tbuckley/cabot-search huggingface dataset:
Association of functional thrombin‐activatable fibrinolysis inhibitor (TAFI) with conventional cardiovascular risk factors and its correlation with other hemostatic factors in a Spanish population
Authors: Amparo Santamaría, Montserrat Borrell, Arturo Oliver, Rosa Ortín, Ruth Forner, Inmaculada Coll, Jose Mateo, Juan Carlos Souto, Jordi Fontcuberta
Journal: American Journal of Hematology (2004)

Abstract Our aim was to determine the associations of functional thrombin‐activatable fibrinolysis inhibitor (TAFI) levels in plasma with conventional cardiovascular risk factors, sex and age, and possible correlations with other hemostatic factors in a Spanish population. We included 303 individuals from a Spanish population. Hemostatic factors such as von Willebrand Factor, VII ag, VIIIc, XIc, XIIc, APCR, protein S, protein C, antithrombin, fibrinogen, and t‐PA antigen were assayed. The functional TAFI assay was based on the activation of plasma TAFI with thrombin–thrombomodulin, and the measure of TAFIa activity on the hippuryl‐Arg substrate. There were no statistical differences in mean values of functional TAFI among the various female age groups or among the different male age groups, with or without cardiovascular risk factors. Only women younger than 30 years of age showed lower levels of functional TAFI compared to older women. No differences were found among men of different ages. Adjusted for sex and age, hemostatic factors did not show a correlation with functional TAFI levels in plasma. Women with hypercholesterolemia showed higher levels of TAFI; other conventional cardiovascular risk factors did not modify functional TAFI levels either in men or in women. We also found no correlation of functional TAFI levels related to any other hemostatic factors. Am. J. Hematol. 76:348–352, 2004. © 2004 Wiley‐Liss, Inc.
Letter: Stresses of management selection courses.
Authors: P Hall
Journal: BMJ (1974)

cancer patients in view of its effect as a stimulator of prolactin release.Unfortunately, a suitable alternative agent may be difficult to find as the phenothiazine derivatives, which include prochlorperazine, are also known to stimulate lactation and to raise serum prolactin levels.It is possible that for susceptible patients we may have to return to the uFe of older remedies such as pyridoxine.-I am, etc.,
Elevated hepatic multidrug resistance-associated protein 3/ATP-binding cassette subfamily C 3 expression in human obstructive cholestasis is mediated through tumor necrosis factor alpha and c-Jun NH2-terminal kinase/stress-activated protein kinase-signali
Authors: Jin Chai, Yu He, Shi-Ying Cai, Zhongyong Jiang, Huaizhi Wang, Qiong Li, Lei Chen, Zhihong Peng, Xiaochong He, Xiaoping Wu, Tianli Xiao, Rongquan Wang, James L. Boyer, Wensheng Chen
Journal: Hepatology (2011)

Abstract Multidrug resistance-associated protein 3 (MRP3, ABC subfamily C [ABCC]3) plays an important role in protecting hepatocytes and other tissues by excreting an array of toxic organic anion conjugates, including bile salts. MRP3/ABCC3 expression is increased in the liver of some cholestatic patients, but the molecular mechanism of this up-regulation remains elusive. In this report, we assessed liver MRP3/ABCC3 expression in patients (n = 22) with obstructive cholestasis caused by gallstone blockage of bile ducts and noncholestatic patient controls (n = 22). MRP3/ABCC3 messenger RNA (mRNA) and protein expression were significantly increased by 3.4- and 4.6-fold, respectively, in these cholestatic patients where elevated plasma tumor necrosis factor alpha (TNFα) (4.7-fold; P &lt; 0.01) and hepatic specificity protein 1 transcription factor (SP1) and liver receptor homolog 1 expression (3.1- and 2.1-fold at mRNA level, 3.5- and 2.5-fold at protein level, respectively) were also observed. The induction of hepatic MRP3/ABCC3 mRNA expression is significantly positively correlated with the level of plasma TNFα in these patients. In HepG2 cells, TNFα treatment induced SP1 and MRP3/ABCC3 expression in a dose- and time-dependent manner, where increased phosphorylation of c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) was also detected. These inductions were significantly reduced in the presence of the JNK inhibitor, SP600125. TNFα treatment enhanced HepG2 cell nuclear extract-binding activity to the MRP3/ABCC3 promoter, but was abolished by SP600125, as demonstrated by electrophoretic mobility shift assay (EMSA). An increase in nuclear protein-binding activity to the MRP3/ABCC3 promoter, consisting primarily of SP1, was also observed in liver samples from cholestatic patients, as assessed by supershift EMSA assays. Conclusions: Our findings indicate that up-regulation of hepatic MRP3/ABCC3 expression in human obstructive cholestasis is likely triggered by TNFα, mediated by activation of JNK/SAPK and SP1. (Hepatology 2012)
Advantages of computerized psychiatric history taking
Authors: M. H. Klein
Journal: JAMA (1972)

