tbuckley/cabot-search huggingface dataset:
Daytime mechanical ventilation in chronic respiratory insufficiency
Authors: B Schonhofer, M Geibel, M Sonneborn, P Haidl, D Kohler
Journal: European Respiratory Journal (1997)

Chronic respiratory insufficiency (CRI) is associated with nocturnal hypoventilation. Treatment with noninvasive mechanical ventilation (NIMV) performed overnight relieves symptoms of hypoventilation and improves daytime blood gases in CRI. In order to test whether the efficacy of NIMV depends on it being applied during sleep, we conducted a prospective case-controlled study comparing daytime mechanical ventilation (dMV) in awake patients with nocturnal mechanical ventilation (nMV) given in equal quantities. We enrolled 34 clinically stable patients (age 56.1+/-12.1 yrs, 20 females, 14 males) with CRI due to restrictive lung and chest wall disorders and neuromuscular disease. Using a prospective case-control design, matched subjects were allocated alternately to dMV and nMV. After 1 month of NIMV there was considerable symptomatic improvement in both dMV and nMV patients. There were no significant differences between groups in the improvement in daytime arterial carbon dioxide tension (Pa,CO2) (dMV from 7.5+/-0.6 to 5.7+/-0.6 kPa; nMV from 7.2+/-0.5 to 5.8+/-0.5 kPa, p&lt;0.0001) and during the unassisted spontaneous night-time ventilation in terms of transcutaneous Pa,CO2 (dMV from 8.4+/-1.2 to 6.6+/-0.7 kPa; nMV from 8.2+/-1.2 to 6.8+/-0.5 kPa, p&lt;0.0001). We conclude that in many respects, when compared to nocturnal mechanical ventilation, daytime mechanical ventilation in awake patients is equally effective at reversing chronic respiratory insufficiency. Since long-term safety issues were not addressed in this study, we recommend that nocturnal mechanical ventilation should remain the modality of choice for noninvasive mechanical ventilation.
Detection of anti-listeriolysin O for serodiagnosis of human listeriosis
Authors: P. Berche, M. Bonnichon, J.L. Beretti, J. Raveneau, J.L. Gaillard, M. Veron, H. Kreis, K.A. Reich, P. Cossart, C. Geoffroy, P. Geslin
Journal: The Lancet (1990)
Phase II Study of Bevacizumab With Concurrent Capecitabine and Radiation Followed by Maintenance Gemcitabine and Bevacizumab for Locally Advanced Pancreatic Cancer: Radiation Therapy Oncology Group RTOG 0411
Authors: Christopher H. Crane, Kathryn Winter, William F. Regine, Howard Safran, Tyvin A. Rich, Walter Curran, Robert A. Wolff, Christopher G. Willett
Journal: Journal of Clinical Oncology (2009)

Purpose The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR). Patients and Methods Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m 2 orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m 2 weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA). Results Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05). Conclusion The addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials.
Impaired autophagy in mouse embryonic fibroblasts null for Krüppel-like Factor 4 promotes DNA damage and increases apoptosis upon serum starvation
Authors: Changchang Liu, Elise P DeRoo, Catherine Stecyk, Margaret Wolsey, Mateusz Szuchnicki, Engda G Hagos
Journal: Molecular Cancer (2015)

