tbuckley/cabot-search huggingface dataset:
Urinary Metabolites of 2-Acetylaminofluorene and Related Compounds in the Rhesus Monkey
Authors: Makoto Enomoto, Prabhakar Lotlikar, James A. Miller, Elizabeth C. Miller
Journal: Cancer Research (1962)

The urinary metabolites of 2-acetylaminofluorene (AAF) and related compounds were determined by paper chromatography after oral administration to young, adult, female monkeys ( Macacus rhesus ). AAF, N -hydroxy-AAF, and 2-aminofluorene each gave rise to AAF and conjugates of N -hydroxy-AAF and 7-hydroxy-AAF in the urine. Thus the rhesus monkey has the ability to hydroxylate AAF on the nitrogen and 7-carbon atoms, to reduce N -hydroxy-AAF to AAF, and to N -acetylate 2-aminofluorene. No 1-, 3-, or 5-hydroxy derivatives of AAF were detected in these urines. Only small amounts of 1- and 3-hydroxy-AAF were excreted in the urine when large amounts of these respective compounds were fed. N -Hydroxy-AAF was isolated in crystalline form from the urine after administration of AAF by a procedure which involved the intermediate isolation of the poorly soluble cupric chelate of N -hydroxy-AAF.

4-Aminobiphenyl appeared to be metabolized by the rhesus monkey to yield small amounts of N -hydroxy-4-acetylaminobiphenyl in the urine. Ingestion of either 2-aminonaphthalene or its N -acetyl derivative appeared to give a trace of a urinary metabolite with the properties of the corresponding N -hydroxy- N -acetyl derivative.
The Destruction of Red Cells by Antibodies in Man. I. Observations on the Sequestration and Lysis of Red Cells Altered by Immune Mechanisms1
Authors: James H. Jandl, A. Richardson Jones, William B. Castle
Journal: Journal of Clinical Investigation (1957)

Much of our present knowledge of the pathologic physiology of the acquired hemolytic anemias origi- nated from observations of the fate of heterologous red cells in immunized animals and of the syn- dromes produced in animals by injections of heter- ologous anti-red cell sera (1-17).The frank he- molysins present in anti-red cell sera seemed to provide a complete explanation for the experimental findings, but it was early stressed by Muir and M'Nee (6) and by Banti (8) that the hemo- lytic action of hemolysin-containing sera was greater in extent and slower in evolution when in- jected into the intact animal than when added to red cells in vitro.It was also pointed out by Banti
Sui generis: gene therapy and delivery systems for the treatment of glioblastoma
Authors: J Robert Kane, Jason Miska, Jacob S Young, Deepak Kanojia, Julius W Kim, Maciej S Lesniak
Journal: Neuro-Oncology (2015)

Gene therapy offers a multidimensional set of approaches intended to treat and cure glioblastoma (GBM), in combination with the existing standard-of-care treatment (surgery and chemoradiotherapy), by capitalizing on the ability to deliver genes directly to the site of neoplasia to yield antitumoral effects. Four types of gene therapy are currently being investigated for their potential use in treating GBM: (i) suicide gene therapy, which induces the localized generation of cytotoxic compounds; (ii) immunomodulatory gene therapy, which induces or augments an enhanced antitumoral immune response; (iii) tumor-suppressor gene therapy, which induces apoptosis in cancer cells; and (iv) oncolytic virotherapy, which causes the lysis of tumor cells. The delivery of genes to the tumor site is made possible by means of viral and nonviral vectors for direct delivery of therapeutic gene(s), tumor-tropic cell carriers expressing therapeutic gene(s), and "intelligent" carriers designed to increase delivery, specificity, and tumoral toxicity against GBM. These vehicles are used to carry genetic material to the site of pathology, with the expectation that they can provide specific tropism to the desired site while limiting interaction with noncancerous tissue. Encouraging preclinical results using gene therapies for GBM have led to a series of human clinical trials. Although there is limited evidence of a therapeutic benefit to date, a number of clinical trials have convincingly established that different types of gene therapies delivered by various methods appear to be safe. Due to the flexibility of specialized carriers and genetic material, the technology for generating new and more effective therapies already exists.
Bimodal effect of stimulation on light fluctuation transients monitoring spontaneous sarcoplasmic reticulum calcium release in rat cardiac muscle.
Authors: A A Kort, E G Lakatta
Journal: Circulation Research (1988)

