tbuckley/cabot-search huggingface dataset:
THE INFECTION OF MICE WITH SWINE INFLUENZA VIRUS
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1935)

The experiments confirm the earlier observation of Andrewes, Laidlaw and Smith that the swine influenza virus is pathogenic for white mice when administered intranasally. Two field strains of the swine influenza virus were found to differ in their initial pathogenicity for mice. One strain was apparently fully pathogenic even in its 1st mouse passage while the other required 2 or 3 mouse passages to acquire full virulence for this species. Both strains, however, were initially infectious for mice, without the necessity of intervening ferret passages. There is no evidence that bacteria play any significant rôle in the mouse disease though essential in that of swine, and fatal pneumonias can be produced in mice by pure virus infections. Mice surviving the virus disease are immune to reinfection for at least a month. In mice the disease is not contagious though it is notably so in swine. The virus, while regularly producing fatal pneumonias when administered intranasally to mice, appears to be completely innocuous when given subcutaneously or intraperitoneally. Prolonged serial passage of the virus in mice does not influence its infectivity or virulence for swine or ferrets. It is a stable virus so far as its infectivity is concerned, and can be transferred at will from any one of its three known susceptible hosts to any other. In discussing these facts the stability of the swine influenza virus has been contrasted with the apparent instability of freshly isolated strains of the human influenza virus. Though the mouse is an un-natural host for the virus it is, nevertheless, useful for the study of those aspects of swine influenza which have to do with the virus only.
The Anti-Fibrotic Effect of Mycophenolic Acid–Induced Neutral Endopeptidase
Authors: Maria Pia Dell'Oglio, Gianluigi Zaza, Michele Rossini, Chiara Divella, Paola Pontrelli, Raffaella Verrienti, Monica Rutigliano, Pasquale Ditonno, Patrizia Stifanelli, Nicola Ancona, Francesco Paolo Schena, Giuseppe Grandaliano
Journal: Journal of the American Society of Nephrology (2010)

Mycophenolic acid (MPA) appears to have anti-fibrotic effects, but the molecular mechanisms underlying this are unknown. We prospectively studied 35 stable kidney transplant recipients maintained on cyclosporine and azathioprine. We converted 20 patients from azathioprine to enteric-coated mycophenolate sodium (EC-MPS) and continued the remaining 15 patients on azathioprine. Exploratory mRNA expression profiling, performed on five randomly selected EC-MPS patients, revealed significant upregulation of neutral endopeptidase (NEP), which is an enzyme that degrades angiotensin II. We confirmed these microarray data by measuring levels of NEP expression in all subjects; in addition, we found that NEP gene expression correlated inversely with proteinuria. In an additional 33 patients, glomerular and tubular NEP protein levels from renal graft biopsies were significantly higher among the 13 patients receiving cyclosporine + EC-MPS than among the 12 patients receiving cyclosporine + azathioprine or 8 patients receiving cyclosporine alone. Glomerular NEP expression inversely correlated with glomerulosclerosis and proteinuria, and tubular NEP expression inversely correlated with interstitial fibrosis. Incubation of human proximal tubular cells with MPA increased NEP gene expression in a dose- and time-dependent manner. Moreover, MPA reduced angiotensin II-induced expression of the profibrotic factor plasminogen activator inhibitor-1, and a specific NEP inhibitor completely reversed this effect. Taken together, our data suggest that MPA directly induces expression of neutral endopeptidase, which may reduce proteinuria and slow the progression of renal damage in kidney transplant recipients.
Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma
Authors: Wen Zhou, Xiangling Feng, Caiping Ren, Xingjun Jiang, Weidong Liu, Wei Huang, Zhihong Liu, Zan Li, Liang Zeng, Lei Wang, Bin Zhu, Jia Shi, Jie Liu, Chang Zhang, Yanyu Liu, Kaitai Yao
Journal: Molecular Cancer (2013)

