tbuckley/cabot-search huggingface dataset:
An Epidemiological and Molecular Study of the Relationship Between Smoking, Risk of Nasopharyngeal Carcinoma, and Epstein–Barr Virus Activation
Authors: Feng-Hua Xu, Dan Xiong, Ya-Fei Xu, Su-Mei Cao, Wen-Qiong Xue, Hai-De Qin, Wen-Sheng Liu, Jing-Yan Cao, Ying Zhang, Qi-Sheng Feng, Li-Zhen Chen, Man-Zhi Li, Zhi-Wei Liu, Qing Liu, Ming-Huang Hong, Yin Yao Shugart, Yi-Xin Zeng, Mu-Sheng Zeng, Wei-Hua Jia
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundElevated levels of antibodies against antigens in the Epstein–Barr virus (EBV) lytic phase are important predictive markers for nasopharyngeal carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also been associated with NPC risk. We hypothesized that some specific lifestyle factors induce transformation of EBV from the latent to the lytic stage and contribute to NPC occurrence.
Integrin Targeted Delivery of Chemotherapeutics
Authors: Kai Chen, Xiaoyuan Chen
Journal: Theranostics (2011)

Targeted delivery of chemotherapeutics is defined in the sense, that is, to maximize the therapeutic index of a chemotherapeutic agent by strictly localizing its pharmacological activity to the site or tissue of action.Integrins are a family of heterodimeric transmembrane glycoproteins involved in a wide range of cell-to-extracellular matrix (ECM) and cell-to-cell interactions.As cell surface receptors, integrins readily interact with extracellular ligands and play a vital role in angiogenesis, leukocytes function and tumor development, which sets up integrins as an excellent target for chemotherapy treatment.The peptide ligands containing the arginine-glycine-aspartic acid (RGD), which displays a strong binding affinity and selectivity to integrins, particularly to integrin αvβ3, have been developed to conjugate with various conventional chemotherapeutic agents, such as small molecules, peptides and proteins, and nanoparticle-carried drugs for integtrin targeted therapeutic studies.This review highlights the recent advances in integrin targeted delivery of chemotherapeutic agents with emphasis on target of integrin αvβ3, and describes the considerations for the design of the diverse RGD peptide-chemotherapeutics conjugates and their major applications.
Association of <i>NCOA3</i> Polymorphisms with Breast Cancer Risk
Authors: Barbara Burwinkel, Michael Wirtenberger, Rüdiger Klaes, Rita K. Schmutzler, Ewa Grzybowska, Asta Försti, Bernd Frank, Justo Lorenzo Bermejo, Peter Bugert, Barbara Wappenschmidt, Dorota Butkiewicz, Jolanta Pamula, Wioletta Pekala, Helena Zientek, Danuta Mielzynska, Ewa Siwinska, Claus R. Bartram, Kari Hemminki
Journal: Clinical Cancer Research (2005)

Abstract The nuclear receptor coactivator 3 (NCOA3, also known as AIB1) is a coactivator of nuclear receptors like the estrogen receptor. NCOA3 is overexpressed in ∼60% of primary human breast tumors, and high levels of NCOA3 expression are associated with tamoxifen resistance and worse survival rate. In contrast, NCOA3 deficiency suppresses v-Ha-ras–induced breast cancer initiation and progression in mice. Here, we analyzed the influence of NCOA3 coding single nucleotide polymorphisms on breast cancer risk by performing a case-control study using a German and a Polish study population and identified an association between NCOA3 polymorphisms and breast cancer. A joint analysis of the German and the Polish study population revealed a significant protective effect for the 1758G&amp;gt;C (Q586H) and 2880A&amp;gt;G (T960T) variants. In addition, haplotype analysis showed a protective effect of the 1758C-2880A and 1758G-2880G haplotypes (odds ratio 0.79; 95% confidence interval, 0.67-0.93; P = 0.004). Because of the impact of NCOA3 in antiestrogen therapy resistance, these polymorphisms might also influence therapy outcome in breast cancer.
Disodium etidronate in hypercalcaemia due to immobilisation.
Authors: E Hagg, M Eklund, O Torring
Journal: BMJ (1984)

