tbuckley/cabot-search huggingface dataset:
PLASMA AND RED CELL RADIOIRON FOLLOWING INTRAVENOUS INJECTION
Authors: C. L. Yuile, C. G. Bly, W. B. Stewart, A. J. Izzo, J. C. Wells, G. H. Whipple
Journal: The Journal of Experimental Medicine (1949)

Sterile inflammation induced by repeated subcutaneous injections of turpentine in non-anemic, non-iron-deficient dogs, leads to a fall in plasma iron concentration, the development of a moderate anemia, and a marked delay in the uptake by the red blood cells of intravenous radioiron. Similar periods of inflammation in anemic, iron-deficient dogs on a diet low in iron cause no increase in the degree of anemia and no inhibition of red blood cell uptake of intravenous radioiron. Radioiron appears only in traces in abscess exudates. Intravenous iron disappearance curves following a single injection are uninfluenced by sterile inflammation in either anemic or non-anemic dogs. The impairment of hemoglobin synthesis caused by inflammation is at most a relative matter, since the anemia that develops is seldom severe or progressive, and since the inhibition can be overcome if the marrow is sufficiently stimulated by the demands of a severe continuing anemia.
Methacoline challenge test as an evaluator of response to statins in bronchial hyperresponsiveness
Authors: Majid Malek Mohammad, Fanak Fahimi, Atefeh Fakharian, Masoumeh Karimi Gamishan, Mohammad Sistanizad, Nader Fayazi, Soheila Khalilzadeh, Shahid Beheshti
Journal: European Respiratory Journal (2012)

hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins), are effective serum cholesterol-lowering agents which also have anti-inflammatory properties. The objective of this study was to evaluate the effect of atorvastatin on bronchial hyperresponsiveness. Adult patients (age 14 to 65 years) with bronchial hyperresponsiveness (BHR) diagnosis based on the spirometry with methacholine challenge test were entered into the study. The study was conducted in the National Research Institute of Tuberculosis and Lung Disease. Patients were randomized to receive either atorvastatin 20 mg/day or placebo for 4 weeks. Spirometric parameters were determined at baseline and at completion of the study. Twenty two patients with the age of 32.95±10.30 years completed the trial. Changes in airway responsiveness categories (moderate to severe, mild, borderline, normal) after the intervention were not significant in atorvastatin group as in placebo group (p-value= 0.131 for atorvastatin group and p-value = 0.305 for placebo group). Also, changes in methacholine solution number (different concentrations of methacholine) which caused at least 20% decrease in FEV1 were not significant between groups (p-value = 0.089). Although we could not find a significant difference, the patients' fall in FEV1 in atorvastatin group was observed in higher concentrations of methacholine. Median before treatment versus after treatment in atorvastatin group was 1 versus 4 mg/mL, while those were 2 versus 1 mg/mL in placebo group. This study showed a better but not significant hyperresponsiveness control in the treatment group. The result might be presented more pronounced, if we could increase the sample size.
Complement inhibitors and immunoconglutinins in ulcerative colitis and Crohn's disease.
Authors: B J Potter, D J Brown, A Watson, D P Jewell
Journal: Gut (1980)

The serum concentrations of the complement inactivators C1INH, C3bINA and beta 1H have been determined in patients with ulcerative colitis and Crohn9s disease and their correlation with C3 and properdin factor B examined. The incidence of immunoconglutinins (1K) in these patients was investigated. Raised serum concentrations of C1INH and C3bINA have been found in patients with active disease, but no significant alteration was found in serum concentration of beta 1H. An increasing incidence of positive 1K titres was found with increased length of disease history. These results suggest continuing complement activation in these diseases.
Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI
Authors: Patrick G. Hogan, Richard S. Lewis, Anjana Rao
Journal: Annual Review of Immunology (2010)

