tbuckley/cabot-search huggingface dataset:
TNF and chemerin cross-talk in rheumatoid arthritis
Authors: M. C. Lebre, M. I. Ramos, C. L. Hofstra, H. van Eenennaam, S. Aarrass, P. P. Tak
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) synovium is characterised by a dense infiltrate, consisting of macrophages, T and B cells, plasma cells and dendritic cells (DC). Inflammatory chemokines present in RA synovium may contribute to the accumulation of these immune cells. The authors have recently shown that plasmacytoid DC (pDC) are enriched in RA synovial tissue (ST) compared to CD1c myeloid DC. In line with these observations, the authors have shown that chemerin (and its receptor ChemR23) expression is upregulated in RA ST compared to non-RA arthritis patients. Moreover, in RA ST ChemR23 was specifically expressed by CD68 macrophages and pDC, while chemerin expression was confined to endothelial cells (CD31 and von Willebrand factor positive). Therefore the authors aimed at investigating the regulation of chemerin expression in an ex vivo model of human RA. <h3>Materials and methods</h3> Arthroscopic ST biopsies were obtained from patients with active RA and cultured in medium or in the presence of recombinant (r)-tumour necrosis factor α (TNFα) or r-chemerin. After 6 days, cell-free supernatants were harvested and the levels of TNFα or chemerin were analysed by Luminex or ELISA, respectively. When indicated, antichemerin or anti-ChemR23 neutralising antibodies were added to TNFα-stimulated cultures. <h3>Results</h3> RA synovial biopsies released chemerin spontaneously. Interestingly, TNFα stimulation induced significantly higher levels of chemerin compared to medium control. In addition, RA synovial biopsies released TNFα spontaneously and addition of chemerin to the cultures strongly induced TNFα release, suggesting a vicious cycle. Of importance, spontaneous and TNFα-induced chemerin could be blocked by the addition of neutralising antibodies against chemerin. Moreover, spontaneous TNFα could also be blocked by the addition of neutralising antibodies against chemerin. <h3>Conclusions</h3> These findings suggest that elevated levels of chemerin in RA ST might regulate local TNFα release and vice-versa in a positive feedback loop. The reciprocal interplay between chemerin and TNFα is novel and might represent an attractive candidate for future drug development by blocking the chemerin/ChemR23 system to disrupt disease perpetuation.
Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Authors: Takeshi Shimamura, Danan Li, Hongbin Ji, Henry J. Haringsma, Elizabeth Liniker, Christa L. Borgman, April M. Lowell, Yuko Minami, Kate McNamara, Samanthi A. Perera, Sara Zaghlul, Roman K. Thomas, Heidi Greulich, Susumu Kobayashi, Lucian R. Chirieac, Robert F. Padera, Shigeto Kubo, Masaya Takahashi, Daniel G. Tenen, Matthew Meyerson, Kwok-Kin Wong, Geoffrey I. Shapiro
Journal: Cancer Research (2008)

The epidermal growth factor receptor (EGFR) secondary kinase domain T790M non-small cell lung cancer (NSCLC) mutation enhances receptor catalytic activity and confers resistance to the reversible tyrosine kinase inhibitors gefitinib and erlotinib. Currently, irreversible inhibitors represent the primary approach in clinical use to circumvent resistance. We show that higher concentrations of the irreversible EGFR inhibitor CL-387,785 are required to inhibit EGFR phosphorylation in T790M-expressing cells compared with EGFR mutant NSCLC cells without T790M. Additionally, CL-387,785 does not fully suppress phosphorylation of other activated receptor tyrosine kinases (RTK) in T790M-expressing cells. These deficiencies result in residual Akt and mammalian target of rapamycin (mTOR) activities. Full suppression of EGFR-mediated signaling in T790M-expressing cells requires the combination of CL-387,785 and rapamycin. In contrast, Hsp90 inhibition overcomes these limitations in vitro and depletes cells of EGFR, other RTKs, and phospho-Akt and inhibits mTOR signaling whether or not T790M is present. EGFR-T790M-expressing cells rendered resistant to CL-387,785 by a kinase switch mechanism retain sensitivity to Hsp90 inhibition. Finally, Hsp90 inhibition causes regression in murine lung adenocarcinomas driven by mutant EGFR (L858R) with or without T790M. However, efficacy in the L858R-T790M model requires a more intense treatment schedule and responses were transient. Nonetheless, these findings suggest that Hsp90 inhibitors may be effective in T790M-expressing cells and offer an alternative therapeutic strategy for this subset of lung cancers.
Successful cell‐mediated cytokine‐activated immunotherapy for relapsed acute myeloid leukemia after hematopoietic stem cell transplantation
Authors: Benjamin Gesundheit, Michael Y. Shapira, Igor B. Resnick, Avraham Amar, Don Kristt, Lilianne Dray, Einat Budowski, Reuven Or
Journal: American Journal of Hematology (2008)

