wentao Yang, Kenji Yokoi, Douglas B. Evans, James L. Abbruzzese, Kenneth R. Hess, Wei Zhang, Isaiah J. Fidler, Paul J. Chiao
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Pancreatic adenocarcinoma is currently the fourth leading cause of cancer death in the United States, and most pancreatic cancers develop locally advanced disease or metastasis at the time of diagnosis. The mechanisms by which it invades and metastasizes are not known. Experimental Design: To identify the genes involved in pancreatic cancer metastasis, we analyzed the gene expression profiles between highly metastatic Colo357L3.6pl and parental Colo357FG pancreatic cancer cell lines using cDNA microarrays and confirmed differential gene expression by reverse transcription-PCR, Western blotting, and immunologic analysis of 54 samples from pancreatic cancer patients. The correlation with clinical outcome was also examined. The possible signaling pathways involved with tropomyosin-related kinase B (TrkB) were analyzed. Results: Our findings showed that TrkB was overexpressed in the highly metastatic Colo357L3.6pl cells, which correlated with perineural invasion (P = 0.026), positive retroperitoneal margin (P = 0.0005), and shorter latency to development of liver metastasis (Cox proportional hazard ratio, 0.3; 95% confidence interval, 0.1-0.8; P = 0.01) in patient samples. Extracellular signal-regulated kinases 1 and 2 were activated and Elk-1 and AP-1 DNA binding activity was induced in Colo357L3.6pl cells. Furthermore, interleukin 8 and vascular endothelial growth factor were more strongly expressed in Colo357L3.6pl than Colo357FG cells, and these findings were confirmed in Colo357L3.6pl and Colo357FG orthotopic tumors. Conclusion: These results suggest that overexpression of TrkB and activation of mitogen-activated protein kinase and AP-1, which may in turn induce the expression of vascular endothelial growth factor and interleukin 8, may mediate the cardinal clinical features of locally aggressive growth and metastasis of pancreatic cancer. Our results also imply that TrkB receptor may be a novel therapeutic target for pancreatic cancer.
Airway stent improves outcome in intubated oesophageal cancer patients
Authors: H-C. Lin, C-L. Chou, H-C. Chen, F-T. Chung
Journal: European Respiratory Journal (2010)

with pulmonary LCH and PH who quit smoking and received corticosteroids [10].Whether antiproliferative therapy such as cladribine might affect PH in patients with pulmonary arterial wall involvement by Langerhan's cells is unknown.In conclusion, these observations demonstrate that long-term improvement of PH may be obtained using bosentan in patients with pulmonary LCH, further supporting the theory of pulmonary vasculopathy.Bosentan therapy may be con-
Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation
Authors: A O O Chan
Journal: Gut (2006)

E-cadherin methylation is important in gastric carcinogenesis. Reversing hypermethylation may halt the carcinogenic process. We have previously reported that Helicobacter pylori infection is associated with E-cadherin methylation in chronic gastritis patients.To examine if eradication of H pylori could reverse E-cadherin methylation.Patients with dyspepsia and positive for H pylori infection, with a mucosal biopsy showing chronic active gastritis, were randomised to receive H pylori eradication therapy (group 1, n = 41) or no treatment (group 2, n = 40), and were followed up prospectively. Gastric mucosae were taken for methylation assay at week 0 (before treatment) and week 6 (after treatment). Archived specimens of intestinal metaplasia with H pylori infection (n = 22) and without (n = 19) were retrieved for methylation analysis. Methylation was assessed using methylation specific polymerase chain reaction and sequencing.Methylation at E-cadherin was detected in 46% (19/41) and 17% (7/41) of patients at weeks 0 and 6, respectively, in group 1 (p = 0.004); 78.9% (15/19) of specimens were unmethylated after eradication of H pylori. Mucosal biopsy showed chronic inactive gastritis in 35 patients, intestinal metaplasia in one, and normal mucosa in five at week 6. Methylation was detected in 47.5% (19/40) and 52.5% (21/40) of patients at weeks 0 and 6, respectively, in group 2 (P = 0.5). Gastric mucosal biopsy showed persistent chronic active gastritis in all cases. Methylation frequency did not differ in H pylori positive or negative intestinal metaplastic specimens (72.7% v 63%; p = 0.5).H pylori eradication therapy could reverse methylation in patients with chronic gastritis. This demonstrates an environmental effect on methylation.
Basophil and Humoral Immune Response Profiles in Adults Reporting a History of Adverse Reactions to Peanut Ingestion
Authors: J.H. Savage, P.M. Sterba, A.S. Parihar, D.C. Kelly, R.A. Wood, R.G. Hamilton, S.S. Saini
Journal: Journal of Allergy and Clinical Immunology (2010)
Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment
Authors: Amy Pruden, D.G. Joakim Larsson, Alejandro Amézquita, Peter Collignon, Kristian K. Brandt, David W. Graham, James M. Lazorchak, Satoru Suzuki, Peter Silley, Jason R. Snape, Edward Topp, Tong Zhang, Yong-Guan Zhu
Journal: Environmental Health Perspectives (2013)