Autophagy is a major cellular process by which cytoplasmic components such as damaged organelles and misfolded proteins are recycled. Although low levels of autophagy occur in cells under basal conditions, certain cellular stresses including nutrient depletion, DNA damage, and oxidative stress are known to robustly induce autophagy. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor activated during oxidative stress to maintain genomic stability. Both autophagy and KLF4 play important roles in response to stress and function in tumor suppression. To explore the role of KLF4 on autophagy in mouse embryonic fibroblasts (MEFs), we compared wild-type with Klf4 deficient cells. To determine the levels of autophagy, we starved MEFs for different times with Earle’s balanced salts solution (EBSS). Rapamycin was used to manipulate mTOR activity and autophagy. The percentage of cells with γ-H2AX foci, a marker for DNA damage, and punctate pattern of GFP-LC3 were counted by confocal microscopy. The effects of the drug treatments, Klf4 overexpression, or Klf4 transient silencing on autophagy were analyzed using Western blot. Trypan Blue assay and flow cytometry were used to study cell viability and apoptosis, respectively. qPCR was also used to assay basal and the effects of Klf4 overexpression on Atg7 expression levels. Here our data suggested that Klf4 −/− MEFs exhibited impaired autophagy, which sensitized them to cell death under nutrient deprivation. Secondly, DNA damage in Klf4-null MEFs increased after treatment with EBSS and was correlated with increased apoptosis. Thirdly, we found that Klf4 −/− MEFs showed hyperactive mTOR activity. Furthermore, we demonstrated that rapamycin reduced the increased level of mTOR in Klf4 −/− MEFs, but did not restore the level of autophagy. Finally, re-expression of Klf4 in Klf4 deficient MEFs resulted in increased levels of LC3II, a marker for autophagy, and Atg7 expression level when compared to GFP-control transfected Klf4 −/− MEFs. Taken together, our results strongly suggest that KLF4 plays a critical role in the regulation of autophagy and suppression of mTOR activity. In addition, we showed that rapamycin decreased the level of mTOR in Klf4 −/− MEFs, but did not restore autophagy. This suggests that KLF4 regulates autophagy through both mTOR-dependent and independent mechanisms. Furthermore, for the first time, our findings provide novel insights into the mechanism by which KLF4 perhaps prevents DNA damage and apoptosis through activation of autophagy.
Antiserum to the cell surface of oral epithelial cells: relationship to pemphigus antiserum
Authors: D.R. WILLIAMS, E. BOLANOS, A.E. DOLBY
Journal: British Journal of Dermatology (1978)

Antisera to human oral epithelial cells were produced in rabbits and found to be specific for epithelial type cells of man, guinea-pig and rabbit. Binding of the antisera to human oral epithelial cells was not affected by pre-incubation in concanavalin A, trypsin or neuraminidase, nor by pre-incubation of the antisera with fetuin. The antisera would appear to differ from pemphigus antiserum.
In Search of the Emotional Self: An fMRI Study Using Positive and Negative Emotional Words
Authors: Philippe Fossati, Stephanie J Hevenor, Simon J Graham, Cheryl Grady, Michelle L Keightley, Fergus Craik, Helen Mayberg
Journal: American Journal of Psychiatry (2003)

The authors used functional magnetic resonance imaging (fMRI) to define the neural regions mediating self-referential processing of emotional stimuli and to explore how these regions are influenced by the emotional valence of the stimulus.Ten healthy subjects were presented with words describing positive and negative personality traits during fMRI scanning in three different conditions. In the self-referential processing condition, subjects judged whether they thought each trait described them. In the other-referential processing condition, subjects judged whether the stimulus described a generally desirable trait. In the letter-recognition control condition, subjects indicated whether the word contained a specific target letter.The self-referential condition induced bilateral activation in the dorsomedial prefrontal cortex, whereas the other-referential condition induced activation in lateral prefrontal areas. Activation in the right dorsomedial prefrontal cortex was unique to the self-referential condition regardless of the valence of the words, although positive words produced a more robust activation than did negative words. In the self-referential condition, differences between the processing of positive and negative words were seen in regions outside the medial frontal cortex, with reductions in the insula, temporal and occipital regions, and inferior parietal regions associated with negative words.A widely distributed network of brain areas contributes to emotional processing. Among these regions, the right dorsomedial prefrontal cortex is one main area mediating self-reference. By providing a personal perspective in the evaluation of emotional stimuli, the right dorsomedial prefrontal cortex may mediate cognitive processes, such as those involved in psychotherapy, that guide self-regulation of emotional experience.
A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes
Authors: Rossella De Cegli, Antonio Romito, Simona Iacobacci, Lei Mao, Mario Lauria, Anthony O Fedele, Joachim Klose, Christelle Borel, Patrick Descombes, Stylianos E Antonarakis, Diego di Bernardo, Sandro Banfi, Andrea Ballabio, Gilda Cobellis
Journal: Genome biology (2010)

Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21. To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis. We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders.
Attenuation of ecto-5'-nucleotidase activity and adenosine release in activated human polymorphonuclear leukocytes.
Authors: M Kitakaze, M Hori, T Morioka, S Takashima, T Minamino, H Sato, M Inoue, T Kamada
Journal: Circulation Research (1993)

To examine whether activation of polymorphonuclear leukocytes attenuates release of adenosine through attenuation of their own ecto-5'-nucleotidase activity, human polymorphonuclear leukocytes were incubated with and without exposure to either N-formyl-methionyl-leucyl-phenylalanine (FMLP) or complement C5a. Ecto-5'-nucleotidase activity of polymorphonuclear leukocytes was attenuated by both FMLP and complement C5a (22.7 +/- 3.6 vs 9.7 +/- 2.6 nmol/min per 10(7) cells at 10(-6) M FMLP, P &lt; .05; 21.5 +/- 2.2 vs 10.2 +/- 1.2 nmol/min per 10(7) cells at 5 x 10(-7) g/mL complement C5a, P &lt; .001), whereas cytosolic 5'-nucleotidase activity was not affected by either FMLP or complement C5a. These reductions of ecto-5'-nucleotidase activity that were caused by both FMLP and complement C5a were dose and time dependent and were inhibited by superoxide dismutase. Desferrioxamine did not inhibit the decreases in ecto-5'-nucleotidase. In accordance with the decreases in ecto-5'-nucleotidase activity, release of adenosine was attenuated in the FMLP-pretreated and complement C5a-pretreated polymorphonuclear leukocytes, which were restored by concomitant administration of superoxide dismutase. The viability of FMLP-pretreated and complement C5a-pretreated polymorphonuclear leukocytes was markedly decreased compared with the untreated group after 60 minutes of hypoxia followed by 60 minutes of reoxygenation. Thus, we conclude that: (1) activation of polymorphonuclear leukocytes attenuates their own ecto-5'-nucleotidase activity and thereby reduces adenosine release, (2) reduction of ecto-5'-nucleotidase activity is attributable to generated superoxide anion in polymorphonuclear leukocytes, and (3) viability of polymorphonuclear leukocytes after hypoxia and reoxygenation largely depends on the extents of decreases in ecto-5'-nucleotidase activity.
Treating Hypertension in Diabetic Nephropathy
Authors: Jeremy W. Tomlinson, Katharine R. Owen, Colin F. Close
Journal: Diabetes Care (2003)

OBJECTIVE—Control of hypertension in patients with diabetic nephropathy improves mortality and slows progression to end-stage renal disease. However, blood pressure is difficult to treat; multiple drug combination therapy is required and treatment algorithms to establish this are lacking. We used a stepped-care algorithm, centered on maximum doses of an ACE inhibitor or angiotensin II receptor blocker, to treat hypertension according to American Diabetes Association recommended blood pressure target goals (&amp;lt;130/80 mmHg) in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS—We treated 49 consecutive patients with diabetes (13 with type 1 and 36 with type 2), diabetic nephropathy, and proteinuria ≥500 mg/24 h with a stepped-care blood pressure treatment algorithm. The level of blood pressure control achieved at most recent follow-up was assessed. RESULTS—Patients were followed for a median of 18 months (range 9–48). Mean blood pressure achieved was 140/75 ± 23/14 mmHg in patients with type 1 diabetes and 146/76 ± 22/14 mmHg in patients with type 2 diabetes. Target blood pressure was reached in 16 (33%) patients, 6 of 13 patients with type 1 diabetes and 10 of 36 patients with type 2 diabetes, whereas systolic blood pressure remained above the target level in the remaining patients. There was no difference in baseline blood pressure, proteinuria, or serum creatinine level between patients who were treated to target and those who were not. CONCLUSIONS—Levels of blood pressure control similar to those achieved in clinical trials in diabetic nephropathy were obtained with a stepped-care algorithm. However, in most patients, systolic blood pressure was difficult to control to target despite the use of multiple drug combination therapy.
The EGFR-STAT3 Oncogenic Pathway Up-regulates the Eme1 Endonuclease to Reduce DNA Damage after Topoisomerase I Inhibition
Authors: Arnaud Vigneron, Erick Gamelin, Olivier Coqueret
Journal: Cancer Research (2008)

