tbuckley/cabot-search huggingface dataset:
Human Mig chemokine: biochemical and functional characterization.
Authors: F Liao, R L Rabin, J R Yannelli, L G Koniaris, P Vanguri, J M Farber
Journal: The Journal of Experimental Medicine (1995)

Mig is a chemokine of the CXC subfamily that was discovered by differential screening of a cDNA library prepared from lymphokine-activated macrophages. The mig gene is inducible in macrophages and in other cells in response to interferon (IFN)-gamma. We have transfected Chinese hamster ovary (CHO) cells with cDNA encoding human Mig and we have derived CHO cell lines from which we have purified recombinant human Mig (rHuMig). rHuMig induced the transient elevation of [Ca2+]i in human tumor-infiltrating T lymphocytes (TIL) and in cultured, activated human peripheral blood-derived lymphocytes. No responses were seen in human neutrophils, monocytes, or Epstein-Barr virus-transformed B lymphoblastoid cell lines. rHuMig was chemotactic for TIL by a modified Boyden chamber assay but rHuMig was not chemotactic for neutrophils or monocytes. The CHO cell lines, IFN-gamma-treated human peripheral-blood monocytes, and IFN-gamma-treated cells of the human monocytic cell line THP-1 all secreted multiple and identical HuMig species as revealed by SDS-PAGE. Using the CHO-derived rHuMig, we have shown that the species' heterogeneity is due to proteolytic cleavage at basic carboxy-terminal residues, and that the proteolysis occurs before and not after rHuMig secretion by the CHO cells. The major species of secreted rHuMig ranged from 78 to 103 amino acids in length, the latter corresponding to the full-length secreted protein predicted from the HuMig cDNA. Carboxy-terminal-truncated forms of rHuMig were of lower specific activity compared to full-length rHuMig in the calcium flux assay, and the truncated species did not block the activity of the full-length species. It is likely that HuMig plays a role in T cell trafficking and perhaps in other aspects of the physiology of activated T cells.
Atrial natriuretic peptide protects against cold ischemic injury in the isolated and in situ rat kidney.
Authors: H Z Zhou, J I Shapiro, L Chan, R W Schrier
Journal: Journal of the American Society of Nephrology (1990)

Journal of the American Society of Nephrology : JASN 1(6):p 927-928, December 1990. | DOI: 10.1681/ASN.V16927
Impairment of the ubiquitin?proteasome system by truncated cardiac myosin binding protein C mutants
Authors: A SARIKAS, L CARRIER, C SCHENKE, D DOLL, J FLAVIGNY, K LINDENBERG, T ESCHENHAGEN, O ZOLK
Journal: Cardiovascular Research (2005)

Objective: Most cardiac myosin binding protein C (cMyBP-C) gene mutations causing familial hypertrophic cardiomyopathy (FHC) result in C-terminal truncated proteins. However, truncated cMyBP-Cs were undetectable in myocardial tissue of FHC patients. In the present study, we investigated whether truncated cMyBP-Cs are subject to accelerated degradation by the lysosome or ubiquitin–proteasome system (UPS).
Novel Therapeutic Strategy to Prevent Chemotherapy-Induced Persistent Sensory Neuropathy By TRPA1 Blockade
Authors: Gabriela Trevisan, Serena Materazzi, Camilla Fusi, Alessandra Altomare, Giancarlo Aldini, Maura Lodovici, Riccardo Patacchini, Pierangelo Geppetti, Romina Nassini
Journal: Cancer Research (2013)