were first reported by Ryan, but no details of the case were given3; and Rubino and Jackson described a patient who developed confusion and paranoia while receiving tocainide but only after the addition of propranolol to the treatment regimen.5Serum drug concentrations during toxic manifestations may vary widely in different subjects' and in our patients the concentrations of tocainide during toxicity were within the peak therapeutic range (5-15 mg/l, mean 10-3 mg/1).3In each case there was a 48 hour delay between initiating the final tocainide dose regimen and the onset of psychosis.This may be explained by an elimination half life ranging from 10 to 17 hours, which delays the onset of steady state peak drug concentrations and hence toxicity.High peak concentrations and toxi- city may be avoided by administering tablets with food4 and by careful prescription in the presence of propranolol5 and in patients with renal disease, since normally 40% of the unchanged drug is excreted in the urine.'We thank Mr M Stapleton for his help and Drs N Coulshed and E J Epstein for permission to report the cases.
Genomic and Evolutionary Insights into Genes Encoding Proteins with Single Amino Acid Repeats
Authors: Pratibha Siwach, Saurabh Dilip Pophaly, Subramaniam Ganesh
Journal: Molecular Biology and Evolution (2006)

Mutations causing expansion of amino acid repeats are responsible for 19 hereditary disorders. Repeats in several other proteins also show length variations. These observations prompted us to identify single amino acid repeat–containing proteins (SARPs) in humans and to understand their functional and evolutionary significance. We identified 8812 SARPs containing 17 146 repeat domains, each harboring 4 or more residues. In all, 5% of SARPs (471) showed repeat length variations, and nearly 84% of them (394) have repeats of 10 residues or less. We find that SARPs are involved in functions that require formation of multiprotein complexes. Nearly 78% (6859) of the SARPs did not find a paralogue in the human proteome, and such proteins are considered as orphan SARPs. Orphan SARPs show longer repeat stretches, longer peptide length, and lower expression levels as compared with SARPs belonging to protein family. Because the intensity of gene expression is known to relate inversely with the rate of protein sequence evolution, our results suggest that the orphan SARPs evolve faster than the familial forms and therefore are under a weaker selection pressure. We also find that while GC-rich codons are favored for coding the repeat tracts of SARPs, specific codons and not nucleotide motifs per se are selected, suggesting functional constraints placed on the usage of codons. One of the constraints could be the mRNA stability as clustering of rare codons is known to destabilize the transcripts and rare codons are not favored for coding repeat tracts. Genes encoding polymorphic SARPs show preferential localization toward the telomeric segments. Further, the sex-specific recombination rates of the chromosomal locus strongly correlate with the parental gender that influence the repeat instability in disorder caused by dynamic mutation. Therefore, instability associated with repeats might be driven by processes that are specific to sperm or oocyte development, and the recombination frequency might play a positive role in this process.
Targeted Disruption of the Mouse <i>Sod I</i> Gene Makes the Hearts Vulnerable to Ischemic Reperfusion Injury
Authors: Tetsuya Yoshida, Nilanjana Maulik, Richard M. Engelman, Ye-Shih Ho, Dipak K. Das
Journal: Circulation Research (2000)

Abstract —The role of Cu/Zn–superoxide dismutase (SOD) in myocardial ischemic reperfusion injury was studied by using a mouse model with targeted disruption of the mouse Sod I gene. Inactivation of the functional mouse Sod I gene in hearts by gene targeting ( Sod I +/− ) resulted in a 50% reduction of Cu/Zn-SOD mRNA and significant reduction of Cu/Zn-SOD enzyme activity compared with that of wild-type Sod I +/+ mice. Cu/Zn-SOD mRNA could not be detected in Sod I −/− heart. The isolated buffer-perfused hearts from the knockout mice devoid of any functional copy of the Sod I ( Sod I −/− ) and matched nontransgenic control mice were subjected to 30 minutes of global ischemia followed by 2 hours of reperfusion. For both groups of mice, the postischemic functional recovery for the hearts was lower than the baseline, but the recovery for the Sod I −/− was less compared with the wild-type mice. Thus, the postischemic recovery of the developed force and the maximum first derivative of the developed force were consistently lower for the Sod I −/− mouse hearts compared with wild-type control hearts. The coronary flow was lower compared with the baseline levels for both groups of hearts, but there was no significant difference between the groups. The myocardial infarction determined from the ratio of infarct size/area of risk was higher for the Sod I −/− mice compared with the control mice. The amount of creatine kinase release from the wild-type mouse hearts was less compared with the Sod I −/− mouse hearts. In concert, a reduced amount of oxidative stress was found in the hearts of wild-type mice compared with Sod I −/− mouse hearts. These results documented that Sod I −/− mouse hearts were more susceptible to ischemic reperfusion injury compared with corresponding wild-type mouse hearts, suggesting that the Sod I gene constitutes an important defense element for the hearts.
QUANTITATIVE EXPERIMENTS WITH ANTIBODIES TO A SPECIFIC PRECIPITATE
Authors: Henry P. Treffers, Dan H. Moore, Michael Heidelberger
Journal: The Journal of Experimental Medicine (1942)

