tbuckley/cabot-search huggingface dataset:
Thrombin-induced platelet membrane glycoprotein IIb and IIIa complex formation. An electron microscope study.
Authors: M J Polley, L L Leung, F Y Clark, R L Nachman
Journal: The Journal of Experimental Medicine (1981)

The topographic relationships of platelet membrane glycoprotein IIb and glycoprotein IIIa have been studied in stimulated and unstimulated human platelets using immunoelectron microscopy. An indirect approach with ferritin-conjugated goat anti-rabbit gamma-globulin was used to localize the rabbit antibody to glycoprotein IIIa. The second ultrastructural label was keyhole limpet hemocyanin conjugated directly to antibody to glycoprotein IIb. Using the double labels, it was demonstrated that glycoprotein IIb and glycoprotein IIIa were distributed randomly in the unstimulated platelet membrane. After platelet stimulation with thrombin, large clusters of glycoprotein IIb-glycoprotein IIIa complexes were formed. No complex formation between glycoprotein Ib and glycoprotein IIb was observed in control experiments. These observations suggest that thrombin stimulation initiates the specific glycoprotein IIb-glycoprotein IIIa macromolecular complex formation on the platelet surface, which may act as the active fibrinogen-binding site required for normal platelet aggregation.
Treatment guidelines for patients with hyperthyroidism and hypothyroidism. Standards of Care Committee, American Thyroid Association
Authors: P. A. Singer
Journal: JAMA (1995)

To develop a set of minimum clinical guidelines for use by primary care physicians in the evaluation and management of patients with hyperthyroidism and hypothyroidism.Guidelines were developed by a nine-member ad hoc Standards of Care Committee of the American Thyroid Association (the authors of this article). The participants were selected by the committee chair and the president of the American Thyroid Association on the basis of their clinical experience. The committee members represented different geographic areas within the United States, in order to take into account different practice styles.Guidelines were developed on the basis of expert opinion of the participants, as well as on available published information.Input was obtained from all of the participants, each of whom wrote an initial section of the document. A complete draft document was then written by three participants (P.A.S., D.S.C., and E.G.L.) and resubmitted to the entire committee for revision. The revised document was then submitted to the entire membership of the American Thyroid Association for written comments, which were then reviewed (mainly by P.A.S., D.S.C., and E.G.L.). Many of the suggestions of the American Thyroid Association members were incorporated into the final draft, which was then approved by the Executive Council of the American Thyroid Association. The entire process, from initial drafts to final approval, took approximately 18 months.A set of minimum clinical guidelines for the diagnosis and treatment of hyperthyroidism and hypothyroidism were developed by consensus of a group of experienced thyroidologists. The guidelines are intended to be used by physicians in their care of patients with thyroid disorders, with the expectation that more effective care can be provided, and at a cost savings.
Adherence to cardiac rehabilitation guidelines: a survey of rehabilitation programmes in the United Kingdom
Authors: R. J P Lewin, R. Ingleton, A. J Newens, D. R Thompson
Journal: BMJ (1998)

Two key recommendations of recent guidelines are that cardiac rehabilitation requires the skills of a range of professionals and that the patient should receive a menu based programme after an individual assessment of needs.1 A previous survey of 25 cardiac rehabilitation programmes found little congruence with these guidelines and noted that physicians were particularly unlikely to be involved.2 We extended this inquiry to include all of the discoverable rehabilitation programmes in the United Kingdom.

We identified 273 cardiac rehabilitation programmes through registers maintained by professional and charitable bodies and conducted a structured telephone interview with the “main coordinator” of 263 (96%) of these programmes between 1 April 1996 and 31 March 1997. If a respondent did not have the competence to answer a particular question the appropriate person was contacted. We asked each participant whether the rehabilitation team included anyone …
TEMPORAL TRENDS IN EARLY FOLLOW-UP AFTER HOSPITALIZATION FOR HEART FAILURE: DATA FROM GET WITH THE GUIDELINES-HEART FAILURE
Authors: Adam DeVore, Margueritte Cox, Zubin Eapen, Clyde Yancy, Deepak Bhatt, Paul Heidenreich, Eric Peterson, Gregg Fonarow, Adrian Hernandez
Journal: Journal of the American College of Cardiology (2014)
Ultrasound Assessment of Left Ventricular Function Following Aortocoronary Saphenous Vein Bypass Grafting
Authors: JOSEPH KISSLO, STEVEN WOLFSON, ALLAN ROSS, RICHARD PASTERNAK, GRAEME HAMMOND, LAWRENCE S. COHEN
Journal: Circulation (1973)

