tbuckley/cabot-search huggingface dataset:
Reply to M.J. Brenner et al and I.R. Vogelius et al
Authors: Alan Pollack, Gail Walker, Eric M. Horwitz, Robert Price, Steven Feigenberg, Andre A. Konski, Radka Stoyanova, Benjamin Movsas, Richard E. Greenberg, Robert G. Uzzo, Charlie Ma, Mark K. Buyyounouski
Journal: Journal of Clinical Oncology (2014)
A Clinical Lecture ON THE IMPORTANCE OF GENERAL PRINCIPLES IN MILITARY SURGERY: Delivered at the Royal Victoria Infirmary, Newcastle-upon-Tyne
Authors: G. G. Turner
Journal: BMJ (1916)

Asthma is a chronic condition with high morbidity and healthcare costs, and cockroach allergens are an established cause of urban pediatric asthma. A better understanding of cell types involved in promoting lung inflammation could provide new targets for the treatment of chronic pulmonary disease. Because of its role in regulating myeloid cell-dependent inflammatory processes, we examined A<sub>2B</sub> R expression by myeloid cells in a cockroach allergen model of murine asthma-like pulmonary inflammation. Both systemic and myeloid tissue-specific A<sub>2B</sub> R deletion significantly decreased pulmonary inflammatory cell recruitment, airway mucin production, and proinflammatory cytokine secretion after final allergen challenge in sensitized mice. A<sub>2B</sub> R deficiency resulted in a dramatic reduction on Th2-type airways responses with decreased pulmonary eosinophilia without augmenting neutrophilia, and decreased lung IL-4, IL-5, and IL-13 production. Chemokine analysis demonstrated that eotaxin 1 and 2 secretion in response to repeated allergen challenge is myeloid cell A<sub>2B</sub> R dependent. In contrast, there were no differences in the levels of the CXC chemokines keratinocyte-derived chemokine and MIP-2 in the myeloid cell A<sub>2B</sub> R-deficient mice, strengthening A<sub>2B</sub> R involvement in the development of Th2-type airways inflammation. Proinflammatory TNF-α, IFN-γ, and IL-17 secretion were also reduced in systemic and myeloid tissue-specific A<sub>2B</sub> R deletion mouse lines. Our results demonstrate Th2-type predominance for A<sub>2B</sub> R expression by myeloid cells as a mechanism of development of asthma-like pulmonary inflammation.
O4.01 * DISTINCT FUNCTIONAL ROLES OF WILD-TYPE EGFR AND ITS MUTANT EGFRVIII IN GLIOBLASTOMA DEVELOPMENT
Authors: H. Miletic, G. V. Rosland, E. Eskilsson, K. Vaelk, O. Keunen, R. Jahedi, F. Azuaje, D. Stieber, S. Foerster, C. Ritter
Journal: Neuro-Oncology (2014)

The epidermal growth factor receptor (EGFR) is a well-known mediator of invasion, proliferation and survival of tumor cells. Amplification and associated overexpression of wild-type (wt) EGFR is the most common genetic alteration in primary glioblastoma (GBM), with a frequency of about 40-50%. Of the GBMs that have an amplification of EGFR, 50-60% also express the mutated EGFRvIII, which lacks the ligand-binding domain resulting in a constitutive activation of the receptor. It has been widely accepted that both wtEGFR and EGFRvIII substantially contribute to GBM pathogenesis, however, their specific in vivo functions are still a matter of debate. In this work we determined distinct functional roles of wtEGFR and the mutant EGFRvIII within human GBM cells in vivo. We genetically modified stem cell cultures of two different human GBM biopsies with low or absent wtEGFR expression to overexpress either wtEGFR or EGFRvIII. By orthotopic transplantation of the different cell-populations into the brains of immune-deficient rats, we were able to distinguish two different phenotypes based on MRI, histology/ immunohistochemistry and molecular analyses. Tumors with overexpression of wtEGFR showed an increased invasive growth pattern, while angiogenesis was either not observed or decreased compared to the original tumor cells. In contrast, EGFRviii overexpressing tumors were more angiogenic and less invasive compared to the control tumors and wtEGFR expressing tumors. Up-regulation of HIF1A as well as a panel of angiogenic factors confirmed angiogenesis in EGFRvIII overexpressing tumors. Integrated bioinformatics of microarray and proteomics data point to differences in signaling pathway activation between wtEGFR and EGFRvIII. In conclusion, our results demonstrate contrasting roles of wtEGFR and its mutant EGFRvIII in invasion and angiogenesis and suggest a concerted action of both receptors to promote the aggressive phenotype of human GBM in vivo.
Farnesoid X receptor, the bile acid sensing nuclear receptor, in liver regeneration
Authors: Guodong Li, Grace L. Guo
Journal: Acta Pharmaceutica Sinica B (2015)