1. Rabbit antisera to a Type II pneumococcus specific precipitate from horse serum were tested with fractions prepared by ultracentrifugation and electrophoresis of normal and immune horse serum. 2. In one instance a rapidly sedimenting protein from normal horse serum had nearly the same quantitative antigenic properties toward the anti-antibody rabbit serum as did the purified pneumococcus antibody solutions previously reported. In another instance a comparable fraction removed only a part of the rabbit antibody. 3. Electrophoretic gamma-globulin from an immune horse serum had quantitatively the same antigenic properties as did antibody solutions prepared by salt-dissociation of specific precipitates. 4. Electrophoretic gamma-globulin from normal horse serum differed in its antigenic behavior from gamma-globulin containing antibody. The data are compared with the antigenic properties of acid and alkali treated pneumococcus specific polysaccharides toward antipneumococcus horse sera. An interpretation in terms of polymers is suggested. 5. The cross-reaction of goat serum gamma-globulin against the anti-antibody serum is reported and the extent of the reaction compared with those of goat and horse serum albumins against a rabbit antiserum to the latter.
Prognostic impact of circulating Her-2-reactive T-cells producing pro- and/or anti-inflammatory cytokines in elderly breast cancer patients
Authors: Jithendra Kini Bailur, Evelyna Derhovanessian, Brigitte Gueckel, Graham Pawelec
Journal: Journal for ImmunoTherapy of Cancer (2015)

Treating elderly breast cancer patients remains a challenge but the increasing availability of immunotherapeutic approaches instills optimism that these tumours may also be susceptible to immune control. Because aging leads to a number of alterations in the immune system ("immunosenescence") reflecting potential exhaustion which could compromise immunomodulatory antibody therapy, here we have assessed the immunocompetence of elderly breast cancer patients compared with a group of younger patients, and related this to the 5-year survival of the former.T-cell responses to Her-2 peptide pools in vitro were assessed by analyzing pro- and anti-inflammatory cytokine production by CD4+ and CD8+ T-cells in 40 elderly and 35 younger breast cancer patients.The proportions of older and younger patients whose peripheral T-cells responded to Her-2 peptides in vitro were found to be similar, although a significantly higher fraction of younger patients possessed IL-2-producing CD4+ Her-2-reactive T-cells than in the elderly (p = 0.03). However, IL-2 production did not impart a survival benefit to the latter. In contrast, there was a survival benefit of possessing Her-2-reactive CD8+ T-cells, but this was abrogated in patients if they also had CD4+ Her-2-responsive T-cells that producedIL-5 and/or IL-17 (p = 0.01). This resulted in a 5-yr survival rate of only 29 % compared to 76 % for patients whose her-2-reactive CD4+ T-cells did not produceIL-5 and/or IL-17. Additionally, patients whose CD8+ T-cells produced TNF had a significantly better survival than those that did not (93 % compared to 52 %, p = 0.01), whereas no survival benefit was attributable to possessing IFN-γ-producing cells.Elderly breast cancer patients appear perfectly immunocompetent to respond to Her-2 peptide pools in vitro, with response patterns very similar to younger patients. The nature of this response is associated with 5-year survival of these elderly patients, suggesting that boosting anti-tumor responses and modulating the nature of the T-cell response is likely to be effective even in potentially immunosenescent elderly breast cancer patients, and might be useful for predicting which patients are most likely to benefit from such treatments.
Osteoporosis, falls, and age in fracture of the proximal femur
Authors: W J Boyce
Journal: BMJ (1987)