Abstract Background Nasopharyngeal carcinoma (NPC) is a common malignant tumor in southern China and Southeast Asia, but its molecular mechanisms of pathogenesis are poorly understood. Our previous work has demonstrated that BCAT1 mRNA is over expressed in NPC and knocking down its expression in 5-8F NPC cell line can potently inhibit cell cycle progression and cell proliferation. However, the mechanism of BCAT1 up-regulation and its functional role in NPC development remain to be elucidated yet. Methods Immunohistochemistry (IHC) method was utilized to detect the expression of BCAT1 protein in NPC at different pathological stages. The roles of gene mutation, DNA amplification and transcription factor c-Myc in regulating BCAT1 expression were analyzed using PCR-sequencing, quantitative polymerase chain reaction (qPCR), IHC, ChIP and luciferase reporter system, respectively. The functions of BCAT1 in colony formation, cell migration and invasion properties were evaluated by RNA interference (RNAi). Results The positive rates of BCAT1 protein expression in normal epithelia, low-to-moderate grade atypical hyperplasia tissues, high-grade atypical hyperplasia tissues and NPC tissues were 23.6% (17/72), 75% (18/24 ), 88.9% (8/9) and 88.8% (71/80), respectively. Only one SNP site in exon1 was detected, and 42.4% (12/28) of the NPC tissues displayed the amplification of microsatellite loci in BCAT1 . C-Myc could directly bind to the c-Myc binding site in promoter region of BCAT1 and up-regulate its expression. The mRNA and protein of c - Myc and BCAT1 were co-expressed in 53.6% (15/28) and 59.1% (13/22) of NPC tissues, respectively, and BCAT1 mRNA expression was also down-regulated in c-Myc knockdown cell lines. In addition, BCAT1 knockdown cells demonstrated reduced proliferation and decreased cell migration and invasion abilities. Conclusions Our study indicates that gene amplification and c-Myc up-regulation are responsible for BCAT1 overexpression in primary NPC, and overexpression of BCAT1 induces cell proliferation, migration and invasion. The results suggest that BCAT1 may be a novel molecular target for the diagnosis and treatment of NPC.
Biliary lipid secretion and bile composition after acute and chronic interruption of the enterohepatic circulation in the rhesus monkey
Authors: R. Hermon Dowling, Eberhard Mack, Donald M. Small
Journal: Journal of Clinical Investigation (1971)

Bile salts and phospholipids are both required to solubilize biliary cholesterol. Since interruption of the enterohepatic circulation (EHC) depletes bile of bile salts, we have examined in the rhesus monkey the effects of controlled interruption of the EHC on biliary secretion of bile salt, phospholipid, and cholesterol and on the relative proportions of these components in bile. Immediately after complete interruption of the EHC, bile secretion and bile composition remained normal for 2-3 hr. During the next 3 hr, however, secretion of all components decreased. Bile salt decreased to a greater extent than phospholipid and cholesterol, and the bile was now supersaturated with cholesterol. 12-24 hr after interruption of the EHC, a new steady state was reached in which there was a relative deficiency of bile salt and a relative increase in phospholipid and cholesterol. The resulting bile, although somewhat more saturated with cholesterol, was not supersaturated with cholesterol but was stable with respect to cholesterol solubility. Thus, bile instability conducive to gallstone formation occurs transiently within hours after interruption of the EHC. Prolonged large interruptions in the steady state animal also produce a relative bile salt deficiency, but in this situation cholesterol remains soluble in the bile of these animals because there occurs a concomitant relative increase in phospholipid. When the EHC was only partially interrupted, secretion rates and the relative concentration of bile salt, phospholipid, and cholesterol did not change significantly from control values until more than 20% of the bile was diverted. Modest changes in the relative composition of bile occurred when 33 and 66% of the bile was diverted, and these changes were very similar to those produced by resection of the distal small bowel.
Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN
Authors: Santhosh V.R. Kumar, Onkar P. Kulkarni, Shrikant R. Mulay, Murthy N. Darisipudi, Simone Romoli, Dana Thomasova, Christina R. Scherbaum, Bernd Hohenstein, Christian Hugo, Susanna Müller, Helen Liapis, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2015)

Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti–glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN.
Cyclic Adenosine 3′,5′-Monophosphate in the Control of Melanoma Cell Replication and Differentiation2
Authors: John W. Kreider, M. Rosenthal, N. Lengle
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Cyclic Adenosine 3′,5′-Monophosphate in the Control of Melanoma Cell Replication and Differentiation Get access John W. Kreider, John W. Kreider Departments of Pathology and Biological Chemistry, College of Medicine, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033 Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Rosenthal, M. Rosenthal Departments of Pathology and Biological Chemistry, College of Medicine, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033 Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Lengle N. Lengle Departments of Pathology and Biological Chemistry, College of Medicine, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 555–558, https://doi.org/10.1093/jnci/50.2.555 Published: 01 February 1973 Article history Received: 29 September 1972 Accepted: 16 November 1972 Published: 01 February 1973
Induction of acute cholecystitis by activation of factor XII.
Authors: C G Becker, T Dubin, F Glenn
Journal: The Journal of Experimental Medicine (1980)