Three serial determinations of left ventricular function were performed by echocardiographic techniques in ten patients undergoing aortocoronary saphenous vein grafting for occlusive coronary artery disease. There were significant increases in maximum posterior wall velocity, mean posterior wall velocity, amplitude of left ventricular wall excursion, and ejection fraction when the preoperative values were compared with those obtained one week and six weeks after surgery. Improvements in these indices seemed independent of heart rate and blood pressure and, therefore, probably reflected an improvement in ventricular function attributable to surgery. These data, of course, must be interpreted with care in patients with coronary artery disease who may have asynchronous ventricular contraction. The findings in this paper support previously reported data showing enhancement of ventricular function following aortocoronary saphenous vein grafting and provide a means for the serial evaluation of large numbers of patients by noninvasive techniques.
Tacrolimus in steroid refractory autoimmune hepatitis
Authors: V. Hegade, K. Tirou, M. Davies
Journal: Gut (2011)

Introduction Standard treatment of autoimmune hepatitis (AIH) consists of corticosteroids and azathioprine (AZA) and is effective in 80% of patients. There have been very few studies using tacrolimus as a novel second line treatment in patients with either steroid refractory or intolerant disease. Methods The authors performed a retrospective analysis of all patients with severe AIH who were treated with tacrolimus. Steroid refractory disease was defined as persistent abnormal ALT (2×ULN) despite 3 months steroids with AZA or mycophenolate mofetil (MMF). Response to treatment was defined as: CR Complete response – sustained normalisation of ALT; PR – Partial response – improvement of ALT by >50%; NR – non-response – <50% improvement in ALT; RP – Relapse – Initial CR or PR followed by worsening of ALT. Results Six patients (4 women, 2 men; mean age at diagnosis 30 years) had received treatment with Tacrolimus. The reasons for starting tacrolimus were as follows: steroid refractory (5 pts), intolerance of AZA (2 pts), non-responder to AZA (1 pt) and non-responder to MMF (1 pt). The mean dose of tacrolimus was 3.3 mg, mean duration of treatment was 15.5 months, and the mean duration of follow-up was 14.8 months. 3 patients had complete response CR and 3 patients had partial response PR following tacrolimus therapy. The median fall in ALT and Bilirubin is recorded on the following [table 1][1]. View this table: Table 1 PTH-092 None of the patients had any significant adverse effect with tacrolimus. Tremors were noted in one patient associated with a high tacrolimus level which improved on dose reduction. Conclusion Tacrolimus is effective and well tolerated in patients with steroid refractory AIH. The use of low dose tacrolimus resulted in successful biochemical remission without significant adverse effect on renal function. This study adds to the limited data available currently on the use of tacrolimus in steroid refractory AIH. [1]: #T1
Is B-Raf a Good Therapeutic Target for Melanoma and Other Malignancies?
Authors: SubbaRao V. Madhunapantula, Gavin P. Robertson
Journal: Cancer Research (2008)

The RAF family members, A-Raf, B-Raf, and C-Raf (or Raf-1), are intermediate molecules in the mitogen-activated protein (MAP) kinase [Ras/Raf/MAP kinase/extracellular signal-regulated kinase (Erk) kinase (MEK)/Erk] pathway, which relays extracellular signals from the cell membrane to the nucleus via a cascade of phosphorylation events ultimately promoting cancer development. This pathway is activated by mutation in approximately 7% of all human cancers. B-Raf is one of the proteins frequently mutated to an active form during tumor development. Therefore, B-Raf is an attractive cancer target but lack of clinical efficacy using agents targeting this protein has raised serious doubts about its therapeutic utility. Design of more effective B-Raf inhibitory agents, targeting other members of the signaling cascade for greater clinical efficacy or inhibiting B-Raf in combination with other targets, is being evaluated to resolve these perplexing issues. Here, we discuss recent progress, using preclinical models and clinical studies, to resolve the controversy of whether B-Raf would be a good therapeutic target for melanoma and other malignancies.
Characterisation of the effect of oxygen tension on response of fetal rabbit ductus arteriosus to vasodilators
Authors: G. C S Smith, J. C McGrath
Journal: Cardiovascular Research (1993)

