tbuckley/cabot-search huggingface dataset:
Unsupervised self-testing of airway obstruction by forced oscillation at the patient's home
Authors: J. Rigau, F. Burgos, C. Hernández, J. Roca, D. Navajas, R. Farré
Journal: European Respiratory Journal (2003)

As active patient cooperation is not required, the forced oscillation technique (FOT) could be suitable for measuring airway obstruction in routine home applications. Nevertheless, FOT has never been used at the patient's home to date. The aim of this study was to assess the feasibility of FOT and the reproducibility of measured respiratory resistance ( R rs ) in routine patient self-testing at home. Altogether, nine asthmatic patients self-measured their R rs with a portable FOT device and spirometry for 10–14 days, in the morning and evening, and before and after bronchodilator inhalation. During each measurement session, the patients carried out four consecutive FOT measurements. Grubbs' discordancy test for detecting outliers was used to evaluate intermeasure reliability. Only 4.9% of R rs data reported by patients were rejected as artefacts. The coefficient of variation of R rs was 7.9±6.3% (mean±sd). When compared with spirometry, the per cent change in R rs for detecting a positive bronchodilator response showed an 83% sensitivity and 72% specificity. Unsupervised self-measurement of respiratory resistance at the patient's home provided results similar to those obtained by a technician in a lung function lab. Forced oscillation technique could be a useful tool for the routine follow-up of asthmatic patients at home.
Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial
Authors: H. Saito, H. Yoshizawa, K. Yoshimori, N. Katakami, N. Katsumata, M. Kawahara, K. Eguchi
Journal: Annals of Oncology (2012)

We evaluated the efficacy and safety of single-dose fosaprepitant in combination with intravenous granisetron and dexamethasone.Patients receiving chemotherapy including cisplatin (≥70 mg/m(2)) were eligible. A total of 347 patients (21% had received cisplatin with vomiting) were enrolled in this trial to receive the fosaprepitant regimen (fosaprepitant 150 mg, intravenous, on day 1 in combination with granisetron, 40 μg/kg, intravenous, on day 1 and dexamethasone, intravenous, on days 1-3) or the control regimen (placebo plus intravenous granisetron and dexamethasone). The primary end point was the percentage of patients who had a complete response (no emesis and no rescue therapy) over the entire treatment course (0-120 h).The percentage of patients with a complete response was significantly higher in the fosaprepitant group than in the control group (64% versus 47%, P = 0.0015). The fosaprepitant regimen was more effective than the control regimen in both the acute (0-24 h postchemotherapy) phase (94% versus 81%, P = 0.0006) and the delayed (24-120 h postchemotherapy) phase (65% versus 49%, P = 0.0025).Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin.
Transforming Growth Factor-β1 and CD105 Promote the Migration of Hepatocellular Carcinoma–Derived Endothelium
Authors: Anna Benetti, Angiola Berenzi, Marco Gambarotti, Emirena Garrafa, Maurizio Gelati, Enrico Dessy, Nazario Portolani, Tullio Piardi, Stefano Maria Giulini, Arnaldo Caruso, Gloria Invernici, Eugenio Agostino Parati, Roberto Nicosia, Giulio Alessandri
Journal: Cancer Research (2008)

Abstract Hepatocellular carcinoma (HCC) is one of most malignant and aggressive human tumors. Transforming growth factor-β1 (TGF-β1) and its coreceptor CD105 have been shown to contribute to HCC malignant progression. TGF-β1 and CD105 have also been implicated in angiogenesis, but their role in the vascularization of HCC has not been investigated. To fill this gap, we studied the effect of TGF-β1 and CD105 on HCC-derived endothelium. By using immunomagnetic beads, we isolated and cultured endothelial cells (ECs) from HCC (HCC-EC) and adjacent nonneoplastic tissue (nNL-ECs) obtained from 24 liver biopsies. HCC and nNL biopsies were also analyzed by immunohistochemistry for the expression of CD105, TGF-β1, Ve-cadherin (Ve-cad), CD44, β-catenin, and E-cadherin. Compared with nNL-ECs, HCC-ECs had higher expression of CD105, enhanced spontaneous motility, and greater capacity to migrate in response to TGF-β1 (5 ng/mL), particularly in the presence of a fibronectin matrix. The chemotactic effect of TGF-β1 was blocked by anti-CD105 antibodies and correlated with the grade of HCC malignancy. Histologic examination of HCC biopsies showed that HCCs with the worse malignant features had the highest expression of TGF-β1, CD105, and angiogenic markers (Ve-cad and CD44). Because CD105 was highly expressed in microvessels at the tumor periphery and TGF-β1 staining was only found in neoplastic hepatocytes, we conclude that HCC-derived TGF-β1 may act as a chemoattractant for CD105-expressing ECs and as a promoter of tumor angiogenesis. Thus, drugs that selectively target the TGF-β1/CD105 axis may interfere with HCC-related angiogenesis and HCC progression. [Cancer Res 2008;68(20):8626–34]
Effects of dietary fish oil on lung phospholipid fatty acid composition and intrinsic pulmonary vascular reactivity
Authors: S. ARCHER, D. NELSON, R. GEBHARD, A. S LEVINE, W. PRIGGE, E K. WEIR
Journal: Cardiovascular Research (1987)

