tbuckley/cabot-search huggingface dataset:
Responses of hyperthermophilic crenarchaea to UV irradiation
Authors: Dorothee Götz, Sonia Paytubi, Stacey Munro, Magnus Lundgren, Rolf Bernander, Malcolm F White
Journal: Genome biology (2007)

DNA damage leads to cellular responses that include the increased expression of DNA repair genes, repression of DNA replication and alterations in cellular metabolism. Archaeal information processing pathways resemble those in eukaryotes, but archaeal damage response pathways remain poorly understood. We analyzed the transcriptional response to UV irradiation in two related crenarchaea, Sulfolobus solfataricus and Sulfolobus acidocaldarius. Sulfolobus species encounter high levels of DNA damage in nature, as they inhabit high temperature, aerobic environments and are exposed to sunlight. No increase in expression of DNA repair genes following UV irradiation was observed. There was, however, a clear transcriptional response, including repression of DNA replication and chromatin proteins. Differential effects on the expression of the three transcription factor B (tfb) genes hint at a mechanism for the modulation of transcriptional patterns in response to DNA damage. TFB3, which is strongly induced following UV irradiation, competes with TFB1 for binding to RNA polymerase in vitro, and may act as a repressor of transcription or an alternative transcription factor for certain promoters. A clear response to DNA damage was observed, with down-regulation of the DNA replication machinery, changes in transcriptional regulatory proteins, and up-regulation of the biosynthetic enzymes for beta-carotene, which has UV protective properties, and proteins that detoxify reactive oxygen species. However, unlike eukaryotes and bacteria, there was no induction of DNA repair proteins in response to DNA damage, probably because these are expressed constitutively to deal with increased damage arising due to high growth temperatures.
Tuberculosis: pictures of a ticking time bomb
Authors: Rob Hyde
Journal: The Lancet (2009)

Mortal danger has been part and parcel of his trade for the past 30 years, having dodged machetes, snipers' bullets, tank wheels, and even napalm bombs in some of the most gruesome conflict zones on earth. But as he greets those attending his Struggle For Life exhibition in the heart of Berlin, it is surprising how shy and humble James Nachtwey appears. Although officially the star of tonight's show, the award-winning war photographer chooses to give only a short speech, quietly apologising for being "a man of pictures, not words" as he emphasises the humanitarian aspects of his work: "Unlike paparazzi, the people I photo are inherently non-commercial.
Outcomes of Using High- or Low-Dose Atorvastatin in Patients 65 Years of Age or Older with Stable Coronary Heart Disease
Authors: Nanette K. Wenger, Sandra J. Lewis, David M. Herrington, Vera Bittner, Francine K. Welty
Journal: Annals of Internal Medicine (2007)

