tbuckley/cabot-search huggingface dataset:
Smoking rates in the staff of a military field hospital before and after wartime deployment
Authors: C J Boos, A M Croft
Journal: Journal of the Royal Society of Medicine (2003)

In the past, high rates of cigarette smoking have been reported in the British Armed Forces. We conducted an anonymous questionnaire survey in the 623 employees and attached staff of 34 Field Hospital on their sixth week of deployment to Iraq, in the course of Gulf War II. Information was sought on smoking status before and during the deployment, and self-declared reasons for smoking. 556 questionnaires were returned (response rate 89%). The median age of respondents was 33.3 SD 7.9 years (range 18-62) and 61% were male. Before deployment the number of regular smokers was 160 (29%) but it had now risen by 52 to 212 (38%). Of the extra smokers 33 were restarting an old habit but 19 were first-timers. Moreover, those who were regular smokers before deployment increased their daily consumption from a mean of 15 cigarettes to 21. Smoking rates did not differ between clinical and non-clinical staff or between men and women; the rates were lower in officers than in non-officers, and in reservists than in regular Army personnel. The reasons most commonly cited for starting smoking or increasing consumption were boredom, social factors and stress. Few respondents could recall having received smoking-related health education during previous service with the military. Smoking rates in this medical unit increased substantially during the overseas deployment. There were no data on cigarette consumption after return to ordinary duties, so we cannot say whether these effects are short-term or long-term. However, even the pre-existing rate of 42% in regular army personnel is high enough to demand urgent action by an employer.
Protein Interactions Limit the Rate of Evolution of Photosynthetic Genes in Cyanobacteria
Authors: Tuo Shi, Thomas S Bibby, Lin Jiang, Andrew J Irwin, Paul G Falkowski
Journal: Molecular Biology and Evolution (2005)

Using a bioinformatic approach, we analyzed the correspondence in genetic distance matrices between all possible pairwise combinations of 82 photosynthetic genes in 10 species of cyanobacteria. Our analysis reveals significant correlations between proteins linked in a conserved gene order and between structurally identified interacting protein scaffolds that coordinate the binding of cofactors involved in photosynthetic electron transport. Analyses of amino acid substitution rates suggest that the tempo of evolution of genes encoding core metabolic processes in the photosynthetic apparatus is highly constrained by protein-protein, protein-lipid, and protein-cofactor interactions (collectively called "protein interactions"). These interactions are critical for energy transduction, primary charge separation, and electron transport and effectively act as an internal selection pressure governing the conservation of clusters of photosynthetic genes in oxygenic prokaryotic photoautotrophs. Consequently, although several proteins within the photosynthetic apparatus are biophysically and physiologically inefficient, selection has not significantly altered the genes encoding these essential proteins over billions of years of evolution. In effect, these core proteins have become "frozen metabolic accidents."
PSYCHIATRIC SYNDROMES, ANXIETY SYMPTOMS AND RESPONSES TO STRESS IN MEDICAL STUDENTS
Authors: FERRIS N. PITTS, GEORGE WINOKUR, MARK A. STEWART
Journal: American Journal of Psychiatry (1961)

1. A random sample of 40 sophomore medical students out of 80 was given structured psychiatric interviews. 2. Six (15%) of the group were psychiatrically ill ; of these 3 were manic-depressives, one an anxiety neurotic, one a chronic alcoholic, and one ill but undiagnosed. 3. The psychiatrically ill subjects had an incidence of positive family history of psychiatric illness that was markedly greater than that of the well subjects; this difference was statistically significant to the 0.0001 level. In addition, the ill relatives of ill subjects were not only genetically much closer than those of the well subjects but appeared to suffer different illnesses. 4. Anxiety symptoms did not increase in pre-exam periods in the psychiatrically ill; but those of well subjects, previously quite different, approached those of the ill in pre-exam periods. 5. Anxiety ratings in ordinary circumstances do not correlate with those of pre-exam periods for the group. 6. In ordinary circumstances our group resembled a control population rather than anxiety neurotics in terms of incidence of anxiety symptoms. In pre-exam periods the group resembled the "scared soldiers" reported by Cohen, White, et al. Differences, however, were present. 7. The incidence of psychiatric symptoms such as dreams, nightmares, hallucinations, suicidal thoughts, and phobias was quite high in our subjects but the quality of such symptoms was innocuous in all but the 6 ill subjects.
<i>Chlamydia pneumoniae</i> Stimulates Proliferation of Vascular Smooth Muscle Cells Through Induction of Endogenous Heat Shock Protein 60
Authors: Satoru Hirono, Elena Dibrov, Cecilia Hurtado, Annette Kostenuk, Robin Ducas, Grant N. Pierce
Journal: Circulation Research (2003)