A fish oil diet has been shown to lower systemic blood pressure in man and alter vascular reactivity to exogenous noradrenaline in man and rats. The effects of a fish oil diet on the vascular reactivity of the pulmonary circulation have not been assessed. The effect of dietary lipid composition on pulmonary artery pressure and vascular reactivity of 30 adult male Sprague-Dawley rats (250-300 g) was assessed in vivo (n = 9) and in the isolated perfused lung (n = 21). Isocaloric diets containing 20% lipid (% by weight) as fish oil, corn oil, or lard were given in unlimited quantities to the rats. After one month of the diet, pulmonary vascular reactivity to angiotensin II (0.15 micrograms) and hypoxia (fractional inspired oxygen 0.025) were assessed in the isolated perfused rat lung. The haemodynamic effects of the diet on resting normoxic pulmonary artery pressure (in vivo) were assessed in chloralose anaesthetised rats. The fish oil diet appreciably increased the content of eicosapentaenoic acid (C20:5) and docosahexaenoic acid (C22:6) in lung phospholipids but had no effect on pulmonary vascular reactivity. The arachidonic acid (C20:4) content of the lung was considerably decreased. Platelet counts were lower in the rats fed fish oil. The study indicates that a fish oil diet does not alter acute intrinsic pulmonary vascular reactivity despite pronounced changes in lung phospholipid fatty acid profile.
iVAPS (intelligent volume assured pressure support) for non-invasive ventilation - a case-control study
Authors: Christian M. Horvath, Martin H. Brutsche, Florent Baty, Jochen J. Rüdiger
Journal: European Respiratory Journal (2014)

Background   iVAPS is a recent mode of non-invasive ventilation (NIV) developed by ResMed Ltd, Bella Vista, Australia, which relies on applying an alveolar target volume and adjusts pressure and respiratory rate automatically to achieve optimal ventilatory support. Whether iVAPS leads to a better outcome over classical NIV adaptation (cNIV) is uncertain.    Methods and Setting   We performed a retrospective case-control study. Primary endpoint was daily usage and value of paCO 2  on the first follow up (usually within 90 days after discharge). Patients were included if admitted between 01.01.2012 and 31.01.2014 using a Stellar (100 or 150, ResMed) or a VPAP ST (ResMed) machine. We identified 57 patients, 18 patients with iVAPS and 39 patients with CNIV. Patients were then matched 1:1 for age (± 10 years) and diagnoses. We defined 4 groups: (1) neuromuscular, (2) COPD, (3) COPD and obesity overlap, and (4) sleep apnea and obesity hypoventilation.    Results   Overall usage was not different either in %-daily usage (iVAPS vs cNIV 97 (87-100), 94 (77-100); p=0.44) or min/day (443 (310-479) vs (242-471); p=0.62). HCO3 -  was similar between iVAPS and cNIV (27.0 (25.9-27.0) mmol/L vs. 28.45 (24.95-31.10) mmol/L; p=0.61). There was a trend towards a lower paCO 2  in the iVAPS group (5.53 (5.12-5.99) kPa vs 6.20 (5.35-6.39) kPa; p=0.11). Subgroup analysis revealed statistical significant improvement in groups 3 and 4: 6.29 (6.20-7.10) kPa vs 5.45 (5.24-5.78) kPa (pl0.05), 6.80 (6.65-8.35) kPa (pl0.05) vs 5.12 (4.95-5.30) kPa.   Conclusion   Our case-control study indicates that iVAPS mode is not inferior to cNIV, in obese patients iVAPS reduced paCO 2 -levels to a larger extent than cNIV at the first follow-up.
High Phospho-Stathmin(Serine38) Expression Identifies Aggressive Endometrial Cancer and Suggests an Association with PI3K Inhibition
Authors: Elisabeth Wik, Even Birkeland, Jone Trovik, Henrica M.J. Werner, Erling A. Hoivik, Siv Mjos, Camilla Krakstad, Kanthida Kusonmano, Karen Mauland, Ingunn M. Stefansson, Frederik Holst, Kjell Petersen, Anne M. Oyan, Ronald Simon, Karl H. Kalland, William Ricketts, Lars A. Akslen, Helga B. Salvesen
Journal: Clinical Cancer Research (2013)

