tbuckley/cabot-search huggingface dataset:
Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice
Authors: Jennifer W. Hill, Kevin W. Williams, Chianping Ye, Ji Luo, Nina Balthasar, Roberto Coppari, Michael A. Cowley, Lewis C. Cantley, Bradford B. Lowell, Joel K. Elmquist
Journal: Journal of Clinical Investigation (2008)

Normal food intake and body weight homeostasis require the direct action of leptin on hypothalamic proopiomelanocortin (POMC) neurons. It has been proposed that leptin action requires PI3K activity. We therefore assessed the contribution of PI3K signaling to leptin's effects on POMC neurons and organismal energy balance. Leptin caused a rapid depolarization of POMC neurons and an increase in action potential frequency in patch-clamp recordings of hypothalamic slices. Pharmacologic inhibition of PI3K prevented this depolarization and increased POMC firing rate, indicating a PI3K-dependent mechanism of leptin action. Mice with genetically disrupted PI3K signaling in POMC cells failed to undergo POMC depolarization or increased firing frequency in response to leptin. Insulin's ability to hyperpolarize POMC neurons was also abolished in these mice. Moreover, targeted disruption of PI3K blunted the suppression of feeding elicited by central leptin administration. Despite these differences, mice with impaired PI3K signaling in POMC neurons exhibited normal long-term body weight regulation. Collectively, these results suggest that PI3K signaling in POMC neurons is essential for leptin-induced activation and insulin-induced inhibition of POMC cells and for the acute suppression of food intake elicited by leptin, but is not a major contributor to the regulation of long-term organismal energy homeostasis.
Effects of Action Potential Duration on Excitation-Contraction Coupling in Rat Ventricular Myocytes
Authors: R. A. Bouchard, R. B. Clark, W. R. Giles
Journal: Circulation Research (1995)

Although each of the fundamental processes involved in excitation-contraction coupling in mammalian heart has been identified, many quantitative details remain unclear. The initial goal of our experiments was to measure both the transmembrane Ca2+ current, which triggers contraction, and the Ca2+ extrusion due to Na(+)-Ca2+ exchange in a single ventricular myocyte. An action potential waveform was used as the command for the voltage-clamp circuit, and the membrane potential, membrane current, [Ca2+]i, and contraction (unloaded cell shortening) were monitored simultaneously. Ca(2+)-dependent membrane current during an action potential consists of two components: (1) Ca2+ influx through L-type Ca2+ channels (ICa-L) during the plateau of the action potential and (2) a slow inward tail current that develops during repolarization negative to approximately -25 mV and continues during diastole. This slow inward tail current can be abolished completely by replacement of extracellular Na+ with Li+, suggesting that it is due to electrogenic Na(+)-Ca2+ exchange. In agreement with this, the net charge movement corresponding to the inward component of the Ca(2+)-dependent current (ICa-L) was approximately twice that during the slow inward tail current, a finding that is predicted by a scheme in which the Ca2+ that enters during ICa is extruded during diastole by a 3 Na(+)-1 Ca2+ electrogenic exchanger. Action potential duration is known to be a significant inotropic variable, but the quantitative relation between changes in Ca2+ current, action potential duration, and developed tension has not been described in a single myocyte. We used the action potential voltage-clamp technique on ventricular myocytes loaded with indo 1 or rhod 2, both Ca2+ indicators, to study the relation between action potential duration, ICa-L, and cell shortening (inotropic effect). A rapid change from a "short" to a "long" action potential command waveform resulted in an immediate decrease in peak ICa-L and a marked slowing of its decline (inactivation). Prolongation of the action potential also resulted in slowly developing increases in the magnitude of Ca2+ transients (145 +/- 2%) and unloaded cell shortening (4.0 +/- 0.4 to 7.6 +/- 0.4 microns). The time-dependent nature of these effects suggests that a change in Ca2+ content (loading) of the sarcoplasmic reticulum is responsible. Measurement of [Ca2+]i by use of rhod 2 showed that changes in the rate of rise of the [Ca2+]i transient (which in rat ventricle is due to the rate of Ca2+ release from the sarcoplasmic reticulum) were closely correlated with changes in the magnitude and the time course of ICa-L.(ABSTRACT TRUNCATED AT 400 WORDS)
Lymphatic Vessel Invasion As a Prognostic Factor in Patients With Primary Resected Adenocarcinomas of the Esophagogastric Junction
Authors: Burkhard H.A. von Rahden, Hubert J. Stein, Marcus Feith, Karen Becker, J. Rüdiger Siewert
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the value of lymphatic vessel invasion (LVI) as a predictor of survival in patients with primary resected adenocarcinomas of the esophagogastric junction (AEG). Patients and Methods We prospectively evaluated 459 patients undergoing primary surgical resection for tumors of the esophagogastric junction at our institution between 1992 and 2000 (180 adenocarcinomas of the distal esophagus, AEG I; 140 carcinomas of the cardia, AEG II; and 139 subcardial gastric cancers, AEG III). Median follow-up was 36.8 months. The prevalence of LVI was evaluated by two independent pathologists. Univariate and multivariate analysis of prognostic factors was performed. Results The total rate of LVI was 49.9%, with a significant difference between AEG I (38.9%) and AEGII/III (57.0%, P = .0002). Univariate analysis showed a significant correlation between LVI and T category (P &lt; .0001), N category (P &lt; .0001), and resection status (R [residual tumor] category; P &lt; .0001). This was shown for the group of all AEG tumors, as well as for the subgroups AEG I and AEG II/III. On multivariate analysis, LVI was identified as a significant and independent prognostic factor (P = .050) in the population of all patients and in patients with AEG II/III, but not in the subgroup with AEG I. Conclusion These data demonstrate the prognostic significance of LVI in patients with AEG tumors, with marked differences between the subgroups AEG I versus AEG II/III. The lower prevalence and lack of prognostic significance of LVI in AEG I might be explained by inflammation involved in the pathogenesis of this entity.
Rate Control
Authors: Paul J. Wang
Journal: Circulation (2006)

