tbuckley/cabot-search huggingface dataset:
The Role of Somatostatin in the Regulation of Anterior Pituitary Hormone Secretion and the Use of Its Analogs in the Treatment of Human Pituitary Tumors
Authors: STEVEN W. J. LAMBERTS
Journal: Endocrine Reviews (1988)

THE PRESENCE of GH-inhibitory substances in hypothalamic extracts was originally detected accidentally by Krulich et al. (1) during investigations into the distribution of GH-releasing factors throughout the rat hypothalamus. Several years later Brazeau et al. (2) isolated and characterized this somatotropin releaseinhibiting factor, called somatostatin (SRIF), which turned out to be a cyclic peptide consisting of 14 amino acids. SRIF was the first hormone to broaden the classic concepts of endocrinology because it has physiological effects both at the periphery and the central nervous system (3). Several reviews and proceedings from international symposia are available, which summarize the developments in the field of SRIF (4–12). In recent years SRIF analogs have been developed which can be used clinically. In the present review the physiological role of SRIF in the regulation of anterior pituitary function has been summarized as far as it contributes to the understanding of the use and effectiveness of SRIF analogs in patients with anterior pituitary tumors. In addition, the current clinical indications for long term treatment with SRIF analogs and the adverse effects of these compounds are reviewed.
Enigma of the Peripheral Benzodiazepine Receptor
Authors: Moshe Gavish, Idit Bachman, Rami Shoukrun, Yeshayahu Katz, Leo Veenman, Gary Weisinger, Abraham Weizman
Journal: Pharmacological Reviews (1999)

Benzodiazepines (BZs)2 are used clinically as muscle relaxants, anticonvulsants, anxiolytics, and sedative-hypnotics. These effects are mediated primarily via the central BZ receptors (CBRs) located in the central nervous system (CNS;[Braestrup and Squires, 1977][1]; [Mohler and Okada, 1977][2]; [
Neoadjuvant Percutaneous 4-Hydroxytamoxifen Decreases Breast Tumoral Cell Proliferation: A Prospective Controlled Randomized Study Comparing Three Doses of 4-Hydroxytamoxifen Gel to Oral Tamoxifen
Authors: Philippe Rouanet, Gustavo Linares-Cruz, François Dravet, Sylvain Poujol, Sophie Gourgou, Joelle Simony-Lafontaine, Jean Grenier, Andrew Kramar, Jean Girault, Elisabeth Le Nestour, Thierry Maudelonde
Journal: Journal of Clinical Oncology (2005)

Purpose Two chemoprevention randomized studies using tamoxifen showed drug efficacy; however, adverse effects such as hot flushes, endometrial cancer, and above all, thromboembolism, remain a problem. 4 hydroxytamoxifen (4-OHT) is a very active metabolite of tamoxifen. This randomized study was designed to analyze if 4-OHT gel, administered percutaneously on the breast skin, can inhibit the proliferation of malignant breast cells to the same extent as orally administered tamoxifen. Patients and Methods Fifty-five postmenopausal women with an invasive estrogen receptor–positive breast cancer were randomly assigned to receive (for 2 to 3 weeks) either 4-OHT gel (0.5, 1, or 2 mg/d) or oral tamoxifen (20 mg/d) or no treatment. Response was evaluated using proliferation markers (Ki-67, proliferating cell nuclear antigen) and apoptosis markers in tissue samples obtained by Tru-cut biopsy before treatment, and at surgery after treatment. Results Administration of 4-OHT gel resulted in reductions in tumor tissue proliferation indexes (Ki-67 and PCNA), with approximate equivalence between the1.0 mg/d or 2.0 mg/d 4-OHT dose, and oral tamoxifen, but had no effect on apoptotic markers. Plasma levels of 4-OHT were consistently higher in the oral tamoxifen group than in the gel groups. No dose-related pattern was shown for estrogen or progesterone receptor levels, and topical 4-OHT gel appeared to be generally well tolerated. Hot flushes are as common in the two higher gel doses as with tamoxifen. Conclusion Percutaneous 4-OHT gel has a local impact on tumor proliferation. It could be tested in future propective trials of chemoprevention or ductal carcinoma in situ adjuvant hormonotherapy.
Banning pregnant netballers—is this the answer?
Authors: S White
Journal: British Journal of Sports Medicine (2002)