Increased life expectancy is associated with an increase in the burden of chronic cardiovascular disease.To assess the efficacy and safety of high-dose atorvastatin in patients 65 years of age or older.A prespecified secondary analysis of the Treating to New Targets study, a randomized, double-blind clinical trial.256 sites in 14 countries participating in the Treating to New Targets study.10,001 patients (3809 patients > or =65 years of age) with coronary heart disease (CHD) and low-density lipoprotein cholesterol levels less than 3.4 mmol/L (<130 mg/dL).Patients were randomly assigned to receive atorvastatin, 10 or 80 mg/d.The primary end point was the occurrence of a first major cardiovascular event (death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke).In patients 65 years of age or older, absolute risk was reduced by 2.3% and relative risk by 19% for major cardiovascular events in favor of the high-dose atorvastatin group (hazard ratio, 0.81 [95% CI, 0.67 to 0.98]; P = 0.032). Among the components of the composite outcome, the mortality rates from CHD, nonfatal non-procedure-related myocardial infarction, and fatal or nonfatal stroke (ischemic, embolic, hemorrhagic, or unknown origin) were all lower in older patients who received high-dose atorvastatin, although the difference was not statistically significant for each individual component. The improved clinical outcome in patients 65 years of age or older was not associated with persistent elevations in creatine kinase levels.Because the study was a secondary analysis, the findings should be interpreted within the context of the main study results.The analysis suggests that additional clinical benefit can be achieved by treating older patients with CHD more aggressively to reduce low-density lipoprotein cholesterol levels to less than 2.6 mmol/L (<100 mg/dL). The findings support the use of intensive low-density lipoprotein cholesterol-lowering therapy in high-risk older persons with established cardiovascular disease. Click here for related information on atorvastatin.
HLA-MATCHING AND PRETRANSPLANT BLOOD TRANSFUSIONS IN CADAVERIC RENAL TRANSPLANTATION—A CHANGING PICTURE WITH CYCLOSPORIN
Authors: G. Lundgren, D. Albrechtsen, A. Flatmark, H. Gäbel, G. Klintmalm, H. Persson, C.G. Groth, H. Brynger, L. Frödin, B. Husberg, W. Maurer, E. Thorsby
Journal: The Lancet (1986)
Impact of <i>Helicobacter pylori</i> eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial
Authors: J Athene Lane, Liam J Murray, Sian Noble, Matthias Egger, Ian M Harvey, Jenny L Donovan, Prakash Nair, Richard F Harvey
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To determine the impact of a community based Helicobacter pylori screening and eradication programme on the incidence of dyspepsia, resource use, and quality of life, including a cost consequences analysis. <b>Design</b> H pylori screening programme followed by randomised placebo controlled trial of eradication. <b>Setting</b> Seven general practices in southwest England. <b>Participants</b> 10 537 unselected people aged 20-59 years were screened for H pylori infection (<sup>13</sup>C urea breath test); 1558 of the 1636 participants who tested positive were randomised to <i>H pylori</i> eradication treatment or placebo, and 1539 (99%) were followed up for two years. <b>Intervention</b> Ranitidine bismuth citrate 400 mg and clarithromycin 500 mg twice daily for two weeks or placebo. <b>Main outcome measures</b> Primary care consultation rates for dyspepsia (defined as epigastric pain) two years after randomisation, with secondary outcomes of dyspepsia symptoms, resource use, NHS costs, and quality of life. <b>Results</b> In the eradication group, 35% fewer participants consulted for dyspepsia over two years compared with the placebo group (55/787 v 78/771; odds ratio 0.65, 95% confidence interval 0.46 to 0.94; P = 0.021; number needed to treat 30) and 29% fewer participants had regular symptoms (odds ratio 0.71, 0.56 to 0.90; P = 0.05). NHS costs were £84.70 (£74.90 to £93.91) greater per participant in the eradication group over two years, of which £83.40 ($146; €121) was the cost of eradication treatment. No difference in quality of life existed between the two groups. <b>Conclusions</b> Community screening and eradication of <i>H pylori</i> is feasible in the general population and led to significant reductions in the number of people who consulted for dyspepsia and had symptoms two years after treatment. These benefits have to be balanced against the costs of eradication treatment, so a targeted eradication strategy in dyspeptic patients may be preferable.
Development of a Model System to Evaluate Local Recurrence in Osteosarcoma and Assessment of the Effects of Bone Morphogenetic Protein-2
Authors: David S. Geller, Michael Y. Singh, Wendong Zhang, Jonathan Gill, Michael E. Roth, Mimi Y. Kim, Xianhong Xie, Christopher K. Singh, Howard D. Dorfman, Esperanza Villanueva-Siles, Amy Park, Sajida Piperdi, Richard Gorlick
Journal: Clinical Cancer Research (2014)

It is increasingly relevant to better define what constitutes an adequate surgical margin in an effort to improve reconstructive longevity and functional outcomes following osteosarcoma surgery. In addition, nonunion remains a challenging problem in some patients following allograft reconstruction. Bone morphogenetic protein-2 (BMP-2) could enhance osseous union, but has been historically avoided due to concerns that it may promote tumor recurrence.An orthotopic xenograft murine model was utilized to describe the natural temporal course of osteosarcoma growth. Tumors were treated either with surgery alone, surgery and single-agent chemotherapy, or surgery and dual-agent chemotherapy to assess the relationship between surgical margin and local recurrence. The effect of BMP-2 on local recurrence was similarly assessed.Osteosarcoma tumor growth was categorized into reproducible phases. Margins greater than 997 μm resulted in local control following surgery alone. Margins greater than 36 μm resulted in local control following surgery and single-agent chemotherapy. Margins greater than 12 μm resulted in local control following surgery and dual-agent chemotherapy. The application of exogenous BMP-2 does not confer an increased risk of local recurrence.This model reliably reproduces the clinical, radiographic, and surgical conditions encountered in human osteosarcoma. It successfully incorporates relevant chemotherapy, further paralleling the human experience. Surgical margins required to achieve local control in osteosarcoma can be reduced using single-agent chemotherapy and further decreased using dual-agent chemotherapy. The application of BMP-2 does not increase local recurrence in this model.
Osterix, a Transcription Factor for Osteoblast Differentiation, Mediates Antitumor Activity in Murine Osteosarcoma
Authors: Ying Cao, Zhichao Zhou, Benoit de Crombrugghe, Kazuhisa Nakashima, Hui Guan, Xiaoping Duan, Shu-Fang Jia, Eugenie S. Kleinerman
Journal: Cancer Research (2005)