Microscopic, myofilament motion caused by spontaneous oscillatory Ca2+ release from the sarcoplasmic reticulum (SR) of unstimulated rat papillary muscles produces scattered light intensity fluctuations (SLIF) in a laser beam scattered by the tissue. SLIF frequency increases with Ca2+ loading of resting muscle. We used novel time-gated SLIF measurements to determine how electrical stimulation (which per se both induces SR Ca2+ release and modulates total cellular Ca2+ loading) affects SLIF. Stimulation of thin rat, right ventricular muscles at 1 Hz in bathing [Ca2+] (Ca0) of 1.5 mM at 29 degrees C abolished SLIF for 5-7 seconds; SLIF then reappeared and monotonically increased for 10-15 seconds to reach the steady resting level. Resting force transients paralleled those of SLIF. The magnitude of depression and time course of recovery of both resting force and SLIF at this Ca0 vary inversely with the rate of prior stimulation and the number of stimuli given. An increase in Ca0 or disablement of the Na-K pump increased both resting SLIF and force; transient stimulation under these conditions (i.e., in a 2.5-5.5-second "diastolic window" after cessation of stimulation) augmented SLIF and force above the resting level. Isoproterenol caused a modest reduction of resting SLIF, but it transiently increased SLIF after stimulation up to 10-fold above the resting level. Nifedipine did not affect resting SLIF but transiently depressed SLIF after stimulation. Ryanodine abolished SLIF both after stimulation and at rest.(ABSTRACT TRUNCATED AT 250 WORDS)
Isolated Endarteritis and Kidney Transplant Survival
Authors: Banu Sis, Serena M. Bagnasco, Lynn D. Cornell, Parmjeet Randhawa, Mark Haas, Belinda Lategan, Alex B. Magil, Andrew M. Herzenberg, Ian W. Gibson, Michael Kuperman, Kotaro Sasaki, Edward S. Kraus
Journal: Journal of the American Society of Nephrology (2014)

Isolated endarteritis of kidney transplants is increasingly recognized. Notably, microarray studies revealed absence of immunologic signatures of rejection in most isolated endarteritis biopsy samples. We investigated if isolated endarteritis responds to rejection treatment and affects kidney transplant survival. We retrospectively enrolled recipients of kidney transplant who underwent biopsies between 1999 and 2011 at seven American and Canadian centers. Exclusion criteria were recipients were blood group-incompatible or crossmatch-positive or had C4d-positive biopsy samples. After biopsy confirmation, patients were divided into three groups: isolated endarteritis (n=103), positive controls (type I acute T cell-mediated rejection with endarteritis; n=101), and negative controls (no diagnostic rejection; n=103). Primary end points were improved kidney function after rejection treatment and transplant failure. Mean decrease in serum creatinine from biopsy to 1 month after rejection treatment was 132.6 µmol/L (95% confidence interval [95% CI], 78.7 to 186.5) in patients with isolated endarteritis, 96.4 µmol/L (95% CI, 48.6 to 143.2) in positive controls (P=0.32), and 18.6 µmol/L (95% CI, 1.8 to 35.4) in untreated negative controls (P<0.001). Functional improvement after rejection treatment occurred in 80% of patients with isolated endarteritis and 81% of positive controls (P=0.72). Over the median 3.2-year follow-up period, kidney transplant survival rates were 79% in patients with isolated endarteritis, 79% in positive controls, and 91% in negative controls (P=0.01). In multivariate analysis, isolated endarteritis was associated with an adjusted 3.51-fold (95% CI, 1.16 to 10.67; P=0.03) risk for transplant failure. These data indicate that isolated endarteritis is an independent risk factor for kidney transplant failure.
Risk factors for ulcer development in patients with non-ulcer dyspepsia: a prospective two year follow up study of 209 patients
Authors: P-I Hsu, K-H Lai, G-H Lo, H-H Tseng, C-C Lo, H-C Chen, W-L Tsai, H-S Jou, N-J Peng, C-H Chien, J-L Chen, P-N Hsu
Journal: Gut (2002)

