tbuckley/cabot-search huggingface dataset:
The Anatomy of a Delirium
Authors: ROBERT M. MORSE, EDWARD M. LITIN
Journal: American Journal of Psychiatry (1971)

The authors describe characteristics of postoperative delirium observed in 60 patients. The typical delirious patient was over 60, had undergone cardiac or orthopedic surgery, became delirious on the third postoperative day and recovered by the seventh, was as likely to be retarded and apathetic as restless and fearful, and had a 50 percent chance of minor cognitive impairment or dismissal. The patient's age and length of illness affected his prognosis; type of treatment did not.
Tumor Repressive Functions of Estrogen Receptor β in SW480 Colon Cancer Cells
Authors: Johan Hartman, Karin Edvardsson, Karolina Lindberg, Chunyan Zhao, Cecilia Williams, Anders Ström, Jan-Åke Gustafsson
Journal: Cancer Research (2009)

Abstract Estrogen receptor β (ERβ) is the predominant ER in the colorectal epithelium. Compared with normal colon tissue, ERβ expression is reduced in colorectal cancer. Our hypothesis is that ERβ inhibits proliferation of colon cancer cells. Hence, the aim of this study has been to investigate the molecular function of ERβ in colon cancer cells, focusing on cell cycle regulation. SW480 colon cancer cells have been lentivirus transduced with ERβ expression construct with or without mutated DNA-binding domain or an empty control vector. Expression of ERβ resulted in inhibition of proliferation and G1 phase cell cycle arrest and this effect was dependent on a functional DNA-binding region. c-Myc is overexpressed in an overwhelming majority of colorectal tumors. By Western blot and real-time PCR, we found c-Myc to be down-regulated in the ERβ-expressing cells. Furthermore, the c-Myc target gene p21(Waf1/Cip1) was induced and Cdc25A was reduced by ERβ at the transcriptional level. The second cdk2-inhibitor, p27Kip1, was induced by ERβ, but this regulation occurred at the posttranscriptional level, probably through ERβ-mediated repression of the F-box protein p45Skp2. Expression of the ERβ-variant with mutated DNA binding domain resulted in completely different cell cycle gene regulation. We performed in vivo studies with SW480 cells ± ERβ transplanted into severe combined immunodeficient/beige mice; after three weeks of ERβ-expression, a 70% reduction of tumor volume was seen. Our results show that ERβ inhibits proliferation as well as colon cancer xenograft growth, probably as a consequence of ERβ-mediated inhibition of cell-cycle pathways. Furthermore, this ERβ-mediated cell cycle repression is dependent on functional ERE binding. [Cancer Res 2009;69(15):6100–6]
Acquired and inherited risk factors for developing venous thromboembolism in cancer patients receiving adjuvant chemotherapy: a prospective trial
Authors: M. Mandalà, S. Barni, M. Prins, R. Labianca, C. Tondini, L. Russo, A. Milesi, M. Cremonesi, M. Zaccanelli, C. Regonesi, C. Moro, A. Falanga
Journal: Annals of Oncology (2009)

BackgroundAcquired and inherited risk factors for venous thromboembolism (VTE) and the incidence of symptomatic VTE were investigated in patients on adjuvant chemotherapy for breast or gastrointestinal cancer (GI).Patients and methodsIn a prospective observational study (January 2003 and February 2006), 199 GI (82 women/117 men; age range, 26–84 years) and 182 breast (180 women/2 men; age range, 29–85 years) cancer patients were enrolled and followed-up for symptomatic VTE during adjuvant chemotherapy. The effect of acquired (i.e. age, chemotherapy, tumour histotype, history of thrombosis, body mass index and smoking) and inherited risk factors [i.e. antithrombin, protein C (PC), protein S, homocysteine, activated PC resistance, factor V Leiden (FVL) and prothrombin (PT) mutations) was prospectively evaluated.ResultsOverall, 30 VTE events (7.87%) were recorded: 28 (7.35%) during treatment and 2 (0.52%) during the subsequent follow-up. Among all the 381 cancer patients, FVL was detected in 14 cases (3.67%) and PT mutation in 10 cases (2.62%). Multivariate analysis showed a significant association between the development of VTE and both thrombocytosis [hazard ratio (HR) 1.65; 95% confidence interval (CI), 1.04–2.637, P <0.0341] and a prior episode of thrombosis (HR 7.6; 95% CI, 1.77–33.1, P <0.006). FVL and PT mutations were not associated with the risk for VTE.ConclusionThe present data indicate thrombocytosis and history of thrombosis as risk factors for development of a thrombotic event during adjuvant chemotherapy in patients with malignant diseases.
Viral adaptation to immune selection pressure by HLA class I–restricted CTL responses targeting epitopes in HIV frameshift sequences
Authors: Christoph T. Berger, Jonathan M. Carlson, Chanson J. Brumme, Kari L. Hartman, Zabrina L. Brumme, Leah M. Henry, Pamela C. Rosato, Alicja Piechocka-Trocha, Mark A. Brockman, P. Richard Harrigan, David Heckerman, Daniel E. Kaufmann, Christian Brander
Journal: The Journal of Experimental Medicine (2010)