Objective: The aims of the study were (1) to elucidate the effects of raised oxygen tension on the response of the ductus arteriosus to a range of vasodilators; and (2) to establish the effect, if any, of cyclo-oxygenase inhibition on the interaction between oxygen and prostaglandin (PG)E2. Methods: Rings of ductus arteriosus were isolated from fetal New Zealand White rabbits at 28 d gestation (term = 31) and precontracted with 10 μM noradrenaline in the presence of the cyclo-oxygenase inhibitor indomethacin (1 μM). Cumulative relaxation response curves were obtained from a range of vasodilators and their pEC50 (−log10 of the interpolated molar concentration causing 50% of the maximum response) and maximum relaxant response (MRR) were determined in 15% oxygen (neonatal oxygen tension, 13-14.3 kPa) and 2% oxygen (fetal oxygen tension, 2.5-3.0 kPa). In addition, the effects of (1) omitting indomethacin and (2) its substitution by 1 μM flubriprofen were studied on the interaction between oxygen and PGE2. Results: In 1 μM indomethacin, nifedipine and atrial natriuretic peptide had no effect on ductal tone in either oxygen tension. In 15% oxygen, the rank order of MRR was forskolin > cicaprost >PGE2 ≫ cromakalim ≫ sodium nitroprusside ≈ adenosine ≈ 0. The MRR of all agonists was increased in 2% oxygen except forskolin which caused complete relaxation in 15% oxygen. In 15% oxygen, the rank order of pEC50 was PGE2 ≫ cicaprost ≈ cromakalim ≈ forskolin. PGE2 was 70.8 times more potent than cicaprost. The pEC50 of all four agonists was increased in 2% oxygen. The increase in pEC50 could not be explained by a decreased extent of precontraction. The MRR to PGE2 in 15% oxygen and the magnitude of the increase in pEC50 to PGE2 going from 15% to 2% oxygen were the same in 1 μM flubriprofen, 1 μM indomethacin, or in the absence of these drugs. However, in 2% oxygen, the MRR to PGE2 was increased in 1 μM indomethacin or 1 μM flubriprofen compared with control. Conclusions: (1) Increasing oxygen tension from fetal to neonatal levels desensitises the ductus arteriosus to a range of vasodilators. (2) There is evidence that prostacyclin has a physiological role in the control of the rabbit ductus arteriosus. (3) The effect of oxygen on the potency of PGE2 is independent of cyclo-oxygenase products, whereas its effect on the efficacy of PGE2 is modulated by an endogenous cyclo-oxygenase product. Cardiovascular Research 1993;27:2205-2211
Reassurance After Diagnostic Testing With a Low Pretest Probability of Serious Disease
Authors: Alexandra Rolfe, Christopher Burton
Journal: JAMA Internal Medicine (2013)