There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance.Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action.We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture.We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action.Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action.
Jeremy Alan Sherman
Authors: D. S. M. Simpson
Journal: BMJ (2013)

Jeremy Alan Sherman was educated at City of London School. After dental qualification at King’s he trained in oromaxillofacial surgery in Edinburgh and London before completing a medical degree at Manchester. Before his appointment as consultant at QEII Hospital in Welwyn Garden City and the Lister Hospital in Stevenage in 2000 he was senior registrar at Guy’s, Ipswich, and Addenbrooke’s, …
Autoantibodies against granulocyte-macrophage colony stimulating factor and interleukin-3 are rare in patients with Felty's syndrome
Authors: B Hellmich
Journal: Annals of the Rheumatic Diseases (2004)

Antibodies against granulocyte colony stimulating factor are frequently found in patients with Felty's syndrome (FS). In this study, we examined the prevalence of antibodies against two other granulopoietic cytokines: granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL3).Sera of 32 patients with FS, 20 normocytic patients with rheumatoid arthritis (RA), and 72 healthy individuals were screened for the presence of antibodies against GM-CSF and IL3 by ELISA and bioassays, using the human erythroleukaemia cell line TF-1.In two of the 32 patients with FS, antibodies to GM-CSF and IL3 were detectable by ELISA. Binding anti-GM-CSF antibodies were also detected in one of the 72 healthy controls, while in another healthy subject and in one of the patients with normocytic RA, anti-IL3 antibodies were present. Serum from one of the two patients with FS who tested positive for anti-IL3 and anti-GM-CSF antibodies by ELISA showed strong neutralising capacity to the biological effect of IL3, but not to GM-CSF in vitro. Patients with FS had significantly higher serum levels of GM-CSF (median; 2.82 pg/mL; interquartile range 2.64-3.19 pg/mL) compared with patients with RA (2.52 pg/mL; 2.28-2.72 pg/mL; p = 0.012) and healthy controls (2.23 pg/mL; 2.04-2.52; p<0.001). In addition, serum levels of IL3 in patients were significantly higher in FS (10.05 pg/mL; 8.94-11.98) compared with controls (4.79 pg/mL; 3.72-7.22; p<0.001), but not compared with RA patients (9.52 pg/mL; 8.32-10.42; p = 0.17).Antibodies to GM-CSF and IL3 are rare in patients with FS and RA and in healthy subjects. In individual patients with FS, the presence of neutralising anti-IL3 antibodies may contribute to the development of cytopenia.
<i>Chlamydia pneumoniae</i> Infection of the Central Nervous System Worsens Experimental Allergic Encephalitis
Authors: Caigan Du, Song-Yi Yao, Åsa Ljunggren-Rose, Subramaniam Sriram
Journal: The Journal of Experimental Medicine (2002)

Experimental allergic encephalitis (EAE) is considered by many to be a model for human multiple sclerosis. Intraperitoneal inoculation of mice with Chlamydia pneumoniae, after immunization with neural antigens, increased the severity of EAE. Accentuation of EAE required live infectious C. pneumoniae, and the severity of the disease was attenuated with antiinfective therapy. After immunization with neural antigens, systemic infection with C. pneumoniae led to the dissemination of the organism into the central nervous system (CNS) in mice with accentuated EAE. Inoculation with Chlamydia trachomatis did not worsen EAE and infectious organisms were not seen in the CNS. These observations suggest that dissemination of C. pneumoniae results in localized infection in CNS tissues in animals with EAE. We propose that infection of the CNS by C. pneumoniae can amplify the autoreactive pool of lymphocytes and regulate the expression of an autoimmune disease.
Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study
Authors: M. Grosse-Sundrup, J. P. Henneman, W. S. Sandberg, B. T. Bateman, J. V. Uribe, N. T. Nguyen, J. M. Ehrenfeld, E. A. Martinez, T. Kurth, M. Eikermann
Journal: BMJ (2012)