CD8+ cytotoxic T lymphocyte (CTL)-mediated immune responses to HIV contribute to viral control in vivo. Epitopes encoded by alternative reading frame (ARF) peptides may be targeted by CTLs as well, but their frequency and in vivo relevance are unknown. Using host genetic (human leukocyte antigen [HLA]) and plasma viral sequence information from 765 HIV-infected subjects, we identified 64 statistically significant (q<0.2) associations between specific HLA alleles and sequence polymorphisms in alternate reading frames of gag, pol, and nef that did not affect the regular frame protein sequence. Peptides spanning the top 20 HLA-associated imprints were used to test for ex vivo immune responses in 85 HIV-infected subjects and showed responses to 10 of these ARF peptides. The most frequent response recognized an HLA-A*03-restricted +2 frame-encoded epitope containing a unique A*03-associated polymorphism at position 6. Epitope-specific CTLs efficiently inhibited viral replication in vitro when viruses containing the wild-type sequence but not the observed polymorphism were tested. Mutating alternative internal start codons abrogated the CTL-mediated inhibition of viral replication. These data indicate that responses to ARF-encoded HIV epitopes are induced during natural infection, can contribute to viral control in vivo, and drive viral evolution on a population level.
LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway
Authors: H Hasegawa, Y Yamada, K Tsukasaki, N Mori, K Tsuruda, D Sasaki, T Usui, A Osaka, S Atogami, C Ishikawa, Y Machijima, S Sawada, T Hayashi, Y Miyazaki, S Kamihira
Journal: Leukemia (2011)

Adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm etiologically associated with human T-lymphotropic virus type-1 (HTLV-1), is resistant to treatment. In this study, we examined the effects of a new inhibitor of deacetylase enzymes, LBH589, on ATLL cells. LBH589 effectively induced apoptosis in ATLL-related cell lines and primary ATLL cells and reduced the size of tumors inoculated in SCID mice. Analyses, including with a DNA microarray, revealed that neither death receptors nor p53 pathways contributed to the apoptosis. Instead, LBH589 activated an intrinsic pathway through the activation of caspase-2. Furthermore, small interfering RNA experiments targeting caspase-2, caspase-9, RAIDD, p53-induced protein with a death domain (PIDD) and RIPK1 (RIP) indicated that activation of RAIDD is crucial and an event initiating this pathway. In addition, LBH589 caused a marked decrease in levels of factors involved in ATLL cell proliferation and invasion such as CCR4, IL-2R and HTLV-1 HBZ-SI, a spliced form of the HTLV-1 basic zipper factor HBZ. In conclusion, we showed that LBH589 is a strong inducer of apoptosis in ATLL cells and uncovered a novel apoptotic pathway initiated by activation of RAIDD.
Nucleotide sequence divergence in the A+T-rich region of mitochondrial DNA in Drosophila simulans and Drosophila mauritiana
Authors: K. Inohira, T. Hara, E. T. Matsuura
Journal: Molecular Biology and Evolution (1997)