Assessment and Research Centre (FIFA, F-MARC), and the International Olympic Committee Medical Commission (IOC).The aim of the symposium was to provide recommendations for the improvement of safety and health of athletes who suffer concussive injuries in ice hockey, football (soccer), and other sports.To this end a range of experts were invited to address specific issues of epidemiology, basic and clinical science, grading systems, cognitive assessment, new research methods, protective equipment, management, prevention, and long term outcome, and to discuss a unitary model for understanding concussive injury.At the conclusion of the conference, a small group of experts were given a mandate by the conference delegates and organising bodies to draft a document describing the agreement position reached by those in attendance at that meeting.For the purpose of this paper, this group will be called the Concussion in Sport Group (CISG).
CC and C chemokine expression in pulmonary sarcoidosis
Authors: M. Petrek, V. Kolek, J. Szotkowská, R.M. du Bois
Journal: European Respiratory Journal (2002)

The chemokines RANTES (regulated on activation, T-cell expressed and secreted; CC chemokine ligand (CCL)-5) and monocyte inflammatory protein (MIP)-1α (CCL-3) have been implicated in the development of alveolitis in pulmonary sarcoidosis. The novel C chemokine single cysteine motif (SCM)-1α (XCL-1) and the CC chemokine monocyte chemoattractant protein (MCP)-1 (CCL-2) are also mononuclear-cell attractants and represent alternative candidate mediators of alveolitis. Therefore, the expression of MCP-1 and SCM-1α was investigated together with the expression of RANTES and MIP-1α in bronchoalveolar lavage fluid (BALF) from control subjects and patients with sarcoidosis. The relationship between chemokine expression and sarcoidosis clinical course was also explored. Messenger ribonucleic acid (mRNA) expression for all four chemokines was determined by semiquantitative reverse transcriptase-polymerase chain reaction of RNA extracted from unseparated bronchoalveolar cells (17 patients, 12 controls). RANTES, MIP-1α and MCP-1 proteins were measured by enzyme-linked immunosobent assay of unconcentrated BALF (60 patients, 17 controls). MCP-1, and namely RANTES and SCM-1α mRNA expression was upregulated in sarcoidosis, particularly in patients with more advanced disease. RANTES, and namely MCP-1 concentrations were elevated in BALF samples obtained from patients; MCP-1 levels were most increased in patients with chest radiographic stage 2 disease and also in patients with persistent and recurrent disease. In conclusion, chemokines monocyte chemotactive protein-1 and single cysteine motif-1α are, in addition to RANTES, associated with the development of alveolitis in sarcoidosis and their expression parallels the disease course.
5-Hydroxymethylcytosine is an essential intermediate of active DNA demethylation processes in primary human monocytes
Authors: Maja Klug, Sandra Schmidhofer, Claudia Gebhard, Reinhard Andreesen, Michael Rehli
Journal: Genome biology (2013)

Cytosine methylation is a frequent epigenetic modification restricting the activity of gene regulatory elements. Whereas DNA methylation patterns are generally inherited during replication, both embryonic and somatic differentiation processes require the removal of cytosine methylation at specific gene loci to activate lineage-restricted elements. However, the exact mechanisms facilitating the erasure of DNA methylation remain unclear in many cases. We previously established human post-proliferative monocytes as a model to study active DNA demethylation. We now show, for several previously identified genomic sites, that the loss of DNA methylation during the differentiation of primary, post-proliferative human monocytes into dendritic cells is preceded by the local appearance of 5-hydroxymethylcytosine. Monocytes were found to express the methylcytosine dioxygenase Ten-Eleven Translocation (TET) 2, which is frequently mutated in myeloid malignancies. The siRNA-mediated knockdown of this enzyme in primary monocytes prevented active DNA demethylation, suggesting that TET2 is essential for the proper execution of this process in human monocytes. The work described here provides definite evidence that TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine initiates targeted, active DNA demethylation in a mature postmitotic myeloid cell type.
436 IMPROVED DENDRITIC CELL-BASED IMMUNIZATION AGAINST HEPATITIS C VIRUS USING A PEPTIDE INHIBITOR OF INTERLEUKIN 10
Authors: N. Díaz-Valdés, L. Manterola, I. Echeverria, L. Silva, V. Belsúe, J. Prieto, J.J. Lasarte, F. Borrás-Cuesta, P. Sarobe
Journal: Journal of Hepatology (2010)
Locus for Elevated Apolipoprotein B Levels on Chromosome 1p31 in Families With Familial Combined Hyperlipidemia
Authors: Hooman Allayee, Kelly L. Krass, Päivi Pajukanta, Rita M. Cantor, Carla J.H. van der Kallen, Rebecca Mar, Jerome I. Rotter, Tjerk W.A. de Bruin, Leena Peltonen, Aldons J. Lusis
Journal: Circulation Research (2002)