High Stathmin expression has recently been associated with clinical progress in endometrial cancers. Stathmin protein activity is modulated by phosphorylation, and the Serine38 site is one of four Stathmin phospho-sites. The presence and significance of pStathmin(S38) is largely unknown in human cancers, and we here examined the associations between this marker and tumor cell proliferation, clinicopathologic phenotype, and survival impact in endometrial cancer. A relationship with possible treatment targets was explored by integrated analysis of transcriptional alterations.Primary endometrial cancers from two independent patient series (n = 518/n = 286) were analyzed. Biomarkers were assessed by immunohistochemistry, FISH, flow cytometry, DNA oligonucleotide microarray, single-nucleotide polymorphism array, and Sanger sequencing, and related to clinicopathologic annotations and follow-up information.High pStathmin(S38) level was associated with poor prognosis, independent of other features, and correlated to increased tumor cell proliferation as well as high Stathmin levels. On the basis of transcriptional differences between high/low pStathmin(S38) tumors, phosphoinositide 3-kinase (PI3K)/mTOR/HSP90 were suggested as possible targets in pStathmin(S38)-high cases. High pStathmin(S38) was associated with several PI3K pathway alterations: amplification of the 3q26 region, increased PIK3CA copy number (FISH) and a PI3K activation score (all P < 0.05).High pStathmin(S38) is a novel biomarker of increased tumor cell proliferation and impaired prognosis as reported here for independent cohorts of endometrial cancer and not previously shown in human cancer. Our data support a rationale for further studies exploring effects of drugs inhibiting the PI3K signaling pathway in pStathmin(S38)-high endometrial cancer, including a potential value of pStathmin(S38) in predicting response to PI3K/mTOR/HSP90 inhibitors.
Phytoestrogen Supplements for the Treatment of Hot Flashes: The Isoflavone Clover Extract (ICE) Study
Authors: Jeffrey A. Tice, Bruce Ettinger, Kris Ensrud, Robert Wallace, Terri Blackwell, Steven R. Cummings
Journal: JAMA (2003)

