tbuckley/cabot-search huggingface dataset:
Basophils are not the key antigen‐presenting cells in allergic patients
Authors: J. Eckl‐Dorna, A. Ellinger, K. Blatt, V. Ghanim, I. Steiner, M. Pavelka, P. Valent, R. Valenta, V. Niederberger
Journal: Allergy (2012)

Abstract Background Recent data obtained in mouse models have initiated a controversy whether basophils are the key antigen‐presenting cells ( APC s) in allergy. Here, we investigate whether basophils are of importance for the presentation of allergen and the induction of T cell proliferation in allergic patients. Methods T cells, basophils, and APC s depleted of basophils were purified from allergic patients. Co‐culture systems based on purified major allergens were established to study allergen‐specific T cell responses using proliferation assays. Results Only co‐cultures of T cells with APC s depleted of basophils but not with basophils proliferated in response to allergen. Even addition of IL ‐3 to T cell–basophil co‐cultures failed to induce allergen‐specific T cell proliferation. Conclusions Our data demonstrate by classical in vitro proliferation assays that basophils are not key antigen‐presenting cells that promote T cell proliferation in secondary immune responses to allergen in allergic patients.
The effect of exchanger inhibitory peptide (XIP) on sodium-calcium exchange current in guinea pig ventricular cells.
Authors: T K Chin, K W Spitzer, K D Philipson, J H Bridge
Journal: Circulation Research (1993)

We investigated the effect of exchanger inhibitory peptide (XIP) on Na-Ca exchange current (INa-Ca) in guinea pig ventricular cells. Cells were voltage-clamped with microelectrodes containing 20 mM Na+ and 14.0 mM EGTA ([Ca]i = 100 nM). An outward putative exchange current was stimulated when extracellular Na+ was reduced from 144 mM to zero (Li+ replaced Na+). This outward current showed a significant dependence on extracellular Ca2+. When Na+ removal was delayed for up to 40 minutes (in the absence of extracellular K+ or the presence of 3.0 mM ouabain to block the Na+ pump), outward INa-Ca increased presumably because [Na]i increased. Time-dependent increases of outward current in the absence of K+ could be abolished by reapplication of K+, which presumably reactivates the Na+ pump and reduces intracellular Na+. This effect is blocked in the presence of 3.0 mM ouabain. The dependence of this current on extracellular Ca2+, its dependence on intracellular Na+, and activation by extracellular Na+ reduction, together with its resistance to ouabain all suggest that it is a Na-Ca exchange current. After dialyzing the cell with 10 microM XIP, outward INa-Ca was largely abolished. This indicates that XIP, which is a rather large molecule, can enter the heart cell via the microelectrode in sufficient quantities to inhibit exchange. Inward INa-Ca was blocked secondary to the blockade of outward INa-Ca. L-type Ca2+ current (ICa) was not measurably affected by XIP.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 5365: Cdt2-mediated XPG degradation promotes DNA repair synthesis following DNA damage excision in nucleotide excision repair
Authors: Chunhua Han, Ran Zhao, Jiang Qian, Nidhi Sharma, Gulzar Wani, Jinshan He, Qianzheng Zhu, Qi-En Wang, Altaf A. Wani
Journal: Cancer Research (2014)

Abstract Xeroderma pigmentosum group G (XPG) protein is a structure-specific repair endonuclease, which cleaves DNA strands on the 3′ side of the DNA damage during nucleotide excision repair (NER). In addition, XPG plays a crucial role in initiating DNA repair synthesis through recruitment of PCNA to the repair sites. However, the fate of XPG protein subsequent to the excision of DNA damage has remained unresolved. Here, we show that XPG is degraded through proteasome-mediated proteolysis upon induction of bulky lesions from exposures to UV irradiation and cisplatin. NER process is required for XPG degradation because both UV and cisplatin treatment-induced XPG degradation is compromised in NER-deficient XP-A, XP-B, XP-C, and XP-F cells. In addition, the NER-related XPG degradation requires Cdt2, a component of an E3 ubiquitin ligase, CRL4Cdt2. Micropore local UV irradiation and in situ Proximity Ligation assays demonstrated that Cdt2 is recruited to the UV-damage sites and interacts with XPG in the presence of PCNA. Importantly, Cdt2-mediated XPG degradation is crucial to the subsequent recruitment of DNA polymerase δ and DNA repair synthesis. Collectively, our data supports the idea of PCNA recruitment to damage sites in conjunction with XPG, recognition of the PCNA-bound XPG by CRL4Cdt2 for specific ubiquitylation and protein degradation. Thus, XPG removal clears the space needed at the damage site for the subsequent recruitment of DNA pol δ and initiation of DNA synthesis. (This work was supported by grants from NIH). Note: This abstract was not presented at the meeting. Citation Format: Chunhua Han, Ran Zhao, Jiang Qian, Nidhi Sharma, Gulzar Wani, Jinshan He, Qianzheng Zhu, Qi-En Wang, Altaf A. Wani. Cdt2-mediated XPG degradation promotes DNA repair synthesis following DNA damage excision in nucleotide excision repair. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5365. doi:10.1158/1538-7445.AM2014-5365
Regression of Melanoma in a Murine Model by RLIP76 Depletion
Authors: Sharad S. Singhal, Yogesh C. Awasthi, Sanjay Awasthi
Journal: Cancer Research (2006)