2][3] Oral or intravenous agents are routinely administered to achieve adequate control of the ventricular rate by modulating atrioventricular nodal function.The systemic effects of calcium channel antagonists and ␤-adrenergic receptor antagonists on blood pressure and other adverse effects, however, may limit use of these agents in some patients.In other patients, it may be difficult to achieve adequate rate control with the use of pharmacological agents.
Quantifying oscillatory ventilation during exercise in patients with heart failure
Authors: Thomas Olson, Kenneth Beck, Bruce Johnson
Journal: European Respiratory Journal (2011)

Background: This study tested the validity of a data analysis scheme to quantify measures of oscillatory ventilation at rest and during exercise in heart failure patients (HF).  Methods: Eleven patients (age=53±8yrs, LVEF=17±4%, NYHA Class=II (7)/IV (4)) were recruited. Ventilation (VE) and gas exchange were measured. Amplitude and period of oscillations in VE, tidal volume (VT), end-tidal carbon dioxide (PETCO2), and oxygen consumption (VO2) were measured manually (MAN), using novel software which included a peak detection algorithm (PK), sine wave fitting algorithm (SINE), and Fourier analysis (FOUR).  Results: During PB, there were no differences between MAN and PK for amplitude of VE, VT, PETCO2, or VO2. Similarly, there were no differences between MAN and SINE for amplitude of VE or VT although PETCO2 and VO2 were lower with SINE (p  Conclusion: These data suggest 1) PK consistently captures amplitudes but underestimates period, 2) SINE and FOUR consistently capture period although SINE underestimates amplitude. Thus, an optimal algorithm for quantifying oscillatory ventilation in HF might combine multiple analysis methods. NIH grants HL71478/KL2-RR024151
Hemodynamic Determinants of the Amplitude of the First Heart Sound
Authors: TSUGUYA SAKAMOTO, REIZO KUSUKAWA, DONALD M. MACCANON, ALDO A. LUISADA, Ivan Harvey
Journal: Circulation Research (1965)