Abstract Osterix is a novel zinc finger–containing transcription factor that is essential for osteoblast differentiation and bone formation. We hypothesized that osterix might have a role in osteosarcoma tumor growth and metastasis. Northern blot analysis showed that the mRNA level of osterix was decreased in two mouse osteosarcoma cell lines compared with its level in normal mouse osteoblasts. Osterix expression was also decreased in three human osteosarcoma cell lines. Transfection of the osx gene into the mouse osteosarcoma cells inhibited tumor cell growth in vitro and in vivo and significantly reduced tumor incidence, tumor volume, and lung metastasis following intratibial injection. Osterix expression was also associated with decreased osteolysis. Using an in vitro migration assay, osterix suppressed the migration of tumor cells to lung extracts. These results suggest that osterix expression may play a role in osteosarcoma tumor growth and metastasis.
Maximal Actomyosin ATPase Activity and In Vitro Myosin Motility Are Unaltered in Human Mitral Regurgitation Heart Failure
Authors: The-Tin T. Nguyen, Eric Hayes, Louis A. Mulieri, Bruce J. Leavitt, Henk E.D.J. ter Keurs, Norman R. Alpert, David M. Warshaw
Journal: Circulation Research (1996)

Myofibrillar but not actomyosin ATPase is depressed in failing myocardium from patients with dilated cardiomyopathy. Since there is a similar depression of myofibrillar ATPase in mitral regurgitation myocardium, we investigated whether or not the hydrolytic and mechanical performances of myosin are altered by comparing the maximal actomyosin ATPase activity and the in vitro myosin motility of myocardial myosin from patients with mitral regurgitation heart failure with that of patients with normal ventricular function. The results show that there is no significant difference ( P &gt;.05) between nonfailing and failing values for either the maximal actomyosin ATPase activity (0.3 s −1 ·head −1 ) or the myosin motility (1 μm/s). These observations suggest that changes, other than in the myosin heavy chain, contribute to the altered myocardial performance in mitral regurgitation myocardium.
Pneumocystis colonisation is common among hospitalised HIV infected patients with non-Pneumocystis pneumonia
Authors: J L Davis, D A Welsh, C B Beard, J L Jones, G G Lawrence, M R Fox, K Crothers, A Morris, D Charbonnet, A Swartzman, L Huang
Journal: Thorax (2007)

<h3>Background:</h3> When <i>Pneumocystis</i> DNA is recovered from respiratory specimens of patients without <i>Pneumocystis</i> pneumonia (PCP), patients are said to be colonised with <i>Pneumocystis</i>, although the significance of this state is unknown. Understanding risk factors for and outcomes of colonisation may provide insights into the life cycle and transmission dynamics of <i>Pneumocystis jirovecii</i>. <h3>Methods:</h3> We performed a cross sectional study of the prevalence and clinical predictors of <i>Pneumocystis</i> colonisation in 172 HIV infected, PCP negative inpatients undergoing diagnostic evaluation of 183 episodes of pneumonia at either the Medical Center of Louisiana at New Orleans between 2003 and 2005 or San Francisco General Hospital between 2000 and 2005. DNA was extracted from sputum and bronchoalveolar lavage specimens and amplified using a nested PCR assay at the mitochondrial large subunit (18S) ribosomal RNA locus. Colonisation was deemed present if <i>Pneumocystis</i> DNA was identified by both gel electrophoresis and direct DNA sequencing. <h3>Results:</h3> 68% (117/172) of all patients were colonised with <i>Pneumocystis</i>. No strong associations with colonisation were identified for any demographic factors. Among clinical factors, having a CD4+ T cell count ⩽50 cells/μl (unadjusted OR 2.4, 95% CI 1.09 to 5.48; p = 0.031) and using PCP prophylaxis (unadjusted OR 0.55, 95% CI 0.29 to 1.07; p = 0.077) were associated with <i>Pneumocystis</i> colonisation, although the latter association may have been due to chance. After adjustment for CD4+ T cell count, use of PCP prophylaxis was associated with a decreased odds of colonisation (adjusted OR 0.45, 95% CI 0.21 to 0.98; p = 0.045). 11 patients who were colonised were subsequently readmitted for evaluation of a second episode of pneumonia; three were found to be colonised again, but none had PCP. <h3>Conclusions:</h3> The majority of hospitalised HIV infected patients with non-PCP pneumonia are colonised with <i>Pneumocystis</i>. Failure to use co-trimoxazole prophylaxis and severe immunosuppression are associated with an increase in the odds of colonisation. <i>Pneumocystis</i> colonisation among hospitalised patients does not commonly lead to PCP.
Inhibition of the Androgen Receptor as a Novel Mechanism of Taxol Chemotherapy in Prostate Cancer
Authors: Lu Gan, Shuai Chen, Yuwei Wang, Akira Watahiki, Laura Bohrer, Zhen Sun, Yuzhuo Wang, Haojie Huang
Journal: Cancer Research (2009)