To the Editor.—  Two EDITORIALS, Patient History Under Scrutiny and Medical Care: Acceptability and Adequacy question whether increasingly complex and impersonal health delivery systems can sustain a sufficiently trusting patient-physician relationship to encourage the patient to reveal his problems (219:1208, 1972).  The dilemma is this: Can a patient-physician communication be standardized to the point where   (especially those that distort or overlook problems) can be minimized without making the process so impersonal that the relationship breaks down and communication becomes impaired? This ultimately raises questions of the usefulness and the humanity of indirect methods of information-getting such as questionnaires and structured interviews. In communication, it is important to distinguish the frailties of the human participants from the frailties inherent in the communication process itself. Humans may well be stronger than the communication bridge between them. Rejection of impersonal communication methods on the grounds of inhumanity may lose sight of
EXPERIMENTS WITH "CACTINA" AND "CACTIN"
Authors: E. P. LYON
Journal: JAMA (1910)

The continued use by some physicians of the preparations of Cactus grandiflorus is perhaps sufficient justification for the publication of another investigation into their pharmacologic properties.  PART I.—EXPERIMENTS WITH CACTINA (SULTAN DRUG CO.)  The experiments to be described were begun at the request of Mr. F. Sultan, of St. Louis, Mo., who furnished the Cactina and also the Erlanger sphygmomanometer employed in part of the work. The investigation of Cactina was undertaken with the understanding that Mr. Sultan should furnish any apparatus needed, but that no compensation was to be made for the work, and that the results should be published after a report had been made to Mr. Sultan. Such a report was sent to him on July 4, 1908. Since that date some further experiments with Cactina and all those with Cactin (Abbott Alkaloidal Co.) have been performed.  EXPERIMENTS ON ANIMALS  It has been claimed that the effects
The Management of Early Breast Cancer
Authors: George P. Canellos, Samuel Hellman, Umberto Veronesi
Journal: New England Journal of Medicine (1982)

Breast cancer is a heterogenous disease, and after three quarters of a century of conformity in the treatment of primary breast cancer, a quiet change in treatment has occurred. Many alternative approaches are being tried. Surgical options now range from the classic Halsted mastectomy to removal of the tumor alone (lumpectomy). Irradiation may be the sole treatment or may not be used at all. Adjuvant systemic therapy, if used, has ranged from giving a single agent briefly after mastectomy to giving combination chemotherapy and hormonal therapy for as long as two years. Because it is not at all clear which . . .
Effects of Chloroquine, Mefloquine and Quinine on Natural Killer Cell Activity <i>in vitro</i>
Authors: B. K. Pedersen, I. C. Bygbjerg, T. G. Theander, B. J. Andersen
Journal: Allergy (1986)

Natural killer (NK) cell activity against K 562 target cells was inhibited by pharmacological concentrations of chloroquine, mefloquine and quinine. The most potent were mefloquine and quinine. The drug‐induced inhibition of the NK cell activity was abolished by addition of α interferon (IF) or interleukin 2 (II‐2); preincubation of mononuclear cells with IF or II‐2 followed by addition of anti‐malarial drugs decreased the inhibitory effects of the drugs. The drug‐induced inhibition of the NK cell activity was not dependent on the presence of monocytes. Using monocyte depleted Percoll fractionated NK cell enriched populations in a single cell agarose assay, it was shown that the inhibitory effects of mefloquine, but not of chloroquine and quinine were due to an inhibition of the formation of effector/target cell conjugates.
BMA opens door on human reproductive cloning
Authors: R. Woodman
Journal: BMJ (1999)

Public opposition to human reproductive cloning may be based on nothing more than an “illogical and transient fear of new technology,” according to a British Medical Association discussion paper.

The paper, which is being presented at this week's World Medical Association meeting in Tel Aviv, assumes that the potential hazards of cloning by cell nuclear replacement—the method used to clone Dolly the sheep—will eventually be overcome.