Acute myeloid leukemia (AML) is an extremely aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (HSCT). We report the successful outcome of cell-mediated cytokine-activated immunotherapy in a high-risk pediatric AML patient who relapsed shortly after allogeneic HSCT. Donor lymphocyte infusion along with interferon induced a graft-versus-leukemia effect, presenting as a reversible episode of graft-versus-host disease, which led to stable complete donor chimerism and total eradication of AML for over 24 months, at the time of this report. The curative potential of immunotherapy in hematological malignancies is discussed.
Quality improvement report: Effect of a formal education programme on safety of transfusions
Authors: P. Clark, I. Rennie, S. Rawlinson
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Problem:</b> Failure of correct identification and insufficient monitoring of patients receiving transfusions continue to be appreciable and avoidable causes of morbidity and mortality. <b>Design:</b> A study by a regional transfusion service and a transfusion nurse specialist of the effects of an education programme based on the current national guidelines on identification and monitoring of patients receiving transfusions. <b>Setting:</b> A large United Kingdom teaching hospital which houses the headquarters of the regional transfusion service. <b>Key measures for improvement:</b> Improvement in compliance with published national guidelines on the prescription and administration of blood transfusions. <b>Strategy for change:</b> An audit of current compliance followed by dissemination by a transfusion nurse specialist of a clinical skills package (based on the best practice for transfusion) to all staff involved in giving transfusions. This was supported by trained instructors and the display of standard operating procedures for transfusion in all clinical areas. <b>Effect of change:</b> An improvement in compliance with the national guidelines to over 95% in six out of seven of the recommendations on best practice was seen 18 months after the initial intervention. <b>Lessons learnt:</b> The study shows that education of those who prescribe and administer transfusions, as recommended by bodies concerned with the hazards of transfusion, can improve the safety of transfusions.
CHLORPROMAZINE AND CHRONIC NEUROTIC TENSION
Authors: JULIUS MERRY, R. A. PARGITER, H. MUNRO
Journal: American Journal of Psychiatry (1957)

1. A controlled study was made of the effects of oral chlorpromazine on chronic neurotic tension states in 21 male inpatients. 2. The dosage ranged from 150-300 mg. daily. 3. Cases treated with chlorpromazine showed no greater improvement than those treated with inert tablets.
Civilian War Casualties and Medical Care in South Vietnam
Authors: E. A. VASTYAN
Journal: Annals of Internal Medicine (1971)

A study of nonclassified government documents and medical literature discloses that relatively little research or scholarship has been directed toward the problems of civilian war casualties and the medical care provided for them in South Vietnam. War casualties among civilians have been sustained in great numbers since 1965 and continue at high levels today. Treatment facilities and personnel, grossly inadequate to meet needs when hostilities increased, have been improved through American aid under the Agency for International Development, but such efforts have been severely criticized as inadequate in terms of finances, facilities, manpower, and policy.
Disturbance of the GH-IGF-I-IGFBPs axis and renal function changes incirrhosis
Authors: C.M. Fernández-Rodriguez, J.I.R. Prada, M. Moreiras, A. Andrade, R. Aller, J.L. Lledó, J.A. González, G. Cacho, J. Quiroga, J. Prieto
Journal: Journal of Hepatology (2000)
MALARIA IN THE TROPICS.
Authors: WILLIAM C. GORGAS
Journal: JAMA (1906)

Since 1898 I have served almost continuously in the tropics—four years in Cuba and two years at Panama-part of the time with troops, but most of this time being connected with municipal sanitation. At Santiago, Cuba, I was with the army at the Base Hospital at Siboney, where all the seriously sick were sent during the entire campaign against Santiago until the army returned home. In Havana I had charge of the yellow-fever wards at Las Animas Hospital. Las Animas was the hospital for contagious diseases for the Sanitary Department of Havana, and, while a large majority of the patients treated by me there had yellow fever, a considerable number of malarial cases were also received, being mistaken for yellow fever. Here at Panama I am in charge of the yellow-fever ward. All non-immunes with fever from any cause coming into Ancon Hospital are sent to these wards, and much the
Autologous and Aged Blood Donors-Reply
Authors: Tibor J. Greenwalt
Journal: JAMA (1987)