A subset of non-ulcer dyspepsia (NUD) disorders can evolve into peptic ulcer disease. This prospective study attempted to determine the independent risk factors for ulcer formation in NUD patients, and compared the natural history of Helicobacter pylori positive and negative NUD subjects.From May 1997 to April 1999, consecutive NUD patients were enrolled into the study. Endoscopy was performed routinely on enrolment, at the end of the second and 12th months, and whenever there was a dyspepsia attack. Patients were prospectively followed up for two years.Peptic ulcers occurred in 16 of 209 NUD patients during the two year follow up period. Multivariate analysis of 13 host and bacterial factors demonstrated that advanced age (odds ratio 2.90), H pylori infection (odds ratio 3.59), and use of non-steroidal anti-inflammatory drugs (NSAID; odds ratio 4.46) were independently significant in predicting subsequent peptic ulcer development. NUD patients with all three risk factors had a 75% (3/4) risk of developing peptic ulcer but the ulcer incidence in patients without any of the risk parameters was only 1.2% (1/84). The resolution rate of symptoms in the H pylori positive NUD patients was similar to the H pylori negative patients (57.9% v 49.1%; 95% confidence interval (CI) -5 to 22). However, rates for subsequent peptic ulcer and erosion development were significantly higher in H pylori positive patients than in H pylori negative patients (ulcer 12.6% v 3.5%, 95% CI 1-16; erosion 23.2% v 12.3%, 95% CI 1-21).A small but significant proportion of NUD patients develop peptic ulcer after long term follow up. H pylori infection, NSAID use, and advanced age are independent risk factors for subsequent ulcer formation. Follow up endoscopy is strongly indicated for an NUD patient with multiple risk factors for ulcer formation when symptoms recur.
Effectiveness of customised foot orthoses for Achilles tendinopathy: a randomised controlled trial
Authors: Shannon E Munteanu, Lisa A Scott, Daniel R Bonanno, Karl B Landorf, Tania Pizzari, Jill L Cook, Hylton B Menz
Journal: British Journal of Sports Medicine (2014)

Aim To evaluate the effectiveness of customised foot orthoses in chronic mid-portion Achilles tendinopathy. Methods This was a participant-blinded, parallel-group randomised controlled trial at a single centre (La Trobe University, Melbourne, Australia). One hundred and forty participants aged 18–55 years with mid-portion Achilles tendinopathy were randomised to receive eccentric calf muscle exercises with either customised foot orthoses (intervention group) or sham foot orthoses (control group). Allocation to intervention was concealed. The Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire was completed at baseline, then at 1, 3, 6 and 12 months, with 3 months being the primary end point. Differences between groups were analysed using intention to treat with analysis of covariance. Results After randomisation into the customised foot orthoses group (n=67) or sham foot orthoses group (n=73), there was 70.7% follow-up of participants at 3 months. There were no significant differences between groups at any time point. At 3 months, the mean (SD) VISA-A score was 82.1 (16.3) and 79.2 (20.0) points for the customised and sham foot orthosis groups, respectively (adjusted mean difference (95% CI)=2.6 (−2.9 to 8.0), p=0.353). There were no clinically meaningful differences between groups in any of the secondary outcome measures. Conclusions Customised foot orthoses, prescribed according to the protocol in this study, are no more effective than sham foot orthoses for reducing symptoms and improving function in people with mid-portion Achilles tendinopathy undergoing an eccentric calf muscle exercise programme. Trial Registration Number Australian New Zealand Clinical Trials Registry: number ACTRN12609000829213.
Unconjugated hyperbilirubinaemia in achalasia
Authors: J. Fevery, K. P. M. Heirwegh, J. De Groote
Journal: Gut (1974)

Moderate unconjugated hyperbilirubinaemia decreasing after pneumatic dilatation of the gastrooesophageal sphincter, so permitting a normal amount of food to be taken was observed in two patients with achalasia. Liver biopsy was performed, and hepatic digitonin-activated bilirubin UDP-glucuronyltransferase activity was decreased in both, as is usually found in patients with Gilbert9s syndrome. In the patients examined the slight and variable hyperbilirubinaemia associated with Gilbert9s syndrome seemed thus to have been aggravated because of the decreased food intake due to achalasia. This situation may be compared to the jaundice sometimes found in neonates with pyloric stenosis or other types of obstruction of the upper gastrointestinal tract. Observations in rats and man favour a complex mechanism for fasting-induced hyperbilirubinaemia.
Defective venous beta-adrenergic response in borderline hypertensive subjects is corrected by a low sodium diet.
Authors: R D Feldman
Journal: Journal of Clinical Investigation (1990)