This method involves the implantation of a donor nucleus into a host egg which has had its original nucleus removed. The cloned embryo …
Reply to Matsushita et al. Regarding Management of a Distally Migrated Self-Expanding Metal Stent
Authors: C. P. Shaver, P. Brady, H. Pinkas
Journal: Endoscopy (2005)

We appreciated the alternative approach to management of an occluded, distally migrated biliary self-expanding metal stent (SEMS) as outlined by Matsushita et al. Distal migration of SEMSs has resulted in a number of notable complications, including pressure necrosis and ulceration, gastrointestinal bleeding, and duodenal perforation [1] [2] [3]. Furthermore, their relative permanency makes endoscopic extraction difficult if not impossible.
Abstract 2953: Anticipating new biochemical mechanisms of resistance to Raf inhibition in Melanoma
Authors: Rajee Antony, Caroline Emery, Levi A. Garraway
Journal: Cancer Research (2012)

Abstract More than 50% of melanoma's harbor the V600E activating mutation in BRAF, which constitutively activates the Mek/Erk signaling cascade leading to tumor cell proliferation. The BRAF(V600E) mutation predicts responsiveness to RAF inhibitors, which led to FDA approval of the RAF inhibitor vemurafenib (PLX4032) in 2011. Although several mechanisms of resistance to RAF inhibition have been described, no resistance-associated point mutations involving the RAF genes themselves have been detected in the clinical setting thus far. This is in contrast to well described resistance mechanisms to receptor tyrosine kinase inhibitors, which frequently involve secondary mutations within the target kinase. To gain additional insights in this regard, we created randomly mutagenized cDNA library of BRAF (V600E) and it's homolog C-RAF and expressed individually in A375(V600E B-RAF) cells in the presence of PLX4720, an analogue of PLX4032. The resistance clones emerged from the screen were characterized by massive parallel sequencing and the mutant alleles were further recreated via site directed mutageneis in the respective cDNA's. However, no candidate mutations occuring in BRAF (V600E) could be validated as bona fide resistance alleles. In contrast, we identified 11 alleles that engendered sustained Mek phosphorylation in the setting of PLX4720 exposure. Upon ectopic expression, three of these alleles conferred profound pharmacologic resistance to PLX4720. Two of these resistance alleles clustered within the 14-3-3 consensus binding site of C-RAF, and the third occurred in the kinase domain (ATP binding domain, activation segment). 14-3-3 proteins are known to stabilize and activate C-RAF through phosphorylation of key serine and tyrosine residues. Toward this end, some C-RAF resistance alleles promoted increased BRAF heterodimerization and increased kinase activity. Each of these alleles remained sensitive to the Mek inhibitor AZD6244. On the basis of these findings, we speculate that mutations in C-RAF that alter 14-3-3 binding, promoted dimerization, and/or enhance intrinsic kinase activity may conceivably mediate resistance to RAF inhibition - particularly as more potent inhibitors become utilized. Ongoing work involves investigating the clinical relevance of this phenomenon. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2953. doi:1538-7445.AM2012-2953
Sports causing most injuries in Hong Kong.
Authors: K M Chan, Y Yuan, C K Li, P Chien, G Tsang
Journal: British Journal of Sports Medicine (1993)

A prospective survey was carried out on 2293 patients attending the Sports Injury Clinic in the Prince of Wales Hospital between May 1984 and December 1990. A Sports Injury Report Form was completed for each patient. Subjects in this study represent a group of nonprofessional and non-élite athletes in a metropolitan area. Soccer, basketball, volleyball, long-distance running and cycling in descending order were the five most common sports causing injury. Different sports produced different injury patterns. In four of the five sports, the knee (27.27-50.47%) and the ankle (16.78-24.67%) were the commonest sites of injury. In cycling, the face (19.46%) was the commonest site of injury. There was a higher injury rate to the lower than the upper limb in soccer, basketball, volleyball and long-distance running, with a ratio of upper- to lower-limb injury ranging from 1:1.13 to 1:46.10. In cycling, upper limb injury was more frequent (upper- to lower-limb injury ratio was 1:0.53). Sprain was the commonest injury overall (44.60%). It was also the commonest injury condition in volleyball (55.15%), basketball (55.34%), soccer (51.41%) and long-distance running (39.33%). In cycling, abrasion (24.83%) was commonest.
Crosstalk between the cGAS DNA Sensor and Beclin-1 Autophagy Protein Shapes Innate Antimicrobial Immune Responses
Authors: Qiming Liang, Gil Ju Seo, Youn Jung Choi, Mi-Jeong Kwak, Jianning Ge, Mary A. Rodgers, Mude Shi, Benjamin J. Leslie, Karl-Peter Hopfner, Taekjip Ha, Byung-Ha Oh, Jae U. Jung
Journal: Cell Host & Microbe (2014)
Experimentation with a transcranial magnetic stimulation system for functional brain mapping
Authors: Gil J. Ettinger, Michael E. Leventon, W.Eric L. Grimson, Ron Kikinis, Laverne Gugino, Wayne Cote, Larry Sprung, Linda Aglio, Martha E. Shenton, Geoff Potts, Victor L. Hernandez, Eben Alexander
Journal: Medical Image Analysis (1998)
A3-05: Phase III study of vinflunine versus docetaxel in patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC) previously treated with a platinum containing regimen
Authors: Rodryg Ramlau, Jaafar Bennouna, Eng Huat Tan, Bonne Biesma, Armando Santoro, Corrado Boni, Helmut Klein, Krzysztof Lesniewski, Ricard Mesia, Urlich Gatzemeier
Journal: Journal of Thoracic Oncology (2007)
The Clinical Spectrum of Echo-Virus Infection
Authors: Jay P. Sanford, S. Edward Sulkin
Journal: New England Journal of Medicine (1959)

