tbuckley/cabot-search huggingface dataset:
Phylogenetic data bearing on the REM sleep learning connection
Authors: J. M. Siegel
Journal: Behavioral and Brain Sciences (2000)

The phylogenetic data are inconsistent with the hypothesis that REM sleep duration is correlated with learning or learning ability. Humans do not have uniquely high amounts of REM sleep. The platypus, marsupials, and other mammals not generally thought to have extraordinary learning abilities have the largest amounts of REM sleep. The whales and dolphins (cetaceans) have the lowest amounts of REM sleep and may go without REM sleep for extended periods of time, despite their prodigious learning abilities. [Vertes & Eastman, 2000].
High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis
Authors: Tarun Kewalramani, Andrew D. Zelenetz, Eric E. Hedrick, Gerard B. Donnelly, Sonia Hunte, Anna C. Priovolos, Jing Qin, Nancy Coady Lyons, Joachim Yahalom, Stephen D. Nimer, Craig H. Moskowitz
Journal: Blood (2000)
Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis
Authors: Richard B. Moss
Journal: European Respiratory Journal (2013)

Severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis encompass two closely related subgroups of patients with severe allergic asthma. Pulmonary disease is due to pronounced host inflammatory responses to noninvasive subclinical endobronchial infection with filamentous fungi, usually Aspergillus fumigatus . These patients usually do not achieve satisfactory disease control with conventional treatment of severe asthma, i.e. high-dose inhaled corticosteroids and long-acting bronchodilators. Although prolonged systemic corticosteroids are effective, they carry a substantial toxicity profile. Supplementary or alternative therapies have primarily focused on use of antifungal agents including oral triazoles and inhaled amphotericin B. Immunomodulation with omalizumab, a humanised anti-IgE monoclonal antibody, or "pulse" monthly high-dose intravenous corticosteroid, has also been employed. This article considers the experience with these approaches, with emphasis on recent clinical trials.
Transcriptional Blocks Limit Adenoviral Replication in Primary Ovarian Tumor
Authors: Meredith A. Preuss, John T. Lam, Minghui Wang, Charles A. Leath, Manjula Kataram, Parameshwar J. Mahasreshti, Ronald D. Alvarez, David T. Curiel
Journal: Clinical Cancer Research (2004)

Despite the success of conditionally replicating adenoviruses in tumor models, clinical success has been limited when they are used as a single modality agent. Overcoming the disparity in efficacy between in vivo animal models and human use is a key hurdle for better conditionally replicating adenovirus therapy in humans. We endeavored to identify biological blocks to adenoviral infection and replication in tumor cells.We hypothesized that the differences in adenoviral replication between ovarian cancer cell lines and patient tumor samples are the result of a block in viral RNA transcription. To test this hypothesis, established ovarian cancer cell lines and purified patient ovarian cancer cells were infected with wild-type adenovirus. RNA for early adenoviral genes E1A and E1B as well as the late transcripts for fiber and hexon were measured using real-time PCR.Established ovarian cancer cell lines treated with wild-type virus had a lower E1A:E1B ratio than the patient samples. Additionally, the levels of fiber and hexon relative to E1A were also decreased in the patient samples compared with the established cell lines. These findings were consistent with an early- to late-phase block in the adenovirus replication cycle.These data suggest that the biology of abortive infection in the patient samples may be linked to a defect in the production of early and late viral transcripts. Identification of factors leading to abortive infection will be crucial to understanding the low viral replication in patient samples.
Acetylation Suppresses the Proapoptotic Activity of GD3 Ganglioside
Authors: Florence Malisan, Luigi Franchi, Barbara Tomassini, Natascia Ventura, Ivano Condò, Maria Rita Rippo, Alessandra Rufini, Laura Liberati, Claudia Nachtigall, Bernhard Kniep, Roberto Testi
Journal: The Journal of Experimental Medicine (2002)