Acute, acalculous cholecystitis is seen among patients suffering with bacterial sepsis, burns, trauma, or cancer; clinical conditions that could lead to activation of factor XII-dependent pathways and result in inflammation of the gall bladder. To test this hypothesis, dogs were injected intravenously with ellagic acid or rutin, known polyphenol activators of factor XII, or with Escherichia coli endotoxin, also known to activate factor XII, and monkeys were injected intravenously with ellagic acid. In both species, in vivo activation of factor XII-dependent pathways with polyphenol activator resulted in rapid and selective development of acute vasculitis in the serosa and muscularis of the gallbladder and margination of polymorphonuclear neutrophils in pulmonary blood vessels. Intravenous injection of E. coli endotoxin in dogs resulted in necrosis and thrombosis of vessels that were especially severe in the serosa and muscularis of the gallbladder but also present in vessels of many other organs. These observations indicate that blood vessels of the gall bladder and, to a lesser degree, the lung are especially sensitive to injury consequent to in vivo activation of factor XII-dependent pathways and, in view of the common ingestion of plant polyphenols, may provide important insight into the pathogenesis of cholecystitis in man.
Therapeutic Induction of Arteriogenesis in Hypoperfused Rat Brain Via Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Ivo R. Buschmann, Hans-Jörg Busch, Günter Mies, Konstantin-Alexander Hossmann
Journal: Circulation (2003)

Colony-stimulating factors (CSFs) have been shown to effectively induce arteriogenesis in the hindlimb. Moreover, clinical trials demonstrated positive effects of CSFs on arteriogenesis in patients with coronary artery disease. However, patients with cerebrovascular disease have not yet profited from treatments aimed at the growth of brain vessels. Thus far, angiogenesis studies have failed to demonstrate improvement of stroke outcome. Arteriogenesis differs from angiogenesis in that it substitutes arterial collaterals for the occluded artery.We tested in a novel brain arteriogenesis rat model (occlusion of vertebral plus left carotid artery [3-VO]) the application of CSFs or saline over 7 or 21 days. On 3-VO postmortem, latex perfusion demonstrated a time- and treatment-dependent arteriogenesis of the posterior cerebral artery (PCA). In saline-treated animals, the PCA diameter increased by 39%; in granulocyte-macrophage (GM)-CSF-treated animals, this increase was significantly faster (72% after 1 week). Functionally, saline-treated animals exhibited a decline of CO2 reactivity (mm Hg) from 1.48% to 0.1% compared with GM-CSF-treated animals (1.43% arterial pCo2 change after 1 week). This difference remained significant after 3 weeks. This functional improvement correlated with increased numbers of CD68-positive macrophages in histological sections of the PCA in GM-CSF--treated animals and only a few macrophages in saline-treated animals.To the best of our knowledge, this is the first report of stimulation of arteriogenesis in the brain. The subcutaneous application of GM-CSF led to functional improvement of brain hemodynamic parameters.
Osteoprotegerin, Thiazolidinediones Treatment, and Silent Myocardial Ischemia in Type 2 Diabetic Patients
Authors: Ariane Sultan, Antoine Avignon, Florence Galtier, Christophe Piot, Denis Mariano-Goulart, Anne Marie Dupuy, Jean Paul Cristol
Journal: Diabetes Care (2008)

Thiazolidinediones (TZDs) are widely prescribed for the treatment of type 2 diabetes. They were reported to have vasculoprotective properties like a reduction in carotid artery intima-media thickness progression (1) but may also reduce bone formation and favor bone loss (2,3). The decoy receptor osteoprotegerin, a member of the receptor activator of nuclear factor-κB ligand/osteoprotegerin system, involved in osteoclast development and function (4), might also be a regulator of vascular calcification and an indicator of vascular disease (5). In diabetic patients, this latter point is supported by our previous data showing a positive association between silent myocardial ischemia (SMI) and osteoprotegerin levels (6,7). We tested, in a case-control study, the a priori hypothesis that TZDs might be associated with decreased osteoprotegerin levels and lower prevalence of SMI in patients treated with TZDs.

A total of 198 consecutive asymptomatic non–insulin-treated type 2 diabetes patients (age 60.1 ± 9.1, 68% male, A1C 8.1 ± 1.7%, BMI 30.7 ± 4.6 kg/m2) with one or more additional risk factor underwent SMI screening, using dipyridamole combined with exercise myocardial perfusion imaging (MPI) as previously described (6,7). SMI was defined as positive MPI (mean activity  1 mm).

The 46 type 2 diabetic patients …
Metacognition as evidence for explicit representation in nonhumans
Authors: Robert Russell Hampton
Journal: Behavioral and Brain Sciences (2003)

Metacognition is either direct, as when information is recalled before making a confidence judgment, or indirect, as when the probability of successful future retrieval is determined inferentially. Direct metacognition may require an explicit mental representation as its object and can only be demonstrated under specific experimental circumstances. Other forms of metacognition can be based on publicly observable stimuli rather than introspection.
Hypertension, Pregnancy, and Risk of Breast Cancer
Authors: W. D. Thompson, H. I. Jacobson, B. Negrini, D. T. Janerich
Journal: JNCI Journal of the National Cancer Institute (1989)