THE ECHO viruses, though recognized only recently, are clearly capable of producing a varied spectrum of clinical illness. Melnick and Sabin,1 in observations based on recent epidemic outbreaks of infection, have emphasized the development of different clinical syndromes which were attributed to the specific type of ECHO virus responsible for the infection. On the other hand, evaluation of sporadic infections due to these viruses, as well as a general comparison of clinical features based upon epidemic outbreaks, points to predominance of common group features shared not only by most types of ECHO viruses but also by the entire group of . . .
Noninvasive Assessment of E2F-1–Mediated Transcriptional Regulation <i>In vivo</i>
Authors: Parisa Monfared, Alexandra Winkeler, Markus Klein, Hongfeng Li, Anke Klose, Marianna Hoesel, Yannic Waerzeggers, Sigrun Korsching, Andreas H. Jacobs
Journal: Cancer Research (2008)

Abstract Targeted therapies directed against individual cancer-specific molecular alterations offer the development of disease-specific and individualized treatment strategies. Activation of the transcription factor E2F-1 via alteration of the p16-cyclinD-Rb pathway is one of the key molecular events in the development of gliomas. E2F-1 binds to and activates the E2F-1 promoter in an autoregulatory manner. The human E2F-1 promoter has been shown to be selectively activated in tumor cells with a defect in the pRb pathway. Paradoxically, E2F-1 also carries tumor suppressor function. Our investigations focused on analyzing the dynamics of the activity of the E2F-1 responsive element under basal conditions and certain stimuli such as chemotherapy using molecular imaging technology. We constructed a retrovirus bearing the Cis-E2F-TA-LITG reporter system to noninvasively assess E2F-1–dependent transcriptional regulation in culture and in vivo. We show that our reporter system is sensitive to monitor various changes in cellular E2F-1 levels and its transcriptional control of our reporter system to follow the state of the Rb/E2F pathway and the DNA damage–induced up-regulation of E2F-1 activity in vivo. Exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea leads to increased E2F-1 expression levels in a dose- and time-dependent manner, which can be quantified by imaging in vivo, leading to an alteration of cell cycle progression and caspase 3/7 activity. In summary, noninvasive imaging of E2F-1 as a common downstream regulator of cell cycle progression using the Cis-E2F-TA-LUC-IRES-TKGFP reporter system is highly attractive for evaluating the kinetics of cell cycle regulation and the effects of novel cell cycle targeting anticancer agents in vivo. [Cancer Res 2008;68(14):5932–40]
538 Effects of candoxatrilat, a neutral endopeptidase inhibitor, on sodium and free water urinary excretion in the rat model of CCL4-induced cirrhosis with ascites
Authors: G SANSOE, M ARAGNO, R MASTROCOLA, S SILVANO, G MENGOZZI, G TOUSCOZ, F ROSINA, A SMEDILE, O DANNI, M RIZZETTO
Journal: Hepatology (2003)

This research aims to develop targeted nanoparticles as drug carriers to the injured arterial wall under fluid shear stress by mimicking the natural binding ability of platelets via interactions of glycoprotein Ib-alpha (GPIbα) of platelets with P-selectin of damaged endothelial cells (ECs) and/or with von Willebrand factor (vWF) of the subendothelium. Drug-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles were formulated using a standard emulsion method and conjugated with glycocalicin, the external fraction of platelet GPIbα, via carbodiimide chemistry. Surface-coated and cellular uptake studies in ECs showed that conjugation of PLGA nanoparticles, with GPIb, significantly increased nanoparticle adhesion to P-selectin- and vWF-coated surfaces as well as nanoparticle uptake by activated ECs under fluid shear stresses. In addition, effects of nanoparticle size and shear stress on adhesion efficiency were characterized through parallel flow chamber studies. The observed decrease in bound nanoparticle density with increased particle sizes and shear stresses is also explained through a computational model. Our results demonstrate that the GPIb-conjugated PLGA nanoparticles can be used as a targeted and controlled drug delivery system under flow conditions at the site of vascular injury.
Steroids and osteoporosis: the quest for mechanisms
Authors: Stavros C. Manolagas
Journal: Journal of Clinical Investigation (2013)