Ca 2+ entry into cells of the peripheral immune system occurs through highly Ca 2+ -selective channels known as CRAC (calcium release-activated calcium) channels. CRAC channels are a very well-characterized example of store-operated Ca 2+ channels, so designated because they open when the endoplasmic reticulum (ER) Ca 2+ store becomes depleted. Physiologically, Ca 2+ is released from the ER lumen into the cytoplasm when activated receptors couple to phospholipase C and trigger production of the second messenger inositol 1,4,5-trisphosphate (IP 3 ). IP 3 binds to IP 3 receptors in the ER membrane and activates Ca 2+ release. The proteins STIM and ORAI were discovered through limited and genome-wide RNAi screens, respectively, performed in Drosophila cells and focused on identifying modulators of store-operated Ca 2+ entry. STIM1 and STIM2 sense the depletion of ER Ca 2+ stores, whereas ORAI1 is a pore subunit of the CRAC channel. In this review, we discuss selected aspects of Ca 2+ signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca 2+ entry.
Preclinical Analysis of Tasidotin HCl in Ewing's Sarcoma, Rhabdomyosarcoma, Synovial Sarcoma, and Osteosarcoma
Authors: Vaani Garg, Wendong Zhang, Pooja Gidwani, Mimi Kim, E. Anders Kolb
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Dolastatins are a group of structurally unique peptides originally isolated from a sea hare, Dolabella auricularia, which seem to inhibit tubulin polymerization and mitosis. Tasidotin hydrochloride (tasidotin), a novel synthetic analogue of dolastatin 15, is evaluated in preclinical models of pediatric tumors. Experimental Design: The cytotoxicity of tasidotin was evaluated in a panel of pediatric sarcoma cell lines in vitro and in vivo. Results: The IC50 in Ewing's sarcoma, rhabdomyosarcoma, osteosarcoma, and synovial sarcoma lines ranged from 0.002 μ to 0.32 μmol/L. In the SK-ES1 and RH30 cell lines, tasidotin induced a G2-M arrest that persisted for 48 h after the drug was washed from the cells. In vitro, more than half the cells were in the early or late phase of apoptosis 48 h after treatment with tasidotin. In vivo, a significant increase in apoptotic nuclei was apparent in xenograft tumors harvested within 24 h after a 5-day course of tasidotin. In vivo response was determined in severe combined immunodeficient xenograft models of pediatric sarcomas implanted heterotopically. Significant antitumor activity was observed in all tumor lines tested. A complete response was observed in 2 synovial sarcoma lines, 1 osteosarcoma line, 1 rhabdomyosarcoma line, and 1 Ewing's sarcoma line. A partial response was observed in 1 rhabdomyosarcoma and 1 Ewing's sarcoma. Conclusions: Tasidotin induces a G2-M block in treated cells ultimately resulting in apoptosis. Antitumor activity is confirmed in vivo in preclinical xenograft models of pediatric sarcomas.
International Congress of Gynaecology and Obstetrics
Authors: W. J. Smyly, H. Macnaugbton-Jones, A. E. Giles
Journal: BMJ (1900)

International Congress of Gynecology and Obstetrics, has written a letter to the secretary of the British Gynecological Society thanking it for its efforts in regard to the pro- posal to hold the next session of the Congress in London in the year 1902, and expressing a hope that at some future time the Congress may meet here.By postponing the meeting for some years it is to be hoped that when it does take place the Congress will receive a hearty welcome, not from one or other society or group of practitioners but from the gynaecologists of England.
Prevention of panic attacks and panic disorder in COPD
Authors: N. Livermore, L. Sharpe, D. McKenzie
Journal: European Respiratory Journal (2009)

This study examined whether cognitive behavioural therapy (CBT) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease (COPD). 41 patients with COPD, who had undergone pulmonary rehabilitation, were randomised to either a four-session CBT intervention condition (n = 21) or a routine care condition (n = 20). Assessments were at baseline, post-intervention, and at 6-, 12- and 18-month follow-ups. Primary outcomes were the rates of panic attacks, panic disorder and anxiety symptoms. Secondary outcomes were depressive symptoms, catastrophic cognitions about breathing difficulties, disease-specific quality of life and hospital admission rates. There were no significant differences between the groups on outcome measures at baseline. By the 18-month follow-up assessment, 12 (60%) routine care group participants had experienced at least one panic attack in the previous 6 months, with two (17%) of these being diagnosed with panic disorder, while no CBT group participants experienced any panic attacks during the follow-up phase. There were also significant reductions in anxiety symptoms and catastrophic cognitions in the CBT group at all three follow-ups and a lower number of hospital admissions between the 6- and 12-month follow-ups. The study provides evidence that a brief, specifically targeted CBT intervention can treat panic attacks in COPD patients and prevent the development and worsening of panic-spectrum psychopathology and anxiety symptoms.
Genetic or Pharmacologic Blockade of EGFR Inhibits Renal Fibrosis
Authors: Na Liu, Jian-Kan Guo, Maoyin Pang, Evelyn Tolbert, Murugavel Ponnusamy, Rujun Gong, George Bayliss, Lance D. Dworkin, Haidong Yan, Shougang Zhuang
Journal: Journal of the American Society of Nephrology (2012)