Hypertensive patients have reduced lymphocyte beta-adrenergic responsiveness which is corrected by a low sodium (Na) diet. To determine if this represents a more generalized abnormality in beta adrenoceptor response, we studied beta adrenergic-mediated vasodilation in hand veins of borderline hypertensive subjects and controls. Subjects received a 5-d diet containing high Na/low potassium (K), high Na/high K, or low Na/high K. Venous distension, as evaluated by a linear variable differential transformer, was measured in relation to infusion of phenylephrine followed by isoproterenol and nitroglycerin. On both the high Na/high K and high Na/low K diets, hypertensive subjects had significantly decreased isoproterenol-mediated vasodilation (47% decrease, P less than 0.01 and 36% decrease, P less than 0.01, respectively). On the low Na/high K diet, isoproterenol-mediated vasodilation in hypertensive subjects increased 41% (P less than 0.01) to a level not different from controls. Nitroglycerin-mediated vasodilation was not different in normotensive and hypertensive subjects, nor was it altered with Na intake. Phenylephrine-mediated vasoconstriction did not differ between normotensive and hypertensive groups. Venous beta-adrenergic response correlated with lymphocyte beta adrenoceptor density in normotensive (r = 0.53, P less than 0.005) but not hypertensive subjects. This study demonstrates that beta-adrenergic responsiveness is selectively reduced in peripheral veins of borderline hypertensive subjects, and this is corrected by a low Na diet. In view of our previous findings of reduced lymphocyte beta-adrenergic responsiveness in borderline hypertension, these studies suggest a generalized defect of beta adrenoceptor responsiveness in human hypertension. Further, dietary Na may play an important role in regulating this abnormality.
Recognition of a leukemia-related antigen by an antiidiotypic antiserum to an anti-gp70 monoclonal antibody.
Authors: B Ardman, R H Khiroya, R S Schwartz
Journal: The Journal of Experimental Medicine (1985)

The possibility that receptors for retroviral gp70 share structural elements with the antigen-binding sites of anti-retroviral gp70 antibodies was investigated. A monoclonal antibody (1416) was produced that reacted with the gp70 of a cloned recombinant leukemogenic retrovirus, termed P1. An antiidiotypic antiserum raised to 1416 was tested for its ability to bind to the thymic leukemia induced by P1 (P1 Thy). A membrane structure was identified on the surface of P1 Thy that reacted with the antibody against the idiotypic determinant of 1416. A similar structure was identified on the surface of several different, independently derived murine leukemias of T cell, B cell, and erythroid lineage. The expression of the idiotype-like determinant on these leukemia cells was independent of the serological relatedness of their expressed retroviral envelope glycoproteins to P1 gp70. The determinant recognized by the antiidiotype was not detected on normal lymphoid cells. The recognition by the anti-(anti-gp70) idiotype of determinants on unrelated murine leukemias suggests that receptors for different leukemogenic viruses may share common structures.
Antibodies from patients with rheumatoid arthritis target citrullinated histone 4 contained in neutrophils extracellular traps
Authors: Federico Pratesi, Ilaria Dioni, Cristina Tommasi, Maria Claudia Alcaro, Ilaria Paolini, Francesca Barbetti, Francesca Boscaro, Filomena Panza, Ilaria Puxeddu, Paolo Rovero, Paola Migliorini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Histone deimination regulates gene function and contributes to antimicrobial response, allowing the formation of neutrophil extracellular traps (NETs). Deiminated proteins are target of anti-citrullinated peptides antibodies (ACPA) in rheumatoid arthritis (RA). <h3>Objective</h3> The objective of this paper is to test the hypothesis that RA sera react with deiminated histones contained in NETs. <h3>Methods</h3> Neutrophils from peripheral blood were stimulated with A23187 and acid treated; NETosis was induced by phorbol myristate acetate, and NET proteins were isolated. Sera were tested by immunoblot on acid extracted proteins from neutrophils and from NETs, and by ELISA on deiminated histone H4 or H4-derived peptides. Bands reactive with RA sera were excised from gels, digested with trypsin and subjected to matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) analysis, before and after derivatisation to detect citrullinated peptides. <h3>Results</h3> RA sera reacted with a deiminated antigen of 11 KDa from activated neutrophils, recognised also by anti-H4 and antideiminated H4 antibodies. A similar reactivity was observed with NET proteins. The antigen from neutrophils or NETs was identified as citrullinated H4 by MALDI-TOF analysis. By ELISA, RA sera bound in vitro citrullinated H4. Citrullinated H4 14–34 and 31–50 peptides detected antibodies in 67% and 63% of RA sera and in less than 5% of controls; antibody titre was correlated with anti-CCP2. <h3>Conclusions</h3> Citrullinated H4 from activated neutrophils and NETs is a target of antibodies in RA, and synthetic citrullinated H4-derived peptides are a new substrate for ACPA detection. As NETosis can generate antigens for ACPA, these data suggest a novel connection between innate and adaptive immunity in RA.
Calcium channel blockers in myocardial infarction
Authors: J F. Hansen
Journal: BMJ (1990)