AUTHORS' REPLY,-As Dr Anderson states, the possibility of reduced clearance should be con- sidered when increased concentrations of atrial natriuretic peptide are found in patients with preeclampsia.Dr Anderson thinks that the raised concentrations of atrial natriuretic peptide are probably caused by impairment of renal function; we must disagree with this for several reasons.Firstly, there was no significant correlation between plasma atrial natriuretic peptide con- centrations and either creatinine clearance (mean 99 ml/min, range 77-124 ml/min) or plasma creati- nine (mean 78 imol/l, range 66-97 Rmol/l) in patients with pre-eclampsia, and none of the patients presented with oliguria.Secondly, no studies, including those cited by Dr Anderson, provide evidence that slight renal impairment like that in our patients gives rise to a substantial increase in plasma atrial natriuretic peptide con- cntrations.Thirdly, although many agree that renal degradation is important in the elimination of atrial natriuretic peptide, this is not a uniform finding.' 2 Finally, data have been presented to show tlhait the placenta produces atrial natriuretic peptide, and we thus have to consider this to be a possible source of increased production of atrial natriuretic peptide.Admittedly, these arguments were not stated clearly in our report, and the conclusion was too strongly worded.We still believe, however, that our data suggest that factors other than atrial pressures may be related to the release of atrial natriuretic peptide in patients with pre-eclampsia.
<i>In vitro</i> and <i>In vivo</i> Anticancer Activity of Novel Synthetic Makaluvamine Analogues
Authors: Wei Wang, Elizabeth R. Rayburn, Sadanandan E. Velu, Dwayaja H. Nadkarni, Srinivasan Murugesan, Ruiwen Zhang
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The present study was designed to determine biological structure-activity relationships for four newly synthesized analogues of natural compounds (makaluvamines). The compounds, 7-(4-fluorobenzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (FBA-TPQ); 7-(phenethylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (PEA-TPQ); 7-(3,4-methylenedioxyphenethylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (MPA-TPQ); and 7-(3,4-dimethoxyphenethylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (DPA-TPQ), were synthesized and purified, and their chemical structures were elucidated on the basis of physicochemical constants and nuclear magnetic resonance spectra. Experimental Design: The structure-activity relationship of the compounds was initially evaluated by comparing their in vitro cytotoxicity against 14 human cell lines. Detailed in vitro and in vivo studies were then done in MCF-7 and MDA-MB-468 breast cancer cell lines. Results: The in vitro cytotoxicity was compound, dose, and cell line dependent. Whereas all of the compounds exerted some activity, FBA-TPQ was the most potent inducer of apoptosis and the most effective inhibitor of cell growth and proliferation, with half maximal inhibitory concentration values for most cell lines in the range of 0.097 to 2.297 μmol/L. In MCF-7 cells, FBA-TPQ exposure led to an increase in p53/p-p53, Bax, ATM/p-ATM, p-chk1 and p-chk2, and p-H2AX; and cleavage of poly(ADP)ribose polymerase, caspase-3, caspase-8, and caspase-9. It also decreased the levels of MDM2, E2F1, Bcl-2, chk1/2, and proteins associated with cell proliferation [cyclin-dependent kinase (Cdk)2, Cdk4, Cdk6, cyclin D1, etc.]. Moreover, FBA-TPQ inhibited the growth of breast cancer xenograft tumors in nude mice in a dose-dependent manner. Western blot analysis ofthe xenograft tumors indicated that similar changes in protein expression also occur in vivo. Conclusion: Our preclinical data indicate that FBA-TPQ is a potential therapeutic agent for breast cancer, providing a basis for the development of the compound as a novel anticancer agent.
Acute lateral ankle ligament injuries
Authors: Evert Verhagen
Journal: British Journal of Sports Medicine (2010)

Approximately 25% of all injuries across all sports are acute lateral ankle ligament injuries. Thus, anyone involved with athlete care will frequently see patients with such an injury. Because they can limit future sports participation, there is a clear need for specific knowledge on the diagnostic workup, treatment and prevention for this type of injury.