Chlamydia pneumoniae infection has been linked with atherosclerosis. However, the mechanism responsible for the atherogenic effects of C pneumoniae remains unclear. Heat shock proteins (HSPs) have been found in atherosclerotic lesions. HSPs of HSP70 and HSP90 families are involved in the regulation of cell cycle progression and cell proliferation. We assessed the hypothesis that HSP60 is induced in vascular cells infected with C pneumoniae and stimulates cell proliferation. Rabbit vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were infected with C pneumoniae. Western blot analysis demonstrated the induction of endogenous HSP60 expression in C pneumoniae-infected VSMCs. C pneumoniae infection significantly increased the number of VSMCs, and the mitogenic effect correlated with the expression level of endogenous HSP60. In contrast to VSMCs, C pneumoniae infection had no effect on the expression level of HSP60 and did not stimulate cell proliferation in HUVECs. Exogenous addition of recombinant chlamydial HSP60 had no mitogenic effect on VSMCs and HUVECs. However, overexpression of HSP60 within VSMCs by infection with adenovirus encoding human HSP60 resulted in a significant increase in cell numbers compared with uninfected VSMCs. These results suggest that overexpression of endogenous HSP60 may be a central intracellular event responsible for the mitogenic effects induced by C pneumoniae infection. In addition to C pneumoniae, other infectious agents and atherogenic risk factors may also stimulate VSMC proliferation and contribute to the lesion formation through the induction of HSP60.
Eribex: a Retrospective, International, Multicenter Study on the Efficacy and Safety of Eribuline Mesylate in Metastatic Breast Cancer
Authors: M. Dell'Ova, E. De Maio, S. Guiu, L. Roca, F. Dalenc, W. Jacot, A. Durigova, F. Pinguet, K. Bekhtari, S. Pouderoux
Journal: Annals of Oncology (2014)
TH2 Cytokines from Malignant Cells Suppress TH1 Responses and Enforce a Global TH2 Bias in Leukemic Cutaneous T-cell Lymphoma
Authors: Emmanuella Guenova, Rei Watanabe, Jessica E. Teague, Jennifer A. Desimone, Ying Jiang, Mitra Dowlatshahi, Christoph Schlapbach, Knut Schaekel, Alain H. Rook, Marianne Tawa, David C. Fisher, Thomas S. Kupper, Rachael A. Clark
Journal: Clinical Cancer Research (2013)

Abstract Purpose: In leukemic cutaneous T-cell lymphoma (L-CTCL), malignant T cells accumulate in the blood and give rise to widespread skin inflammation. Patients have intense pruritus, increased immunoglobulin E (IgE), and decreased T-helper (TH)-1 responses, and most die from infection. Depleting malignant T cells while preserving normal immunity is a clinical challenge. L-CTCL has been variably described as a malignancy of regulatory, TH2 and TH17 cells. Experimental Design: We analyzed phenotype and cytokine production in malignant and benign L-CTCL T cells, characterized the effects of malignant T cells on healthy T cells, and studied the immunomodulatory effects of treatment modalities in patients with L-CTCL. Results: Twelve out of 12 patients with L-CTCL overproduced TH2 cytokines. Remaining benign T cells were also strongly TH2 biased, suggesting a global TH2 skewing of the T-cell repertoire. Culture of benign T cells away from the malignant clone reduced TH2 and enhanced TH1 responses, but separate culture had no effect on malignant T cells. Coculture of healthy T cells with L-CTCL T cells reduced IFNγ production and neutralizing antibodies to interleukin (IL)-4 and IL-13 restored TH1 responses. In patients, enhanced TH1 responses were observed following a variety of treatment modalities that reduced malignant T-cell burden. Conclusions: A global TH2 bias exists in both benign and malignant T cells in L-CTCL and may underlie the infectious susceptibility of patients. TH2 cytokines from malignant cells strongly inhibited TH1 responses. Our results suggest that therapies that inhibit TH2 cytokine activity, by virtue of their ability to improve TH1 responses, may have the potential to enhance both anticancer and antipathogen responses. Clin Cancer Res; 19(14); 3755–63. ©2013 AACR.
TREATMENT OF PYELITIS
Authors: J. N. Cruickshank
Journal: BMJ (1936)