RLIP76/RALBP1 is a stress-responsive membrane protein implicated in the regulation of multiple cellular signaling pathways. It represents the predominant glutathione-conjugate transporter in cells, and our previous studies have shown that its inhibition by antibodies or depletion by short interfering RNA (siRNA) causes apoptosis in a number of cancer cell types. The present studies were done to explore the potential clinical applicability of our previous observations by comparing the relative expression of RLIP76 in cancer versus normal cell lines and to determine whether depletion of RLIP76 activity can exert cancer-specific apoptosis. RLIP76 expression was found to be significantly greater in malignant cells compared to nonmalignant cells. Inhibition of RLIP76, using antibodies towards a cell surface epitope, or depletion of RLIP76 using either siRNA or antisense phosphorothioate oligonucleotides preferentially caused apoptosis in malignant cells. More importantly, in vivo studies showed that administration of RLIP76 antibodies, siRNA, or antisense oligonucleotides to mice bearing syngeneic B16 mouse melanoma cells caused complete tumor regression within 10 days. These findings strongly suggest that RLIP76 depletion by genetic approaches or inhibition by antibodies may be a clinically viable antineoplastic therapy, particularly for melanoma.
Molecular and genetic ecotoxicologic approaches to aquatic environmental bioreporting.
Authors: B J Beaty, W C Black, J O Carlson, W H Clements, N DuTeau, E Harrahy, J Nuckols, E Kenneth, K E Olson, A Rayms-Keller
Journal: Environmental Health Perspectives (1998)

Molecular and population genetic ecotoxicologic approaches are being developed for the utilization of arthropods as bioreporters of heavy metal mixtures in the environment. The explosion of knowledge in molecular biology, molecular genetics, and biotechnology provides an unparalleled opportunity to use arthropods as bioreporter organisms. Interspecific differences in aquatic arthropod populations have been previously demonstrated in response to heavy metal insult in the Arkansas River (AR) California Gulch Superfund site (CGSS). Population genetic analyses were conducted on the mayfly Baetis tricaudatus. Genetic polymorphisms were detected in polymerase chain reaction amplified 16S mitochondrial rDNA (a selectively neutral gene) of B tricaudatus using single-strand conformation polymorphism analysis. Genetic differences may have resulted from impediments to gene flow in the population caused by mortality arising from exposure to heavy metal mixture pollution. In laboratory studies a candidate metal-responsive mucinlike gene, which is metal and dose specific, has been identified in Chironomus tentans and other potential AR-CGSS bioreporter species. Population genetic analyses using the mucinlike gene may provide insight into the role of this selectable gene in determining the breeding structure of B. tricaudatus in the AR-CGSS and may provide mechanistic insight into determinants of aquatic arthropod response to heavy metal insult. Metal-responsive (MR) genes and regulatory sequences are being isolated, characterized, and assayed for differential gene expression in response to heavy metal mixture pollution in the AR-CGSS. Identified promoter sequences can then be engineered into previously developed MR constructs to provide sensitive in vitro assays for environmental bioreporting of heavy metal mixtures. The results of the population genetic studies are being entered into an AR geographic information system that contains substantial biological, chemical, and geophysical information. Integrated spatial, structural, and temporal analyses of these parameters will provide invaluable information concerning environmental determinants that restrict or promote gene flow in bioreporter populations.
Drugs and Phagocytes
Authors: Martin J. Cline
Journal: New England Journal of Medicine (1974)