<h3>In Reply.—</h3> I am familiar with all the resources quoted in the response to my editorial. The data can be used to justify the vested interests of entrepreneurs in providing frozen red blood cell (RBC) programs. However, they are used by the writer in a one-sided fashion. First, let me say that I am not opposed to frozen storage of autologous blood. My blood center offers this service but does not encourage it because we do not want to profiteer from the public hysteria regarding acquired immunodeficiency syndrome. The major reasons for our position are that (1) the needs of patients undergoing elective surgery, eg, coronary artery bypass graft surgery, are readily met by liquid autologous and intraoperative blood salvage and (2) in emergencies, frozen RBC cannot be made available rapidly enough, even if the patient has not moved. I heartily agree that the decision regarding the use of autologous
Uptake of blood coagulation factor VIII by dendritic cells is mediated via its C1 domain
Authors: Eszter Herczenik, Simon D. van Haren, Aleksandra Wroblewska, Paul Kaijen, Maartje van den Biggelaar, Alexander B. Meijer, Luisa Martinez-Pomares, Anja ten Brinke, Jan Voorberg
Journal: Journal of Allergy and Clinical Immunology (2011)
TCT-6 Biodegradable polymer-based Biolimus A9-eluting stent for the treatment of infrapopliteal arteries in critical limb ischemia: long-term clinical and angiographic follow-up
Authors: Eugenio Stabile, Luigi Salemme, Giovanni Sorropago, Angelo Cioppa, Vittorio Ambrosini, Grigore Popusoi, Armando Pucciarelli, Linda Cota, Tullio Tesorio, Paolo Rubino
Journal: Journal of the American College of Cardiology (2012)
Coronary Revascularization Surgery After Myocardial Infarction: Impact of Bypass Surgery on Survival After Thrombolysis
Authors: Barbara E Tardiff, Robert M Califf, Douglas Morris, Eric Bates, Lynn H Woodlief, Kerry L Lee, Cindy Green, Wolfgang Rutsch, Amadeo Betriu, Philip E Aylward, Eric J Topol
Journal: Journal of the American College of Cardiology (1997)
Atlas of Diagnostic Oncology
Authors: Ramona Chapman
Journal: JAMA (1993)

This is a beautiful book—large, well-made, handsomely designed. The 14 chapters were prepared by 12 contributors, all of the Harvard Medical School. The chapter topics conform to the organ systems and bodily regions, eg, "Cancer of the Head and Neck," "Cancer of the Gastrointestinal Tract," "Endocrine Tumors and Malignancies." Three chapters are given to the blood: leukemias, lymphomas, myeloma. Each chapter is appropriately subdivided, eg, "Gynecologic Tumors" includes "Ovarian Carcinoma," "Endometrial Carcinoma," "Cervical Carcinoma," and "Other Gynecologic Malignancies." Tables are appropriately selected to demonstrate staging, incidence, classification, and so forth. The tables are tinted, thus blending with the color photographs and micrographs, which are the gist of this atlas. The large pages (25×30 cm, almost square) hold without crowding two, four, sometimes six illustrations. In addition to anatomic photographs plus cytologic and histologic micrographs, there are neat pen-and-ink drawings of much of the histology to permit labeling of details. In
Protection afforded by preconditioning to the diabetic heart against ischaemic injury
Authors: J Bouchard
Journal: Cardiovascular Research (1998)

Objective: The aim of this study was to assess whether the cardioprotective effect of ischaemic preconditioning (IPC) on endothelial function in coronary arteries and myocardial function is affected in the streptozotocin-induced diabetic rat heart. Methods: Isolated hearts, perfused under constant flow conditions, were exposed to 30 min of partial ischaemia (flow rate 1 ml min−1) followed by 20 min of reperfusion. Results: In the diabetic group (without ischaemia or IPC), infusion of 10 μM serotonin (5-HT), an endothelium-dependent, and 3 μM sodium nitroprusside (SNP), an endothelium-independent vasodilator, in the coronary bed preconstricted with 0.1 μM U-46619 induced a marked vasodilation. Ischaemia, either without or with preconditioning with a single 5 min ischaemia and 10 min reperfusion (IPC1) before ischaemia, was accompanied by a reduced 5-HT-induced vasodilation in diabetic hearts. In contrast, IPC1 preserved the response to 5-HT in non-diabetic hearts. A more extensive IPC with 3 periods of 5 min ischaemia followed by 5 min reperfusion (IPC3) preserved the vasodilation produced by 5-HT in both diabetic and non-diabetic hearts. IPC3 increased the recovery of dP/dtmax and dP/dtmin during the 30 min ischaemic period and during reperfusion in all hearts. In contrast, IPC1 had no effect on myocardial recovery in either groups. Adenosine pre-treatment started 30 min before ischaemia mimicked IPC3, preserving the vasodilation to 5-HT and improving myocardium recovery in both groups. When adenosine was started 15 min before ischaemia, vasodilation to 5-HT was preserved in non-diabetic hearts only. Conclusions: These results suggest that IPC affords protection to endothelial function in resistance coronary arteries of diabetic hearts. To achieve this protection, a more extensive IPC is needed, which may be related to a longer exposure to adenosine.
Fluoride: a whiter than white reputation?
Authors: Rod Griffiths
Journal: BMJ (2007)