In this module you are presented with an amateur volleyball player who has forcefully inverted his ankle. Through a series of four …
Effect of particle size of bronchodilator aerosols on lung distribution and pulmonary function in patients with chronic asthma.
Authors: D M Mitchell, M A Solomon, S E Tolfree, M Short, S G Spiro
Journal: Thorax (1987)

The particle size of bronchodilator aerosols may be important in determining the site of deposition in the lung and their therapeutic effect. The distribution of aerosols (labelled with technetium-99m diethylene triamine pentacetic acid) of two different particle sizes has been studied by gamma camera imaging. The particles had mass median aerodynamic diameters (geometric standard deviations) of 1.4 (1.4) and 5.5 (2.3) micron, and they were administered from a jet nebuliser to eight patients with chronic severe stable asthma. There was no significant difference in peripheral lung deposition with the two aerosols in any patient. The bronchodilator effect of the two aerosols was determined from cumulative dose-response studies. To avoid large doses that might mask possible differences in effect due to aerosol size, small, precisely determined incremental amounts of salbutamol (25-250 micrograms total lung dose) were used. The two doses were given via a nebuliser on separate occasions and the bronchodilator response was measured from FEV1, forced vital capacity, and peak expiratory flow 30 minutes after each dose. Bronchodilatation was similar with the two aerosols at each dose of salbutamol. There was therefore no difference in distribution within the lung or any difference in bronchodilator effect between an aerosol of small (1.4 micron) particle size and an aerosol of 5.5 microns in patients with severe but stable asthma.
Aortic-Valve Stenosis — From Patients at Risk to Severe Valve Obstruction
Authors: Catherine M. Otto, Bernard Prendergast
Journal: New England Journal of Medicine (2014)

Aortic-valve stenosis is a progressive condition; end-stage disease leads to death due to obstruction of left ventricular outflow. Aortic-valve replacement is the only effective therapy. Transcatheter aortic-valve replacement is appropriate in patients at very high surgical risk.
Changes in sleep-wake behavior may be more than just an epiphenomenon of ADHD
Authors: Aribert Rothenberger, Roumen Kirov
Journal: Behavioral and Brain Sciences (2005)

sleep disturbances are common for children with attention-deficit/hyperactivity disorder (adhd) and are of great clinical significance. brain dopamine plays an important role for both adhd symptoms and sleep-wake regulation. we therefore suggest that one basic aspect of integrative brain-behavior relationship such as the sleep-wake cycle may certainly be addressed in a dynamic developmental theory of adhd.
Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group
Authors: Richard Herrmann, György Bodoky, Thomas Ruhstaller, Bengt Glimelius, Emilio Bajetta, Johannes Schüller, Piercarlo Saletti, Jean Bauer, Arie Figer, Bernhard Pestalozzi, Claus-Henning Köhne, Walter Mingrone, Salomon M. Stemmer, Karin Tàmas, Gabriela V. Kornek, Dieter Koeberle, Susanne Cina, Jürg Bernhard, Daniel Dietrich, Werner Scheithauer
Journal: Journal of Clinical Oncology (2007)

This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer.Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent.A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms.GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.
Multiple Cytokine-Producing Solitary Plasmacytoma of Bone With Expression of Cytokine Receptors
Authors: Shoko Nakayama-Ichiyama, Taiji Yokote, Kazuki Iwaki, Yuji Hirata, Toshikazu Akioka, Takuji Miyoshi, Satoko Oka, Uta Nishiwaki, Yuki Masuda, Motomu Tsuji, Toshiaki Hanafusa
Journal: Journal of Clinical Oncology (2011)
G-CSF and peripheral blood progenitor cells
Authors: NelsonJ. Chao, GwynnD. Long, RobertS. Negrin, JeffreyR. Schriber, CathleenM. Raimondi, SherriL. Brown, KarlG. Blume, J. Reiffers, C. Faberes, G. Marit, Simona Sica, Prassede Salutari, Luciana Teofili, Giacomo Menichella, Giuseppe Leone
Journal: The Lancet (1992)