Although enhanced activation of the EGF receptor (EGFR) associates with the development and progression of renal fibrosis, the mechanisms linking these observations are not completely understood. Here, after unilateral ureteral obstruction (UUO), wild-type mice exhibited sustained EGFR phosphorylation in the kidney and developed renal fibrosis that was more severe than the renal fibrosis observed in waved-2 mice, which have reduced EGFR tyrosine kinase activity. Waved-2 mice also showed fewer renal tubular cells arrested at G2/M, reduced expression of α-smooth muscle actin (α-SMA), downregulation of multiple genes encoding profibrogenic cytokines, including TGF-β1, and dephosphorylation of Smad3, STAT3, and ERK1/2. Administration of the specific EGFR inhibitor gefitinib recapitulated this phenotype in wild-type mice after UUO. Furthermore, inactivation of either EGFR or STAT3 reduced UUO-induced expression of lipocalin-2, a molecule associated with the pathogenesis of CKD. In cultured renal interstitial fibroblasts, inhibition of EGFR also abrogated TGF-β1- or serum-induced phosphorylation of EGFR, STAT3, ERK1/2, and Smad3 as well as expression of α-SMA and extracelluar matrix proteins. Taken together, these data suggest that EGFR may mediate renal fibrogenesis by promoting transition of renal epithelial cells to a profibrotic phenotype, increased production of inflammatory factors, and activation of renal interstitial fibroblasts. Inhibition of EGFR may have therapeutic potential for fibrotic kidney disease.
Hepatocellular carcinoma in woodchuck hepatitis virus-infected woodchucks: Presence of viral DNA in tumor tissue from chronic carriers and animals serologically recovered from acute infections
Authors: Brent E. Korba, Frances V. Wells, Betty Baldwin, Paul J. Cote, Bud C. Tennant, Hans Popper, John L. Gerin
Journal: Hepatology (1989)

During long-term studies of the natural history of woodchuck hepatitis virus infection, five cases of histologically confirmed, primary hepatocellular carcinoma were observed in a total of 92 woodchucks which had recovered, by analysis of viral serologic markers (WHsAG − , anti-WHc + , anti-WHs + ), from experimental acute woodchuck hepatitis virus infections 20 to 30 months prior to the detection of hepatocellular carcinoma. No hepatocellular carcinoma was observed in 167 uninfected controls at least 3 years of age and held in the same laboratory environment. Southern blot hybridization analysis of liver tissue taken from four of these recovered woodchucks revealed the presence of low levels (0.1 to 0.3 copies per cell) of integrated woodchuck hepatitis virus DNA in hepatocellular carcinoma (four of four animals) and nonneoplastic tissue (three of four animals). Similarly, hepatocellular carcinoma tissue obtained from two wild-caught, naturally infected and serologically recovered woodchucks also contained low levels of integrated woodchuck hepatitis virus DNA. Liver tissues from another 27 of these 92 recovered woodchucks (without hepatocellular carcinoma) were examined for woodchuck hepatitis virus nucleic acids 13 to 31 months following experimental woodchuck hepatitis virus infection. Nonreplicating woodchuck hepatitis virus DNA was present in the liver of eight (30%) and in the peripheral blood lymphocytes from eight (30%) of these 27 animals. These results were in marked contrast to the analysis of woodchuck hepatitis virus DNA in the liver tissue of chronic woodchuck hepatitis virus carriers (20 experimentally infected and nine naturally infected). In these animals, high levels of replicating woodchuck hepatitis virus DNA (up to 2,000 copies per cell) were observed in all hepatocellular carcinoma and nonneoplastic liver tissue. Integrated woodchuck hepatitis virus DNA was found in eight of 60 individual hepatocellular carcinomas detected in 29 chronic carriers, 15 to 40 months postinfection. Integrated woodchuck hepatitis virus DNA was present in the nonneoplastic tissue from four of these 29 chronic woodchuck hepatitis virus carriers.
High-Risk Prostate Cancer: From Definition to Contemporary Management
Authors: Patrick J. Bastian, Stephen A. Boorjian, Alberto Bossi, Alberto Briganti, Axel Heidenreich, Stephen J. Freedland, Francesco Montorsi, Mack Roach, Fritz Schröder, Hein van Poppel, Christian G. Stief, Andrew J. Stephenson, Michael J. Zelefsky
Journal: European Urology (2012)
INTRATHECAL ADMINISTRATION OF HYALURONIDASE: EFFECTS UPON THE BEHAVIOR OF PATIENTS SUFFERING FROM SENILE AND ARTERIOSCLEROTIC BEHAVIOR DISORDERS
Authors: D. EWEN CAMERON, L. LEVY, W. HUNZINGER
Journal: American Journal of Psychiatry (1957)