<b>Objective</b> To determine whether use of intermediate acting neuromuscular blocking agents during general anesthesia increases the incidence of postoperative respiratory complications. <b>Design</b> Prospective, propensity score matched cohort study. <b>Setting</b> General teaching hospital in Boston, Massachusetts, United States, 2006-10. <b>Participants</b> 18 579 surgical patients who received intermediate acting neuromuscular blocking agents during surgery were matched by propensity score to 18 579 reference patients who did not receive such agents. <b>Main outcome measures</b> The main outcome measures were oxygen desaturation after extubation (hemoglobin oxygen saturation &lt;90% with a decrease in oxygen saturation after extubation of &gt;3%) and reintubations requiring unplanned admission to an intensive care unit within seven days of surgery. We also evaluated effects on these outcome variables of qualitative monitoring of neuromuscular transmission (train-of-four ratio) and reversal of neuromuscular blockade with neostigmine to prevent residual postoperative neuromuscular blockade. <b>Results</b> The use of intermediate acting neuromuscular blocking agents was associated with an increased risk of postoperative desaturation less than 90% after extubation (odds ratio 1.36, 95% confidence interval 1.23 to 1.51) and reintubation requiring unplanned admission to an intensive care unit (1.40, 1.09 to 1.80). Qualitative monitoring of neuromuscular transmission did not decrease this risk and neostigmine reversal increased the risk of postoperative desaturation less than 90% (1.32, 1.20 to 1.46) and reintubation (1.76, 1.38 to 2.26). <b>Conclusion</b> The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications. Our data suggest that the strategies used in our trial to prevent residual postoperative neuromuscular blockade should be revisited.
Radioactive Bromide Partition Test in Differential Diagnosis of Tuberculous Meningitis
Authors: B. K. Mandal, D. I. K. Evans, A. G. Ironside, B. R. Pullan
Journal: BMJ (1972)

In 19 cases of lymphocytic meningitis, the radioactive bromide partition test showed that four were tuberculous and 15 viral in origin. In all the tuberculous cases the serum/cerebrospinal fluid bromide ratio was below a critical value of 1.6, and in all the cases of viral meningitis the ratio was above this value. The test may be particularly helpful when diagnosis is difficult. The test may prove to be a valuable and justified additional procedure in the early diagnosis of tuberculous meningitis.
STUDIES OF THE MECHANISM OF ACTION OF URETHANE IN INITIATING PULMONARY ADENOMAS IN MICE
Authors: Stanfield Rogers
Journal: The Journal of Experimental Medicine (1957)

The process of carcinogenesis following exposure of mice to urethane is demonstrated in the present work to be intimately related to nucleic acid synthesis. Injection of animals with a DNA hydrolysate immediately prior to a single exposure of the animals to urethane markedly reduced the number of pulmonary adenomas initiated. Aminopterin, known to interfere in nucleic acid synthesis (46), potentiated the carcinogenic action of urethane and this potentiation was blocked by injection of a DNA hydrolysate. Of the components and precursors of nucleic acids the pyrimidine series seemed especially concerned. Alterations in the utilization of oxaloacetate, ureidosuccinic acid, dihydro-orotic acid, orotic acid, cytidylic acid, and thymine appeared to be critical steps in the oncogenic process, following upon the primary disorder of cellular metabolism initiated by the carcinogen. All these substances except oxaloacetate profoundly reduced the number of tumors initiated by urethane. Oxaloacetate potentiated the carcinogenic effect. When these results are viewed together and in relation to known facts concerning nucleic acid synthesis they provide evidence suggesting that the point of action of the carcinogen is in the pathway of nucleic acid synthesis below orotic acid and perhaps at the level of ureidosuccinic acid. The potentiating influence of adenine, 4-amino-5-imidazole carboxamide, and aminopterin, the lack of effect of uracil, and the inhibitory influence of thymine together suggest that DNA rather than RNA is the nucleic acid critical to the oncogenic response of mice to urethane.
The Signaling and Biological Implications of FAK Overexpression in Cancer
Authors: Priscila M.F. Siesser, Steven K. Hanks
Journal: Clinical Cancer Research (2006)