Abstract The epidermal growth factor receptor (EGFR)-src-signal transducers and activators of transcription 3 (STAT3) oncogenic pathway plays a central role in tumorigenesis and is involved not only in cell transformation but also in tumor escape to genotoxic treatments. Despite its importance, the molecular mechanisms by which this signaling pathway induces resistance to DNA damage remain most of the time to be characterized. In this study, we show that the EGFR-src pathway is activated in response to topoisomerase I inhibition. After treatment, this signaling cascade induced the activation of STAT3 and the binding of the transcription factor to the promoter of the Eme1 gene. Eme1 is an endonuclease involved in the processing of DNA damage after topoisomerase I inhibition. These results suggest a model by which the STAT3-mediated activation of Eme1 prevents DNA damage and enhances cell survival in response to topoisomerase inhibition. This survival pathway was inhibited by a combined treatment with a src inhibitor, SKI, and with cetuximab, a monoclonal antibody directed against the EGFR that is widely used in the treatment of colorectal cancers. We therefore propose that the benefit of anti-EGFR therapy relies on an increase of DNA damage generated by topoisomerase I inhibition. [Cancer Res 2008;68(3):815–25]
Congenital dyserythropoietic anemia type III associated with congenital atrioseptal defect has led to severe cardiac problems in a 32-year-old patient
Authors: G. R�hrig, H. Kilter, D. Beuckelmann, A. Kr�ner, C. Scheid, V. Diehl, D. S�hngen
Journal: American Journal of Hematology (2000)

We report the case of a 32-year-old woman who was admitted at hospital because of ortho-dyspnea, arrhythmia, and paleness. Clinical examination showed continuous arrhythmia, systolic heart murmur, enlargement of spleen and liver, and pathologic hematological parameters, thus indicating an intravasal hemolysis (elevated HBDH, bilirubin, and reticulocytes; reduced hemoglobin and haptoglobin levels), and bone-marrow-smears showed a typical cytomorphology of CDA III. The patient's diagnosis was heart failure caused by mitral valve insufficiency due to congenital atrioseptal defect associated with congenital dyserythropoietic anemia type III (CDA III). Am. J. Hematol 64:314–316, 2000. © 2000 Wiley-Liss, Inc.
Let-7g targets collagen type I α2 and inhibits cell migration in hepatocellular carcinoma
Authors: Junfang Ji, Lei Zhao, Anuradha Budhu, Marshonna Forgues, Hu-Liang Jia, Lun-Xiu Qin, Qing-Hai Ye, Jinming Yu, Xuetao Shi, Zhao-You Tang, Xin Wei Wang
Journal: Journal of Hepatology (2010)
AKT Inhibition Relieves Feedback Suppression of Receptor Tyrosine Kinase Expression and Activity
Authors: Sarat Chandarlapaty, Ayana Sawai, Maurizio Scaltriti, Vanessa Rodrik-Outmezguine, Olivera Grbovic-Huezo, Violeta Serra, Pradip K. Majumder, Jose Baselga, Neal Rosen
Journal: Cancer Cell (2011)
Survival following gastrostomy insertion: are there differences in mortality according to referral indication?
Authors: M. Kurien, J. S. Leeds, H. E. Robson, G. James, B. Hoeroldt, K. Dear, K. Kapur, J. Grant, M. E. McAlindon, D. S. Sanders
Journal: Gut (2011)