Clinical trials demonstrating increased risk of cardiovascular disease and breast cancer among women randomized to hormone replacement therapy have increased interest in other therapies for menopausal symptoms. Dietary supplements containing isoflavones are widely used as alternatives to hormonal therapies for hot flashes, but there is a paucity of data supporting their efficacy.To compare the efficacy and safety of 2 dietary supplements derived from red clover with placebo in symptomatic menopausal women.Randomized, double-blind, placebo-controlled trial of menopausal women, aged 45 to 60 years, who were experiencing at least 35 hot flashes per week. The study was conducted between November 1999 and March 2001 at 3 US medical centers and included women who were recently postmenopausal (mean [SD], 3.3 [4.5] years since menopause) experiencing 8.1 hot flashes per day. Women were excluded if they were vegetarians, consumed soy products more than once per week, or took medications affecting isoflavone absorption.After a 2-week placebo run-in, 252 participants were randomly assigned to Promensil (82 mg of total isoflavones per day), Rimostil (57 mg of total isoflavones per day), or an identical placebo, and followed-up for 12 weeks.The primary outcome measure was the change in frequency of hot flashes measured by participant daily diaries. Secondary outcome measures included changes in quality of life and adverse events.Of 252 participants, 246 (98%) completed the 12-week protocol. The reductions in mean daily hot flash count at 12 weeks were similar for the Promensil (5.1), Rimostil (5.4), and placebo (5.0) groups. In comparison with the placebo group, participants in the Promensil group (41%; 95% confidence interval [CI], 29%-51%; P =.03), but not in the Rimostil group (34%; 95% CI, 22%-46%; P =.74) reduced hot flashes more rapidly. Quality-of-life improvements and adverse events were comparable in the 3 groups.Although the study provides some evidence for a biological effect of Promensil, neither supplement had a clinically important effect on hot flashes or other symptoms of menopause.
Aberrant RNA Processing in a Neurodegenerative Disease: the Cause for Absent EAAT2, a Glutamate Transporter, in Amyotrophic Lateral Sclerosis
Authors: Chien-Liang Glenn Lin, Lynn A. Bristol, Lin Jin, Margaret Dykes-Hoberg, Thomas Crawford, Lora Clawson, Jeffrey D. Rothstein
Journal: Neuron (1998)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by selective upper and lower motor neuron degeneration, the pathogenesis of which is unknown. About 60%–70% of sporadic ALS patients have a 30%–95% loss of the astroglial glutamate transporter EAAT2 (excitatory amino acid transporter 2) protein in motor cortex and spinal cord. Loss of EAAT2 leads to increased extracellular glutamate and excitotoxic neuronal degeneration. Multiple abnormal EAAT2 mRNAs, including intron-retention and exon-skipping, have now been identified from the affected areas of ALS patients. The aberrant mRNAs were highly abundant and were found only in neuropathologically affected areas of ALS patients but not in other brain regions. They were found in 65% of sporadic ALS patients but were not found in nonneurologic disease or other disease controls. They were also detectable in the cerebrospinal fluid (CSF) of living ALS patients, early in the disease. In vitro expression studies suggest that proteins translated from these aberrant mRNAs may undergo rapid degradation and/or produce a dominant negative effect on normal EAAT2 resulting in loss of protein and activity. These findings suggest that the loss of EAAT2 in ALS is due to aberrant mRNA and that these aberrant mRNAs could result from RNA processing errors. Aberrant RNA processing could be important in the pathophysiology of neurodegenerative disease and in excitotoxicity. The presence of these mRNA species in ALS CSF may have diagnostic utility.
Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells
Authors: Sammy Bedoui, Paul G Whitney, Jason Waithman, Liv Eidsmo, Linda Wakim, Irina Caminschi, Rhys S Allan, Magdalena Wojtasiak, Ken Shortman, Francis R Carbone, Andrew G Brooks, William R Heath
Journal: Nature Immunology (2009)
Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing
Authors: Amy D. Klion, Jamie Robyn, Irina Maric, Weiming Fu, Laura Schmid, Steven Lemery, Pierre Noel, Melissa A. Law, Marilyn Hartsell, Cheryl Talar-Williams, Michael P. Fay, Cynthia E. Dunbar, Thomas B. Nutman
Journal: Blood (2007)
Akt Stimulates Aerobic Glycolysis in Cancer Cells
Authors: Rebecca L. Elstrom, Daniel E. Bauer, Monica Buzzai, Robyn Karnauskas, Marian H. Harris, David R. Plas, Hongming Zhuang, Ryan M. Cinalli, Abass Alavi, Charles M. Rudin, Craig B. Thompson
Journal: Cancer Research (2004)

Abstract Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival.
Patient and graft survival after liver transplantation for hereditary hemochromatosis: Implications for pathogenesis
Authors: Darrell H.G. Crawford, Linda M. Fletcher, Stefan G. Hubscher, Katherine A. Stuart, Edward Gane, Peter W. Angus, Gary P. Jeffrey, Geoffrey W. McCaughan, Paul Kerlin, Lawrie W. Powell, Elwyn E. Elias
Journal: Hepatology (2004)