The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy (PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids (BAs) are ligands of farnesoid X receptor (FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potential use of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.
The Reversibility of Whipple's Disease
Authors: Peter R. Holt, Kurt J. Isselbacher, Chester M. Jones
Journal: New England Journal of Medicine (1961)

AS an unusual cause of malabsorption, Whipple's uf disease (intestinal lipodystrophy) has excited the interest of clinicians because of the diffuse manifestations, the progressive clinical course and speculation over possible pathogenesis.The typical clinical picture is that of a debilitating disease manifested by abdominal pain, steatorrhea, gastrointestinal bleeding, lymphadenopathy, arthritis and pigmentation that, without treatment, usually leads to death within twelve months of the diagnosis. Diagnosis is based on the histologic demonstration of an accumulation of macrophages filled with cytoplasmic inclusions that give a positive periodic acidSchiff (PAS) reaction. These macrophages are present in the small-bowel mucosa, peripheral lymph nodes . . .
Cyst infection in acquired renal cystic disease.
Authors: J Bonal, A Caralps, R Lauzurica, A Serra, R Romero, L Inaraja
Journal: BMJ (1987)

Cyst infection in acquired renal cystic diseaseCystic degeneration of the kidney in patients with advanced renal failure is common'; whether cysts can harbour infection remains to be shown.2We report on three cases of infected cysts in acquired renal cystic disease. Case reportsCase I-A 60 year old man was admitted to hospital because of uraemia, hypertension, recurrent fever, and leucocytosis.The plasma concentration of creatinine was 821 !umol/l, and a urine culture was positive for Escherichia coli.Ultrasonography showed normal sized hyperechogenic kidneys with more than three 1-2 cm cysts in each.There was a 6 cm cyst that was hyperechogenic at the upper pole of the left kidney.Renal computed tomography confirmed the presence of bilateral multiple cysts.A thick wall, enhanced by contrast infusion, was seen around a slightly dense cyst on the upper pole of the left kidney (figure).
Exercise training ameliorates the effects of rosiglitazone on traditional and novel cardiovascular risk factors in patients with type 2 diabetes mellitus
Authors: Nikolaos P.E. Kadoglou, Fotios Iliadis, Nikolaos Sailer, Zoi Athanasiadou, Ioulia Vitta, Alikistis Kapelouzou, Panayotis E. Karayannacos, Christos D. Liapis, Miltiadis Alevizos, Nikoletta Angelopoulou, Ioannis S. Vrabas
Journal: Metabolism (2009)
Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling
Authors: Clare V Logan, György Szabadkai, Jenny A Sharpe, David A Parry, Silvia Torelli, Anne-Marie Childs, Marjolein Kriek, Rahul Phadke, Colin A Johnson, Nicola Y Roberts, David T Bonthron, Karen A Pysden, Tamieka Whyte, Iulia Munteanu, A Reghan Foley, Gabrielle Wheway, Katarzyna Szymanska, Subaashini Natarajan, Zakia A Abdelhamed, Joanne E Morgan, Helen Roper, Gijs W E Santen, Erik H Niks, W Ludo van der Pol, Dick Lindhout, Anna Raffaello, Diego De Stefani, Johan T den Dunnen, Yu Sun, Ieke Ginjaar, Caroline A Sewry, Matthew Hurles, Rosario Rizzuto, Michael R Duchen, Francesco Muntoni, Eamonn Sheridan
Journal: Nature Genetics (2013)
PD-L1 Expression and Tumor-Infiltrating Lymphocytes Define Different Subsets of MAPK Inhibitor–Treated Melanoma Patients
Authors: Hojabr Kakavand, James S. Wilmott, Alexander M. Menzies, Ricardo Vilain, Lauren E. Haydu, Jennifer H. Yearley, John F. Thompson, Richard F. Kefford, Peter Hersey, Georgina V. Long, Richard A. Scolyer
Journal: Clinical Cancer Research (2015)

