tbuckley/cabot-search huggingface dataset:
Role for Endothelin-1–Induced Superoxide and Peroxynitrite Production in Rebound Pulmonary Hypertension Associated With Inhaled Nitric Oxide Therapy
Authors: Stephen Wedgwood, D. Michael McMullan, Janine M. Bekker, Jeffrey R. Fineman, Stephen M. Black
Journal: Circulation Research (2001)

Our previous studies have demonstrated that inhaled nitric oxide (NO) decreases nitric oxide synthase (NOS) activity in vivo and that this inhibition is associated with rebound pulmonary hypertension upon acute withdrawal of inhaled NO. We have also demonstrated that inhaled NO elevates plasma endothelin-1 (ET-1) levels and that pretreatment with PD156707, an ETA receptor antagonist, blocks the rebound hypertension. The objectives of this study were to further elucidate the role of ET-1 in the rebound pulmonary hypertension upon acute withdrawal of inhaled NO. Inhaled NO (40 ppm) delivered to thirteen 4-week-old lambs decreased NOS activity by 36.2% in control lambs ( P &lt;0.05), whereas NOS activity was preserved in PD156707-treated lambs. When primary cultures of pulmonary artery smooth muscle cells were exposed to ET-1, superoxide production increased by 33% ( P &lt;0.05). This increase was blocked by a preincubation with PD156707. Furthermore, cotreatment of cells with ET-1 and NO increased peroxynitrite levels by 26% ( P &lt;0.05), whereas preincubation of purified human endothelial nitric oxide synthase (eNOS) protein with peroxynitrite generated a nitrated enzyme with 50% activity relative to control ( P &lt;0.05). Western blot analysis of peripheral lung extracts obtained after 24 hours of inhaled NO revealed a 90% reduction in 3-nitrotyrosine residues ( P &lt;0.05) in PD156707-treated lambs. The nitration of eNOS was also reduced by 40% in PD156707-treated lambs ( P &lt;0.05). These data suggest that the reduction of NOS activity associated with inhaled NO therapy may involve ETA receptor–mediated superoxide production. ETA receptor antagonists may prevent rebound pulmonary hypertension by protecting endogenous eNOS activity during inhaled NO therapy.
Intrinsic factor secretion in gastric atrophy.
Authors: S Ardeman, I Chanarin
Journal: Gut (1966)

EDITORIAL SYNOPSIS The appearance of the gastric biopsy histologically has been correlated with assay of the intrinsic factor and acid content of the gastric juice, and also with vitamin B12 absorption studies.The loss of intrinsic factor parallels the loss of gastric secretory cells.The assay of intrinsic factor proved a better index of secretory capacity of the mucosa than either acid production or vitamin B12 absorption.
Safety for Patients With Celiac Disease of Baked Goods Made of Wheat Flour Hydrolyzed During Food Processing
Authors: Luigi Greco, Marco Gobbetti, Renata Auricchio, Raffaella Di Mase, Francesca Landolfo, Francesco Paparo, Raffaella Di Cagno, Maria De Angelis, Carlo Giuseppe Rizzello, Angela Cassone, Gaetano Terrone, Laura Timpone, Martina D'Aniello, Maria Maglio, Riccardo Troncone, Salvatore Auricchio
Journal: Clinical Gastroenterology and Hepatology (2010)
Transcutaneous glucose measurement using near-infrared spectroscopy during hypoglycemia.
Authors: I Gabriely, R Wozniak, M Mevorach, J Kaplan, Y Aharon, H Shamoon
Journal: Diabetes Care (1999)