In 1964, when I was a medical student, Birmingham City Council decided to fluoridate its water supply. Over the weekend that the fluoride was supposed to be added, the Sunday Mirror carried many letters from people who could taste the difference and felt a variety of symptoms. On Monday the Medical Office of Health announced that a technical hitch meant that the fluoride would not in fact be added for another month. There were no further protests.

Thirty years later I was regional director of public health for the West Midlands (which includes Birmingham). From time to time the issue of fluoridation was raised, most often as some sort of scare about cancer, bone fractures, dental fluorosis, or allergies. A little over half of the region was fluoridated, and we knew in some detail which areas had fluoridated water and which did not. We examined every claim made against fluoride, and like most of the international public health agencies we were never able to find any evidence of the various allegations of harm. We even found that the incidence of some cancers seemed to be less in fluoridated areas, although such results may be …
Substances used for Pediculosis Capitis
Authors: E. B. S. Scobbie
Journal: BMJ (1945)

40 m.55 m.I11.Study: (a) Course .. .. (30%) 1 h. 8m. (27%) 1 h. 0m.(b) Language .. 33 m.23 m.(c) General .. 59 m. 50m. 2 h.40m. 2 h.13 m.IV.Handicrafts 18 m. 9m.V. Art .. .5 m. 9 m.VI.Music: (a) Performer .. 8 m. 10 m.(b) Listener .. 15 m. 12 m.VII.
Spontaneous expression of the c-sis gene and release of a platelet-derived growth factorlike molecule by human alveolar macrophages.
Authors: J F Mornex, Y Martinet, K Yamauchi, P B Bitterman, G R Grotendorst, A Chytil-Weir, G R Martin, R G Crystal
Journal: Journal of Clinical Investigation (1986)

Alveolar macrophages from normal individuals and patients with interstitial lung diseases spontaneously expressed a 4.2-kilobase mRNA complementary to the c-sis gene, a proto-oncogene coding for one of the chains of platelet-derived growth factor (PDGF). Concomitantly, these cells released a mediator with the properties of PDGF, including: chemotactic factor for smooth muscle cells whose activity was resistant to heat and acid, but sensitive to reduction; mitogenic (competence) activity for fibroblasts; ability to compete with PDGF for its receptor; and precipitated by an anti-PDGF antibody. While blood monocytes did not contain c-sis mRNA transcripts, monocytes matured in vitro expressed c-sis, consistent with the concept that expression of c-sis occurs during the differentiation of monocytes into alveolar macrophages. Together with the known actions of PDGF, these observations suggest that the c-sis proto-oncogene and its PDGF product are part of the armamentarium available to the alveolar macrophages for normal lung defense and participation in lung inflammation.
A NEW APPARATUS FOR THE ADMINISTRATION OF FLUIDS
Authors: Edward F. Lane
Journal: JAMA (1923)

This apparatus has been designed with a view to providing a safe, easy method for the intravenous, intramuscular, intraperitoneal and subcutaneous administration of fluids—saline, glucose and sodium bicarbonate solutions. It is simple and at the same time surpasses in asepsis, convenience and adaptability any apparatus at present in common use.  The instrument consists of a flask ( A ) of any desired capacity, though I have found that one of 500 c.c. is the most suitable for general use, with the highest graduation at the top, provided with a rubber stopper with a single hole ( B ) through which passes a glass tube ( C ) so constructed that it at the same time empties the flask and admits the air necessary to empty the flask. Attached to the rubber stopper is a framework ( D ) of German silver, on which the rubber tubing ( E ), of sufficient length to allow a good head of pressure, is
The ionic control of 1,25-dihydroxyvitamin D3 production in isolated chick renal tubules.
Authors: D D Bikle, H Rasmussen
Journal: Journal of Clinical Investigation (1975)