To evaluate the expression of tumor PD-L1 and changes in tumor-infiltrating lymphocyte (TIL) populations in patients with metastatic melanoma treated with targeted MAPK inhibitors.Ninety-three tumors were analyzed from 40 patients treated with a BRAF inhibitor alone (BRAFi; n = 28) or combination of BRAF and MEK inhibitors (Combi; n = 12). Tumors were excised before treatment (PRE), early during treatment (EDT), and at progression (PROG). Immunohistochemical staining was performed for CD4, CD8, CD68, FOXP3, LAG3, PD-1, and PD-L1 and correlated with clinical outcome.Patients' tumors that were PD-L1 positive at baseline showed a significant decrease in PD-L1 expression at PROG (P = 0.028), whereas patients' tumors that were PD-L1 negative at baseline showed a significant increase in PD-L1 expression at PROG (P = 0.008) irrespective of treatment with BRAFi or Combi. Overall PD-L1 expression highly correlated with TIL immune markers. BRAFi-treated patients showed significant increases in CD4(+), CD8(+), and PD-1(+) lymphocytes from PRE to EDT (P = 0.001, P = 0.001, P = 0.017, respectively), and Combi-treated patients showed similar increases in CD4(+) and CD8(+) lymphocytes from PRE to EDT (P = 0.017, P = 0.021).The addition of MEKi to BRAFi did not result in significant reduction in immune infiltration in EDT biopsies. This provides support for conducting trials that combine MAPKi with immune checkpoint inhibitors in the hope of improving complete and durable response rates. PD-L1 expression at PROG on MAPK inhibitors varied according to baseline expression suggesting that combining MAPKi with immunotherapies concurrently may be more effective in patients with PD-L1 expression and TILs in baseline melanoma samples.
The social toll of Crohn's disease.
Authors: B G Gazzard, H L Price, G W Libby, A M Dawson
Journal: BMJ (1978)

Eighty-five outpatients with Crohn's disease who knew their diagnosis and that the disease was subject to relapse were interviewed. The personalities of the women as measured by the Eysenck personality questionnaire were similar to those of a control group, but the men were more neurotic and introverted. Most patients continued to live optimistic, useful lives; they felt well, continued to work, hoped that their disease would not deteriorate in the future, and often had an improved relationship with their spouse despite less frequent sexual intercourse. We found that the successful adaptation of patients to this chronic disease was more closely related to their personality than to the activity or extent of the disease.
Gonadal Activity and Chemotherapy-Induced Gonadal Damage
Authors: L. Michael Glode
Journal: JAMA (1988)

To the Editor.—  The recent article by Drs Rivkees and Crawford1again reveals the tantalizing possibility that gonadal protection from cytotoxic drugs might be achieved by hormonal induction of gonadal quiescence. Our preliminary observation that this was possible in mice has been difficult to confirm2,3; however, a growing body of evidence in other species supports the concept. The most convincing experiments are those in which gonadal protection has been achieved in a rat model2by pretreatment suppression of spermatogenesis using testosterone.4Rodent models, however, are far from perfect, as indicated by the fact that it is procarbazine, not alkylating agent therapy, that most closely mimics human testicular damage.2  Human trials of the suppression/protection concept have been carried out using inappropriately low doses of gonadotropin-releasing hormone analogues with durations too short to induce gonadal suppression prior to cytotoxic treatment.5,6As protection, if it can be
Desmoid Tumor of Abdominal Wall Infiltrating Splenic Flexure of the Colon
Authors: Franz S. Steinitz
Journal: JAMA (1961)

THE DESMOID TUMOR is an infrequent, but by no means exceptional, finding. Pack and Ehrlich 1 reported 0.03% desmoids among 50,000 tumor admissions at the Memorial Hospital in New York City and 0.13% among 16,000 tumor cases in Viennese hospitals. At the Edgewater Hospital in Chicago among 22,694 surgical cases, 3 desmoid tumors were found, or 0.013%, in the period from 1953 to 1959.  According to Pack and Ehrilich, 1 the definition of a desmoid tumor is an encapsulated, infiltrating fibroma of fascial or aponeurotic origin, with a microscopic appearance which varies from that of an acellular fibroma to that of a cellular, low-grade fibrosarcoma. The first tumors of this kind were reported by McFarlane 2 of Glasgow; however, the term desmoid was coined in 1858 by Muller, 2 who used this term because he was impressed with the dense, tendon-like consistency of the tumor (desmos, Greek:band). 2   Knowledge
The Kinetocardiogram
Authors: E. E. EDDLEMAN, KATHRYN WILLIS, LYNN CHRISTIANSON, J. R. PIERCE, R. P. WALKER
Journal: Circulation (1953)