The term " pyelitis" is used in a general way to include not only suppurative inflammation of the renal pelvis but also the accompanying inflammation of the ureter and bladder.Pyelitis may be acute, subacute, or chronic, -and may develop rapidly or insidiously.The infection may occur in a previously healthy urinary tract, or may arise as a complication of some other abnormality such as calculus or tumour.Acute pyelitis is common in pregnancy on account of the tendency to dilatation of the ureter and achalasia of the ureteric sphincters, which predispose to stagnation of the urinary flow and favour the growth of organisms.Pyuria and bacilluria are the signs pathognomonic of 'infection of the urinary tract.The pus may be so abundant as to be visible to the naked eye, or so scanty that it can be detected only with the microscope.Ahjghly purulent urine will' give the " rope test" with hquor potassiae, but if this test is negative there is no Justification for the conclusion that the urine is free from pus.The microscope is the only reliable means of ascer- taining that pus and organisms have disappeared from the urine; the amount of pus may vary from day to day,
Hypertension-Linked Mutation in the Adducin α-Subunit Leads to Higher AP2-μ2 Phosphorylation and Impaired Na <sup>+</sup> ,K <sup>+</sup> -ATPase Trafficking in Response to GPCR Signals and Intracellular Sodium
Authors: Riad Efendiev, Rafael T. Krmar, Goichi Ogimoto, Jean Zwiller, Grazia Tripodi, Adrian I. Katz, Giuseppe Bianchi, Carlos H. Pedemonte, Alejandro M. Bertorello
Journal: Circulation Research (2004)

Alpha-adducin polymorphism in humans is associated with abnormal renal sodium handling and high blood pressure. The mechanisms by which mutations in adducin affect the renal set point for sodium excretion are not known. Decreases in Na+,K+-ATPase activity attributable to endocytosis of active units in renal tubule cells by dopamine regulates sodium excretion during high-salt diet. Milan rats carrying the hypertensive adducin phenotype have a higher renal tubule Na+,K+-ATPase activity, and their Na+,K+-ATPase molecules do not undergo endocytosis in response to dopamine as do those of the normotensive strain. Dopamine fails to promote the interaction between adaptins and the Na+,K+-ATPase because of adaptin-mu2 subunit hyperphosphorylation. Expression of the hypertensive rat or human variant of adducin into normal renal epithelial cells recreates the hypertensive phenotype with higher Na+,K+-ATPase activity, mu2-subunit hyperphosphorylation, and impaired Na+,K+-ATPase endocytosis. Thus, increased renal Na+,K+-ATPase activity and altered sodium reabsorption in certain forms of hypertension could be attributed to a mutant form of adducin that impairs the dynamic regulation of renal Na+,K+-ATPase endocytosis in response to natriuretic signals.
APR-246 potently inhibits tumour growth and overcomes chemoresistance in preclinical models of oesophageal adenocarcinoma
Authors: David S H Liu, Matthew Read, Carleen Cullinane, Walid J Azar, Christina M Fennell, Karen G Montgomery, Sue Haupt, Ygal Haupt, Klas G Wiman, Cuong P Duong, Nicholas J Clemons, Wayne A Phillips
Journal: Gut (2015)