GD3 synthase is rapidly activated in different cell types after specific apoptotic stimuli. De novo synthesized GD3 accumulates and contributes to the apoptotic program by relocating to mitochondrial membranes and inducing the release of apoptogenic factors. We found that sialic acid acetylation suppresses the proapoptotic activity of GD3. In fact, unlike GD3, 9-O-acetyl-GD3 is completely ineffective in inducing cytochrome c release and caspase-9 activation on isolated mitochondria and fails to induce the collapse of mitochondrial transmembrane potential and cellular apoptosis. Moreover, cells which are resistant to the overexpression of the GD3 synthase, actively convert de novo synthesized GD3 to 9-O-acetyl-GD3. The coexpression of GD3 synthase with a viral 9-O-acetyl esterase, which prevents 9-O-acetyl-GD3 accumulation, reconstitutes GD3 responsiveness and apoptosis. Finally, the expression of the 9-O-acetyl esterase is sufficient to induce apoptosis of glioblastomas which express high levels of 9-O-acetyl-GD3. Thus, sialic acid acetylation critically controls the proapoptotic activity of GD3.
Organising unrestricted open access gastroscopy in South Tees.
Authors: M G Bramble, W M Cooke, W A Corbett, P A Cann, D Clarke, B Contractor, A S Hungin
Journal: Gut (1993)

Increasing demand for upper gastrointestinal endoscopy has forced many clinicians to reconsider the policy of seeing all patients in a specialist clinic before gastroscopy. The following are considered essential in setting up an open access gastroscopy service. (1) Assessment of the need by examination of waiting times for the outpatient clinic and the proportion of patients requiring upper gastrointestinal endoscopy, and consultation with colleagues in general practice. During the first 2 years of the service the average waiting time for a medical gastrointestinal outpatient appointment has fallen from over 120 days to 37 days in this area. (2) An adequately staffed and equipped gastrointestinal unit with well motivated nurses (the workload will increase) and sufficient clinical support to allocate patients to the next available gastroscopy list is vital. A safe mechanism for relaying information back to the GP (including histology reports) is essential otherwise medicolegal problems could arise. Open access gastroscopy now accounts for 29% of the total endoscopy workload in South Tees. (3) Close cooperation between medical and surgical gastroenterologists must be achieved to ensure a uniform approach to the provision of this service and equal distribution of the endoscopy workload. This will require close examination of the potential numbers and may necessitate appointment of a clinical assistant or additional consultant. Clinical assistants perform just over 50% of the open access gastroscopies in South Tees and the waiting time has been kept short (average 17 days). (4) A comprehensive request form with guidelines for GPs and a specific box identifying whether the GP requires a report and brief advice only or follow up at the discretion of the endoscopist (often a clinical assistant) is required. (5) Management must be involved in identifying adequate resources. (6) Methods of monitoring requests and outcome measures to ensure effective audit must be established.
Induction Therapy for Poor-Prognosis Anal Canal Carcinoma: A Phase II Study of the Cancer and Leukemia Group B (CALGB 9281)
Authors: Neal J. Meropol, Donna Niedzwiecki, Brenda Shank, Thomas A. Colacchio, John Ellerton, Frank Valone, Susan Budinger, Jeannette M. Day, Judy Hopkins, Joel Tepper, Richard M. Goldberg, Robert J. Mayer
Journal: Journal of Clinical Oncology (2008)

Although most patients with anal canal cancer are cured with sphincter-preserving, nonsurgical, combined-modality therapy, those with large tumors and lymph node involvement have a poor prognosis. To establish the safety and efficacy of induction chemotherapy with infusional fluorouracil (FU) plus cisplatin followed by FU plus mitomycin C with concurrent radiation in patients with poor-prognosis squamous cell cancers of the anal canal.Patients with previously untreated anal canal cancers with T3 or T4 tumors and/or extensive nodal involvement (bulky N2 or N3) received two 28-day cycles of induction treatment with infusional FU plus cisplatin followed by two 28-day cycles of FU plus mitomycin C with concurrent split-course radiation. A third cycle of FU and cisplatin with radiation boost was given to patients with persistent primary site disease or bulky N2 or N3 disease at presentation.Forty-five assessable patients received protocol therapy. Treatment was generally well tolerated, and gastrointestinal and hematologic toxicities were the most common. Induction chemotherapy resulted in eight complete and 21 partial responses. After induction, combined-modality, and boost therapy, 37 (82%) of 45 assessable high-risk patients achieved a complete response. After 4 years of follow-up, 68% of patients are alive, 61% are disease-free, and 50% are colostomy- and disease-free.A combined-modality approach that includes induction treatment with FU and cisplatin followed by combined-modality therapy with FU, mitomycin C, and concurrent radiation results in long-term disease control in the majority of patients with poor-prognosis anal canal cancer.
IL-9 as a mediator of Th17-driven inflammatory disease
Authors: Elizabeth C. Nowak, Casey T. Weaver, Henrietta Turner, Sakhina Begum-Haque, Burkhard Becher, Bettina Schreiner, Anthony J. Coyle, Lloyd H. Kasper, Randolph J. Noelle
Journal: The Journal of Experimental Medicine (2009)