An analysis of the patterns and amplitudes of the precordial movements is presented. Normal young adult subjects had three types of patterns. Type I occurred in 78 per cent, type II in 14 per cent, and type III in 8 per cent of the subjects studied. The variations of the kinetocardiogram from apex cardiograms and pneumocardiograms are discussed.
Case Number 25: A butterfly rash
Authors: J M G Canvin
Journal: Annals of the Rheumatic Diseases (2002)

Objective: To study the effect of meloxicam (MXC) and diclofenac (DCF) on the recruitment of leucocytes during acute experimental arthritis.Methods: Rabbits with antigen-induced arthritis were treated with MXC, DCF, or not treated.After 48 hours, synovial fluid (SF) leucocyte influx and prostaglandin E 2 (PGE 2 ) levels were evaluated.Interleukin 8 (IL8) and monocyte chemotactic peptide-1 (MCP-1) expression and synthesis were studied in the inflamed tissues.Results: Arthritic knees showed synovial effusion with a high leucocyte count and PGE 2 concentration, and an increased expression of IL8 and MCP-1.Both non-steroidal anti-inflammatory drugs (NSAIDs) reduced PGE 2 levels and the polymorphonuclear cell (PMN) concentration in SF, while the mononuclear cell (MN) concentration was unchanged in the treated groups in comparison with controls.A definite reduction of IL8 levels was obtained with the treatments, but the drugs did not prevent the up regulation of MCP-1. Conclusion:The effect of these NSAIDs in acute arthritis may be related to the down regulation of IL8 production.The results suggest a differential effect of anti-inflammatory drugs on PMN and MN recruitment to the joint.
Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles
Authors: Yelena Vachutinsky, Makoto Oba, Kanjiro Miyata, Shigehiro Hiki, Mitsunobu R. Kano, Nobuhiro Nishiyama, Hiroyuki Koyama, Kohei Miyazono, Kazunori Kataoka
Journal: Journal of Controlled Release (2010)
GASTROSCOPY: REPORT OF ADDITIONAL CASES.
Authors: CHEVALIER JACKSON
Journal: JAMA (1907)

The principal object of this paper is to report such cases as have presented themselves for gastroscopy since my paper<sup>1</sup>read before the New York Academy of Medicine in January, 1907. Discussion with different physicians and expressions of surprise by spectators at different demonstrations have shown that I had not sufficiently emphasized certain important points, and it is well to speak of them here. <h3>THE EXPLORABLE AREA.</h3> There is a widespread impression that a solid tube passed through the esophagus is held rigidly in position and that we can view through it only such small area of the gastric mucous membrane as happens to lie opposite its extremity. To show how erroneous this view is I present a radiograph (Fig. 8) made in the office of Dr. Russell H. Boggs of Pittsburg. The plate contains two exposures, one with tube lying to the left, another after it had been
Id-1 Is a Key Transcriptional Regulator of Glioblastoma Aggressiveness and a Novel Therapeutic Target
Authors: Liliana Soroceanu, Ryuichi Murase, Chandani Limbad, Eric Singer, Juanita Allison, Isabel Adrados, Rumi Kawamura, Arash Pakdel, Yayoi Fukuyo, Daniel Nguyen, Sabeena Khan, Robert Arauz, Garret L. Yount, Dan H. Moore, Pierre-Yves Desprez, Sean D. McAllister
Journal: Cancer Research (2012)