OBJECTIVE: To analyze a transcutaneous near-infrared spectroscopy system as a technique for in vivo noninvasive blood glucose monitoring during euglycemia and hypoglycemia. RESEARCH DESIGN AND METHODS: Ten nondiabetic subjects and two patients with type 1 diabetes were examined in a total of 27 studies. In each study, the subject's plasma glucose was lowered to a hypoglycemia level (approximately 55 mg/dl) followed by recovery to a glycemic level of approximately 115 mg/dl using an intravenous infusion of insulin and 20% dextrose. Plasma glucose levels were determined at 5-min intervals by standard glucose oxidase method and simultaneously by a near-infrared spectroscopic system. The plasma glucose measured by the standard method was used to create a calibration model that could predict glucose levels from the near-infrared spectral data. The two data sets were correlated during the decline and recovery in plasma glucose, within 10 mg/dl plasma glucose ranges, and were examined using the Clarke Error Grid Analysis. RESULTS: Two sets of 1,704 plasma glucose determinations were examined. The near-infrared predictions during the fall and recovery in plasma glucose were highly correlated (r = 0.96 and 0.95, respectively). When analyzed during 10 mg/dl plasma glucose segments, the mean absolute difference between the near-infrared spectroscopy method and the chemometric reference ranged from 3.3 to 4.4 mg/dl in the nondiabetic subjects and from 2.6 to 3.8 mg/dl in the patients with type 1 diabetes. Using the Error Grid Analysis, 97.7% of all the near-infrared predictions were assigned to the A-zone. CONCLUSIONS: Our findings suggest that the near-infrared spectroscopy method can accurately predict plasma glucose levels during euglycemia and hypoglycemia in humans.
Extraordinary Conservation, Gene Loss, and Positive Selection in the Evolution of an Ancient Neurotoxin
Authors: Shauna A. Murray, Troco K. Mihali, Brett A. Neilan
Journal: Molecular Biology and Evolution (2010)

The recent determination of the genetic basis for the biosynthesis of the neurotoxin, saxitoxin, produced by cyanobacteria, has revealed a highly complex sequence of reactions, involving over 30 biosynthetic steps encoded by up to 26 genes clustered at one genomic locus, sxt. Insights into evolutionary–ecological processes have been found through the study of such secondary metabolites because they consist of a measurable phenotype with clear ecological consequences, synthesized by known genes in a small number of species. However, the processes involved in and timing of the divergence of prokaryotic secondary metabolites have been difficult to determine due to their antiquity and the possible frequency of horizontal gene transfer and homologous recombination. Through analyses of gene synteny, phylogenies of individual genes, and analyses of recombination and selection, we identified the evolutionary processes of this cluster in five species of cyanobacteria. Here, we provide evidence that the sxt cluster appears to have been largely vertically inherited and was therefore likely present early in the divergence of the Nostocales, at least 2,100 Ma, the earliest reliably dated appearance of a secondary metabolite. The sxt cluster has been extraordinarily conserved through stabilizing selection. Genes have been lost and rearranged, have undergone intra- and interspecific recombination, and have been subject to duplication followed by positive selection along the duplicated lineage, with likely consequences for the toxin analogues produced. Several hypotheses exist as to the ecophysiological role of saxitoxin: as a method of chemical defense, cellular nitrogen storage, DNA metabolism, or chemical signaling. The antiquity of this gene cluster indicates that potassium channels, not sodium channels, may have been the original targets of this compound. The extraordinary conservation of the machinery for saxitoxin synthesis, under radically changing environmental conditions, shows that it has continued to play an important adaptive role in some cyanobacteria.
Integrins in Kidney Disease
Authors: Ambra Pozzi, Roy Zent
Journal: Journal of the American Society of Nephrology (2013)

A major hallmark of chronic kidney injury is fibrosis, which is characterized by increased accumulation of extracellular matrix components that replace the damaged tissue. Normally, the synthesis and degradation of extracellular matrix components are finely regulated; however, when matrix replacement goes unchecked, there is unwanted and irreversible tissue scarring with consequent organ damage, organ failure, and, in certain cases, death. Many factors, including cell-matrix interactions, play a role in the development of renal fibrosis. Cell-matrix interactions are made possible by integrins, a family of transmembrane receptors that, upon binding to the extracellular matrix, activate intracellular signaling. Thus, they control various cell functions, including survival, proliferation, migration, and matrix homeostasis. Genetic mutations in humans and the development of animal models lacking integrins in selective parts of the kidney have improved our understanding of molecular mechanisms and pathways controlling matrix remodeling in kidney disease. Here we outline the major integrins involved in kidney disease and some of the major molecular mechanisms whereby integrins contribute to kidney fibrosis.
Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry
Authors: Júlia Balog, László Sasi-Szabó, James Kinross, Matthew R. Lewis, Laura J. Muirhead, Kirill Veselkov, Reza Mirnezami, Balázs Dezső, László Damjanovich, Ara Darzi, Jeremy K. Nicholson, Zoltán Takáts
Journal: Science Translational Medicine (2013)

Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique that allows near-real-time characterization of human tissue in vivo by analysis of the aerosol ("smoke") released during electrosurgical dissection. The coupling of REIMS technology with electrosurgery for tissue diagnostics is known as the intelligent knife (iKnife). This study aimed to validate the technique by applying it to the analysis of fresh human tissue samples ex vivo and to demonstrate the translation to real-time use in vivo in a surgical environment. A variety of tissue samples from 302 patients were analyzed in the laboratory, resulting in 1624 cancerous and 1309 noncancerous database entries. The technology was then transferred to the operating theater, where the device was coupled to existing electrosurgical equipment to collect data during a total of 81 resections. Mass spectrometric data were analyzed using multivariate statistical methods, including principal components analysis (PCA) and linear discriminant analysis (LDA), and a spectral identification algorithm using a similar approach was implemented. The REIMS approach differentiated accurately between distinct histological and histopathological tissue types, with malignant tissues yielding chemical characteristics specific to their histopathological subtypes. Tissue identification via intraoperative REIMS matched the postoperative histological diagnosis in 100% (all 81) of the cases studied. The mass spectra reflected lipidomic profiles that varied between distinct histological tumor types and also between primary and metastatic tumors. Thus, in addition to real-time diagnostic information, the spectra provided additional information on divergent tumor biochemistry that may have mechanistic importance in cancer.
Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118G&amp;gt;A, 190G&amp;gt;A, and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia
Authors: Joan-Lluis Vives Corrons, Estefania Garcia, Joan J. Tusell, Kottayil I. Varughese, Carol West, Ernest Beutler
Journal: Blood (2003)
Progress and applications of mouse models for human lung cancer
Authors: S. de Seranno, R. Meuwissen
Journal: European Respiratory Journal (2010)

The continued progress of modelling lung cancer in mice has led not only to new means of understanding the molecular pathways governing human lung cancer, but it has also created a vast reservoir of alternative tools to test treatments against this malignancy. More sophisticated somatic mouse models for nonsmall cell lung cancer, small cell lung cancer and pulmonary squamous cell carcinoma have been generated that closely mimic human lung cancer. These models enable us to identify the cells of origin and the role of stem cells in the maintenance of the various types of lung cancer. Moreover, results of lung cancer intervention studies are now starting to reveal the full potential of these somatic mouse models as powerful pre-clinical models.
Hepatotoxicity and antituberculosis therapy: time to revise UK guidance?
Authors: N F Walker, M Kliner, D Turner, S Bhagani, I Cropley, S Hopkins, M Lipman
Journal: Thorax (2009)

Hepatotoxicity associated with antituberculosis therapy is an important clinical problem. Guidelines recommend baseline liver function tests (LFTs) before commencing treatment. In patients with risk factors for hepatotoxicity (ie, chronic viral hepatitis or liver disease, pregnancy or significant alcohol history) or abnormal baseline LFTs, further monitoring is indicated whilst on treatment.1 2 In all other cases repeat liver function testing is reserved for patients developing symptoms suggestive of liver dysfunction (fever, malaise, nausea, vomiting, abdominal pain, jaundice or unexplained fatigue). HIV co-infection is not specifically mentioned within UK guidance. Given increasing national rates of tuberculosis/HIV,3 we assessed how this might impact upon current guidelines.

A retrospective case-note review was undertaken of patients treated for active tuberculosis over a year (1 June 2006–31 May 2007) …
Assessment of inflammation in the rheumatoid knee joint: correlation between clinical, radioisotopic, and thermographic methods.
Authors: M de Silva, V Kyle, B Hazleman, R Salisbury, P Page Thomas, P Wraight
Journal: Annals of the Rheumatic Diseases (1986)

Standard clinical methods of assessing joint inflammation are being supplemented increasingly by radioisotopic and thermographic studies. However, the correlation between these different methods has not been firmly established. In the quantification of synovitis by infrared thermography we have shown that the heat distribution index (HDI) based on thermal pattern is more reliable and is less affected by diurnal variations in joint temperature than the commonly used thermographic index, which is based on average skin temperature values. In 20 patients with rheumatoid arthritis whose knees were being treated with intra-articular steroid we obtained 184 serial paired observations over a period of 24 weeks for clinical assessment, HDI, and 99mTc pertechnetate uptake. We found significant correlations (p less than 0.001) between the three methods of assessment (except for pain and HDI (p = 0.116)).
Dual specificity phosphatase 1 (DUSP1) regulates a subset of LPS-induced genes and protects mice from lethal endotoxin shock
Authors: Michael Hammer, Jörg Mages, Harald Dietrich, Angela Servatius, Norma Howells, Andrew C.B. Cato, Roland Lang
Journal: The Journal of Experimental Medicine (2005)