Familial combined hyperlipidemia (FCH), a common cause of premature coronary artery disease, is genetically complex and poorly understood. Recently, a major locus on chromosome 1q21-23 exhibiting highly significant linkage was identified in Finnish FCH families by use of a parametric analysis. We now report highly significant evidence of linkage (maximum LOD score 3.8, recombination fraction 0) of an important FCH phenotype, elevated apolipoprotein B (apoB) levels, to a distinctly separate locus on chromosome 1p31 in Dutch pedigrees. ApoB is the major protein on very low density and low density lipoproteins, and elevated apoB levels have been used as a surrogate trait for FCH. Additional microsatellite markers in the 1p31 region were genotyped, and evidence of linkage improved (maximum LOD score 4.7) in a multipoint analysis of two markers in the peak region. The leptin receptor gene resides within this locus and is involved in obesity and insulin/glucose homeostasis. However, there was no evidence of an association between leptin receptor and apoB levels, raising the possibility that another gene on this chromosomal region contributes to elevated apoB levels in this Dutch population. This is one of the first loci identified for apoB levels in humans and is the second major locus implicated in the genetic etiology of FCH.
Kinetic Analysis of Epidermal Growth Factor Receptor Somatic Mutant Proteins Shows Increased Sensitivity to the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Erlotinib
Authors: Kendall D. Carey, Andrew J. Garton, Maria S. Romero, Jennifer Kahler, Stuart Thomson, Sarajane Ross, Frances Park, John D. Haley, Neil Gibson, Mark X. Sliwkowski
Journal: Cancer Research (2006)

Abstract We show that two commonly occurring epidermal growth factor receptor (EGFR) somatic mutations, L858R and an in-frame deletion mutant, Del(746-750), exhibit distinct enzymatic properties relative to wild-type EGFR and are differentially sensitive to erlotinib. Kinetic analysis of the purified intracellular domains of EGFR L858R and EGFR Del(746-750) reveals that both mutants are active but exhibit a higher KM for ATP and a lower Ki for erlotinib relative to wild-type receptor. When expressed in NR6 cells, a cell line that does not express EGFR or other ErbB receptors, both mutations are ligand dependent for receptor activation, can activate downstream EGFR signaling pathways, and promote cell cycle progression. As expected from the kinetic analysis, the EGFR Del(746-752) is more sensitive to erlotinib inhibition than the EGFR L858R mutant. Further characterization shows that these mutations promote ligand-dependent and anchorage-independent growth, and cells harboring these mutant receptors form tumors in immunocompromised mice. Analysis of tumor lysates reveals that the tumorigenicity of the mutant EGFR cell lines may be due to a differential pattern of mutant EGFR autophosphorylation as compared with wild-type receptor. Significant inhibition of tumor growth, in mice harboring wild-type EGFR receptors, is only observed at doses of erlotinib approaching the maximum tolerated dose for the mouse. In contrast, the growth of mutant tumors is inhibited by erlotinib treatment at approximately one third the maximum tolerated dose. These findings suggest that EGFR somatic mutations directly influence both erlotinib sensitivity and cellular transformation. (Cancer Res 2006; 66(16): 8163-71)
Transgenic Modeling of a Cardiac Troponin I Mutation Linked to Familial Hypertrophic Cardiomyopathy
Authors: Jeanne James, Yan Zhang, Hanna Osinska, Atsushi Sanbe, Raisa Klevitsky, Timothy E. Hewett, Jeffrey Robbins
Journal: Circulation Research (2000)