Diagnostic tests are often ordered by physicians in patients with a low pretest probability of disease to rule out conditions and reassure the patient.To study the effect of diagnostic tests on worry about illness, anxiety, symptom persistence, and subsequent use of health care resources in patients with a low pretest probability of serious illness.Systematic review and meta-analysis. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, PsychINFO, CINAHL, and ProQuest Dissertations electronic databases through December 31, 2011, for eligible randomized controlled trials. We independently identified studies for inclusion and extracted the data. Disagreements were resolved by discussion. We performed meta-analysis if heterogeneity was low or moderate (I2 < 50%).Fourteen randomized controlled trials that included 3828 patients met the inclusion criteria and were analyzed with outcomes categorized as short term (≤3 months) or long term (>3 months). Three trials showed no overall effect of diagnostic tests on illness worry (odds ratio, 0.87 [95% CI, 0.55-1.39]), and 2 showed no effect on nonspecific anxiety (standardized mean difference, 0.06 [-0.16 to 0.28]). Ten trials showed no overall long-term effect on symptom persistence (odds ratio, 0.99 [95% CI, 0.85-1.15]). Eleven trials measured subsequent primary care visits. We observed a high level of heterogeneity among trials (I2 = 80%). Meta-analysis after exclusion of outliers suggested a small reduction in visits after investigation (odds ratio, 0.77 [95% CI, 0.62-0.96]).Diagnostic tests for symptoms with a low risk of serious illness do little to reassure patients, decrease their anxiety, or resolve their symptoms, although the tests may reduce further primary care visits. Further research is needed to maximize reassurance from medically necessary tests and to develop safe strategies for managing patients without testing when an abnormal result is unlikely.
Abstract 3195: HMGA1 and HMGA2 over-expression in human lung carcinoma
Authors: Salvatore Piscuoglio, Pierlorenzo Pallante, Federico Cappuzzo, Inti Zlobec, Alessandro Lugli, Alfredo Fusco, Luigi M. Terracciano
Journal: Cancer Research (2011)

Abstract Background: Lung cancer is the leading cause of cancer death worldwide with an overall 5-year survival rate of only 15%. Therefore, research focusing on lung carcinogenesis is strongly needed. High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. The HMGA gene family includes HMGA1, which encodes the HMGA1a and HMGA1b protein isoforms, and HMGA2, which encodes HMGA2. These chromatin-binding proteins function in transcriptional regulation and recent studies also suggest a role in cellular senescence. HMGA1 proteins also appear to participate in cell cycle regulation and malignant transformation, whereas HMGA2 has been implicated primarily in the pathogenesis of benign mesenchymal tumors. Aims: The aim of this study was to investigate on the potential role of HMGA 1 and 2 in lung carcinogenesis. Materials and methods: A tissue microarray (TMA) including normal and neoplastic non-small cell lung cancer (NSCLC; n=454) tissues was constructed and HMGA1 and 2 analyzed by immunohistochemistry. HMGA1 was detectable in a 454 patients and HMGA2 in 409 patients, respectively. Immunoreactivity was scored semi-quantitatively by evaluating the number of positive tumor cells over the total number of tumor cells. Scores were assigned using 5% intervals and ranged from 0% to 100%. Median protein expression levels were used as cut-off scores to define protein marker positivity and the findings were associated with clinical-pathological parameters. Results: HMGA1 and A2 are over-expressed in NSCLC tissues compared to normal lung (p&amp;lt;0,001), and more specifically, the HMGA2 expression is significant higher in non-adenocarcinomas than in adenocarcinomas (p&amp;lt;0,001. A significant relationship between HMGA2 over-expression and tumor grade (p&amp;lt;0,013), cN stage (p&amp;lt;0,037), cM stage (p&amp;lt;0,002), pT stage (p&amp;lt;0,003), pM stage (p&amp;lt;0,002), and recurrence (p&amp;lt;0,002). Additionally, HMGA1 over-expression showed a significant relationship with gender (p&amp;lt;0,003), tumor grade (p&amp;lt;0,028), pT stage (p&amp;lt;0,006) and recurrence (p&amp;lt;0,002). Conclusion: HMGA1 and A2 over-expression seems to play an important role in lung carcinogenesis and additional studies are needed to demonstrate a potential prognostic impact of HMGA1 and HMGA2 expression in NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3195. doi:10.1158/1538-7445.AM2011-3195
Clinically nonfunctioning pituitary tumors are monoclonal in origin.
Authors: J M Alexander, B M Biller, H Bikkal, N T Zervas, A Arnold, A Klibanski
Journal: Journal of Clinical Investigation (1990)