Activation of the mitogen-activated protein kinase (MAPK) cascade after Toll-like receptor stimulation enables innate immune cells to rapidly activate cytokine gene expression. A balanced response to signals of infectious danger requires that cellular activation is transient. Here, we identify the MAPK phosphatase dual specificity phosphatase 1 (DUSP1) as an essential endogenous regulator of the inflammatory response to lipopolysaccharide (LPS). DUSP1-deficient (DUSP1−/−) bone marrow–derived macrophages showed selectively prolonged activation of p38 MAPK and increased cytokine production. Intraperitoneal challenge of DUSP1−/− mice with LPS caused increased lethality and overshooting production of interleukin (IL)-6 and tumor necrosis factor α. Transcriptional profiling revealed that DUSP1 controls a significant fraction of LPS-induced genes, which includes IL-6 and IL-10 as well as the chemokines CCL3, CCL4, and CXCL2. In contrast, the expression of the important mediators of endotoxin lethality, interferon γ and IL-12, was not significantly altered by the absence of DUSP1. These data together demonstrate a specific regulatory role of DUSP1 in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock.
Llama‐derived single‐domain intrabodies inhibit secretion of hepatitis B virions in mice†
Authors: Benedikte Serruys, Freya Van Houtte, Phebe Verbrugghe, Geert Leroux‐Roels, Peter Vanlandschoot
Journal: Hepatology (2008)

Hepatitis B virus (HBV) infections cause 500,000 to 700,000 deaths per year as a consequence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Efficient and safe antivirals to treat chronically infected patients and consequently to prevent development of hepatocellular carcinoma are still awaited. We isolated five single-domain antibodies (VHHs) that recognize the most abundant envelope protein (S) of HBV. VHHs, when expressed and retained in the endoplasmic reticulum as intrabodies, reduced levels of secreted hepatitis B surface antigen (HBsAg) particles in a cellular HBV model. In a hydrodynamics-based HBV mouse model, these intrabodies caused a marked reduction in HBsAg concentrations and a 10- to >100-fold reduction in the concentration of HBV virions in plasma. Conclusion: VHHs potently inhibited secretion of HBV virions in vivo, showing that this approach might be useful in the treatment of HBV. To our knowledge, this is the first report of intrabody-mediated inhibition of viral secretion in mammals. (HEPATOLOGY 2009;49:39-49.)
New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project.
Authors: J O Armitage, D D Weisenburger
Journal: Journal of Clinical Oncology (1998)

Increasing knowledge about the biology of the non-Hodgkin's lymphomas has led to new approaches in classification. Rather than grouping lymphomas simply based on cell size, cell shape, and growth pattern, it is now possible to identify distinctive clinicopathologic entities. In many cases, the existence of specific immunologic and/or genetic features has confirmed the existence of these distinctive types of lymphoma. Since patients will be given these diagnoses by pathologists, it is important that clinicians be knowledgeable with regard to their clinical characteristics. The findings for the 13 most common lymphoma types that will be encountered in clinical practice are presented here.
Use of Medications of Questionable Benefit in Advanced Dementia
Authors: Jennifer Tjia, Becky A. Briesacher, Daniel Peterson, Qin Liu, Susan E. Andrade, Susan L. Mitchell
Journal: JAMA Internal Medicine (2014)

Advanced dementia is characterized by severe cognitive impairment and complete functional dependence. Patients' goals of care should guide the prescribing of medication during such terminal illness. Medications that do not promote the primary goal of care should be minimized.
A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury
Authors: Daniela Dal-Secco, Jing Wang, Zhutian Zeng, Elzbieta Kolaczkowska, Connie H.Y. Wong, Björn Petri, Richard M. Ransohoff, Israel F. Charo, Craig N. Jenne, Paul Kubes
Journal: The Journal of Experimental Medicine (2015)