A method is described whereby hyaluronidase may be administered intrathecally in the aged by means of the lumbar route. The following findings are recorded: (1) The occurrence of a fleeting meningeal response; (2) a tendency to lower the blood brain barrier; (3) possible general favorable results with respect to behavior. The way seems open for the further development of this technique, especially in the direction of attempting to pass through the lowered blood brain barrier substances important for the metabolism of the aged.
Human anti–HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness
Authors: John Pietzsch, Johannes F. Scheid, Hugo Mouquet, Florian Klein, Michael S. Seaman, Mila Jankovic, Davide Corti, Antonio Lanzavecchia, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2010)

The identification and characterization of conserved epitopes on the HIV-1 viral spike that are immunogenic in humans and targeted by neutralizing antibodies is an important step in vaccine design. Antibody cloning experiments revealed that 32% of all HIV-neutralizing antibodies expressed by the memory B cells in patients with high titers of broadly neutralizing antibodies recognize one or more “core” epitopes that were not defined. Here, we show that anti-core antibodies recognize a single conserved epitope on the gp120 subunit. Amino acids D474, M475, R476, which are essential for anti-core antibody binding, form an immunodominant triad at the outer domain/inner domain junction of gp120. The mutation of these residues to alanine impairs viral fusion and fitness. Thus, the core epitope, a frequent target of anti–HIV-neutralizing antibodies, including the broadly neutralizing antibody HJ16, is conserved and indispensible for viral infectivity. We conclude that the core epitope should be considered as a target for vaccine design.
BACTERICIDAL FLUORESCENCE EXCITED BY X-RAYS
Authors: H. S. Newcomer
Journal: The Journal of Experimental Medicine (1917)

X-ray fluorescence has been pointed out as a mechanism offering exceptional possibilities in the development of physicochemical therapy. Experiments are given which demonstrate that under these conditions the x-rays may have a strong bactericidal effect. The x-rays alone have a partial bactericidal action on water suspensions of typhoid bacilli.
Glycated Hemoglobin and All-Cause and Cause-Specific Mortality in Singaporean Chinese Without Diagnosed Diabetes: The Singapore Chinese Health Study
Authors: Michael P. Bancks, Andrew O. Odegaard, James S. Pankow, Woon-Puay Koh, Jian-Min Yuan, Myron D. Gross, Mark A. Pereira
Journal: Diabetes Care (2014)

Glycated hemoglobin (HbA₁c) is a robust biomarker of the preceding 2 to 3 months average blood glucose level. The aim of this study was to examine the association between HbA₁c and mortality in a cohort of Southeast Asians.Analysis of 7,388 men and women, mean age 62 years, from the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999-2004) and reported no history of diabetes, previous adverse cardiovascular events, or cancer. A total of 888 deaths were identified through 31 December 2011 via registry linkage. Participants represented a random study sample of potential control subjects for a nested case-control genome-wide association study of type 2 diabetes in the population. Hazard ratios (HRs) for all-cause and cause-specific mortality by six categories of HbA1c were estimated with Cox regression models.Relative to participants with an HbA₁c of 5.4-5.6% (36-38 mmol/mol), participants with HbA₁c ≥6.5% (≥48 mmol/mol) had an increased risk of all-cause, cardiovascular, and cancer mortality during an average of 10.1 years of follow-up; HRs (95% CIs) were 1.96 (1.56-2.46), 2.63 (1.77-3.90), and 1.51 (1.04-2.18), respectively. No level of HbA1c was associated with increased risk of respiratory mortality. Levels <6.5% HbA₁c were not associated with mortality during follow-up. The results did not materially change after excluding observation of first 3 years post-blood draw.HbA₁c levels consistent with undiagnosed type 2 diabetes (≥6.5%) are associated with an increased risk of all-cause and cause-specific mortality in Chinese men and women.
Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial
Authors: Wolfgang Hueber, Bruce E Sands, Steve Lewitzky, Marc Vandemeulebroecke, Walter Reinisch, Peter D R Higgins, Jan Wehkamp, Brian G Feagan, Michael D Yao, Marek Karczewski, Jacek Karczewski, Nicole Pezous, Stephan Bek, Gerard Bruin, Bjoern Mellgard, Claudia Berger, Marco Londei, Arthur P Bertolino, Gervais Tougas, Simon P L Travis
Journal: Gut (2012)