Glioblastoma is the most common form of primary adult brain tumors. A majority of glioblastomas grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control glioblastoma invasiveness and target them therapeutically. We show here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of glioblastoma cell lines and primary glioblastoma cells. Id-1 expression levels positively correlate with glioma cell invasiveness in culture and with histopathologic grades in patient biopsies. Id-1 knockdown dramatically reduces glioblastoma cell invasion that is accompanied by profound morphologic changes and robust reduction in expression levels of "mesenchymal" markers, as well as inhibition of self-renewal potential and downregulation of glioma stem cell markers. Importantly, genetic knockdown of Id-1 leads to a significant increase in survival in an orthotopic model of human glioblastoma. Furthermore, we show that a nontoxic compound, cannabidiol, significantly downregulates Id-1 gene expression and associated glioma cell invasiveness and self-renewal. In addition, cannabidiol significantly inhibits the invasion of glioblastoma cells through an organotypic brain slice and glioma progression in vivo. Our results suggest that Id-1 regulates multiple tumor-promoting pathways in glioblastoma and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of patients with glioblastoma.
CASES OCCURRING IN THE MEDICAL PRACTICE OF THE SUSSEX COUNTY HOSPITAL DURING THE YEARS 1849, 1850, AND 1851
Authors: G. S. Jenks
Journal: BMJ (1853)

From this great sea, both the name and sowrce of the Gulf Stream are derived.AfterpassingbetweenCubaand Florida, and taking the direction of the American coast, it turns eastward, preserving a mean velocity, from the commence- ment of its course to the Azores, of 38 miles a day; having a temperature of about 90 Fahr.above that of the surround- ing ocean in the Strait of Florida, which deecreases so gradually in its passage to the east, as to have lost only 50 Fahr.Opposite the south bank of Newfoundland, a dis- tance of 1,300 miles, it still retains a heat of 80 or 100 above that of the adjacent seas, communicating its temper- ature to the superincumbent atmosphere.The warmth diffused over the Atlantic Ocean by this means would be sufficient-such is the calculation-to raise the entire column of air covering France and the British Isles, on a winter day, from freezing point to summer heat -a fact which accounts for the comparative absence of ice in the North seas, and affords the true explanation of the mildncss of our climate, an(l that of adjacent couintries.But, while its influence, by means of the atmosphere, thus affects a large extent of climate, the Gulf Stream itself washes our westerni shores.The waters of the Atlantic are still warm as they wash the coasts of Connaught, while their effect is perceptible along the shores of Norway, and to the very borders of the Arctic Ocean.And lastly, among the tributaries of our temperate cli- mate, is the south-wvest current of air, which is the preva- lent wind of the northern hemisphere.Its gusts occupy the track of the Gulf Stream.They waft the warm moist air, arising from the contact and evaporation of its waters, over the coasts of Western Europe; thev are felt in the same warm fitful gusts, from Cape Fiuisterre to the North Cape, as in thle Atlantic, penetrating inito the Baltic, and reaching to the Russian plains.It is the influence of this current which gives to the western coasts of these islands, from Cornwall to the Ilebrides, almost the same isothermal line.
Enhanced Umbilical Blood Flow During Acute Hypoxemia After Chronic Umbilical Cord Compression
Authors: David S. Gardner, Dino A. Giussani
Journal: Circulation (2003)

The continuing incidence of intrapartum morbidity may be partly due to antenatal compromise, which influences the fetal defense to labor and delivery. We have shown that antenatal exposure of the ovine fetus to partial compression of the umbilical cord suppresses femoral vasoconstriction during subsequent acute hypoxemia through elevated nitric oxide (NO) activity. This study investigated whether elevated NO activity in cord-compressed fetuses enhanced the vasodilator response to hypoxemia in circulations in which blood flow is known to increase during acute hypoxemia, such as the umbilical vascular bed.Fifteen fetal sheep were chronically instrumented between 117 and 120 days of gestation with vascular catheters and an umbilical flow probe. In 8 of these fetuses, umbilical blood flow was reduced by 30% for 3 days between 125 and 128 days. The remaining 7 fetuses acted as sham-operated controls. Between 2 and 7 days after umbilical cord/sham compression, fetuses were exposed to 2 episodes of acute hypoxemia, on separate days, during infusion with either saline or treatment with a combination of NG-nitro-l-arginine methyl ester and sodium nitroprusside. The data show that umbilical cord compression significantly enhances the umbilical hyperemia through NO-dependent mechanisms during a subsequent episode of acute hypoxemia.Increased fetal NO activity after chronic cord compression has opposing effects in circulations that either constrict or dilate during subsequent acute hypoxemia. The data imply that antenatal compromise switches the fetal strategy to withstand episodes of subsequent acute hypoxemia of the type that may occur during labor and delivery from a reliance on vasoconstrictor mechanisms to those promoting NO-dependent vasodilation.