Isolated renal tubules prepared from vitamin D-deficient chicks catalyze the 1 alpha-hydroxylation of 25-hydroxyvitamin D3 (250HD3) in vitro. The effect of calcium and phosphate on the rate of synthesis of the product, 1, 25-dihydroxyvitamin D3 (1,25(OH)2D3), was studied at two levels: the long-term effects of various dietary calcium and phosphate contents on the ability of the tubules to produce 1, 25 (OH)2D3, and the acute effects of different calcium and phosphate concentrations in the incubation medium on the rate of synthesis of 1,25(OH)2D3 by the tubules. Manipulation of dietary calcium and phosphate sufficient to produce marked changes in the concentration of calcium and phosphate in the serum led to altered rates of 1,25(OH)2D3 synthesis by the isolated renal tubules. The renal tubules isolated from chicks raised on a vitamin D-deficient diet containing 0.43% calcium and 0.3% P as inorganic phosphate showed the highest rate of synthesis of 1,25(OH)2D3. Diets containing more or less of either calcium or phosphate produced chicks whose renal tubules had a slower rate of 1,25(OH)2D3 production. The calcium, phosphate, and hydrogen ion content of the incubation medium were manipulated to determine the possible factors concerned with the immediate regulation of 1,25(OH)2D3 production. A calcium concentration of 0.5-1.0 mM was necessary for optimal enzymatic activity. Concentrations of calcium greater than this optimal concentration inhibited 1,25(OH)2D3 production if phosphate was also present, and this inhibition was more pronounced as the phosphate concentration was increased. The stimulation of 1,25(OH)2D3 production by calcium was less at pH 6.7 than at 7.4. Raising the phosphate concentration from 0 to 6 mM in the absence of calcium also stimulated the rate of synthesis of 1,25(OH)2D3. This stimulatory effect was blocked by 4 mM calcium. However, at 1-2 mM calciu, phosphate had a biphasic influence on 1,25(OH)2D3 production; extracellular concentrations of phosphate from 0.6 to 1.2 mM resulted in less 1,25(OH)2D3 production than higher or lower phosphate concentrations. This biphasic effect was seen both at pH 7.4 and 6.8.
P669High pressure perfusion augments infarct size through a ROS dependent mechanism, protection by allopurinol
Authors: K Ytrehus, NT Boardman, M Martin-Armas, JV Norvik, TG Jensen, I Toft
Journal: Cardiovascular Research (2014)

Although uric acid is known as the most effective reactive oxygen species (ROS) scavenger within the extracellular space of the body, elevated serum concentration is correlated with inflammation, kidney pathology and impaired prognosis of heart disease. This experimental study in the isolated rat heart investigated the effect of A) extracellular uric acid and B) reduced intracellular uric acid and ROS by xanthine oxidase inhibition in the acute response to ischemic insult with or without a preconditioning stimulus (IPC) and following perfusion pressure overload. Tissue superoxide generation was visualized by dihydroethidium staining (DHE). The protective effects of ischemic preconditioning (IPC) against myocardial infarction were completely abolished when combined with uric acid (500μM) but not abolished with xanthine oxidase inhibitor allopurinol (1 nM). Perfusion pressure overload exacerbated ischemic injury as shown by increased infarct size (50.3±2.1 vs. 30.9±3.1, for HP vs. LP respectively) and increased DHE staining. The effect on infarct size was reversed following exposure to 500 μM uric acid (39.3±5.5 vs. 50.3±2.1, HP+uric acid vs. HP respectively). Inhibition of xanthine oxidase with allopurinol (1 mM) also reduced infarct size in pressure-overloaded hearts (41.1±3.9 vs. 50.3±2.1, HP+allopurinol vs. HP respectively). Furthermore, pressure overloaded hearts displayed increased phosphorylation of kinases Akt, ERK and GSK-3β by Western Blot, but this was unchanged following exposure to uric acid or allopurinol indicating that corresponding signaling pathways were not affected by the two treatments. We conclude that high pressure perfusion leads to increase in ROS load. The observed acute cardioprotection by uric acid or xanthine oxidase inhibition is probably due to reduction of ROS related factors.
Staphyloccoccus Aureus Induces a Th2 Response Via TSLP and IL-33 Release in Human Airway Mucosa
Authors: Feng Lan, Nan Zhang, Gabriele Holtappels, Natalie De Ruyck, Nikolaos G. Papadopoulos, Sebastian L. Johnston, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2015)