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and painful adverse reaction of cancer treatment in patients that is little understood or treated. Cytotoxic drugs that cause CIPN exert their effects by increasing oxidative stress, which activates the ion channel TRPA1 expressed by nociceptors. In this study, we evaluated whether TRPA1 acted as a critical mediator of CIPN by bortezomib or oxaliplatin in a mouse model system. Bortezomib evoked a prolonged mechanical, cold, and selective chemical hypersensitivity (the latter against the TRPA1 agonist allyl isothiocyanate). This CIPN hypersensitivity phenotype that was stably established by bortezomib could be transiently reverted by systemic or local treatment with the TRPA1 antagonist HC-030031. A similar effect was produced by the oxidative stress scavenger α-lipoic acid. Notably, the CIPN phenotype was abolished completely in mice that were genetically deficient in TRPA1, highlighting its essential role. Administration of bortezomib or oxaliplatin, which also elicits TRPA1-dependent hypersensitivity, produced a rapid, transient increase in plasma of carboxy-methyl-lysine, a by-product of oxidative stress. Short-term systemic treatment with either HC-030031 or α-lipoic acid could completely prevent hypersensitivity if administered before the cytotoxic drug. Our findings highlight a key role for early activation/sensitization of TRPA1 by oxidative stress by-products in producing CIPN. Furthermore, they suggest prevention strategies for CIPN in patients through the use of early, short-term treatments with TRPA1 antagonists. Cancer Res; 73(10); 3120–31. ©2013 AACR.
Low-dose liposomal amphotericin B in the prevention of invasive fungal infections in patients with prolonged neutropenia: results from a randomized, single-center trial
Authors: O. Penack, S. Schwartz, P. Martus, M. Reinwald, M. Schmidt-Hieber, E. Thiel, I.W. Blau
Journal: Annals of Oncology (2006)
Morphine and Atropine
Authors: W. H. Calvert
Journal: BMJ (1894)

<h3>Abstract</h3> Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month. Apart from fever and respiratory complications, acute kidney injury has been observed in some patients with 2019-nCoV. In a short period of time, angiotensin converting enzyme II (ACE2), have been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same for severe acute respiratory syndrome coronavirus (SARS). To investigate the possible cause of kidney damage in 2019-nCoV patients, we used both published kidney and bladder cell atlas data and an independent unpublished kidney single cell RNA-Seq data generated in-house to evaluate ACE2 gene expressions in all cell types in healthy kidneys and bladders. Our results showed the enriched expression of all subtypes of proximal tubule cells of kidney and low but detectable levels of expression in bladder epithelial cells. These results indicated the urinary system is a potential route for 2019-nCoV infection, along with the respiratory system and digestion system. Our findings suggested the kidney abnormalities of SARS and 2019-nCoV patients may be due to proximal tubule cells damage and subsequent systematic inflammatory response induced kidney injury. Beyond that, laboratory tests of viruses and related indicators in urine may be needed in some special patients of 2019-nCoV.
Integrated Genomic Profiling, Therapy Response, and Survival in Adult Acute Myelogenous Leukemia
Authors: Brian Parkin, Peter Ouillette, Mehmet Yildiz, Kamlai Saiya-Cork, Kerby Shedden, Sami N. Malek
Journal: Clinical Cancer Research (2015)