We have determined the nucleotide sequences of two regions within the A+T-rich region of mitochondrial DNA (mtDNA) in the siIII type of Drosophila simulans and the maI type of D. mauritiana. The sequences of the two regions in siIII and maI are almost identical. The sequences include elements corresponding to the type I and type II repeats elements and the T-stretches as reported in D. melanogaster; an approximately 340-bp region (A region) adjacent to the tRNA(Ile) gene includes a part of the type II repeat element, and an approximately 440-bp region (B region) includes a central portion of the A+T-rich region between the type I and type II repeat arrays. Each sequence of the two species was compared with those of D. melanogaster and D. yakuba. The sequences of the A region are relatively well conserved among the four species. The alignment of the two sequences of the B region with those of D. melanogaster and D. yakuba requires numerous insertions/deletions. For both regions, nucleotide differences between D. simulans or D. mauritiana and D. melanogaster are similar to those between the two and D. yakuba. The tendency is obvious in a subregion within the type II repeat element in the A region. These findings suggest that the rate of nucleotide substitution in the subregion is accelerated in the lineage leading to D. melanogaster. Loss of functional constraint in the stem-loop-forming sequence is proposed for this acceleration.
Age of Transfused Blood in Critically Ill Adults
Authors: Jacques Lacroix, Paul C. Hébert, Dean A. Fergusson, Alan Tinmouth, Deborah J. Cook, John C. Marshall, Lucy Clayton, Lauralyn McIntyre, Jeannie Callum, Alexis F. Turgeon, Morris A. Blajchman, Timothy S. Walsh, Simon J. Stanworth, Helen Campbell, Gilles Capellier, Pierre Tiberghien, Laurent Bardiaux, Leo van de Watering, Nardo J. van der Meer, Elham Sabri, Dong Vo
Journal: New England Journal of Medicine (2015)

Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage.In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality.Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses.Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).
Immune Responses to a Class II Helper Peptide Epitope in Patients with Stage III/IV Resected Melanoma
Authors: Raymond Wong, Roy Lau, Jenny Chang, Tina Kuus-Reichel, Vincent Brichard, Claudine Bruck, Jeffrey Weber
Journal: Clinical Cancer Research (2004)

Abstract The importance of CD8+ cytolytic T cells for protection from viral infection and in the generation of immune responses against tumors has been well established. In contrast, the role of CD4+ T-helper cells in human infection and in cancer immunity has yet to be clearly defined. In this pilot study, we show that immunization of three resected, high-risk metastatic melanoma patients with a T-helper epitope derived from the melanoma differentiation antigen, melanoma antigen recognized by T cells-1, results in CD4+ T-cell immune responses. Immune reactivity to that epitope was detected by DR4-peptide tetramer staining, and enzyme-linked immunospot assay of fresh and restimulated CD4+ T cells from patients over the course of the 12-month vaccine regimen. The postvaccine CD4+ T cells exhibited a mixed T-helper 1/T-helper 2 phenotype, proliferated in response to the antigen and promiscuously recognized the peptide epitope bound to different human leukocyte antigen-DRβ alleles. For 1 DRβ1*0401+ patient, antigen-specific CD4+ T cells recognized human leukocyte antigen-matched antigen-expressing tumor cells, secreted granzyme B, and also exhibited cytolysis that was MHC class II-restricted. These data establish the immunogenicity of a class II epitope derived from a melanoma-associated antigen and support the inclusion of class II peptides in future melanoma vaccine therapies.
Autocrine production of IL-11 mediates tumorigenicity in hypoxic cancer cells
Authors: Barbara Onnis, Nicole Fer, Annamaria Rapisarda, Victor S. Perez, Giovanni Melillo
Journal: Journal of Clinical Investigation (2013)

IL-11 and its receptor, IL-11Ra, are expressed in human cancers; however, the functional role of IL-11 in tumor progression is not known. We found that IL11 is a hypoxia-inducible, VHL-regulated gene in human cancer cells and that expression of IL11 mRNA was dependent, at least in part, on HIF-1. A cooperative interaction between HIF-1 and AP-1 mediated transcriptional activation of the IL11 promoter. Additionally, we found that human cancer cells expressed a functional IL-11Ra subunit, which triggered signal transduction either by exogenous recombinant human IL-11 or by autocrine production of IL-11 in cells cultured under hypoxic conditions. Silencing of IL11 dramatically abrogated the ability of hypoxia to increase anchorage-independent growth and significantly reduced tumor growth in xenograft models. Notably, these results were phenocopied by partial knockdown of STAT1 in a human prostate cancer cell line (PC3), suggesting that this pathway may play an important role in mediating the effects of IL-11 under hypoxic conditions. In conclusion, these results identify IL11 as an oxygen- and VHL-regulated gene and provide evidence of a pathway “hijacked” by hypoxic cancer cells that may contribute to tumor progression.
Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839) in Japanese patients with solid malignant tumors
Authors: K. Nakagawa, T. Tamura, S. Negoro, S. Kudoh, N. Yamamoto, N. Yamamoto, K. Takeda, H. Swaisland, I. Nakatani, M. Hirose, R.-P. Dong, M. Fukuoka
Journal: Annals of Oncology (2003)
Diazoxide-Induced Cardioprotection Requires Signaling Through a Redox-Sensitive Mechanism
Authors: Robert A. Forbes, Charles Steenbergen, Elizabeth Murphy
Journal: Circulation Research (2001)