Abstract —Multiple mutations in cardiac troponin I (cTnI) have been associated with familial hypertrophic cardiomyopathy. Two mutations are located in the cTnI inhibitory domain, a highly negatively charged region that alternately binds to either actin or troponin C, depending on the intracellular concentration of calcium. This region is critical to the inhibition of actin-myosin crossbridge formation when intracellular calcium is low. We modeled one of the inhibitory domain mutations, arginine145→glycine (TnI 146Gly in the mouse sequence), by cardiac-specific expression of the mutated protein in transgenic mice. Multiple lines were generated with varying degrees of expression to establish a dose relationship; the severity of phenotype could be correlated directly with transgene expression levels. Transgenic mice overexpressing wild-type cTnI were generated as controls and analyzed in parallel with the TnI 146Gly animals. The control mice showed no abnormalities, indicating that the phenotype of TnI 146Gly was not simply an artifact of transgenesis. In contrast, TnI 146Gly mice showed cardiomyocyte disarray and interstitial fibrosis and suffered premature death. The functional alterations that seem to be responsible for the development of cardiac disease include increased skinned fiber sensitivity to calcium and, at the whole organ level, hypercontractility with diastolic dysfunction. Severely affected lines develop a pathology similar to human familial hypertrophic cardiomyopathy but within a dramatically shortened time frame. These data establish the causality of this mutation for cardiac disease, provide an animal model for understanding the resultant pathogenic structure-function relationships, and highlight the differences in phenotype severity of the troponin mutations between human and mouse hearts.
A sneaking suspicion: The semantics of emotional beliefs and delusions
Authors: Angus W. MacDonald
Journal: Behavioral and Brain Sciences (2008)

Abstract This commentary challenges Rogers &amp; McClelland (R&amp;M) to use their model to account for delusional belief formation and maintenance. The gradual development of delusions and the nature of disconnectivity in Capgras delusions are used to illustrate the role of emotional salience in delusions. It is not clear how this kind of emotional saliency can be represented within the current architecture.
Expression of interleukin 2 receptors on activated human B cells.
Authors: T A Waldmann, C K Goldman, R J Robb, J M Depper, W J Leonard, S O Sharrow, K F Bongiovanni, S J Korsmeyer, W C Greene
Journal: The Journal of Experimental Medicine (1984)

Using anti-Tac, a monoclonal anti-interleukin 2 (IL-2) receptor antibody, we have explored the possibility that certain activated B cells display receptors for IL-2. Resting normal B cells and unselected B cell lines established from normal individuals were Tac antigen negative. In contrast, the cell surface Tac antigen expression was demonstrable on 6 of 10 B cell lines from patients with Burkitt's lymphoma, 5 of 6 B cell lines derived from patients with HTLV-I-associated adult T cell leukemia (including all four that had integrated HTLV-I into their genome), and on certain normal B cells activated with pokeweed mitogen. Furthermore, cloned Epstein-Barr virus-transformed B cell lines derived from Tac-positive normal B cells continued to express the Tac antigen in long-term cultures and manifested high affinity IL-2 receptors identified in binding studies with purified radiolabeled IL-2. The line 5B4 developed in the present study could be induced with purified JURKAT-derived or recombinant IL-2 to express a larger number of IL-2 receptors. Furthermore, the addition of IL-2 to the 5B4 B cell line augmented IgM synthesis, which could be blocked by the addition of anti-Tac. The size of the IL-2 receptors expressed on the cloned normal B cell lines was similar (53,000-57,000 daltons) to that of receptors on phytohemagglutinin-stimulated T cell lymphoblasts. Thus, certain malignant and activated normal B cells display the Tac antigen and manifest high affinity receptors for IL-2. These data suggest that IL-2 may play a role in the differentiation of activated B cells into immunoglobulin-synthesizing and -secreting cells.
Effect of exogenous angiotensin II on renal hemodynamics in the awake rat. Measurement of afferent arteriolar diameter by the microsphere method.
Authors: C H Hsu, T W Kurtz, J M Slavicek
Journal: Circulation Research (1980)