Recurrent gene mutations, chromosomal translocations, and acquired genomic copy number aberrations (aCNA) have been variously associated with acute myelogenous leukemia (AML) patient outcome. However, knowledge of the co-occurrence of such lesions and the relative influence of different types of genomic alterations on clinical outcomes in AML is still evolving.We performed SNP 6.0 array-based genomic profiling of aCNA/copy neutral loss-of-heterozygosity (cnLOH) along with sequence analysis of 13 commonly mutated genes on purified leukemic blast DNA from 156 prospectively enrolled non-FAB-M3 AML patients across the clinical spectrum of de novo, secondary, and therapy-related AML.TP53 and RUNX1 mutations are strongly associated with the presence of SNP-A-based aCNA/cnLOH, while FLT3 and NPM1 mutations are strongly associated with the absence of aCNA/cnLOH. The presence of mutations in RUNX1, ASXL1, and TP53, elevated SNP-A-based genomic complexity, and specific recurrent aCNAs predicted failure to achieve a complete response to induction chemotherapy. The presence of ≥1 aCNA/cnLOH and higher thresholds predicted for poor long-term survival irrespective of TP53 status, and the presence of ≥1 aCNA/cnLOH added negative prognostic information to knowledge of mutations in TET2, IDH1, NPM1, DNMT3A, and RUNX1. Results of multivariate analyses support a dominant role for TP53 mutations and a role for elevated genomic complexity as predictors of short survival in AML.Integrated genomic profiling of a clinically relevant adult AML cohort identified genomic aberrations most associated with SNP-A-based genomic complexity, resistance to intensive induction therapies, and shortened overall survival. Identifying SNP-A-based lesions adds prognostic value to the status of several recurrently mutated genes.
The PDGFRβ–AKT Pathway Contributes to CDDP-Acquired Resistance in Testicular Germ Cell Tumors
Authors: M. Juliachs, C. Muñoz, C.A. Moutinho, A. Vidal, E. Condom, M. Esteller, M. Graupera, O. Casanovas, J.R. Germà, A. Villanueva, F. Viñals
Journal: Clinical Cancer Research (2013)

We examined whether PI3K-AKT or extracellular signal-regulated kinase (ERK) signaling pathways could play a role in the development of cisplatin (CDDP) resistance in testicular germ cell tumor (TGT) cells.We compared AKT and ERK activation levels in CDDP-sensitive testicular tumor cells and in their corresponding CDDP-resistant-derived cells. We also analyzed these pathways in orthotopic testicular tumors and human patient samples.Our results indicated that there was overactivation of AKT in CDDP-resistant cells compared with sensitive cells, but no effect on activated ERK levels. We observed an increase in mRNA and protein levels for platelet-derived growth factor (PDGF) receptor β and PDGF-B ligand. These were responsible for AKT overactivation in CDDP-resistant cells. When PDGFRβ levels were decreased by short hairpin RNA (shRNA) treatment or its activation was blocked by pazopanib, CDDP-resistant cells behaved like sensitive cells. Moreover, CDDP-resistant cells were more sensitive to incubation with PDGFRβ inhibitors such as pazopanib or sunitinib than sensitive cells, a finding consistent with these cells being dependent on this signaling pathway. We also found overexpression of PDGFRβ and pAKT in CDDP-resistant choriocarcinoma orthotopic tumor versus their CDDP-sensitive counterparts. Finally, we found high PDGFRβ levels in human testicular tumors, and overexpression in CDDP-resistant testicular choriocarcinomas compared with the CDDP-sensitive and nontreated tumors.The PDGFRβ-AKT pathway plays a critical role in the development of CDDP resistance in testicular tumoral cells.
AN OUTBREAK OF PNEUMONIA IN DAIRY COWS ATTRIBUTED TO BACILLUS BOVISEPTICUS
Authors: F. S. Jones, Ralph B. Little
Journal: The Journal of Experimental Medicine (1921)

All outbreak of pneumonia in dairy cows attributed to Bacillus bovisepticus is described. About twenty cows and two calves were affected. The first cases were noted in cows purchased in Michigan. The disease next appeared in another lot of cows from Pennsylvania and subsequently attacked native stock. Of the ten cases which came under our observation, five apparently recovered, two died, and two severely affected cows were killed. The other case developed multiple abscesses of the lung and was finally killed. The more characteristic symptoms observed were high temperature, rapid respiration, dyspnea, cough, dullness on percussion, bronchial breathing, and albuminuria. The pneumonia was diffuse but first affected the cephalic and more dependent lobes. The process varied from hyperemia and hemorrhage to exudation of fibrin and leucocytes within the air spaces. The plugging of the interlobular lymph channels and blood vessels with fibrin was frequent. Bacillus bovisepticus was isolated in pure cultures from all involved portions of lung at autopsy. It was not found in blood cultures during the height of the disease, nor could it be obtained from the spleen and kidney after death.
Optimal loading: key variables and mechanisms
Authors: Philip Glasgow, Nicola Phillips, Christopher Bleakley
Journal: British Journal of Sports Medicine (2015)

The acronym PRICE (protection, rest, ice, compression and elevation) has traditionally been the cornerstone for treating acute soft tissue injury. Recently, its relevance in some cases has been questioned;1 of particular concern is that protection and rest may correspond with an excessively conservative approach that fails to harness the benefits of progressive tissue loading through exercise.