<h3>Objective</h3> The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn9s disease. <h3>Design</h3> In a double-blind, randomised, placebo-controlled proof-of-concept study, 59 patients with moderate to severe Crohn9s disease (Crohn9s Disease Activity Index (CDAI) ≥220 to ≤450) were assigned in a 2:1 ratio to 2×10 mg/kg intravenous secukinumab or placebo. The primary end point, addressed by Bayesian statistics augmented with historical placebo information, was the probability that secukinumab reduces the CDAI by ≥50 points more than placebo at week 6. Ancillary analyses explored associations of 35 candidate genetic polymorphisms and faecal calprotectin response. <h3>Results</h3> 59 patients (39 secukinumab, 20 placebo, mean baseline CDAI 307 and 301, respectively) were recruited. 18/59 (31%) patients discontinued prematurely (12/39 (31%) secukinumab, 6/20 (30%) placebo), 10/59 (17%) due to insufficient therapeutic effect (8/39 (21%) secukinumab, 2/20 (10%) placebo). Fourteen serious adverse events occurred in 10 patients (seven secukinumab, three placebo); 20 infections, including four local fungal infections, were seen on secukinumab versus none on placebo. Primary end point analysis estimated &lt;0.1% probability (∆CDAI (SD) =33.9 (19.7), 95% credible interval −4.9 to 72.9) that secukinumab reduces CDAI by ≥50 points more than placebo. Secondary area under the curve analysis (weeks 4–10) showed a significant difference (mean ΔCDAI=49; 95% CI (2 to 96), p=0.043) in favour of placebo. Post hoc subgroup analysis showed that unfavourable responses on secukinumab were driven by patients with elevated inflammatory markers (CRP≥10 mg/l and/or faecal calprotectin≥200 ng/ml; mean ΔCDAI=62; 95% CI (−1 to 125), p=0.054 in favour of placebo). Absence of the minor allele of tumour necrosis factor-like ligand 1A was strongly associated with lack of response measured by baseline-adjusted changes in calprotectin at week 6 (p=0.00035 Bonferroni-corrected). <h3>Conclusions</h3> Blockade of IL-17A was ineffective and higher rates of adverse events were noted compared with placebo. <h3>Clinical trial registration</h3> This trial was registered at ClinicalTrial.gov with the number NCT01009281.
Treatment of patients with cirrhosis and refractory ascites using LeVeen shunt with titanium tip: Comparison with therapeutic paracentesis
Authors: Angels Ginès, Ramon Planas, Paolo Angeli, Carlos Guarner, Francesco Salerno, Pere Ginès, Joan Saló, Nivardo Rodriguez, Eugeni Domènech, Germán Soriano, Luis Anibarro, Miguel Angel Gassull, Angelo Gatta, Vicente Arroyo, Juan Rodés
Journal: Hepatology (1995)

It has recently been suggested that insertion of a titanium tip at the venous end of the LeVeen shunt drastically reduces the rate of shunt obstruction. To assess whether the LeVeen shunt with titanium tip improves the results obtained with therapeutic paracentesis, 81 patients with cirrhosis and refractory ascites were randomly assigned to therapy with paracentesis plus intravenous albumin (42 patients) or LeVeen shunt with titanium tip (39 patients). If patients were readmitted for ascites during follow-up, those in the first group were treated with paracentesis, and those in the LeVeen shunt group by the insertion of a new valve or a new shunt if obstruction was demonstrated. During first hospitalization, both treatments were equally effective in removing ascites. Complications were similar in both groups except for a higher rate of severe bacterial infection in the LeVeen shunt group. The mean duration of hospitalization was shorter in the paracentesis group than in the shunt group. During follow-up, the total number of readmissions and the number of readmissions for ascites were higher in the paracentesis group than in the shunt group (252 vs. 99, P &lt; .001; and 193 vs. 43, P &lt; .001, respectively). The total time in hospital, however, was similar (38 ± 38 vs. 39 ± 43 days, P = NS). Three patients had obstruction of the shunt during first hospitalization and 14 patients had a total of 22 obstructions during follow-up. Long-term survival was similar in both groups. The insertion of a titanium tip at the venous end of the LeVeen shunt does not prevent obstruction. The LeVeen shunt with titanium tip does not provide significant improvement over therapeutic paracentesis in the management of cirrhotic patients with refractory ascites. (Hepatology 1995; 22:124-131.)
1416 PLASMA PHOSHOLIPID PROFILING BY METABONOMICS: HIGHLY ACCURATE OUTCOME PREDICTION IN DECOMPENSATED CIRRHOSIS
Authors: M.J.W. McPhail, D. Shawcross, M. Lewis, I. Coltart, R.D. Abeles, N. Taylor, J. O'Grady, N. Heaton, G. Auzinger, W. Bernal, E. Want, E. Holmes, J. Wendon, S. Taylor-Robinson
Journal: Journal of Hepatology (2012)