In this issue of Clinical Cancer Research , Canel et al. ([1][1]) describe a new study investigating the role of focal adhesion kinase (FAK) in head and neck squamous cell carcinoma (HNSCC). Using immunohistochemical analysis of >200 HNSCC clinical specimens, they show FAK overexpression in the
A1C in Children and Adolescents With Diabetes in Relation to Certain Clinical Parameters
Authors: Lena Hanberger, Ulf Samuelsson, Bengt Lindblad, Johnny Ludvigsson
Journal: Diabetes Care (2008)

OBJECTIVE—We explored the relationship between A1C and insulin regimen, duration of diabetes, age, sex, and BMI as well as the differences between clinical mean A1C levels at pediatric diabetes clinics in Sweden. RESEARCH DESIGN AND METHODS—Data from 18,651 clinical outpatient visits (1,033 girls and 1,147 boys) at 20 pediatric clinics during 2001 and 2002 registered in the Swedish Childhood Diabetes Registry SWEDIABKIDS, a national quality registry, were analyzed. RESULTS—A1C was &amp;lt;7.0% (target value ∼8% per Diabetes Control and Complications Trial/National Glycohemoglobin Standardization Program standards) at 35% of the visits. Girls had significantly higher mean A1C than boys during adolescence. High mean A1C was correlated with high mean insulin dose, long duration of diabetes, and older age. Mean A1C varied between clinics (6.8–8.2%). Differences between centers could not be explained by differences in diabetes duration, age, BMI, or insulin dose. CONCLUSIONS—Adolescents with a high insulin dose and a long duration of diabetes, especially girls, need to be focused on. Differences in mean values between centers remained inexplicable and require further investigation.
Association of Carotid Intima-Media Thickness and Arterial Stiffness With Diabetic Retinopathy
Authors: Mohan Rema, Viswanathan Mohan, Raj Deepa, Radhakrishnan Ravikumar
Journal: Diabetes Care (2004)

The aim of this study was to assess the association of intima-media thickness (IMT) and arterial stiffness with diabetic retinopathy in an Asian-Indian population that has very high prevalence rates of diabetes and coronary artery disease.The study was conducted on 600 type 2 diabetic subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), which is an ongoing population-based study of a representative population of Chennai. When present, retinopathy was graded according to a modified Early Treatment Diabetic Retinopathy Study grading system. IMT was determined using high-resolution B-mode ultrasonography. Arterial stiffness was measured by assessing the augmentation index (AI) using the Sphygmocor apparatus.Retinopathy was diagnosed in 116 of 590 (19.6%) subjects in whom retinal photography was possible. Mean values of IMT (0.93 +/- 0.36 vs. 0.85 +/- 0.21 mm, P = 0.001) and AI (27.9 +/- 8.9 vs. 25.8 +/- 9.6%, P = 0.031) were significantly higher among diabetic subjects with retinopathy compared with those without. Both IMT (P = 0.024) and AI (P = 0.050) showed a significant association to diabetic retinopathy, even after adjusting for age, duration of diabetes, HbA(1c), serum cholesterol, serum triglycerides, and microalbuminuria.Diabetic retinopathy is associated with IMT and AI, suggesting that common pathogenic mechanisms might predispose to diabetic micro- and macroangiopathy.
Epigenetic regulation of cardiovascular differentiation
Authors: K. Ohtani, S. Dimmeler
Journal: Cardiovascular Research (2011)

Epigenetic control mechanisms play a key role in the regulation of embryonic development and tissue homeostasis and modulate cardiovascular diseases. Increasing evidence suggests that lineage commitment of stem/progenitor cells is tightly regulated by epigenetic mechanisms. These epigenetic control mechanisms include DNA and histone modifications, which modulate the chromatin structure thereby regulating access of transcription factors. Particularly, the modification of histone acetylation and methylation, which is controlled by families of histone acetylases/deacetylases and methyltransferases/demethylases, respectively, controls stem cell maintenance, differentiation, and function. This review article summarizes our current understanding of epigenetic mechanisms regulating the differentiation of cardiovascular cells, specifically endothelial cells and cardiac muscle lineages. In particular, the article will focus on the enzymes which modify histones and are involved in chromatin remodelling.