Optimal loading may be defined as the load applied to structures that maximises physiological adaptation. Achieving optimal loading is challenging but should be driven by variables such as the tissue type, pathological presentation and the required tissue adaptation for eventual activity. Specific loading goals may include increased tensile strength, collagen reorganisation, increased muscle–tendon unit stiffness or neural reorganisation.

Optimal loading works through various cellular and neural mechanisms to induce a wide range of changes (summarised in figure 1). Manipulation of loading variables can have profound effects on the nature, structure and function of the wider neuromusculoskeletal system.



Figure 1 
Effects of mechanical loading.



One variable with …
Validation of Comorbid Conditions on the End-Stage Renal Disease Medical Evidence Report
Authors: J. CRAIG LONGENECKER, JOSEF CORESH, MICHAEL J. KLAG, ANDREW S. LEVEY, ALICE A. MARTIN, NANCY E. FINK, NEIL R. POWE
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Since 1995, the Medical Evidence Report for endstage renal disease (Form 2728) has been used nationally to collect information on comorbid conditions. To date, these data have not been validated. A national cross-sectional study of 1005 incident dialysis patients (734 hemodialysis and 271 peritoneal dialysis) enrolled between October 1995 and June 1998 was conducted using clinical data to validate 17 comorbid conditions on Form 2728. Sensitivity and specificity were calculated for each condition. The relationship between patient characteristics and sensitivity was assessed in multivariate analysis. Sensitivity was fairly high (0.67 to 0.83) for HIV disease, diabetes, and hypertension; intermediate (0.40 to 0.52) for peripheral vascular disease, neoplasm, myocardial infarction, cerebrovascular disease, coronary artery disease, cardiac arrest, and congestive heart failure; and poor (&lt;0.36) for dysrhythmia, ambulation status, pericarditis, chronic obstructive pulmonary disease, and smoking. Sensitivity did not change significantly over calendar time. The sensitivity of Form 2728 averaged across all 17 conditions was 0.59 (95% confidence interval, 0.43 to 0.75). The average sensitivity was 0.10 greater in peritoneal dialysis than hemodialysis patients, 0.11 greater in diabetic patients than nondiabetic patients, and 0.04 less with each added comorbid condition. The specificity was very good for hypertension (0.91) and excellent (&gt;0.95) for the other 16 conditions. Comorbid conditions are significantly underreported on Form 2728, but diagnoses are not falsely attributed to patients. Scientific research, quality of care comparisons, and payment policies that use Form 2728 data should take into account these limitations. Considerable effort should be expended to improve Form 2728 coding if it is to provide accurate estimates of total disease burden in end-stage renal disease patients.
Adenosine signaling contributes to ethanol-induced fatty liver in mice
Authors: Zhongsheng Peng, Pier Andrea Borea, Tuere Wilder, Herman Yee, Luis Chiriboga, Michael R. Blackburn, Gianfranco Azzena, Giuseppe Resta, Bruce N. Cronstein
Journal: Journal of Clinical Investigation (2009)

Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the biochemical and pharmacological mechanisms by which ethanol stimulates these molecular changes remain unknown. During ethanol metabolism, adenosine is generated by the enzyme ecto-5′-nucleotidase, and adenosine production and adenosine receptor activation are known to play critical roles in the development of hepatic fibrosis. We therefore investigated whether adenosine and its receptors play a role in the development of alcohol-induced fatty liver. WT mice fed ethanol on the Lieber-DeCarli diet developed hepatic steatosis, including increased hepatic triglyceride content, while mice lacking ecto-5′-nucleotidase or adenosine A1 or A2B receptors were protected from developing fatty liver. Similar protection was also seen in WT mice treated with either an adenosine A1 or A2B receptor antagonist. Steatotic livers demonstrated increased expression of genes involved in fatty acid synthesis, which was prevented by blockade of adenosine A1 receptors, and decreased expression of genes involved in fatty acid metabolism, which was prevented by blockade of adenosine A2B receptors. In vitro studies supported roles for adenosine A1 receptors in promoting fatty acid synthesis and for A2B receptors in decreasing fatty acid metabolism. These results indicate that adenosine generated by ethanol metabolism plays an important role in ethanol-induced hepatic steatosis via both A1 and A2B receptors and suggest that targeting adenosine receptors may be effective in the prevention of alcohol-induced fatty liver.
How to Read a Systematic Review and Meta-analysis and Apply the Results to Patient Care
Authors: Mohammad Hassan Murad, Victor M. Montori, John P. A. Ioannidis, Roman Jaeschke, P. J. Devereaux, Kameshwar Prasad, Ignacio Neumann, Alonso Carrasco-Labra, Thomas Agoritsas, Rose Hatala, Maureen O. Meade, Peter Wyer, Deborah J. Cook, Gordon Guyatt
Journal: JAMA (2014)

ScenarioYou are consulted regarding the perioperative management of a 66year-old man undergoing hip replacement.He is a smoker and has a history of type 2 diabetes and hypertension.Because he has multiple cardiovascular risk factors, you consider using perioperative β-blockers to reduce the risk of postoperative cardiovascular complications.You identify a recently published systematic review and meta-analysis evaluating the effect of perioperative β-blockers on death, nonfatal myocardial infarction, and stroke. 1 How should you use this meta-analysis to help guide your clinical decision making?
Medical Costs and Quality of Life 10 to 12 Years After Randomization to Angioplasty or Bypass Surgery for Multivessel Coronary Artery Disease
Authors: Mark A. Hlatky, Derek B. Boothroyd, Kathryn A. Melsop, Maria M. Brooks, Daniel B. Mark, Bertram Pitt, Guy S. Reeder, William J. Rogers, Thomas J. Ryan, Patrick L. Whitlow, Robert D. Wiens
Journal: Circulation (2004)

Background— Coronary bypass surgery (CABG) and angioplasty (PTCA) have been compared in several randomized trials, but data about long-term economic and quality-of-life outcomes are limited. Methods and Results— Cost and quality-of-life data were collected prospectively from 934 patients who were randomized in the Bypass Angioplasty Revascularization Investigation (BARI) and followed up for 10 to12 years. CABG had 53% higher costs initially, but the gap closed to &lt;5% during the first 2 years; after 12 years, the mean cumulative cost of CABG patients was $123 000 versus $120 750 for PTCA, yielding a cost-effectiveness ratio of $14 300/life-year added. CABG patients experienced significantly greater improvement in their physical functioning for the first 3 years but not in later follow-up. Recurrent angina substantially reduced all quality-of-life measures throughout follow-up. Cumulative costs were significantly higher among patients with diabetes, heart failure, and comorbid conditions and among women; costs also were increased by angina, by the number of revascularization procedures, and among patients who died. Conclusion— Early differences between CABG and PTCA in costs and quality of life were no longer significant at 10 to 12 years of follow-up. CABG was cost-effective as compared with PTCA for multivessel disease.
Tropical chronic pancreatitis: a historical perspective
Authors: V. Balakrishnan
Journal: Gut (2010)