p53 is a critical tumour suppressor and is mutated in 70% of oesophageal adenocarcinomas (OACs), resulting in chemoresistance and poor survival. APR-246 is a first-in-class reactivator of mutant p53 and is currently in clinical trials. In this study, we characterised the activity of APR-246 and its effect on p53 signalling in a large panel of cell line xenograft (CLX) and patient-derived xenograft (PDX) models of OAC.In vitro response to APR-246 was assessed using clonogenic survival, cell cycle and apoptosis assays. Ectopic expression, gene knockdown and CRISPR/Cas9-mediated knockout studies of mutant p53 were performed to investigate p53-dependent drug effects. p53 signalling was examined using quantitative RT-PCR and western blot. Synergistic interactions between APR-246 and conventional chemotherapies were evaluated in vitro and in vivo using CLX and PDX models.APR-246 upregulated p53 target genes, inhibited clonogenic survival and induced cell cycle arrest as well as apoptosis in OAC cells harbouring p53 mutations. Sensitivity to APR-246 correlated with cellular levels of mutant p53 protein. Ectopic expression of mutant p53 sensitised p53-null cells to APR-246, while p53 gene knockdown and knockout diminished drug activity. Importantly, APR-246 synergistically enhanced the inhibitory effects of cisplatin and 5-fluorouracil through p53 accumulation. Finally, APR-246 demonstrated potent antitumour activity in CLX and PDX models, and restored chemosensitivity to a cisplatin/5-fluorouracil-resistant xenograft model.APR-246 has significant antitumour activity in OAC. Given that APR-246 is safe at therapeutic levels our study strongly suggests that APR-246 can be translated into improving the clinical outcomes for OAC patients.
Current View of Advances in Epilepsy
Authors: Pat Phillips
Journal: JAMA (1997)

A NEW ERA in the treatment of epilepsy has been ushered in with approval by the US Food and Drug Administration (FDA) of the first implantable medical device to reduce the number of seizures, development of a plethora of new antiepileptic drugs (AEDs), and advances in surgery, imaging techniques, and genetics research.  At the 22nd International Epilepsy Congress, held this summer in Dublin, Ireland, more than 5000 neurologists, neurosurgeons, primary care physicians, and allied health professionals from more than 70 countries heard presentations that reflected the spectrum of change in the diagnosis and treatment of the disorder.  The number of options that have become available to physicians and patients is enormous, said David W. Chadwick, MD, professor of neurology at the University of Liverpool, in Liverpool, England. Once, you could teach medical students all they needed to know about the management of epilepsy, fairly confident that the information about
Agonist-induced impairment of glycocalyx exclusion properties: contribution to coronary effects of adenosine
Authors: J. W. G. E. VanTeeffelen, J. Brands, H. Vink
Journal: Cardiovascular Research (2010)

The endothelial glycocalyx is the negatively charged, gel-like mesh residing at the luminal side of the vascular endothelium and forming the interface between the flowing blood and the vessel wall. The vast majority of glycocalyx volume resides in the microcirculation, particularly in the capillaries. Intravital microscopic observations of capillaries in striated muscle preparations illustrate that under resting conditions, the glycocalyx is not accessible for flowing red blood cells and greatly hinders plasma flow in the axial direction, causing a significant reduction in functionally perfused capillary volume. Glycocalyx exclusion properties have been shown to be reduced by adenosine and other vasoactive substances. A diminished exclusion of circulating blood by the glycocalyx may facilitate nutrient exchange since it is associated with an increase in functionally perfused blood volume and surface area in the capillaries. Our recent studies have focused on the effect of adenosine on glycocalyx exclusion in the coronary circulation and demonstrate an important role for this mechanism in the increase in circulating coronary blood volume during administration of this vasodilator. The current review elaborates on the glycocalyx as a blood-excluding intravascular layer and how it can be modulated by various agonists. Further, the potential role of adenosine-induced modulation of glycocalyx exclusion properties in coupling increases in blood flow and circulating blood volume in the coronary circulation is discussed. Finally, we consider how degradation of the glycocalyx may impact on coronary blood volume regulation, thereby providing new opportunities to diagnose glycocalyx damage in the clinical setting.
Randomized Trial of Prevention of Catheter-Related Bloodstream Infection by Continuous Infusion of Low-Dose Unfractionated Heparin in Patients With Hematologic and Oncologic Disease
Authors: Abderrahman Abdelkefi, Lamia Torjman, Saloua Ladeb, Tarek Ben Othman, Wafa Achour, Amel Lakhal, Mohamed Hsairi, Leila Kammoun, Assia Ben Hassen, Abdeladhim Ben Abdeladhim
Journal: Journal of Clinical Oncology (2005)