Phagocytic leukocytes must integrate three functions in performance of their antimicrobial defense activities: mobilization of cells from the bloodstream to the site of inflammation; phagocytosis of the invading microbe; and killing of the organism once it is ingested. The vast majority of drugs that interfere with host defense mechanisms do so not by influencing these activities but by injuring hematopoietic stem cells in the bone marrow or adversely affecting the function of differentiated lymphoid cells. For example, cytotoxic chemotherapeutic agents regularly produce neutropenia, monocytopenia, or immunologic impairment by such mechanisms. Other drugs, such as chloramphenicol, do so unpredictably. Few pharmacologic . . .
NATIONAL TEAM RUGBY PLAYER INJURY TYPES, RATES AND RISK FACTORS OVER TWO-YEARS
Authors: P Mathema, C Ranson, I Moore
Journal: British Journal of Sports Medicine (2014)

Background Injury surveillance may provide valuable information regarding relationships between initial and subsequent injuries. Subsequent Injury Categorisation (SIC) may be useful in sports such as rugby that have high rates of re-injury amongst elite players. Objective To identify types, rates and potential risk factors for injury, and subsequent injury, in international rugby players. Design Prospective injury surveillance using consensus methods and SIC. Setting Tier 1 international and professional rugby. Participants Players from one national team squad over two years. Risk factor assessment Injury types, rates and severity, according to team (national or club), mechanism and activity (training or match) at time of injury, and SIC. Main outcome measurement Training and match injury incidence (per 100 days), prevalence (% of players unavailable) and average days-lost per injury were calculated for each variable along with the percentage of injuries within each SIC. Results Overall incidence was 44/100 days (match 30/100 days, training 9/100 days), prevalence was 21% and 16 days were lost per injury. International incidence was highest (25 vs. 19/100 days), but days-lost per injury was greater for club injuries (19 vs. 14 days). Incidence and prevalence was greatest for international impact injuries (11 vs. 6/100 days, 7 vs. 4%), but there were a similar number of days-lost per injury (21 days). During international campaigns the anterior thigh, knee and lower leg regions had the highest injury rates, whilst on Club duty the hip, knee and shoulder were highest. Twenty-nine percent of the 252 subsequent injuries were coded as being related to a previous injury. Fourteen percent of subsequent injuries were a direct recurrence. Conclusions High incidence of impact injuries in international rugby may be due to greater number of contact events. Injury prevention strategies may need to target different body areas for international vs. club rugby. SIC analysis may allow subsequent injury risk to be better managed.
Deficiency of senescence marker protein 30 exacerbates angiotensin II-induced cardiac remodelling
Authors: Tomofumi Misaka, Satoshi Suzuki, Makiko Miyata, Atsushi Kobayashi, Tetsuro Shishido, Akihito Ishigami, Shu-ichi Saitoh, Masamichi Hirose, Isao Kubota, Yasuchika Takeishi
Journal: Cardiovascular Research (2013)

Ageing is an important risk factor of cardiovascular diseases including heart failure. Senescence marker protein 30 (SMP30), which was originally identified as an important ageing marker protein, is assumed to act as a novel anti-ageing factor in various organs. However, the role of SMP30 in the heart has not been previously explored. In this study, our aim was to elucidate the functional role of SMP30 on cardiac remodelling.SMP30 knockout (KO) mice and wild-type (WT) mice were subjected to continuous angiotensin II (Ang II) infusion. After 14 days, the extent of cardiac hypertrophy and myocardial fibrosis was significantly higher in SMP30-KO mice than in WT mice. Echocardiography revealed that SMP30-KO mice had more severely depressed systolic and diastolic function with left ventricular dilatation compared with WT mice. Generation of reactive oxygen species related with activation of nicotinamide adenine dinucleotide phosphate-oxidase was greater in SMP30-KO mice than in WT mice. The number of deoxynucleotidyl transferase-mediated dUTP nick end-labelling positive nuclei was markedly increased in SMP30-KO mice with activation of caspase-3, increases in the Bax to Bcl-2 ratio and phosphorylation of c-Jun N-terminal kinase compared with WT mice. Furthermore, the number of senescence-associated β-galactosidase-positive cells was significantly increased via up-regulation of p21 gene expression in SMP30-KO mice compared with WT mice.This study demonstrated the first evidence that deficiency of SMP30 exacerbates Ang II-induced cardiac hypertrophy, dysfunction, and remodelling, suggesting that SMP30 has a cardio-protective role in cardiac remodelling with anti-oxidative and anti-apoptotic effects in response to Ang II.
Serum hyaluronate in primary biliary cirrhosis—A biochemical marker for progressive liver damage
Authors: Anders Nyberg, Anna Engström-Làurent, Lars Lööf
Journal: Hepatology (1988)