In 1984 the International Commission on Radio- logical Protection first issued a statement indi- cating that no special limitations on exposures were required during the four weeks following the onset of menstruation.4This change and the reasons for it were widely discussed,5" and we looked forward to receiving clear advice to abandon the logistically complicated and operationally inefficient "10 day rule."In the event this was not forthcoming because of the ambiguity inherent in the second clause of the pregnancy question.This means one thing to those patients with an understanding of human physiology and another to those without such understanding.Any informed, sexually active woman in the second half of her cycle must answer "yes," and implicit in this interpretation of the question is retention of the 10 day rule.The basic science suggests that it is the traditional interpretation of pregnancy that is important, and this can be established by asking "Have you missed a period?"This is the question that we now ask, which frees us from the un- necessary constraint of the 10 day rule without ambiguity, and for which we have the support of the director of the National Radiological Protec- tion Board (R H Clarke, personal communication).
Moving Closer to a Prognostic DNA Methylation Signature in Colon Cancer
Authors: F. Javier Carmona, Manel Esteller
Journal: Clinical Cancer Research (2011)

Although large panels of genes undergoing aberrant CpG island methylation in colorectal cancer have been identified, reliable predictors for clinical management in this tumor type remain elusive. A new DNA methylation signature affecting the extracellular matrix (ECM) pathway has been identified with potential prognostic value in colon cancer.
Timeliness of care in patients with lung cancer: a systematic review
Authors: J K Olsson, E M Schultz, M K Gould
Journal: Thorax (2009)

<h3>Background:</h3> Timeliness is an important dimension of health care quality. It is unclear whether timeliness improves clinical outcomes in patients with lung cancer. <h3>Methods:</h3> This study systematically reviewed studies that described timeliness of care, examined associations between timeliness and clinical outcomes or tested an intervention to improve timeliness of care in patients with lung cancer. English language studies published between 1 January 1995 and 1 June 2007 were included. Two reviewers independently abstracted data on study methods, population, sample size, relevant time intervals and outcomes. <h3>Results:</h3> 49 studies were identified that reported at least one time interval in lung cancer care, 18 studies that examined the association between timeliness and clinical outcomes and 8 studies that described interventions aimed at improving timeliness. Most studies were performed in European Union member countries, including 24 studies performed in Great Britain and Ireland. Median times to diagnosis (range 8–60 days) and times to treatment (range 30–84 days) often exceeded published recommendations. Three studies found that timely care was associated with better survival, eight found no association and four reported better survival in patients who received less timely care. Interventions that improved timeliness included nurse-led care coordination, multidisciplinary meetings via teleconference and a standardised expedited “two-stop” diagnostic process. <h3>Conclusions:</h3> Times to diagnosis and treatment of lung cancer are often longer than recommended. Factors associated with timeliness have been incompletely examined, and it remains unclear whether more timely care improves outcomes.