Infection is a serious complication of central venous catheters in immunocompromised patients. Catheter-related infection may be caused by fibrin deposition associated with catheters. Interventions designed to decrease fibrin deposition have the potential to reduce catheter-related infections. The purpose of this study was to evaluate the role of low-dose unfractionated heparin in preventing catheter-related bloodstream infection in patients with hemato-oncological disease.
Breast Cancer Subtypes and the Risk of Local and Regional Relapse
Authors: K. David Voduc, Maggie C.U. Cheang, Scott Tyldesley, Karen Gelmon, Torsten O. Nielsen, Hagen Kennecke
Journal: Journal of Clinical Oncology (2010)

The risk of local and regional relapse associated with each breast cancer molecular subtype was determined in a large cohort of patients with breast cancer. Subtype assignment was accomplished using a validated six-marker immunohistochemical panel applied to tissue microarrays.Semiquantitative analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin (CK) 5/6 was performed on tissue microarrays constructed from 2,985 patients with early invasive breast cancer. Patients were classified into the following categories: luminal A, luminal B, luminal-HER2, HER2 enriched, basal-like, or triple-negative phenotype-nonbasal. Multivariable Cox analysis was used to determine the risk of local or regional relapse associated the intrinsic subtypes, adjusting for standard clinicopathologic factors.The intrinsic molecular subtype was successfully determined in 2,985 tumors. The median follow-up time was 12 years, and there have been a total of 325 local recurrences and 227 regional lymph node recurrences. Luminal A tumors (ER or PR positive, HER2 negative, Ki-67 < 1%) had the best prognosis and the lowest rate of local or regional relapse. For patients undergoing breast conservation, HER2-enriched and basal subtypes demonstrated an increased risk of regional recurrence, and this was statistically significant on multivariable analysis. After mastectomy, luminal B, luminal-HER2, HER2-enriched, and basal subtypes were all associated with an increased risk of local and regional relapse on multivariable analysis.Luminal A tumors are associated with a low risk of local or regional recurrence. Molecular subtyping of breast tumors using a six-marker immunohistochemical panel can identify patients at increased risk of local and regional recurrence.
THE CELLULAR REACTIONS TO ACETONE-SOLUBLE FAT FROM MYCOBACTERIA AND STREPTOCOCCI
Authors: Kenneth C. Smithburn, Florence R. Sabin
Journal: The Journal of Experimental Medicine (1935)

1. The acetone-soluble fat of tubercle bacilli produces a profound cellular reaction when injected into normal animals. The reaction involves every type of connective tissue cell. Hemorrhage, formation of adhesions and of tubercular tissue occur. The extent of the reaction is roughly proportional to the amount of material injected. 2. The reaction induced by the lipoid is much less extensive and much simpler when the material is neutralized with alkali. Neutralization of the acetone-soluble fat, or of phthioic acid, does not diminish the tuberculogenic property. 3. Acetone-soluble fat from streptococci is likewise extremely irritating but does not produce tubercular tissue.
XGAP: a uniform and extensible data model and software platform for genotype and phenotype experiments
Authors: Morris A Swertz, K Joeri Velde, Bruno M Tesson, Richard A Scheltema, Danny Arends, Gonzalo Vera, Rudi Alberts, Martijn Dijkstra, Paul Schofield, Klaus Schughart, John M Hancock, Damian Smedley, Katy Wolstencroft, Carole Goble, Engbert O de Brock, Andrew R Jones, Helen E Parkinson, Ritsert C Jansen
Journal: Genome biology (2010)

We present an extensible software model for the genotype and phenotype community, XGAP. Readers can download a standard XGAP ( http://www.xgap.org ) or auto-generate a custom version using MOLGENIS with programming interfaces to R-software and web-services or user interfaces for biologists. XGAP has simple load formats for any type of genotype, epigenotype, transcript, protein, metabolite or other phenotype data. Current functionality includes tools ranging from eQTL analysis in mouse to genome-wide association studies in humans.