Abstract Taxol chemotherapy is one of the few therapeutic options for men with castration-resistant prostate cancer (CRPC). However, the working mechanisms for Taxol are not fully understood. Here, we showed that treatment of 22Rv1, a PTEN-positive CRPC cell line, with paclitaxel and its semisynthetic analogue docetaxel decreases expression of the androgen receptor (AR)–activated genes prostate-specific antigen (PSA) and Nkx3.1 but increases expression of the AR repression gene maspin, suggesting that Taxol treatment inhibits AR activity. This was further supported by the observation that the activity of AR luciferase reporter genes was inhibited by paclitaxel. In contrast, paclitaxel treatment failed to inhibit AR activity in the PTEN-null CRPC cell line C4-2. However, pretreatment of C4-2 cells with the phosphoinositide 3-kinase inhibitor LY294002 restored paclitaxel inhibition of the AR. Treatment of 22Rv1 xenografts in mice with docetaxel induced mitotic arrest and a decrease in PSA expression in tumor cells adjacent to vascular vessels. We further showed that paclitaxel induces nuclear accumulation of FOXO1, a known AR suppressive nuclear factor, and increases the association of FOXO1 with AR proteins in the nucleus. FOXO1 knockdown with small interfering RNA attenuated the inhibitory effect of paclitaxel on AR transcriptional activity, expression of PSA and Nkx3.1, and cell survival. These data reveal a previously uncharacterized, FOXO1-mediated, AR-inhibitory effect of Taxol in CRPC cells that may play an important role in Taxol-mediated inhibition of CRPC growth. [Cancer Res 2009;69(21):8386–94]
Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair
Authors: Firas L. Tarish, Niklas Schultz, Anna Tanoglidi, Hans Hamberg, Henry Letocha, Katalin Karaszi, Freddie C. Hamdy, Torvald Granfors, Thomas Helleday
Journal: Science Translational Medicine (2015)

Chemical castration improves responses to radiotherapy in prostate cancer, but the mechanism is unknown. We hypothesized that this radiosensitization is caused by castration-mediated down-regulation of nonhomologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs). To test this, we enrolled 48 patients with localized prostate cancer in two arms of the study: either radiotherapy first or radiotherapy after neoadjuvant castration treatment. We biopsied patients at diagnosis and before and after castration and radiotherapy treatments to monitor androgen receptor, NHEJ, and DSB repair in verified cancer tissue. We show that patients receiving neoadjuvant castration treatment before radiotherapy had reduced amounts of the NHEJ protein Ku70, impaired radiotherapy-induced NHEJ activity, and higher amounts of unrepaired DSBs, measured by γ-H2AX foci in cancer tissues. This study demonstrates that chemical castration impairs NHEJ activity in prostate cancer tissue, explaining the improved response of patients with prostate cancer to radiotherapy after chemical castration.
Triazolam in patients with obstructive sleep apnea.
Authors: R B Berry, K Kouchi, J Bower, G Prosise, R W Light
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The purpose of this study was to assess the effect of triazolam (0.25 mg) on apnea duration and the arousal response to airway occlusion during sleep in patients with severe obstructive sleep apnea (OSA). Twelve male subjects with a mean (+/- SD) age of 46.6 +/- 14.1 yr and body weight of 260.8 +/- 55.9 lb were studied on two nights separated by a nonstudy night. They ingested triazolam (0.25 mg) or placebo 0.5 h before bedtime in a randomized double-blind crossover manner. In non-rapid-eye-movement (NREM) sleep, the mean (+/- SEM) duration of apnea/hypopnea was slightly increased (26.8 +/- 1.7 versus 23.8 +/- 1.2 s, p < 0.02) and the mean nadir in arterial oxygen saturation lower (80.1 +/- 1.9 versus 84.2 +/- 1.4%, p < 0.001) on triazolam nights. In NREM sleep, the deflections in esophageal pressure prior to apnea termination were higher on triazolam nights (53.3 +/- 5.4 versus 44.5 +/- 4.8 cm H2O, p < 0.001). However, the rate of increase in inspiratory effort (esophageal pressure deflections) during obstructive events was not decreased by triazolam. We conclude that triazolam increases the arousal threshold to airway occlusion, but that this results in only modest prolongation of event duration and increased desaturation at a dose of 0.25 mg in a group of large sleep apnea patients.
Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression
Authors: N. Agmon-Levin, M. Blank, G. Zandman-Goddard, H. Orbach, P. L. Meroni, A. Tincani, A. Doria, R. Cervera, W. Miesbach, L. Stojanovich, V. Barak, B. S. Porat-Katz, H. Amital, Y. Shoenfeld
Journal: Annals of the Rheumatic Diseases (2010)