The clinical outcome of patients who have undergone liver transplantation for hereditary hemochromatosis (HH) or who have received iron-loaded donor grafts is unclear. We reviewed 3,600 adult primary orthotopic liver transplants and assessed the outcomes in 22 patients with HH. We also evaluated graft function and iron mobilization in 12 recipients of iron-loaded donor grafts. All 22 subjects who received liver transplants for HH were male; 13 had other risk factors for liver disease. HH patients had comparatively poor outcomes following transplantation: survival at 1, 3, and 5 years posttransplantation were 72%, 62%, and 55%, respectively. Recurrent hepatocellular cancer was the most common cause of death. There was no convincing evidence of reaccumulation of iron in the grafted liver in HH; however, 1 subject demonstrated increased serum ferritin concentration and grade 2 hepatic siderosis. Liver iron stores were slow to mobilize in 7 of the 12 recipients of iron-loaded grafts. These recipients had appropriate early graft function, but 2 patients with heavy iron loading and increased hepatic iron developed hepatic fibrosis. In conclusion, (1) HH is an uncommon indication for liver transplantation, and the majority of patients requiring transplantation had other risk factors for chronic liver disease; (2) reaccumulation of liver iron in HH patients is very unusual, but increased iron stores may be slow to mobilize in normal recipients of iron-loaded grafts, potentially compromising late graft function; (3) post-liver transplant survival is reduced in HH, and affected patients require careful clinical evaluation of perioperative and postoperative risk factors. Our data suggest that iron excess in HH does not wholly depend on intestinal iron absorption but is also influenced by liver factors that moderate iron metabolism.
Immunosuppressive Effects of Ultraviolet (280–320 nm) Radiation and Psoralen Plus Ultraviolet (320–400 nm) Radiation in Mice&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Margaret L. Kripke
Journal: JNCI Journal of the National Cancer Institute (1982)

Contact hypersensitivity (CHS), a cell-mediated immunologic reaction, can be induced in mice by application of a contact-sensitizing chemical to the shaved skin. Exposing the animals to UV radiation from FS40 sunlamps inhibits this immune response. This inhibition is systemic, since the sensitizer need not be applied to the irradiated site of the animal. The mechanism whereby UV radiation prevents CHS appears to involve the production of suppressor T-lymphocytes. Recent evidence suggests that UV exposure of mice alters the way in which certain antigens are processed, and this altered processing or presentation of antigen results in the activation of the suppressor cell pathway, rather than leading to immunization. Treatment of mice with a photosensitizer, psoralen, plus UV (320–400 nm) radiation also suppresses CHS systemically, but whether the cellular mechanisms are the same as those underlying the suppression from the shorter UV wavelengths remains to be determined. The possible role of these immunosuppressive events in photocarcinogenesis is discussed.
Clinical impact of copy number variation analysis using high-resolution microarray technologies: advantages, limitations and concerns
Authors: Curtis R Coughlin, Gunter H Scharer, Tamim H Shaikh
Journal: Genome Medicine (2012)

Copy number variation (CNV) analysis has had a major impact on the field of medical genetics, providing a mechanism to identify disease-causing genomic alterations in an unprecedented number of diseases and phenotypes. CNV analysis is now routinely used in the clinical diagnostic laboratory, and has led to a significant increase in the detection of chromosomal abnormalities. These findings are used for prenatal decision making, clinical management and genetic counseling. Although a powerful tool to identify genomic alterations, CNV analysis may also result in the detection of genomic alterations that have unknown clinical significance or reveal unintended information. This highlights the importance of informed consent and genetic counseling for clinical CNV analysis. This review examines the advantages and limitations of CNV discovery in the clinical diagnostic laboratory, as well as the impact on the clinician and family.
Novel insights into immune and inflammatory responses to respiratory viruses
Authors: Jürgen Schwarze, Karen J Mackenzie
Journal: Thorax (2012)

Viral lower respiratory tract infection (LRTI) can lead to severe disease at all ages, but with the exception of influenza vaccination, prevention is not available for most respiratory viruses, hence, effective, disease-limiting therapy is urgently required. To enable the development of novel effective therapeutic approaches, we need to improve understanding of the pathological mechanisms of viral LRTI. Here, we will discuss recently gained new insight into early, innate immune and inflammatory responses to respiratory viruses by airway epithelial cells and mucosal immune cells. Following virus recognition, these cells generate a range of mediators, including innate interferons, proinflammatory cytokines, and growth and differentiation factors which have pivotal roles in effective virus control, and the development of inflammation and disease in viral LRTI.