Advances made during the last 35 years have improved our understanding of the mechanisms of steroid hormone action on bone and how physiologic, pathologic, or iatrogenic changes in hormone levels can lead to increased fracture risk. Estrogens, androgens, and glucocorticoids alter the cellular composition of bone by regulating the supply and lifespan of osteoclasts and osteoblasts. Additionally, they influence the survival of osteocytes, long-lived cells that are entombed within the mineralized matrix and mediate the homeostatic adaptation of bone to mechanical forces. Altered redox balance is a proximal underlying mechanism of some of these effects, and sex steroid deficiency or glucocorticoid excess contributes to the aging of the skeleton.
Prevalence of Bronchial Asthma and Respiratory Symptoms in Schoolchildren in Oslo
Authors: I. J. K. Skarpaas, A. Gulsvik
Journal: Allergy (1985)

During the school year 1980-81 a survey questionnaire was carried out among schoolchildren aged 7 to 15 years in Oslo. The survey population comprised 39,162 children attending compulsory primary school. The questionnaire was distributed to a random sample of 1772 children in 81 classes, forms 1 to 9, and the response rate was 95%. The prevalence of physician-diagnosis of current and cumulative asthma was 1.6% and 3.1%, respectively. Of those with current asthma 68% used asthma drugs regularly. Occasional wheezing and attacks of breathlessness were reported by 9% and 4%, respectively. Wheezing and breathlessness on exposure to pollen (4.5%), animals (3.1%) and exercise (5.5%) was reported more frequently than physician-diagnosis of asthma. The cumulative prevalence of either hay fever, eczema, urticaria or asthma was 17%. More boys than girls under the age of 12 had a physician-diagnosis of asthma.
Increased lysophosphatidylcholine content in lesional psoriatic skin
Authors: A.K. RYBORG, B. GRON, K. KRAGBALLE
Journal: British Journal of Dermatology (1995)

Various cell stimuli occur via activation of phospholipase A2, which hydrolyses polyunsaturated fatty acids from the sn-2 position of membrane phospholipids, resulting in the formation of polyunsaturated fatty acids and lysophospholipids. The level of lysophospholipids is determined by the balance between phospholipase A2 activity and the rate of catabolism of the lysophospholipids. One of the lysophospholipid classes, lysophosphatidylcholine, has been shown to stimulate certain leucocyte activities which are of importance for the induction and maintenance of inflammation. In addition, it has been demonstrated that phospholipase A2 activity is increased in psoriatic skin. In the present study, we analysed the levels of lysophosphatidylcholine, by thin layer chromatography, in lesional psoriatic skin, uninvolved psoriatic skin and normal skin. The lysophosphatidylcholine content, expressed as mumol lysophosphatidylcholine/mumol phosphatidylcholine, was 1.55, 0.21 and 0.12% in lesional psoriatic skin, uninvolved psoriatic skin and normal skin, respectively. The level of lysophosphatidylcholine was significantly elevated in lesional compared with uninvolved psoriatic skin (P = 0.004) and normal skin (P = 0.002). The increased lysophosphatidylcholine levels in psoriatic skin indicate that the phospholipase A2 activation is not accompanied by a corresponding increase in the activity of enzymes catabolizing lysoPC. If present in biologically active concentrations, lysophosphatidylcholine may contribute to the induction and maintenance of the inflammatory and immunological processes occurring in lesional psoriatic skin.
Urinary-Cell mRNA Profile and Acute Cellular Rejection in Kidney Allografts
Authors: Manikkam Suthanthiran, Joseph E. Schwartz, Ruchuang Ding, Michael Abecassis, Darshana Dadhania, Benjamin Samstein, Stuart J. Knechtle, John Friedewald, Yolanda T. Becker, Vijay K. Sharma, Nikki M. Williams, Christina S. Chang, Christine Hoang, Thangamani Muthukumar, Phyllis August, Karen S. Keslar, Robert L. Fairchild, Donald E. Hricik, Peter S. Heeger, Leiya Han, Jun Liu, Michael Riggs, David N. Ikle, Nancy D. Bridges, Abraham Shaked
Journal: New England Journal of Medicine (2013)

The standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable.