tbuckley/cabot-search huggingface dataset:
Angiotensin-induced desensitization of the phosphoinositide pathway in cardiac cells occurs at the level of the receptor.
Authors: M M Abdellatif, C F Neubauer, W J Lederer, T B Rogers
Journal: Circulation Research (1991)

Previous studies show that angiotensin II (Ang II) increases phosphoinositide turnover in cultured neonatal heart cells. Ang II has also been shown to transiently increase spontaneous beating behavior in these cells. In this study we seek to identify the molecular mechanism underlying this rapid (3-5-minute) desensitization. Time-course studies on the accumulation of [3H]inositol phosphates indicate that the loss in functional responsiveness correlates with reduced efficacy of Ang II to activate the phosphoinositide path. Binding studies with 125I-Ang II revealed that there was no change in surface receptor binding capacity during the time in which desensitization developed. Normal phosphoinositide and functional responses are observed when desensitized cells are treated with probes that activate the cardiac phosphoinositide pathway at discrete steps. These studies reveal that the functional status of the major components of the phosphoinositide signaling pathway, including G proteins, phospholipase C, and protein kinase C (PKC), are normal during maintained Ang II desensitization. To study the potential role of PKC in Ang II desensitization, the cells are treated with TPA for 24 hours, which downregulates PKC activity. PKC-depleted cells rapidly desensitize after Ang II application. We conclude that the selective Ang II-evoked biochemical/functional desensitization involves inhibition at the level of the receptor, rather than at a component downstream in the path, and that this process is independent of PKC and loss of surface binding capacity.
Temporomandibular joint osseous morphology in a consecutive sample of ankylosing spondylitis patients
Authors: C. Ramos-Remus, P. Major, A. Gomez-Vargas, G. Petrikowski, A. Hernandez-Chavez, E. Gonzalez-Marin, A. S Russell
Journal: Annals of the Rheumatic Diseases (1997)

<h3>BACKGROUND/AIM</h3> Hereditary hyperferritinaemia cataract syndrome (HHCS) is an autosomal dominant disorder characterised by elevated serum L-ferritin and bilateral cataracts. The ocular manifestations of this disorder are poorly studied. This study therefore sought to determine the origin of cataracts in HHCS. <h3>METHODS</h3> L-ferritin ELISA, immunohistochemical and ultrastructural analysis of a lens nucleus from an HHCS individual. <h3>RESULTS</h3> The HHCS lens L-ferritin content was 147 μg/g dry weight of lens compared with &lt;16 μg/g for a non-HHCS control cataract lens. The cataract comprised discrete crystalline inclusions with positive staining with anti-L-ferritin but not anti-H-ferritin. <h3>CONCLUSIONS</h3> This unusual finding of crystalline opacities in the lens may be unique to HHCS and is likely to result from disturbed metabolism of L-ferritin within the lens or an abnormal interaction between L-ferritin and lens proteins.
5-Hydroxyindole-secreting rectal carcinoid tumour
Authors: I. M. Murray-Lyon, M. Sandler, H. D. Cheetham, J. A. E. Watts, R. Williams
Journal: Gut (1972)

A patient with a 5-hydroxyindole-secreting rectal carcinoid tumour is described, the second on record. There was no clinical evidence of carcinoid syndrome. Prostaglandin-like substances were isolated from hepatic metastases.
Revised Adult Treatment Panel III Guidelines and Cardiovascular Disease Mortality in Men Attending a Preventive Medical Clinic
Authors: Chris I. Ardern, Peter T. Katzmarzyk, Ian Janssen, Timothy S. Church, Steven N. Blair
Journal: Circulation (2005)

Background— National Cholesterol Education Program Adult Treatment Panel III guidelines recommend therapeutic lifestyle changes (TLC) and drug therapy to reduce cardiovascular disease (CVD) risk. These guidelines have been revised recently (ATP III-R); however, the risk of CVD mortality within each intervention window and the effects of cardiorespiratory fitness (CRF) and metabolic syndrome on CVD mortality within the framework of the guidelines are unknown. Methods and Results— Risk factor and CRF data from 19 125 men (aged 20 to 79 years) who attended a preventive medical clinic between 1979 and 1995 were used. Mortality follow-up was completed until December 31, 1996. Participants were assigned to ATP III-R groups (LDL-C goal, TLC initiation, and drug consideration), and risk of CVD mortality was assessed by Cox proportional hazards regression. There were 179 CVD deaths over an average 10.2 years of follow-up. Compared with the LDL-C goal group, men in the TLC initiation and drug consideration groups had an elevated risk of CVD mortality (TLC initiation: HR=2.65, 95% CI 1.67 to 4.19; drug consideration: HR=6.44, 95% CI 4.49 to 9.25). Compared with LDL-C goal/fit, CVD mortality risk was higher in the LDL-C goal/unfit (4.8, 2.5 to 9.1), TLC initiation/fit (3.0, 1.7 to 5.3), TLC initiation/unfit (7.5, 3.7 to 15.2), drug consideration/fit (7.2, 4.6 to 11.4), and drug consideration/unfit (14.9, 9.1 to 24.4) groups. A similar gradient was observed for metabolic syndrome across intervention windows. Conclusions— Men eligible for TLC or drug consideration under ATP III-R were at elevated risk of CVD mortality compared with men who met the LDL-C goal. Furthermore, men who were physically fit or who did not have the metabolic syndrome had a lower risk of CVD mortality.
The Role of Apoptosis in the Regulation of Trophoblast Survival and Differentiation during Pregnancy
Authors: Shawn L. Straszewski-Chavez, Vikki M. Abrahams, Gil Mor
Journal: Endocrine Reviews (2005)

Apoptosis is important for normal placental development, but it may also be involved in the pathophysiology of pregnancy-related diseases. Normal placental development is dependent upon the differentiation and invasion of the trophoblast, the main cellular component of the placenta. Trophoblast apoptosis increases in normal placentas as gestation proceeds, and a greater incidence of trophoblast apoptosis has been observed in pregnancies complicated by preeclampsia or intrauterine growth retardation (IUGR). In response to different stimuli, apoptosis may be initiated extrinsically by the death receptor pathway or intrinsically by the mitochondrial pathway. The central executioners of apoptosis are the caspases, which cleave numerous vital cellular proteins to affect the apoptotic cascade. By inhibiting caspase activation, several endogenous inhibitors, including flice-like inhibitory proteins (FLIPs), inhibitors of apoptosis (IAPs), and antiapoptotic Bcl-2 family members, can prevent further propagation of the death signal. Macrophages present at the maternal-fetal interface may also contribute to trophoblast survival by removing apoptotic cells and producing cytokines and growth factors, which influence the progression of the apoptotic cascade. This review focuses on the role of apoptosis in trophoblast development and differentiation, the molecular mechanisms by which normal trophoblast apoptosis can occur, and how it is regulated to prevent excessive trophoblast apoptosis and possible pregnancy complications.
Local Perivascular Delivery of Basic Fibroblast Growth Factor in Patients Undergoing Coronary Bypass Surgery
Authors: Roger J. Laham, Frank W. Sellke, Elazer R. Edelman, Justin D. Pearlman, J. Anthony Ware, David L. Brown, Jeffrey P. Gold, Michael Simons
Journal: Circulation (1999)

Background —Angiogenesis is a promising treatment strategy for patients who are not candidates for standard revascularization, because it promotes the growth of new blood vessels in ischemic myocardium. Methods and Results —We conducted a randomized, double-blind, placebo-controlled study of basic fibroblast growth factor (bFGF; 10 or 100 μg versus placebo) delivered via sustained-release heparin-alginate microcapsules implanted in ischemic and viable but ungraftable myocardial territories in patients undergoing CABG. Twenty-four patients were randomized to 10 μg of bFGF (n=8), 100 μg of bFGF (n=8), or placebo (n=8), in addition to undergoing CABG. There were 2 operative deaths and 3 Q-wave myocardial infarctions. There were no treatment-related adverse events, and there was no rise in serum bFGF levels. Clinical follow-up was available for all patients (16.0±6.8 months). Three control patients had recurrent angina, 2 of whom required repeat revascularization. One patient in the 10-μg bFGF group had angina, whereas all patients in the 100-μg bFGF group remained angina-free. Stress nuclear perfusion imaging at baseline and 3 months after CABG showed a trend toward worsening of the defect size in the placebo group (20.7±3.7% to 23.8±5.7%, P =0.06), no significant change in the 10-μg bFGF group, and significant improvement in the 100-μg bFGF group (19.2±5.0% to 9.1±5.9%, P =0.01). Magnetic resonance assessment of the target ischemic zone in a subset of patients showed a trend toward a reduction in the target ischemic area in the 100-μg bFGF group (10.7±3.9% to 3.7±6.3%, P =0.06). Conclusions —This study of bFGF in patients undergoing CABG demonstrates the safety and feasibility of this mode of therapy in patients with viable myocardium that cannot be adequately revascularized.
Patterns of increasing beta-agonist use and the risk of fatal or near-fatal asthma
Authors: S Suissa, L Blais, P Ernst
Journal: European Respiratory Journal (1994)

The association between the use of inhaled beta-agonists by metered-dose inhaler and the risk of fatal or near-fatal asthma has been demonstrated. It shows that asthmatics who use one canister of beta-agonist per month more than the number used by other similar asthmatics have twice the risk of fatal or near-fatal asthma. The present investigation assesses the magnitude of this excess risk when an asthmatic increases his/her own monthly use of inhaled beta-agonists over time. From a previous nested case-control study of 129 deaths and near-deaths from asthma (cases) and 655 controls from a cohort of 12,301 asthmatics, the subset using at least 12 inhalers during the 12 month study period was identified (97 cases and 258 controls). A profile score, ranging 0-11, was formed to quantify the patterns of beta-agonist use over time for each subject, covering the entire spectrum extending from decreasing to increasing use. The relative risk was 15.2 (95% confidence interval (CI) 2.4-96.2) per unit increase of the profile score in subjects with a pattern of increasing beta-agonist use (profile score of 6.5 or more), but this relative risk was only 1.5 (95% CI 0.8-2.6) per unit when the profile score was less than 6.5 (non-increasing use). This relative risk was independent of the risk associated with the total quantity of beta-agonist use in the 12 month period, which remained around 1.6 (95% CI 1.3-2.0) per inhaler per month.(ABSTRACT TRUNCATED AT 250 WORDS)
Lessons Learned About Adult Kidney Stem Cells From the Malpighian Tubules of Drosophila
Authors: Shree Ram Singh, Steven X. Hou
Journal: Journal of the American Society of Nephrology (2008)

All multicellular organisms have a specialized organ to concentrate and excrete wastes from the body. The kidneys in vertebrates and the malpighian tubules in Drosophila accomplish these functions. Mammals and Drosophila share some similar features during renal tubular development. Vertebrate kidneys are derived through the mutual induction of the ureteric bud and metanephric mesoderm, whereas the malpighian tubules of Drosophila develop from the hindgut primordium and visceral mesoderm. The vertebrate kidney also has the capacity to recover and regenerate following episodes of acute injury. Previous studies suggest that stem cells and progenitor cells may be involved in the repair and regeneration of injured renal tissue. However, studies differ as to the source of the regenerating renal cells. Recently, multipotent stem cells in Drosophila malpighian tubules were identified, and it was demonstrated that several differentiated cells in the malpighian tubules arise from these stem cells. In this article, the current understanding of kidney development and stem cell fate in mammal and Drosophila is compared. Furthermore, the potential application of the adult renal stem cells in kidney repair and the treatment of kidney cancers are discussed.
Personalized Cancer Therapy With Selective Kinase Inhibitors: An Emerging Paradigm in Medical Oncology
Authors: Ultan McDermott, Jeff Settleman
Journal: Journal of Clinical Oncology (2009)

Selective kinase inhibitors have emerged as an important class of anticancer agents, with demonstrated clinical efficacy and generally favorable toxicity profiles in several common disease settings where conventional treatments have previously provided only modest benefit. Consequently, a substantial effort is now underway to identify additional therapeutically relevant kinase targets and to develop and test inhibitors of those proteins in a variety of human malignancies. However, it has also become clear that the clinical benefit associated with these agents is typically limited to a subset of treated patients, who in many cases are defined by a specific genomic lesion within their tumor cells--frequently, an activating mutation within the gene encoding the target kinase. This discovery has prompted efforts to stratify patients before treatment with kinase inhibitors based on specific genomic biomarkers, with the goal of optimizing clinical outcomes through the effective personalization of treatment (ie, matching the right patients with the right therapies). With recent advances in our understanding of the relationship between tumor genotypes and cancer cell sensitivity to kinase inhibition, together with improved technologies for rapidly genotyping tumor biopsies for relevant lesions, the implementation of personalized cancer care with this exciting new class of inhibitors is now becoming a reality. In this review, we summarize recent developments in this area, and we highlight some of the logistical challenges posed by this emerging paradigm in medical oncology.
Press: The consultant contract
Authors: R. Coombes
Journal: BMJ (2002)

The British media covered the consultants' rejection of a new national contract with surprising intensity last week. Both the Times and the Daily Telegraph splashed the result on their front page.

The Daily Telegraph called it a principled stand against the “lash of Whitehall,” whereas the Daily Mirror warned, “Don't let top docs stitch up the NHS.” Other newspapers ran equally dramatic copy, using military metaphors to show the growing rift between doctors and the health secretary, Alan Milburn. Doctors face “guerrilla war” over contracts, thundered the Times . The fighting talk continued elsewhere, with doctors “on a collision course” or simply “at war” with the government.

Beyond the headlines, however, there was considerable sympathy for why consultants had rejected the contract, which offered an average pay rise of 15% in return for more managerial control over their work. The Sun warned its readers not to assume this was the …
Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells
Authors: DH Katz, LR Katz, CA Bogowitz, PH Maurer
Journal: The Journal of Experimental Medicine (1979)

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.
“A Gene for…”: The Nature of Gene Action in Psychiatric Disorders
Authors: Kenneth S. Kendler
Journal: American Journal of Psychiatry (2005)

A central phrase in the new "GeneTalk" is "X is a gene for Y," in which X is a particular gene on the human genome and Y is a complex human disorder or trait. This article begins by sketching the historical origins of this phrase and the concept of the gene-phenotype relationship that underlies it. Five criteria are then proposed to evaluate the appropriateness of the "X is a gene for Y" concept: 1) strength of association, 2) specificity of relationship, 3) noncontingency of effect, 4) causal proximity of X to Y, and 5) the degree to which X is the appropriate level of explanation for Y. Evidence from psychiatric genetics is then reviewed that address each of these criteria. The concept of "a gene for…" is best understood as deriving from preformationist developmental theory in which genes—like preformationist anlagen—"code for" traits in a simple, direct, and powerful way. However, the genetic contribution to psychiatric disorders fails to meet any of the five criteria for the concept of "X is a gene for Y." The impact of individual genes on risk for psychiatric illness is small, often nonspecific, and embedded in complex causal pathways. The phrase "a gene for…" and the preformationist concept of gene action that underlies it are inappropriate for psychiatric disorders.
Cost of a cardiac surgical and a general thoracic surgical patient to the National Health Service in a London teaching hospital.
Authors: K D Morgan, F C Disbury, M V Braimbridge
Journal: Thorax (1979)

The cost of the inpatient stay for a typical aortic valve replacement and for an oesophagectomy were determined by recording and costing every aspect of the patients9 care from admission until discharge. This method of cost calculation was found to be satisfactory and could be used by other centres to allow comparisons between hospitals or countries. At St Thomas9s Hospital in 1977 the cost of a cardiac operation was 2755 pounds, an oesophagectomy 1870 pounds, and a general surgical operation 564 pounds.
The Chronic Care System
Authors: PHILLIP SIROTKIN
Journal: American Journal of Psychiatry (1968)

In the U.S.S.R., care of chronic mental patients is divided between mental hospitals, under the health authorities, and homes for invalids, under local ministries of social welfare. While there seemed to be some ambivalence in time Soviet attitude toward chronicity, the U.S. team felt that the system provides humane, dignified treatment which maximizes the patient's productivity and contribution to society.
Histone Deacetylase Inhibition As a Mechanism for the Therapeutic Effect of Statins (3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors) in Follicular Lymphoma
Authors: Christopher A. Barker, Joachim Yahalom
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: We read with great interest the study by Nowakowski et al 1 that described the effect of statins (3-hydroxy-3methylglutaryl-coenzyme A reductase inhibitors) on the outcome of patients with non-Hodgkin’s lymphoma (NHL). The authors conducted a detailed analysis of 288 patients with diffuse large B-cell lymphoma (DLBCL) and 293 patients with follicular lymphoma (FL) as a result of preclinical data suggesting a reduction in the therapeutic efficacy of rituximab in patients being treated concurrently with a statin. Interestingly, the authors found that use of a statin was associated with superior event-free survival in patients with FL but not DLBCL. Although the authors mention several reasons why patients with FL taking a statin might have demonstrated superior event-free survival, we wish to suggest another possibility. Statins have recently been described to inhibit enzymatic activity of the histone deacetylases (HDACs). 2 As recently reviewed inJournal of Clinical Oncology, HDAC inhibitors have demonstrated promise as a new class of antineoplastic agents. 3 For example, the HDAC inhibitors vorinostat and romidepsin have been approved for use in cutaneous T-cell lymphoma by the US Food and Drug Administration. HDAC inhibitors have been studied in other forms of NHL in earlyphase clinical studies. In a phase II study of patients with relapsed NHL, eight (40%) of 20 patients with FL demonstrated response to vorinostat, a nonspecific HDAC inhibitor. 4 In a phase I study of patients with relapsed or refractory NHLs, three (75%) of four patients with FL responded to vorinostat; the patient with FL who did not respond demonstrated stable disease. 5 However, phase II studies of vorinostat in patients with DLBCL have not demonstrated significant response rates; for example, one study found that one (6%) of 18 patients responded. 6 Interestingly, preliminary results of a phase II trial of patients with relapsed or refractory NHL demonstrated a 23.5% response rate in patients with DLBCL and a 10% response rate in patients with FL using mocetinostat, a specific inhibitor of the class
A bleeding problem in lung cancer patients
Authors: Pieter Depuydt, Marcio Soares
Journal: European Respiratory Journal (2015)

"Death has a hundred hands and walks by a thousand ways", stated T.S. Eliot [1]. In lung cancer patients, severe haemoptysis is arguably the most terrifying of these [2]. Although definitions of severe haemoptysis are somewhat variable, all refer to an amount and rate of bleeding from the respiratory tract that overwhelm the patient's capacity to clear the airways of blood and sustain respiratory and haemodynamic stability, thus directly jeopardising survival [3]. The expectoration of quantities of blood exceeding 100–200 mL, which is a traumatic experience in itself, may lead to asphyxiation in the absence of prompt interventions to maintain a free airway, support ventilation and halt further bleeding. Towards these aims, a coordinated and streamlined effort by pulmonologists, emergency and critical care physicians, (interventional) radiologists, and thoracic surgeons is needed. However, when severe haemoptysis occurs in the context of a known pulmonary malignancy, it is usually seen as the harbinger of a grim prognosis [4, 5]. As such, physicians may doubt whether an aggressive pursuit of stabilisation, including airway intubation, mechanical ventilation, and a series of diagnostic and therapeutic interventions, is to be preferred instead of a mere relief of anxiety and distress by urgent sedation. While severe haemoptysis is still a dreadful event in lung cancer patients a combined effort may evade imminent death <http://ow.ly/E3RbF>