We report that like other T cells cultured in the presence of transforming growth factor (TGF) β, Th17 cells also produce interleukin (IL) 9. Th17 cells generated in vitro with IL-6 and TGF-β as well as purified ex vivo Th17 cells both produced IL-9. To determine if IL-9 has functional consequences in Th17-mediated inflammatory disease, we evaluated the role of IL-9 in the development and progression of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor deficiency attenuates disease, and this correlates with decreases in Th17 cells and IL-6–producing macrophages in the central nervous system, as well as mast cell numbers in the regional lymph nodes. Collectively, these data implicate IL-9 as a Th17-derived cytokine that can contribute to inflammatory disease.
Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas
Authors: Elise A. Chong, Tahamtan Ahmadi, Nicole A. Aqui, Jakub Svoboda, Sunita D. Nasta, Anthony R. Mato, Kristy M. Walsh, Stephen J. Schuster
Journal: Clinical Cancer Research (2015)

Lenalidomide, an immunomodulatory agent that enhances antibody-dependent cell-mediated cytotoxicity, has the potential to synergize with rituximab, an anti-CD20 mAb. We hypothesized that the addition of lenalidomide to rituximab would improve clinical outcomes in patients with B-cell lymphomas who were previously rituximab resistant, defined as no response to or progression of lymphoma within 6 months of rituximab-based therapy.We conducted a single-center, phase II trial in patients with indolent B-cell or mantle cell lymphomas who were previously rituximab resistant. Patients received 10 mg lenalidomide daily for 8 weeks, and then received four weekly doses of 375 mg/m(2) rituximab; lenalidomide continued during and after rituximab. Response to therapy was assessed after 8 weeks of lenalidomide and 12 weeks after first dose of rituximab. The primary endpoint was overall response rate (ORR) after lenalidomide and rituximab.Fifty patients were enrolled and 43 patients completed both response assessments. ORR after 8 weeks of lenalidomide was 30.2%; 12 weeks after the addition of rituximab to lenalidomide, ORR increased to 62.8% (N = 43). For all patients (N = 50), median progression-free survival (PFS) is 22.2 months (median follow-up, 39.2 months). PFS after lenalidomide-rituximab was significantly longer than the PFS for the antecedent regimen used to define rituximab resistance (22.2 vs. 9.13 months, P = 0.0004).This trial is the first to show that the combination of lenalidomide and rituximab overcomes prior rituximab resistance in patients with indolent B-cell and mantle cell lymphomas.
RETRACTED: A New Class of Quinoline-Based DNA Hypomethylating Agents Reactivates Tumor Suppressor Genes by Blocking DNA Methyltransferase 1 Activity and Inducing Its Degradation
Authors: Jharna Datta, Kalpana Ghoshal, William A. Denny, Swarna A. Gamage, Darby G. Brooke, Pasit Phiasivongsa, Sanjeev Redkar, Samson T. Jacob
Journal: Cancer Research (2009)