To evaluate serum hyaluronate as a marker for progressive liver injury in patients with primary biliary cirrhosis, a longitudinal study including 48 patients was conducted with a mean follow-up time of 40 months. The patients were examined every 6 months with a standardized set of conventional liver function tests, and a liver biopsy was performed every year. The hyaluronate concentration correlated significantly (p &lt; 0.001) with albumin, t 1/2 galactose tolerance test, bilirubin and prothrombin time but not to serum variables reflecting inflammatory activity. Furthermore, there was a close correlation between serum hyaluronate levels and histopathological changes in the liver. The hyaluronate concentration increased significantly over time in all clinical stages of primary biliary cirrhosis (p &lt; 0.01), whereas the conventional liver function tests only changed in the advanced cases. The present data indicate that serum hyaluronate may be a sensitive marker for progressive liver damage in primary biliary cirrhosis. Serial determinations of hyaluronate are therefore of potential value for monitoring liver function during clinical management of the condition.
Successful treatment of Behçet’s disease with lenalidomide
Authors: J. Green, E. Upjohn, C. McCormack, J. Zeldis, H.M. Prince
Journal: British Journal of Dermatology (2007)

Journal Article Successful treatment of Behçet’s disease with lenalidomide Get access J. Green, J. Green Departments of Dermatology and Haematology, Peter McCallum Cancer Centre and University of Melbourne, Australia Search for other works by this author on: Oxford Academic Google Scholar E. Upjohn, E. Upjohn Departments of Dermatology and Haematology, Peter McCallum Cancer Centre and University of Melbourne, Australia Search for other works by this author on: Oxford Academic Google Scholar C. McCormack, C. McCormack Search for other works by this author on: Oxford Academic Google Scholar J. Zeldis, J. Zeldis Departments of Dermatology and Haematology, Peter McCallum Cancer Centre and University of Melbourne, Australia Correspondence: Celgene Corporation, NJ, U.S.A. E‐mail: jack_green@optusnet.com.au; avjak@optusnet.com.au Search for other works by this author on: Oxford Academic Google Scholar H.M. Prince H.M. Prince Departments of Dermatology and Haematology, Peter McCallum Cancer Centre and University of Melbourne, Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 1, 1 January 2008, Pages 197–198, https://doi.org/10.1111/j.1365-2133.2007.08288.x Published: 01 January 2008
Unstable Angina: A Lethal Gun with an Invisible Trigger
Authors: Jeffrey S. Borer
Journal: New England Journal of Medicine (1980)

The clinical syndrome of unstable angina pectoris defines a population with a relatively high risk of imminent myocardial infarction.1 Optimally, attempts to prevent infarction in such patients should be based on an understanding of the pathogenesis and pathophysiology of unstable angina. As yet, our knowledge of this area is importantly deficient; however, recent investigations have effected major changes in our therapeutic approach.For many years it was believed that unstable angina was the result of episodic and often imperceptible changes in myocardial oxygen demand, superimposed on rapidly advancing or completed coronary thrombosis.2 Based on this view, therapy was aimed at . . .
The cytocompatability of polyhydroxyalkanoates coated with a fusion protein of PHA repressor protein (PhaR) and Lys-Gln-Ala-Gly-Asp-Val (KQAGDV) polypeptide
Authors: Cui-Ling Dong, Shi-Yan Li, Yang Wang, Ying Dong, James Zhenggui Tang, Jin-Chun Chen, Guo-Qiang Chen
Journal: Biomaterials (2011)
Biodegradable core-shell nanoassemblies for the delivery of docetaxel and Zn(II)-phthalocyanine inspired by combination therapy for cancer
Authors: C. Conte, F. Ungaro, G. Maglio, P. Tirino, G. Siracusano, M.T. Sciortino, N. Leone, G. Palma, A. Barbieri, C. Arra, A. Mazzaglia, F. Quaglia
Journal: Journal of Controlled Release (2013)
Effect of myocardial infarction on high-frequency QRS potentials.
Authors: A L Goldberger, V Bhargava, V Froelicher, J Covell
Journal: Circulation (1981)

