tbuckley/cabot-search huggingface dataset:
Protein Kinase A–Mediated Acceleration of the Stretch Activation Response in Murine Skinned Myocardium Is Eliminated by Ablation of cMyBP-C
Authors: Julian E. Stelzer, Jitandrakumar R. Patel, Richard L. Moss
Journal: Circulation Research (2006)

β-Adrenergic agonists induce protein kinase A (PKA) phosphorylation of the cardiac myofilament proteins myosin binding protein C (cMyBP-C) and troponin I (cTnI), resulting in enhanced systolic function, but the relative contributions of cMyBP-C and cTnI to augmented contractility are not known. To investigate possible roles of cMyBP-C in this response, we examined the effects of PKA treatment on the rate of force redevelopment and the stretch activation response in skinned ventricular myocardium from both wild-type (WT) and cMyBP-C null (cMyBP-C −/− ) myocardium. In WT myocardium, PKA treatment accelerated the rate of force redevelopment and the stretch activation response, resulting in a shorter time to the peak of delayed force development when the muscle was stretched to a new isometric length. Ablation of cMyBP-C accelerated the rate of force redevelopment and stretch activation response to a degree similar to that observed in PKA treatment of WT myocardium; however, PKA treatment had no effect on the rate of force development and the stretch activation response in null myocardium. These results indicate that ablation of cMyBP-C and PKA treatment of WT myocardium have similar effects on cross-bridge cycling kinetics and suggest that PKA phosphorylation of cMyBP-C accelerates the rate of force generation and thereby contributes to the accelerated twitch kinetics observed in living myocardium during β-adrenergic stimulation.
Big Mitogen-Activated Protein Kinase (BMK1)/ERK5 Protects Endothelial Cells From Apoptosis
Authors: Xinchun Pi, Chen Yan, Bradford C. Berk
Journal: Circulation Research (2003)

Blood flow that is steady and laminar is known to be atheroprotective. One likely mechanism is enhanced endothelial cell (EC) survival. Because the mitogen-activated protein kinases (MAPKs) are known regulators of cell survival, we investigated the role of Big MAPK-1 (BMK1 or ERK5), which is potently stimulated by fluid shear stress. To activate BMK1, we overexpressed constitutively active (CA)-MEK5 in bovine lung microvascular ECs (BLMECs). Cell apoptosis was induced by growth factor deprivation (0% serum for 24 hours). Analysis of cell viability with MTT assay showed that activation of BMK1 by CA-MEK5 significantly improved cell viability from 48% to 87% and decreased apoptotic cells from 49% to 10%. Growth factor deprivation induced caspase-3 activity 5.2-fold, which was inhibited (approximately 60%) by CA-MEK5 overexpression. In contrast, inhibiting BMK1 activity by overexpressing dominant-negative BMK1 (DN-BMK1) stimulated apoptosis in BLMECs. Steady laminar fluid shear stress inhibited BLMEC apoptosis, and this protective effect was also reduced significantly by overexpressing DN-BMK1. Analysis of antiapoptotic mechanisms showed that both shear stress and CA-MEK5 stimulated phosphorylation of Bad on Ser112 and Ser136, whereas DN-BMK1 inhibited phosphorylation. Phosphorylation of Bad induced by BMK1 activation was independent of Akt, PKA, or p90RSK kinase activity. These results suggest that BMK1 activation by steady laminar flow is atheroprotective by inhibiting EC apoptosis via phosphorylation of Bad.
Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life.
Authors: T Abo, C A Miller, G L Gartland, C M Balch
Journal: The Journal of Experimental Medicine (1983)

Virtually all human granular lymphocytes expressed the HNK-1 differentiation antigen when examined in lymphoid compartments from adults, neonates, and fetuses. The HNK-1+ cells were distinguishable into three subsets having distinct antigenic phenotypes: HNK+T3-M1-, HNK+T3+M1-, and HNK+T3-M1+. Thus, greater than 70% of the HNK-1+ cells from 13-17 wk fetuses (less than 0.2% of nucleated cells) lacked T cell antigens (e.g., T3, T8, T4, and T6) and the M1 myeloid antigen. Morphologically, the HNK+T3-M1- cells consisted of three different types: small granular lymphocytes (less than 10% of HNK-1+ cells), agranular small lymphocytes with a narrow rim of cytoplasm (70-80%), and agranular giant cells (greater than 15 micrometers) with considerable neutrophilic cytoplasm (15%). The purified fetal HNK-1+ cells exhibited a low level of cytotoxicity against K562 target cells. On the other hand, almost all of HNK-1+ cells in neonatal tissues as well as adult bone marrow, lymph node, and thymus, exhibited the HNK+T3+M1- phenotype, contained sparse cytoplasmic granules, and had an intermediate level of NK functional activity. Only adult blood and spleen contained a majority of mature HNK-1+ cells. These cells had an HNK+T3-M1- phenotype, abundant cytoplasmic granules, and maximum NK function. We propose that human NK cells may generate from a separate cell lineage and that they alter their phenotype, morphology, and functional capability during differentiation.
The echocardiographic assessment of pulmonary artery pressure and pulmonary vascular resistance.
Authors: S Hirschfeld, R Meyer, D C Schwartz, J Kofhagen, S Kaplan
Journal: Circulation (1975)

Serial assessment of the status of the pulmonary vascular bed requires bed requires cardiac catheterization. We have demonstrated the right ventricular systolic time intervals (RVSTI) may be measured from the pulmonary valve echo. The right ventricular ejection time (RVET) and right pre-ejection period (RPEP) were measured in 45 normal patients. The RVET and RPEP decreased with increasing heart rate but increased with age. The RPEP/RVET, however, was uninfluenced by either age or heart rate. The RPEP/RVET was, therefore, determined from the pulmonary valve echo in 64 patients with congenital heart disease who underwent cardiac catheterization. Increased pulmonary artery diastolic pressure (PADP), pulmonary vascular resistance (PADP), pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (MPAP) resulted inan increased RPEP/RVET. The use of the RPEP/RVET permitted the serial echographic evaluation of the pulmonary vascular bed in selected patients; marked elevation of the ratio indicated the presence of pulmonary hypertension.
ROLE of Ultrasound Guided Transversus Abdominis Plane (ustap) Block in Analgesic Supplementation for Laparoscopic Radical Prostatectomy. Preliminary Findings
Authors: Sashi Kommu, Anna Crosby, Zafar Hashim, Anurag Golash, Christopher Luscombe, Albin Augustine
Journal: International Journal of Surgery (2010)
Urine Podocyte mRNAs Mark Progression of Renal Disease
Authors: Yuji Sato, Bryan L. Wharram, Sang Koo Lee, Larysa Wickman, Meera Goyal, Madhusudan Venkatareddy, Jai Won Chang, Jocelyn E. Wiggins, Chrysta Lienczewski, Matthias Kretzler, Roger C. Wiggins
Journal: Journal of the American Society of Nephrology (2009)

Because loss of podocytes associates with glomerulosclerosis, monitoring podocyte loss by measuring podocyte products in urine may be clinically useful. To determine whether a single episode of podocyte injury would cause persistent podocyte loss, we induced limited podocyte depletion using a diphtheria toxin receptor (hDTR) transgenic rat. We monitored podocyte loss by detecting nephrin and podocin mRNA in urine particulates with quantitative reverse transcriptase–PCR. Aquaporin 2 mRNA served as a kidney reference gene to account for variable kidney contribution to RNA amount and quality. We found that a single injection of diphtheria toxin resulted in an initial peak of proteinuria and podocyte mRNAs (podocin and nephrin) followed 8 d later by a second peak of proteinuria and podocyte mRNAs that were podocin positive but nephrin negative. Proteinuria that persisted for months correlated with podocin-positive, nephrin-negative mRNAs in urine. Animals with persistent podocyte mRNA in urine progressed to ESRD with global podocyte depletion and interstitial scarring. Podocytes in ectatic tubules expressed podocalyxin and podocin proteins but not nephrin, compatible with detached podocytes' having an altered phenotype. Parallel human studies showed that biopsy-proven glomerular injury associated with increased urinary podocin:aquaporin 2 and nephrin:aquaporin 2 molar ratios. We conclude that a single episode of podocyte injury can trigger glomerular destabilization, resulting in persistent podocyte loss and an altered phenotype of podocytes recovered from urine. Podocyte mRNAs in urine may be a useful clinical tool for the diagnosis and monitoring of glomerular diseases.
Hypothesis: in COPD, a pound of cure may be better than an ounce of prevention
Authors: S. I. Rennard, J. Vestbo
Journal: Thorax (2011)

Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the USA.1 Its defining feature is limitation of expiratory airflow, which is usually relentlessly progressive. Current therapies have meaningful, but limited benefits. For those who have resting hypoxaemia, supplemental oxygen improves survival. Rehabilitation can improve health status and exercise performance. However, neither of these treatments alters lung function or the rate at which it declines. Volume reduction surgery, by removing the most dysfunctional parts of the lung, can reduce exacerbations2 and improve lung function, performance, symptoms and survival, but only in a subset of patients, and the effects are limited, both in magnitude and in duration.3 4 Currently available pharmacotherapy, including bronchodilators and combinations of bronchodilators and inhaled corticosteroids, modestly improve airflow and symptoms and reduce exacerbations.5 6 Statistically significant effects in slowing the rate at which lung function is lost have been reported with pharmacotherapy,7 but the clinical importance of the benefits achieved remain uncertain.

With this background, a major goal for novel therapy in COPD is to alter the natural history of the disease.

The classic study of Fletcher and colleagues8 provided the basis for current understanding of the natural history of COPD and has guided attempts at altering its course. The ‘British Postal Worker's Study’ included 792 men who were evaluated for a period of eight years. Based on this study, Fletcher and colleagues suggested that normal individuals lost lung function at an accelerating rate with age. Individuals who were exposed, for example, to cigarette smoke, and who were susceptible, experienced an accelerated rate of decline in lung function. A portion of these would eventually be diagnosed with COPD. To their credit, Fletcher and colleagues recognised that their ‘model’ was an extrapolation based on a limited data …
The effect of altering airway tone on the sensitivity of the cough reflex in normal volunteers
Authors: CA Smith, DL Adamson, NB Choudry, RW Fuller
Journal: European Respiratory Journal (1991)

Cough is frequently the presenting symptom of bronchial asthma, although cough can result from a wide variety of other respiratory disease. Treatment of chronic cough has proved extremely difficult. It has been suggested that treatment with bronchodilators may reduce the symptom of cough. In this study the effect of altering airway tone on the sensitivity of the cough reflex was determined. Twelve normal, healthy volunteers took part. The number of coughs following inhalations of single breaths of doubling concentrations of capsaicin (1.95-500 microM) was recorded before and after doses of salbutamol, methacholine and saline which altered forced expiratory volume in one second (FEV1) by 6.2 +/- 2.6%, -8.8 +/- 3.2% and -0.18 +/- 1.38%, respectively. In a further study the cough response was recorded before and after doses of salbutamol and ipratropium bromide, both of which reduced baseline respiratory resistance and resistance measured after capsaicin. Ipratropium bromide, salbutamol and methacholine, despite having significant effects on airway tone, did not change the sensitivity of capsaicin-induced cough. Thus, if bronchodilator drugs are antitussive in non-asthmatic patients, then this is unlikely to be due to an effect on the sensitivity of the cough reflex.
BASAL METABOLISM IN ICHTHYOSIS
Authors: ARTHUR PORTER
Journal: British Journal of Dermatology (1926)

Journal Article BASAL METABOLISM IN ICHTHYOSIS Get access ARTHUR PORTER, M.B., M.R.C.P ARTHUR PORTER, M.B., M.R.C.P Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 38, Issue 12, 1 December 1926, Pages 475–491, https://doi.org/10.1111/j.1365-2133.1926.tb10008.x Published: 01 December 1926
Physiological responses to rock climbing in young climbers
Authors: Audry Birute Morrison, Volker Rainer Schöffl
Journal: British Journal of Sports Medicine (2007)

Key questions regarding the training and physiological qualities required to produce an elite rock climber remain inadequately defined. Little research has been done on young climbers. The aim of this paper was to review literature on climbing alongside relevant literature characterising physiological adaptations in young athletes. Evidence-based recommendations were sought to inform the training of young climbers. Of 200 studies on climbing, 50 were selected as being appropriate to this review, and were interpreted alongside physiological studies highlighting specific common development growth variables in young climbers. Based on injury data, climbers younger than 16 years should not participate in international bouldering competitions and intensive finger strength training is not recommended. The majority of climbing foot injuries result from wearing too small or unnaturally shaped climbing shoes. Isometric and explosive strength improvements are strongly associated with the latter stages of sexual maturation and specific ontogenetic development, while improvement in motor abilities declines. Somatotyping that might identify common physical attributes in elite climbers of any age is incomplete. Accomplished adolescent climbers can now climb identical grades and compete against elite adult climbers aged up to and &gt;40 years. High-intensity sports training requiring leanness in a youngster can result in altered and delayed pubertal and skeletal development, metabolic and neuroendocrine aberrations and trigger eating disorders. This should be sensitively and regularly monitored. Training should reflect efficacious exercises for a given sex and biological age.
Quality of Life of Older Patients With Early-Stage Breast Cancer Receiving Adjuvant Chemotherapy: A Companion Study to Cancer and Leukemia Group B 49907
Authors: Alice B. Kornblith, Lan Lan, Laura Archer, Ann Partridge, Gretchen Kimmick, Clifford Hudis, Eric Winer, Rebecca Casey, Samantha Bennett, Harvey Jay Cohen, Hyman B. Muss
Journal: Journal of Clinical Oncology (2011)

A phase III trial (Cancer and Leukemia Group B CALGB-49907) was conducted to test whether older patients with early-stage breast cancer would have equivalent relapse-free and overall survival with capecitabine compared with standard chemotherapy. The quality of life (QoL) substudy tested whether capecitabine treatment would be associated with a better QoL than standard chemotherapy.QoL was assessed in 350 patients randomly assigned to either standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin and cyclophosphamide [AC]; n = 182) or capecitabine (n = 168). Patients were interviewed by telephone before treatment (baseline), midtreatment, within 1 month post-treatment, and at 12, 18, and 24 months postbaseline by using questionnaires from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), a breast systemic adverse effects scale (EORTC BR23), and the Hospital Anxiety and Depression Scale (HADS).Compared with patients who were treated with standard chemotherapy, patients who were treated with capecitabine had significantly better QoL, role function, and social function, fewer systemic adverse effects, less psychological distress, and less fatigue during and at the completion of treatment (P ≤ .005). Capecitabine treatment was associated with less nausea, vomiting, and constipation and with better appetite than standard treatment (P ≤ .004), but worse hand-foot syndrome and diarrhea (P < .005). These differences all resolved by 12 months.Standard chemotherapy was superior to capecitabine in improving relapse-free and overall survival for older women with early-stage breast cancer. Although capecitabine was associated with better QoL during treatment, QoL was similar for both groups at 1 year. The brief period of poorer QoL with standard treatment is a modest price to pay for a chance at improved survival.
T<scp>HE</scp>N<scp>EUROBIOLOGY OF</scp>V<scp>ISUAL</scp>-S<scp>ACCADIC</scp>D<scp>ECISION</scp>M<scp>AKING</scp>
Authors: Paul W. Glimcher
Journal: Annual Review of Neuroscience (2003)

Over the past two decades significant progress has been made toward understanding the neural basis of primate decision making, the biological process that combines sensory data with stored information to select and execute behavioral responses. The most striking progress in this area has been made in studies of visual-saccadic decision making, a system that is becoming a model for understanding decision making in general. In this system, theoretical models of efficient decision making developed in the social sciences are beginning to be used to describe the computations the brain must perform when it connects sensation and action. Guided in part by these economic models, neurophysiologists have been able to describe neuronal activity recorded from the brains of awake-behaving primates during actual decision making. These recent studies have examined the neural basis of decisions, ranging from those made in predictable sensorimotor tasks to those unpredictable decisions made when animals are engaged in strategic conflict. All of these experiments seem to describe a surprisingly well-integrated set of physiological mechanisms that can account for a broad range of behavioral phenomena. This review presents many of these recent studies within the emerging neuroeconomic framework for understanding primate decision making.
Localist representations and theoretical clarity
Authors: Norman D. Cook
Journal: Behavioral and Brain Sciences (2000)

In the Localist Manifesto, Page enumerated several computational advantages that localist representations have over distributed representations, but the most important difference between such networks concerns their theoretical clarity. Distributed representations are normally closed to theoretical interpretation and, for that reason, contribute little to psychology, whereas the meaning of the information processing in networks using localist representations can be transparent.
Interleukin-27 Inhibits the Growth of Pediatric Acute Myeloid Leukemia in NOD/SCID/<i>Il2rg−/−</i> Mice
Authors: Alessia Zorzoli, Emma Di Carlo, Claudia Cocco, Emanuela Ognio, Domenico Ribatti, Elisa Ferretti, Carlo Dufour, Franco Locatelli, Daniela Montagna, Irma Airoldi
Journal: Clinical Cancer Research (2012)

Acute myeloid leukemia (AML) accounts for more than half of fatal cases in all pediatric leukemia patients; this observation highlights the need of more effective therapies. Thus, we investigated whether interleukin (IL)-27, an immunomodulatory cytokine, functions as an antitumor agent against pediatric AML cells.Expression of WSX-1 and gp130 on AML cells from 16 pediatric patients was studied by flow cytometry. Modulation of leukemia cell proliferation or apoptosis upon IL-27 treatment in vitro was tested by bromodeoxyuridine/propidium iodide (PI) and Ki67, or Annexin V/PI staining and flow cytometric analysis. The angiogenic potential of AML cells treated or not with IL-27 was studied by chorioallantoic membrane assay and PCR array. In vivo studies were carried out using nonobese diabetic/severe combined immunodeficient (NOD/SCID)/Il2rg(-/-) mice injected intravenously with five pediatric AML cell samples. Leukemic cells engrafted in PBS and IL-27-treated animals were studied by immunohistochemical/morphologic analysis and by PCR array for expression angiogenic/dissemination-related genes.We provided the first demonstration that (i) AML cells injected into NOD/SCID/Il2rg(-/-) mice gave rise to leukemia dissemination that was severely hampered by IL-27, (ii) compared with controls, leukemia cells harvested from IL-27-treated mice showed significant reduction of their angiogenic and spreading related genes, and (iii) similarly to what was observed in vivo, IL-27 reduced in vitro AML cell proliferation and modulated the expression of different genes involved in the angiogenic/spreading process.These results provide an experimental rationale for the development of future clinical trials aimed at evaluating the toxicity and efficacy of IL-27.
Is There a Public Health Function?
Authors: A Wolman
Journal: Annual Review of Public Health (1986)

The world is full of science and technology assessments, performed to prove that what we do has social significance. In recent decades the pressure to pursue this intellectual exercise has had a more important purpose. People must be convinced that what we do will not harm them. Perhaps of greater relevance, people must be made aware of what we are not, but should be, doing. The subject has the tacit blessing of a distinguished public health prac­ titioner. In February 1984, Susan S. Addiss, then President of the American Public Health Association, asked not too innocently (1):
Sports injuries in women: a one-year prospective follow-up study at an outpatient sports clinic.
Authors: P Kannus, S Niittymäki, M Järvinen
Journal: British Journal of Sports Medicine (1987)

A one-year prospective follow-up study of all patients visiting Tampere Research Station of Sports Medicine (TRSSM) was carried out in order to determine the specific features of women's sports injuries compared to those of men. During this period 334 women (31%) and 745 men (69%) visited the station. Women were significantly younger than men and the ten most usual sports events causing the injury differed from those of men. In women acute dislocations, contusions, and fractures were significantly less common in men, while women had more frequent stress-related sports injuries. In both sexes the most common sites of trouble were knee, ankle, and lower back, but in women as opposed to men, the metatarsal area, the toes, and the sole were among the ten most usual sites of the injury. Fourteen women (4%) and 49 men (6%) required operative treatment of the injury. The knee was the most common site of operation in both sexes, in women significantly more frequently than in men.