Monocytes are recruited from the blood to sites of inflammation, where they contribute to wound healing and tissue repair. There are at least two subsets of monocytes: classical or proinflammatory (CCR2hiCX3CR1low) and nonclassical, patrolling, or alternative (CCR2lowCX3CR1hi) monocytes. Using spinning-disk confocal intravital microscopy and mice with fluorescent reporters for each of these subsets, we were able to track the dynamic spectrum of monocytes that enter a site of sterile hepatic injury in vivo. We observed that the CCR2hiCX3CR1low monocytes were recruited early and persisted for at least 48 h, forming a ringlike structure around the injured area. These monocytes transitioned, in situ, from CCR2hiCx3CR1low to CX3CR1hiCCR2low within the ringlike structure and then entered the injury site. This phenotypic conversion was essential for optimal repair. These results demonstrate a local, cytokine driven reprogramming of classic, proinflammatory monocytes into nonclassical or alternative monocytes to facilitate proper wound-healing.
d-Penicillamine in the treatment of keloids
Authors: BRYAN J. MAYOU
Journal: British Journal of Dermatology (1981)

Journal Article d‐Penicillamine in the treatment of keloids Get access BRYAN J. MAYOU BRYAN J. MAYOU Department of Plastic Surgery, St Thomas's Hospital, London SEr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 105, Issue 1, 1 July 1981, Pages 87–89, https://doi.org/10.1111/j.1365-2133.1981.tb00887.x Published: 01 July 1981 Article history Accepted: 22 September 1980 Published: 01 July 1981
Association Between Simian Virus 40 DNA and Lymphoma in the United Kingdom
Authors: J. MacKenzie, K. S. Wilson, J. Perry, A. Gallagher, R. F. Jarrett
Journal: JNCI Journal of the National Cancer Institute (2003)

Recent studies have reported the presence of simian virus 40 (SV40) DNA sequences in approximately 40% of tumor samples from non-Hodgkin's lymphoma (NHL) patients from the United States. We examined a series of 259 tumor and blood samples, including 152 NHL samples, from patients in the U.K. with lymphadenopathy and lymphoid leukemia for the presence of SV40 DNA using a highly sensitive quantitative polymerase chain reaction (PCR) assay and a consensus PCR assay capable of detecting the polyomaviruses SV40, BK, and JC. SV40 DNA sequences were not detected in any sample using either assay. Because the incidence of NHL is similar in the U.K. and the United States, this finding suggests that SV40 is unlikely to have an etiologic role in NHL.
The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D–target-cell interactions
Authors: Giuseppe Sconocchia, Michelle Lau, Maurizio Provenzano, Katayoun Rezvani, Wachanan Wongsena, Hiroshi Fujiwara, Nancy Hensel, Jos Melenhorst, Jonming Li, Soldano Ferrone, A. John Barrett
Journal: Blood (2005)
Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth muscle cell migration
Authors: Chung-Huang Chen, Yen-Chun Ho, Hua-Hui Ho, Il-Chi Chang, Kathrin H. Kirsch, Yung-Jen Chuang, Matthew D. Layne, Shaw-Fang Yet
Journal: Cardiovascular Research (2013)

Cysteine-rich protein (CRP) 2, a member of the LIM-only CRP family that contains two LIM domains, is expressed in vascular smooth muscle cells (VSMCs) of blood vessels and functions to repress VSMC migration and vascular remodelling. The goal of this study was to define the molecular mechanisms by which CRP2 regulates VSMC migration. Transfection of VSMCs with CRP2-EGFP constructs revealed that CRP2 associated with the actin cytoskeleton. In response to chemoattractant stimulation, Csrp2 (mouse CRP2 gene symbol)-deficient (Csrp2−/−) VSMCs exhibited increased lamellipodia formation. Re-introduction of CRP2 abrogated the enhanced lamellipodia formation and migration of Csrp2−/− VSMCs following chemoattractant stimulation. Mammalian 2-hybrid and co-immunoprecipitation assays demonstrated that CRP2 interacts with p130Cas, a scaffold protein important for lamellipodia formation and cell motility. Immunofluorescence staining showed that CRP2 colocalized with phospho-p130Cas at focal adhesions (FAs)/terminal ends of stress fibres in non-migrating cells. Interestingly, in migrating cells phospho-p130Cas localized to the leading edge of lamellipodia and FAs, whereas CRP2 was restricted to FAs and stress fibres. Furthermore, we demonstrated that p130Cas expression and phosphorylation promote neointima formation following arterial injury. These studies demonstrate that CRP2 sequesters p130Cas at FAs, thereby reducing lamellipodia formation and blunting VSMC migration.