<h3>Introduction</h3> Previous studies have demonstrated that certain subgroups of patients have a worse prognosis following gastrostomy insertion (e.g., Dementia). However, these studies have often been retrospective and sample sizes have been small. We wished to examine survival following gastrostomy insertion with particular reference to the referral indication. <h3>Methods</h3> Gastrostomy insertions were examined from six hospitals in South Yorkshire and Derbyshire between January 2004 and September 2010. Data was collected prospectively from two centres (n = 1004) and from four centres retrospectively (n = 679). Age, gender, referral indication, comorbidity, biochemical profile and whether they were alive at 30 days was recorded for each case. Referral indication was divided into five subcategories; dysphagic stroke, neurological, nasopharyngeal cancer, cognitive impairment and other. Analysis for factors associated with death at 30 days was performed. <h3>Results</h3> 1651 patients were included in the study and the lowest 30-day mortality was found in the nasopharyngeal cancer cohort at 36/568 (6.3%). With respect to the other referral indications, 30-day mortality was 2/14 (14.3%, OR 2.5, 0.5–11.4, p = ns) in cognitive impairment, 91/488 (18.6%, OR 3.4, 2.3–5.1, p &lt; 0.001) in dysphagic stroke, 36/324 (11.1%, OR 1.8, 1.1–3.0, p = 0.012) in neurological disease and 28/257 (10.9%, OR1.8, 1.1–3.0, p = 0.024) in the other category. Mortality at 30 days was also associated with increasing age &gt;60 (OR 3.1, 2.1–4.6, p &lt; 0.001), reducing serum albumin (p &lt; 0.001), cardiac comorbidity (OR 2.1, 1.3–3.4, p = 0.0023), renal comorbidity (OR 2.1, 1.3–3.4, p = 0.004) and intercurrent infection (OR 3.0, 1.7–5.1, p &lt; 0.001). At multivariate analysis only age and albumin were independent predictors of death at 30 days (both p &lt; 0.01). <h3>Conclusion</h3> This is the largest UK dataset to assess outcomes following gastrostomy insertion. Indication for gastrostomy does have a bearing on mortality at 30 days with the lowest rates being found in patients with nasopharyngeal cancer. Our observations regarding mortality in these subgroups may be informative for clinicians, patients and relatives when making decisions around gastrostomy insertion.
Immunohistochemical detection of the c-met proto-oncogene product in the congenital melanocytic nevus of an infant with neurocutaneous melanosis
Authors: Hisashi Takayama, Yoji Nagashima, Masamichi Hara, Hitoshi Takagi, Masatomo Mori, Glenn Merlino, Yoichi Nakazato
Journal: Journal of the American Academy of Dermatology (2001)
Interaction of Imatinib with Human Organic Ion Carriers
Authors: Shuiying Hu, Ryan M. Franke, Kelly K. Filipski, Chaoxin Hu, Shelley J. Orwick, Ernst A. de Bruijn, Herman Burger, Sharyn D. Baker, Alex Sparreboom
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The activity of imatinib in leukemia has recently been linked with expression of the organic cation transporter 1 (OCT1) gene SLC22A1. Here, we characterized the contribution of solute carriers to imatinib transport in an effort to further understand mechanisms involved in the intracellular uptake and retention (IUR) of the drug. Experimental Design: IUR of [3H]imatinib was studied in Xenopus laevis oocytes and HEK293 cells expressing OATP1A2, OATP1B1, OATP1B3, OCT1-3, OCTN1-2, or OAT1-3. Gene expression was determined in nine leukemia cell lines using the Affymetrix U133 array. Results: Imatinib was not found to be a substrate for OCT1 in oocytes (P = 0.21), whereas in HEK293 cells IUR was increased by only 1.20-fold relative to control cells (P = 0.002). Furthermore, in 74 cancer patients, the oral clearance of imatinib was not significantly altered in individuals carrying reduced-function variants in SLC22A1 (P = 0.99). Microarray analysis indicated that SLC22A1 was interrelated with gene expression of various transporters, including ABCB1, ABCC4, ABCG2 (negative), and OATP1A2 (positive). Imatinib was confirmed to be a substrate for the three efflux transporters (P &amp;lt; 0.05) as well as for OATP1A2 (P = 0.0001). Conclusions: This study suggests that SLC22A1 expression is a composite surrogate for expression of various transporters relevant to imatinib IUR. This observation provides a mechanistic explanation for previous studies that have linked SLC22A1 with the antitumor activity of imatinib. Because of its high expression in the intestine, ciliary body, gliomas, and leukemia cells, OATP1A2 may play a key role in imatinib pharmacokinetics-pharmacodynamics.