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, obstetric complications and the presence of anti-phospholipid antibodies such as anti-β2GPI-Abs. These antibodies may set off the coagulation cascade via several mechanisms, including the induction of tissue factor (TF) expression. Vitamin D has recently emerged as an immunomodulator that might exert an anti-thrombotic effect. Therefore, we studied serum vitamin D levels in a cohort of APS patients, as well as the effect of vitamin D in an in vitro model of APS-mediated thrombosis.Serum vitamin D levels were measured in 179 European APS patients and 141 healthy controls using the LIAISON chemiluminescent immunoassay, and the levels were evaluated in conjunction with a wide spectrum of clinical manifestations. In an vitro model, anti-β2GPI antibodies were purified from four patients with APS to evaluate the expression of TF in activated starved human umbilical vein endothelial cells. The effect of vitamin D (1,25-dihydroxyvitamin D, 10 nm) on anti-β2GPI-Abs mediated TF expression was analysed by immunoblot.Vitamin D deficiency (serum level ≤15 ng/ml) was documented in 49.5% of our APS patients versus 30% of controls (p<0.001) and was significantly correlated with thrombosis (58% vs 42%; p<0.05), neurological and ophthalmic manifestations, pulmonary hypertension, livedo reticularis and skin ulcerations. In vitro vitamin D inhibited the expression of TF induced by anti-β2GPI-antibodies.Vitamin D deficiency is common among APS patients and is associated with clinically defined thrombotic events. Vitamin D inhibits anti-β2GPI-mediated TF expression in vitro. Thus, vitamin D deficiency might be associated with decreased inhibition of TF expression and increased coagulation in APS. Evaluation of vitamin D status and vitamin D supplementation in APS patients should be considered.
Double-Blind, Placebo-Controlled Trial of the Use of Lithium to Augment Antidepressant Medication in Continuation Treatment of Unipolar Major Depression
Authors: M Bauer, T Bschor, D Kunz, A Berghöfer, A Ströhle, B Müller-Oerlinghausen
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Use of lithium to augment antidepressant medication has been shown to be beneficial in the acute treatment of depression. The authors examined the efficacy of lithium augmentation in the continuation treatment of unipolar major depressive disorder. METHOD: Thirty patients with a refractory major depressive episode who had responded to acute lithium augmentation during an open 6-week study participated in a randomized, parallel-group, double-blind, placebo-controlled trial of lithium augmentation during continuation treatment. After a 2–4-week stabilization period following remission, patients were randomly assigned to receive either lithium or placebo for a 4-month period. Antidepressant medication was continued throughout the study. RESULTS: Relapses (including one suicide) occurred in seven (47%) of the 15 patients who received placebo in addition to antidepressants. None (0%) of the 14 patients who received lithium augmentation with antidepressants suffered a relapse during the double-blind phase of the study. Five of the seven relapsing patients in the placebo group developed a depressive episode, and the other two experienced a manic episode. CONCLUSIONS: Lithium augmentation in the continuation phase of treatment of unipolar major depressive disorder effectively protects patients against a relapse. Patients who respond to lithium augmentation should be maintained on lithium augmentation for a minimum of 6 months or even longer.