I read the article on idiopathic chronic pancreatitis (ICP) in India in which there was reference to tropical chronic pancreatitis (TCP).1 TCP was a form of ICP first described in the 1960s in the south-western state of Kerala in India.2 Even though the aetiology of this new condition was unknown, the clinical features of the new entity of chronic pancreatitis (CP) in young malnourished non-alcoholic subjects in poor tropical countries was so distinctive that, to distinguish it from alcoholic chronic pancreatitis (ACP), the term ‘TCP’ came into usage without much thought into its aetiological connotation and was accepted by the medical community. …
Micro-RNA expression in cisplatin resistant germ cell tumor cell lines
Authors: Matthias Port, Stephanie Glaesener, Christian Ruf, Armin Riecke, Carsten Bokemeyer, Viktor Meineke, Friedemann Honecker, Michael Abend
Journal: Molecular Cancer (2011)

We compared microRNA expression patterns in three cisplatin resistant sublines derived from paternal cisplatin sensitive germ cell tumor cell lines in order to improve our understanding of the mechanisms of cisplatin resistance. Three cisplatin resistant sublines (NTERA-2-R, NCCIT-R, 2102EP-R) showing 2.7-11.3-fold increase in drug resistance after intermittent exposure to increasing doses of cisplatin were compared to their parental counterparts, three well established relatively cisplatin sensitive germ cell tumor cell lines (NTERA-2, NCCIT, 2102EP). Cells were cultured and total RNA was isolated from all 6 cell lines in three independent experiments. RNA was converted into cDNA and quantitative RT-PCR was run using 384 well low density arrays covering almost all (738) known microRNA species of human origin. Altogether 72 of 738 (9.8%) microRNAs appeared differentially expressed between sensitive and resistant cell line pairs (NTERA-2R/NTERA-2 = 43, NCCIT-R/NCCIT = 53, 2102EP-R/2102EP = 15) of which 46.7-95.3% were up-regulated (NTERA-2R/NTERA-2 = 95.3%, NCCIT-R/NCCIT = 62.3%, 2102EP-R/2102EP = 46.7%). The number of genes showing differential expression in more than one of the cell line pairs was 34 between NTERA-2R/NTERA-2 (79%) and NCCIT-R/NCCIT (64%), and 3 and 4, respectively, between these two cell lines and 2102EP-R/2102EP (about 27%). Only the has-miR-10b involved in breast cancer invasion and metastasis and has-miR-512-3p appeared to be up-regulated (2-3-fold) in all three cell lines. The hsa-miR-371-373 cluster (counteracting cellular senescence and linked with differentiation potency), as well as hsa-miR-520c/-520h (inhibiting the tumor suppressor p21) were 3.9-16.3 fold up-regulated in two of the three cisplatin resistant cell lines. Several new micro-RNA species missing an annotation towards cisplatin resistance could be identified. These were hsa-miR-512-3p/-515/-517/-518/-525 (up to 8.1-fold up-regulated) and hsa-miR-99a/-100/-145 (up to 10-fold down-regulated). Examining almost all known human micro-RNA species confirmed the miR-371-373 cluster as a promising target for explaining cisplatin resistance, potentially by counteracting wild-type P53 induced senescence or linking it with the potency to differentiate. Moreover, we describe for the first time an association of the up-regulation of micro-RNA species such as hsa-miR-512-3p/-515/-517/-518/-525 and down-regulation of hsa-miR-99a/-100/-145 with a cisplatin resistant phenotype in human germ cell tumors. Further functional analyses are warranted to gain insight into their role in drug resistance.
Generation of interleukin-13 receptor alpha2 antigen expressing modified vaccinia ankara recombinant virus for potential cancer immunotherapy
Authors: Yuki Sato, Ramjay Vatsan, Bharat H Joshi, Syed R Husain, Raj K Puri
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Genetically modified recombinant poxviruses have shown promise in preclinical models of cancer immunotherapy due to their ability to induce effective cell-mediated immunity against target tumor-associated antigens (TAA). One such vector, recombinant Modified Vaccinia Ankara (MVA