Diazoxide, a selective opener of the mitochondrial ATP-sensitive potassium channel, has been shown to elicit tolerance to ischemia in cardiac myocytes and in perfused heart. However, the mechanism of this cardioprotection is poorly understood. Because reactive oxygen species (ROS) are recognized as important intracellular signaling molecules and have been implicated in ischemic preconditioning, we examined diazoxide-induced ROS production in adult cardiomyocytes. Cells treated with 50 micromol/L diazoxide showed a 173% increase in ROS production relative to baseline. 5-Hydroxydecanoate was found to attenuate the diazoxide-induced increase in ROS generation. The diazoxide-induced increase in ROS also was abrogated by the addition of either the antioxidant N-acetylcysteine (NAC) or N-mercaptopropionylglycine. We also examined the ability of NAC to block the protective effects of diazoxide in the perfused rat heart. After 20 minutes of global ischemia and 20 minutes of reflow, hearts perfused with 100 micromol/L diazoxide before ischemia showed significantly improved postischemic contractile function relative to untreated hearts (84% versus 29% of initial left ventricular developed pressure, respectively). Hearts treated with diazoxide in the presence of 4 mmol/L NAC recovered 53% of initial left ventricular developed pressure, whereas hearts treated with NAC alone recovered 46% of preischemic function. Using (31)P NMR spectroscopy, we found that, similar to preconditioning, diazoxide significantly attenuated ischemia-induced intracellular acidification and enhanced post- ischemic recovery of phosphocreatine levels, both of which were blocked by cotreatment with NAC. These data suggest that the cardioprotective actions of diazoxide are mediated by generation of a pro-oxidant environment.
Use of Drugs in Myopathies
Authors: D Grob
Journal: The Annual Review of Pharmacology and Toxicology (1976)

The most important recent advances in understanding and managing myopathies have occurred in relation to diseases associated with alterations in the immune mechanism: polymyositis and myasthenia gravis. Some progress has also been made in the management of diseases associated with abnormal movement of potassium ions, and in understanding the effects of neuromuscular blocking drugs. Unfortu­ nately, there has been less progress in understanding or managing the muscular dystrophies.
Methylprednisolone acetate induced release of cartilage proteoglycans: determination by high performance liquid chromatography.
Authors: H Saari, R M Tulamo, Y T Konttinen, T Sorsa
Journal: Annals of the Rheumatic Diseases (1992)

A high performance liquid chromatography (HPLC) procedure suitable for the simultaneous determination of the molecular size and concentration of macromolecular hyaluronate and proteoglycans in synovial fluid has been developed. Irrigation of the equine tarsocrural joint with 20 ml physiological saline (PSS) caused a mild inflammation with an increase of proteoglycans in the synovial fluid over the baseline arthrocentesis control sample. Proteoglycan and hyaluronate in the synovial fluid did not interact to form hyaluronate-proteoglycan aggregates, but separated as distinct chromatographic peaks. This suggests that the cartilage derived proteoglycans in synovial fluid in the inflamed joint have been proteolytically cleaved from the non-covalent aggregates containing link protein and hyaluronate. Hyaluronidase digestion completely abolished the hyaluronate peak without affecting the proteoglycans. This seems to indicate that proteoglycan in synovial fluid is unable to interact with hyaluronate in synovial fluid to form cartilage type aggregates. Proteolytic degradation and the time dependent release into the synovial fluid of such digested proteoglycan also resulted from the intra-articular injection of methylprednisolone acetate into normal tarsocrural joints and joints irrigated with PSS. These proteoglycans were insensitive to hyaluronidase but may consist of a protein moiety with attached glycosaminoglycans, as suggested by their sensitivity to proteinase and keratanase/chondroitinase digestion. These observations with cartilage treated with methylprednisolone acetate and mildly stimulated articular cartilage are inconsistent with earlier work on osteoarthritic and rheumatoid articular cartilage and have interesting implications for the pathogenesis and for the therapeutic action of intraarticular corticosteroids. A rapid HPLC procedure applicable to unprocessed small volume samples of synovial fluid gives information simultaneously on hyaluronate and proteoglycan in synovial fluid which is not attainable with immunoradiometric or isotope tracer techniques. It therefore appears to be useful for the analysis of cartilage turnover and destruction in health and disease.
Hemodynamics in Normal Cattle
Authors: John T. Reeves, Robert F. Grover, Donald H. Will, Archibald F. Alexander
Journal: Circulation Research (1962)