Abstract Reactivation of silenced tumor suppressor genes by 5-azacytidine (Vidaza) and its congener 5-aza-2′-deoxycytidine (decitabine) has provided an alternate approach to cancer therapy. We have shown previously that these drugs selectively and rapidly induce degradation of the maintenance DNA methyltransferase (DNMT) 1 by a proteasomal pathway. Because the toxicity of these compounds is largely due to their incorporation into DNA, it is critical to explore novel, nonnucleoside compounds that can effectively reactivate the silenced genes. Here, we report that a quinoline-based compound, designated SGI-1027, inhibits the activity of DNMT1, DNMT3A, and DNMT3B as well M. SssI with comparable IC50 (6-13 μmol/L) by competing with S-adenosylmethionine in the methylation reaction. Treatment of different cancer cell lines with SGI-1027 resulted in selective degradation of DNMT1 with minimal or no effects on DNMT3A and DNMT3B. At a concentration of 2.5 to 5 μmol/L (similar to that of decitabine), complete degradation of DNMT1 protein was achieved within 24 h without significantly affecting its mRNA level. MG132 blocked SGI-1027–induced depletion of DNMT1, indicating the involvement of proteasomal pathway. Prolonged treatment of RKO cells with SGI-1027 led to demethylation and reexpression of the silenced tumor suppressor genes P16, MLH1, and TIMP3. Further, this compound did not exhibit significant toxicity in a rat hepatoma (H4IIE) cell line. This study provides a novel class of DNA hypomethylating agents that have the potential for use in epigenetic cancer therapy. [Cancer Res 2009;69(10):4277–85]
Ascitic fluid pH in alcoholic cirrhosis: a reevaluation of its use in the diagnosis of spontaneous bacterial peritonitis.
Authors: J Scemama-Clergue, C Doutrellot-Philippon, J M Metreau, B Teisseire, D Capron, D Dhumeaux
Journal: Gut (1985)

An ascitic fluid pH less than or equal to 7.31 has been advanced as being the best index in the early diagnosis of spontaneous bacterial peritonitis in cirrhotic patients. In order to test the validity of this criteria, 55 patients with alcoholic cirrhosis and ascites were studied. In each patient, arterial blood and ascitic fluid samples were analysed for pH, PCO2, total CO2 and PO2, and the pH gradient between blood and ascites was calculated. White blood cell and polymorphonuclear cell counts were determined in ascitic fluid, and cultures of ascites were done under aerobic and anaerobic conditions. Twelve patients had a culture proven spontaneous bacterial peritonitis. Their mean ascitic fluid pH (+/- SD) was 7.38 +/- 0.09 (range 7.21-7.49) and differed significantly (p less than 0.05) from that found in patients without spontaneous bacterial peritonitis: 7.44 +/- 0.06 (range 7.34-7.6.3). A marked overlap was observed, however, between the two groups, and only three out of the 12 patients with spontaneous bacterial peritonitis had an ascitic fluid pH less than or equal to 7.31. The pH gradient was 0.10 +/- 0.08 (range -0.01 to +0.28) in the spontaneous bacterial peritonitis group, as compared with 0.02 +/- 0.04 (range -0.09 to +0.12) in the sterile group (p less than 0.01), but a marked overlap was also noted between the two groups. In the spontaneous bacterial peritonitis group, the polymorphonuclear count was 3588 +/- 3849/microliter (range 60-11 776) versus 41 +/- 138/microliter (range 0-813) in the sterile group (p less than 0.0001). All but one patient in the spontaneous bacterial peritonitis group and only two patients in the sterile group had over 250 polymorphonuclear/ microliter. Thus, in our experience, neither the ascitic fluid pH nor the pH gradient values accurately discriminated the individual patients with and without spontaneous bacterial peritonitis. A polymorphonuclear count less than 250/ microliter remained the best criteria for the diagnosis of spontaneous bacterial peritonitis in cirrhotic patients, before having the results of ascitic fluid cultures.
Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers
Authors: S Banerjee
Journal: Gut (2002)

<b>Background and aims:</b><i>Escherichia coli</i> heat labile enterotoxin (LT) at doses of 5 μg or 10 μg has adjuvant activity for oral immunisation in humans infected with <i>Helicobacter pylori,</i> but causes severe diarrhoea. This study was undertaken to establish a safe and effective dose of LT, to confirm the safety of recombinant urease, and to compare the immunogenicity of orally compared with enterically delivered urease. <b>Methods:</b> 42 healthy adults without present or past <i>H pylori</i> infection were randomised to receive 60 mg recombinant <i>H pylori</i> urease in soluble or in encapsulated form, given with doses of LT ranging from 0 μg to 2.5 μg. Four oral doses were administered at day 1, 8, 29, and 57. Specific IgG, IgA, and antibody secreting cells were measured as well as total α4β7 integrin positive lymphocyte responses. <b>Results:</b> Enterically delivered urease was well tolerated and no serious adverse events occurred. Mild diarrhoea (one to four loose stools) occurred after the first immunisation in 50% (6 of 12) of the volunteers exposed to 2.5 μg LT (p=0.06; paired <i>t</i> test, compared with baseline) but not in volunteers exposed to lower LT doses. Immune responses occurred in five (p=0.048; Fisher's exact test), one, two, and one of six subjects exposed to 2.5 μg, 0.5 μg, 0.1 μg, and no LT, respectively. Significant CD4<sup>+</sup>, CD69<sup>+</sup>, and CD45RO<sup>hi</sup> responses occurred over time among α4β7<sup>hi</sup> lymphocytes in volunteers receiving 2.5 μg LT. Enterically delivered urease induced higher lymphocyte responses than soluble urease. <b>Conclusions:</b> The safety of <i>H pylori</i> urease is confirmed. Oral LT may conserve its adjuvant activity at low doses with minimal side effects.
Mechanisms of oxygen-induced contraction of ductus arteriosus isolated from the fetal rabbit.
Authors: T Nakanishi, H Gu, N Hagiwara, K Momma
Journal: Circulation Research (1993)

The present study was designed to investigate the effect of O2 on intracellular Ca concentration ([Ca]i) in the ductus arteriosus and the mechanisms for O2-induced ductal contraction. The force of isometric contraction of the ring of the ductus arteriosus isolated from fetal rabbits at 30 days of gestation (term, 31 days) was measured. The ductus arteriosus was loaded with fura 2, a calcium-sensitive dye, and [Ca]i was determined from the ratio of fluorescence intensity at 340 and 380 nm excitation wavelengths. The ductus arteriosus was initially superfused with hypoxic control solutions and contraction was induced by application of oxygenated solutions. The O2-induced contraction of the ductus arteriosus was associated with increases in [Ca]i and was eliminated in the absence of extracellular calcium. An increase in [K]o from 5 to 50 mM, which causes membrane depolarization, induced ductal contraction. The calcium channel blockers verapamil, diltiazem, and nickel caused a similar inhibition of O2-induced contraction as well as KCl-induced contraction. The role of intracellular calcium stores in O2-induced ductal contraction was examined using ryanodine, an inhibitor of calcium uptake and release from the sarcoplasmic reticulum. The inhibition of O2-induced contraction by ryanodine was minimal. Infusion of glibenclamide, an inhibitor for opening the ATP-sensitive potassium channel, caused contraction of the ductus arteriosus in the hypoxic solution. Cromakalim, an opener of ATP-sensitive potassium channels, completely relaxed the contraction induced by O2. These data suggest that O2 increases [Ca]i and causes contraction in the ductus arteriosus. Application of O2 may change from anaerobic to aerobic metabolism and depolarize membrane potential by closing the ATP-sensitive potassium channel, which in turn increases calcium influx via the voltage-dependent calcium channel. Mechanisms other than the ATP-sensitive potassium channel may also be involved in the O2-induced contraction and remain to be studied.
Coengagement of CD16 and CD94 Receptors Mediates Secretion of Chemokines and Induces Apoptotic Death of Naive Natural Killer Cells
Authors: Anahid Jewett, Nicholas A. Cacalano, Christian Head, Antonia Teruel
Journal: Clinical Cancer Research (2006)

Abstract Down-modulation of CD16 (FcγRIII) receptors and loss of natural killer (NK) cell function have been observed in oral cancer patients. However, neither the mechanisms nor the significance of the decrease in CD16 receptors have been fully understood. The cytotoxic activity and survival of NK cells are negatively regulated by antibodies directed against CD16 surface receptor. The addition of anti-CD94 antibody in combination with either F(ab′)2 fragment or intact anti-CD16 antibody to NK cells resulted in significant inhibition of NK cell cytotoxic function and induction of apoptosis in resting human peripheral blood NK cells. Addition of interleukin-2 to anti-CD16 and/or anti-CD94 antibody-treated NK cells significantly inhibited apoptosis and increased the function of NK cells. There was a significant increase in tumor necrosis factor-α (TNF-α) but not IFN-γ secretion in NK cells treated either with anti-CD16 antibody alone or in combination with anti-CD94 antibodies. Consequently, the addition of anti-TNF-α antibody partially inhibited apoptosis of NK cells mediated by the combination of anti-CD94 and anti-CD16 antibodies. Increase in apoptotic death of NK cells also correlated with an increase in type 2 inflammatory cytokines and in the induction of chemokines. Thus, we conclude that binding of antibodies to CD16 and CD94 NK cell receptors induces death of the NK cells and signals for the release of chemokines.