Studies have shown that the number of high-frequency QRS notches increases after myocardial infarction (MI). To assess overall high-frequency (greater than 80 Hz) potentials more quantitatively, we adapted filtered and the root-mean-square (RMS) voltage of the residual (80-300 Hz) signal computed. High-frequency RMS values were significantly (p less than 0.01) greater in leads II, III and aVf in normal subjects (n = 12) than in patients with inferior infarction (n = 12). Similarly, high-frequency RMS values were higher (p less than 0.01) in leads V2 and V5 in normal subjects (n = 14) than in patients with prior anterior MI (n = 14). A reduction in high-frequency RMS values with inferior infarction was independently confirmed using Fourier analysis of the QRS in lead II. QRS notching in these subjects was also quantified by computing the number of baseline crossings of the first derivative (dV/dt). As predicted, notching was significantly greater (p less than 0.05) both with inferior MI (lead II) and anterior MI (lead V5). However, contrary to classic theory, the number of notches correlated negatively with direct measurements of high-frequency RMS voltage in lead II (r = -0.63) and lead V5 (r = -0.49). Positive correlations were obtained between high-frequency potentials and two new indexes that measure the amplitude of QRS dV/dt-peak-to-peak amplitude of dV/dt and RMS dV/dt. Using these indexes, absolute separation of inferior MI patients and normal subjects was obtained. We conclude that MI increases low-amplitude QRS notching but diminishes total high-frequency voltage, probably because of an overall decrease in electromotive potentials and slowing of ventricular conduction.
THE ADDICTION LIABILITY OF CODEINE
Authors: C. K. HIMMELSBACH
Journal: JAMA (1934)

Discussions have arisen from time to time concerning the addiction liability of codeine and its value as a therapeutic agent for the relief of those withdrawal phenomena seen when morphine is abruptly withheld from persons addicted to its use. Although generally conceded to be nonaddicting, various authors, notably Sollier,<sup>1</sup>Petty,<sup>2</sup>Lambert,<sup>3</sup>White,<sup>4</sup>Rouges de Fursac and Monestier,<sup>5</sup>Terry<sup>6</sup>and Sollmann,<sup>7</sup>have indicated that codeine possesses this propensity. It was therefore considered advisable to investigate the addiction liability of codeine before employing it in the treatment of abrupt morphine deprivation. The studies with which this article deals, however, attempt to record certain preliminary observations necessary for carrying out a cooperative investigation sponsored by the Committee on Drug Addiction of the Medical Science Division of the National Research Council. The Committee on Drug Addiction of that council, supported by funds from the Rockefeller Foundation, in
FIFTEEN CASES OF LIVER ABSCESS: An Analysis of Symptoms and Treatment
Authors: P. Talbot
Journal: BMJ (1919)

sunken, looking very toxic 'and slightly jaundiced, abdomen inot moving with respiration and legs drawn 'up.No passage ' ' f flatus for' thirty-six hours, small quantities of high-coloured :urine passed with difficulty.Maximum tenderness in right qower abdominal quadrant; a tender mass could be felt per rectum on'the right side, and the recto-vesical pouch filt full.Pulse 110, tliread7y; temperature 102.80.Laparatonty performed through right rectus.A gangrenous perforated appendix which was hanging into the pelvis was removed.The pelvis was full of a very offensive fluid and a .concretionwas found free in the fluid.Diffuse peritonitis was well established; the intestine was acutely inflamed and dis- tended; large patches of lymph were present on the small in- testine, whose coils were matted together.The pelvis was mopped dry, but the remainder of the peritoneal cavity was not touched.A small drain was left for forty-eight hours down to the bottom of the recto-vesical pouch.The abdomen was -closed in three layers.Suubsequent History.-Biliaryvomiting continued for three days.No passage of flatus until the third night.A very offensive liquid stool passed naturally on the fourth day.The patient developed bronchopneumonia, but the abdominal ,condition remainecd satisfactory.Distension had entirely gone at the end of the eighth daiy.Tube removed at the end of forty-eight hours.Despite the pneumonia the patient made a very satisfactory recovery.Yreatment.-Continuoussubcutaneous saline up to the third day, .copiousdrinks of water containing bicarbonate and oitrate, glucose per rectum.Morphine gr.i 8-hourly, atropine gr.I,& 12-hourly for forty-eight hours, and discontinued after the end of the third day.No aperient until the ninth day.Very light diet up to the ninth day, when diet was graduall'y increased.SUMMARY OF CASES.Briefly the.series of twenty-one cases is as follows:The cause of the.condition was due to appendix abscess in 6, perforated gastric ulcer in 1, penetrating wounds of v the, abdomen -in 8, intestinal obstruction with gangrene of t#he-gut, i 3, intestinal obstruction with perforation of the gtin li--pneumocWcpl i-n 2, -There was one -death-a .case of inttinal obstruction