We measured cardiac output (CO), renal blood flow (RBF), renal plasma flow (RPF), and afferent arteriolar diameter by the microsphere method, and inulin clearance (GFR) simultaneously in awake rats given an infusion of exogenous angiotensin II (100 ng/min per kg). Angiotensin II did not affect the CO, whereas both RBF and RPF decreased significantly in rats infused with angiotensin II (RBF, 2.88 +/- 0.11, mean +/- SE; RPF, 1.78 +/- 0.09, n = 6) when compared to control animals given saline (RBF, 4.58 +/- 0.31; RPF, 2.80 +/- 0.24 ml/min per 100 g, n = 6, both P less than 0.005, respectively). Both mean arterial pressure (MAP) and renal vascular resistance (RVR) were significantly higher in rats infused with antiogensin II than in controls. The decrease in GFR did not parallel the reduction of RPF in rats infused with angiotensin II as reflected by their higher values of mean filtration fraction (41.1 +/- 1.6%, n = 6) than that of controls (33.7 +/- 2.4%, n = 6, P less than 0.05). Despite significant elevations of MAP and RVR in rats infused with angiotensin II, their mean afferent arteriolar diameter (19.6 +/- 0.24 micron) was not different from that of controls (20.1 +/- 0.39 micron). We conclude that angiotensin II preferentially acts at the site of postglomerular vasculature but not at the afferent arteriole.
Carbon Ion Radiotherapy for Unresectable Sacral Chordomas
Authors: Reiko Imai, Tadashi Kamada, Hiroshi Tsuji, Takeshi Yanagi, Masayuki Baba, Tadaaki Miyamoto, Shingo Kato, Susumu Kandatsu, Jun-etsu Mizoe, Hirohiko Tsujii, Shin-ichiro Tatezaki
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to evaluate the efficacy and toxicity of carbon ion radiotherapy for unresectable sacral chordomas. Experimental Design: We performed a retrospective analysis of 30 patients with unresectable sacral chordomas treated with carbon ion radiotherapy at the Heavy Ion Medical Accelerator in Chiba, Japan. Twenty-three patients presented with no prior treatment, and the remaining 7 patients had locally recurrent disease following previous surgical resection. The median clinical target volume was 546 cm3. The applied carbon ion dose ranged from 52.8 to 73.6 GyE (gray equivalent, median 70.4) in 16 fixed fractions over 4 weeks. Results: At median follow-up of 30 months (range, 9 to 87 months), 26 patients were still alive and 24 patients remained continuously disease-free. Overall and cause-specific survival rates at 5 years were 52 and 94%, respectively. The overall local control rate at 5years was 96%. Two patients experienced severe skin/soft tissue complications requiring skin grafts. No other treatment-related surgical interventions, including colostomy or urinary diversion, were carried out. All patients have remained ambulatory and able to stay at home after carbon ion radiotherapy. Conclusions: Carbon ion radiotherapy is effective and safe in the management of patients with unresectable sacral chordomas and offers a promising alternative to surgery.
Duration of Ventilations During Cardiopulmonary Resuscitation by Lay Rescuers and First Responders
Authors: Stefanie G. Beesems, Lizzy Wijmans, Jan G.P. Tijssen, Rudolph W. Koster
Journal: Circulation (2013)

The 2010 guidelines for cardiopulmonary resuscitation allow 5 seconds to give 2 breaths to deliver sufficient chest compressions and to keep perfusion pressure high. This study aims to determine whether the recommended short interruption for ventilations by trained lay rescuers and first responders can be achieved and to evaluate its consequence for chest compressions and survival.From a prospective data collection of out-of-hospital cardiac arrest, we used automatic external defibrillator recordings of cardiopulmonary resuscitation by rescuers who had received a standard European Resuscitation Council basic life support and automatic external defibrillator course. Ventilation periods and total compressions delivered per minute during each 2 minutes of cardiopulmonary resuscitation cycle were measured, and the chest compression fraction was calculated. Neurological intact survival to discharge was studied in relation to these factors and covariates. We included 199 automatic external defibrillator recordings. The median interruption time for 2 ventilations was 7 seconds (25th-75th percentile, 6-9 seconds). Of all rescuers, 21% took <5 seconds and 83% took <10 seconds for a ventilation period; 97%, 88%, and 63% of rescuers were able to deliver >60, >70, and >80 chest compressions per minute, respectively. The median chest compression fraction was 65% (25th-75th percentile, 59%-71%). Survival was 25% (49 of 199), not associated with long or short ventilation pauses when controlled for covariates.The great majority of rescuers can give 2 rescue breaths in <10 seconds and deliver at least 70 compressions in a minute. Longer pauses for ventilations are not associated with worse outcome. Guidelines may allow longer pauses for ventilations with no detriment to survival.