Clinically nonfunctioning pituitary adenomas are benign neoplasms comprising approximately 25-30% of pituitary tumors. Little is known about the pathogenesis of pituitary neoplasia. Clonal analysis allows one to make the important distinction between a polyclonal proliferation in response to a stimulatory factor versus a monoclonal expansion of a genetically aberrant cell. We investigated the clonal origin of pituitary tumors using X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase and hypoxanthine phosphoribosyl-transferase genes. Restriction enzymes were used to distinguish maternal and paternal X-chromosomes, and combined with a methylation-sensitive restriction enzyme to analyze allelic X-inactivation patterns in six pituitary adenomas. All six tumors showed a monoclonal pattern of X-inactivation. These data indicate that nonfunctioning pituitary adenomas are unicellular in origin, a result consistent with the hypothesis that this tumor type is due to somatic mutation.
Interleukin-27 Activates Natural Killer Cells and Suppresses NK-Resistant Head and Neck Squamous Cell Carcinoma through Inducing Antibody-Dependent Cellular Cytotoxicity
Authors: Masahiro Matsui, Tsunao Kishida, Hiroshi Nakano, Koichiro Yoshimoto, Masaharu Shin-Ya, Taketoshi Shimada, Shigeru Nakai, Jiro Imanishi, Takayuki Yoshimoto, Yasuo Hisa, Osam Mazda
Journal: Cancer Research (2009)

Interleukin (IL)-27 is an IL-12 family cytokine playing a pivotal role in the induction of Th1 immune responses, although its action on natural killer (NK) cells has not been fully elucidated. Here, we show that IL-27 is capable of inducing phosphorylation of signal transducers and activators of transcription 1 and 3, as well as expression of T-bet and granzyme B in murine DX-5+ NK cells. IL-27 also enhances cytotoxic activity of NK cells both in vitro and in vivo, while the in vitro viability of NK cells is also improved by this cytokine. Therapeutic administration of the IL-27 gene drastically suppressed the growth of NK-unsusceptible SCCVII tumors that had been preestablished in syngenic mice, resulting in significant prolongation of the survival of the animals. This can likely be ascribed to the antibody-dependent cellular cytotoxicity machinery because IL-27 successfully induced tumor-specific IgG in the sera of the tumor-bearing mice, and supplementation of the sera enabled IL-27-activated NK cells to kill SCCVII cells in an Fcgamma receptor III-dependent manner. These findings strongly suggest that IL-27 may offer a powerful immunotherapeutic tool to eradicate head and neck squamous cell carcinoma and other poorly immunogenic neoplasms through activating NK cells and inducing tumor-specific immunoglobulin that may cooperatively elicit antibody-dependent cellular cytotoxicity activity.
Rapid diagnosis of pleural tuberculosis by polymerase chain reaction.
Authors: J M Querol, J Mínguez, E García-Sánchez, M A Farga, C Gimeno, J García-de-Lomas
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We have investigated the use of polymerase chain reaction (PCR) for the rapid diagnosis of pleural tuberculosis. The study was composed of 21 patients with pleural tuberculosis, confirmed by culture or pleural biopsy, and 86 control subjects. The PCR assay was based on detecting a 123-bp DNA segment belonging to the insertion sequence IS6110, specific of Mycobacterium tuberculosis complex. In 21 patients diagnosed with pleural tuberculosis, Ziehl-Neelsen staining was positive in three (14%) (95% CI, 7 to 21%) and pleural fluid culture in 11 (52%) (95% CI, 43 to 61%). Pleural biopsy revealed granulomas with caseous necrosis in 72%, and the culture was positive in 67% of the patients. Adenosine deaminase activity determination was positive (> 45 IU/L) in 86% (95% CI, 79 to 93%). The sensitivity and specificity for PCR was 81% (95% CI, 74 to 88%) and 100% (95% CI, 95 to 100%), respectively. All culture-positive specimens were PCR positive. We conclude that PCR is a rapid, sensitive, and specific method for the diagnosis of pleural tuberculosis. However, further prospective studies are required to properly evaluate the yield of the technique.
Dynamics, not kinematics, is an adequate basis for perception
Authors: Andrew Wilson, Geoffrey P. Bingham
Journal: Behavioral and Brain Sciences (2001)

Roger Shepard's description of an abstract representational space defined by landmark objects and kinematic transformations between them fails to successfully capture the essence of the perceptual tasks he expects of it, such as object recognition. Ultimately, objects are recognized in the context of events. The dynamic nature of events is what determines the perceived kinematic behavior, and it is at the level of dynamics that events can be classified as types. [Shepard]