A satisfactory method has been described for conducting hemodynamic studies in cattle. With the animals in normal standing position, and without sedation or tranquilization, cardiac catheterization can be readily performed. With a muzzle mask, ventilatory studies are also feasible. Using this method, each of 10 normal steers was studied four times during a six-month period. This permitted the establishment of normal values for a number of circulatory measurements. In addition, an evaluation of chlorpromazine administration in normal cattle demonstrated some of the numerous complex effects of this drug on the cardiovascular and respiratory systems. These included hemodilution, hypoventilation, and a marked reduction of the arteriovenous oxygen difference.
LPS-Induced TLR4 Signaling in Human Colorectal Cancer Cells Increases β1 Integrin-Mediated Cell Adhesion and Liver Metastasis
Authors: Rich Y.C. Hsu, Carlos H.F. Chan, Jonathan D. Spicer, Mathieu C. Rousseau, Betty Giannias, Simon Rousseau, Lorenzo E. Ferri
Journal: Cancer Research (2011)

Infectious complications resulting from resection of colorectal cancer (CRC) elevates the risk of cancer recurrence and metastasis, but the reason for this risk relationship is unknown. Defining the mechanisms responsible may offer opportunities to improve outcomes in a majority of patients whose tumors are resected as part of their therapy. The complex formed between Toll receptor TLR4 and myeloid differentiation factor MD2 defines a major cell surface receptor for lipopolysaccharide (LPS), a gram-negative bacterial antigen that has been implicated in infectious complications after CRC resection. As the TLR4/MD2 complex is expressed on CRC cells, we hypothesized that LPS may promote liver metastasis in CRC by stimulating TLR4 signaling. In support of this hypothesis, we report here that LPS enhances liver metastasis of human CRC cells that express TLR4/MD2 after intrasplenic graft of immunocompromised nude mice. Compared with TLR4 nonexpressing, nonmetastatic CRC cells, we observed increased in vitro adherence to different extracellular matrices and human umbilical vein endothelial cells (HUVEC). Furthermore, we observed an increased likelihood of in vivo capture within hepatic sinusoids after LPS treatment. No differences were apparent in phosphorylation of p38 and MAPK isoforms, but in metastatic CRC cells expressing surface TLR4 treatment with LPS increased Ser473 phosphorylation of AKT kinase. We showed that enhanced adherence elicited by LPS in these cells could be blocked at three different levels, using Eritoran (TLR4 small molecule antagonist), PI-103 (PI3K inhibitor), or anti-β1 integrin blocking antibodies. Taken together, the results indicate that stimulation of the TLR4/MD2 complex by LPS activates PI3K/AKT signaling and promotes downstream β1 integrin function, thereby increasing the adhesiveness and metastatic capacity of CRC cells. Our findings suggest that inhibiting LPS-induced TLR4 signaling could improve therapeutic outcomes by preventing cancer metastasis during the perioperative period of CRC resection.
Non-alcoholic steatohepatitis and hepatic steatosis in patients with adult onset growth hormone deficiency
Authors: T Ichikawa
Journal: Gut (2003)

Adult onset growth hormone (GH) deficiency closely resembles syndrome X.1 Patients with syndrome X often suffer from obesity, dyslipidaemia, insulin resistance, and hypertension, and hepatic steatosis and non-alcoholic steatohepatitis (NASH) have also been characterised as symptoms of syndrome X.2,3 However, the relationship of GH deficiency to hepatic steatosis and NASH remains unclear.

We looked for the presence of hepatic steatosis using computer tomography (CT) in a study of 18 patients with adult …