We investigated the relationship between hypertension and breast cancer using data from a large case-control study of women younger than 55 years. Among nulliparous women, there was little evidence of an association between hypertension and breast cancer. Among parous women, hypertension reduced the risk of breast cancer if it had been diagnosed at any time in their lives before the end of the most recent pregnancy (odds ratio = 0.73; 95% confidence interval = 0.59–0.92). Several earlier studies indicate that there is an association between hypertension during pregnancy and elevated levels of maternal serum α-fetoprotein. Thus, our results are consistent with the hypothesis that maternal exposure to α-fetoprotein during pregnancy protects women against the subsequent occurrence of breast cancer. [J Natl Cancer Inst 81:1571–1574, 1989]
Acute Coronary Syndrome
Authors: Albrecht Elsaesser, Christian W. Hamm
Journal: Circulation (2004)

oronary heart disease is the leading cause of mortality and morbidity in industrialized countries, in men as well as in women.Women have their first cardiac event 6 to 10 years later than men do.Whereas the cardiovascular death rates are declining in men, they remain constant in women.In cardiovascular studies with age limits, women are naturally the minority, amounting to Ͻ40%.It is well known that distinct gender differences exist in terms of presentation of symptoms, validity of diagnostic tests, drug side effects, and complications.With respect to cardiac risk factors, women have higher rates of diabetes and hypertension but are less frequently smokers.
Studies of Tissue Response to Injections of Enzymes
Authors: SAMUEL T. SCHLAMOWITZ, ARTHUR C. DEGRAFF
Journal: Circulation (1951)

The presence of proteolytic enzymes in blood has been known for a long time. A variety of methods and agents have been employed to activate these enzymes. Among these, is streptokinase, a bacterial kinase obtained from the hemolytic streptococcus. The subcutaneous "nodules" and significant hexosamine alterations which occurred following the single subcutaneous inoculation of crude streptokinase, resembled those obtained with partially purified streptokinase and with trypsin-(crude and crystalline). Although it is possible that the results obtained with streptokinase were due to the direct conversion of the proteolytic enzyme to its active form, and that changes noted with trypsin were due to the nullification of the inhibitor with the concomitant liberation of the free and active enzyme, it is also very possible that both trypsin and streptokinase give rise to the liberation of a tissue activator, which in turn catalyzes the transformation of the proteolytic enzyme to its active form.
ras Oncogene Activation and Occupational Exposures in Acute Myeloid Leukemia
Authors: J. A. Taylor, D. P. Sandler, C. D. Bloomfield, D. L. Shore, E. D. Ball, A. Neubauer, O. R. McIntyre, E. Liu
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article ras Oncogene Activation and Occupational Exposures in Acute Myeloid Leukemia Get access Jack A. Taylor, Jack A. Taylor * Environmental and Molecular Epidemiology Section, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle ParkN.C. Present address : A. Neubauer, Department of Medicine, Univer-sitaetsklinikum Rudolf Virchow, Berlin, Federal Republic of Germany. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dale P. Sandler, Dale P. Sandler Environmental and Molecular Epidemiology Section, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle ParkN.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Clara D. Bloomfield, Clara D. Bloomfield Department of Medicine, Roswell Park Cancer InstituteBuffalo, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar David L. Shore, David L. Shore Westat, Inc.Durham, N.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward D. Ball, Edward D. Ball Section of Hematology/Bone Marrow Transplant, University of Pittsburgh Medical CenterPittsburgh, Pa. Search for other works by this author on: Oxford Academic PubMed Google Scholar Andreas Neubauer, Andreas Neubauer Department of Medicine, University of North Carolina School of MedicineChapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar O. Ross McIntyre, O. Ross McIntyre Cancer and Leukemia Group B, Dartmouth-Hitchcock Medical CenterHanover, N.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edison Liu Edison Liu Department of Medicine, University of North Carolina School of MedicineChapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 21, 4 November 1992, Pages 1626–1632, https://doi.org/10.1093/jnci/84.21.1626 Published: 04 November 1992 Article history Received: 27 April 1992 Revision received: 13 July 1992 Accepted: 31 July 1992 Published: 04 November 1992
The <i>High Mobility Group A1</i> Gene: Transforming Inflammatory Signals into Cancer?
Authors: Linda M.S. Resar
Journal: Cancer Research (2010)

Abstract High mobility group A1 (HMGA1) is highly expressed during embryogenesis and in poorly differentiated cancers, and high levels portend a poor prognosis in some tumors. HMGA1 induces oncogenic transformation in cultured cells and causes aggressive cancers in transgenic mice, whereas blocking it interferes with transformation in experimental models. These findings suggest a pivotal role for HMGA1 in cancer. This review focuses on two recently described HMGA1 transcriptional targets that mediate inflammatory signals and drive malignant transformation because they could serve as biomarkers or therapeutic targets. Further elucidation of HMGA1 function in transformation promises to have a major impact on our war on cancer. Cancer Res; 70(2); 436–9