The relationships between the amplitude of the first heart sound and various hemodynamic parameters and their analog functions were systematically investigated in 51 dogs under morphine and pentobarbital anesthesia. Simultaneous hemodynamic and phonocardiographic tracings were obtained by cardiac catheterization, high speed recording, and analog computers. Changes in cardiodynamics were induced by: l -epinephrine, levarterenol, phenylephrine, isoproterenol, methoxamine, veratrine, vasopressin, histamine, atropine, saline infusion, mechanical obstruction of the aorta, pulmonary artery, or both venae cavae, embolization of the coronary arteries with plastic microspheres, mechanical rupture of aortic valve leaflets, or hemorrhage. In this way, the relationships were examined over a wide range of pressures, volumes, and cardiodynamics. The results showed that the amplitude of the first sound is not directly related to stroke output, P-R interval, heart rate, end diastolic, or systolic ventricular or aortic pressures. Only the peak rate of rise of left ventricular systolic pressure (first derivative maximum) had a consistent relationship to first sound amplitude. The right ventricle seems to contribute very little to the external first sound. These observations suggest that the amplitude of the first sound is related to left ventricular contractility.
SLC11A1 promoter gene polymorphisms and fibrosis progression in chronic hepatitis C
Authors: M Romero-Gomez
Journal: Gut (2004)

<b>Background and aims:</b> The solute carrier family 11 member 1 (SLC11A1) gene (formerly Nramp1) encodes for the protein solute carrier family 11, member 1. It affects susceptibility and clinical outcome of autoimmune and infectious diseases. We investigated the possible role of the functional polymorphism located in the promoter region of SLC11A1 and tumour necrosis factor (TNF) genes in the progression of fibrosis in chronic hepatitis C. <b>Methods:</b> A total of 242 Caucasian Spanish patients with biopsy proven chronic hepatitis C and 194 healthy control subjects were genotyped for SLC11A1 and TNF promoter polymorphisms. <b>Results:</b> No significant differences in the distribution of frequencies among patient and control groups were observed. The SCL11A1 homozygous 2/2 genotype was rarely detected among patients showing advanced fibrosis (2/82; 2.4%) but was highly represented in those with mild fibrosis (29/160; 18.1%; odds ratio (OR) 8.85 (95% confidence interval (CI) 1.9–55.2, p<sub>c</sub> = 0.002). In patients carrying allele 3 of SLC11A1, the presence of −238 TNF A/G was associated with advanced fibrosis (14/26 (53.8%) <i>v</i> 68/216 (31.4%); OR 2.53 (95% CI 1.03–6.23); p = 0.02). <b>Conclusions:</b> SLC11A1 gene promoter polymorphism could influence fibrosis progression in chronic hepatitis C in that the homozygous genotype 2/2 exerts a protective effect against cirrhosis development. Also, the combination of TNF −238 A/G and the presence of allele 3 is conducive to progression to pre-cirrhotic or cirrhotic stages of the disease.
The stigmatisation and denial of mental illness in athletes
Authors: Thomas L Schwenk
Journal: British Journal of Sports Medicine (2000)

A patient asks for your help with fatigue, which she has been experiencing for the past several weeks. She says she is having increasing difficulty carrying out her daily responsibilities, lacks motivation and energy, and is irritable and discouraged. She reports trouble sleeping, is often late to her scheduled responsibilities, is not performing as well as previously in her job and other roles, and has had several minor injuries and mild headache and back pain.

If you are a family doctor or general practitioner, you would suspect that this woman has a major depressive disorder (MDD), although the likelihood that a depressed patient would actually present her symptoms in such a clear and obvious fashion is extraordinarily low. However, if you are a sports doctor and the patient is a competitive athlete, you may label her as being burned out, overtrained or stale, depending on your personal nomenclature for this problem. You may carry out a routine battery of laboratory tests, often including measuring a variety of immunological, hormonal, and haematological variables, consult with the athlete's coach about a modified training schedule, and suggest the athlete consider a trial of rest which may even include cessation of all training and competition. On the other hand, …
Gender and Chronic Obstructive Pulmonary Disease
Authors: MeiLan K. Han, Dirkje Postma, David M. Mannino, Nicholas D. Giardino, Sonia Buist, Jeffrey L. Curtis, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The prevalence of chronic obstructive pulmonary disease (COPD) in women is increasing, as is hospitalization for COPD. The number of women dying of COPD in the United States now surpasses men. Despite this, research suggests that physicians are still more likely to correctly diagnose men with COPD than women. Increased tobacco use in women likely explains some of the increase in the prevalence of COPD in women, but data suggest that women may actually be at greater risk of smoking-induced lung function impairment, more severe dyspnea, and poorer health status for the same level of tobacco exposure. The degree to which these observations represent biologic, physiologic, or sociologic differences is not known. Nonsmokers with COPD are also more likely to be female. In addition, new evidence is emerging that men and women may be phenotypically different in their response to tobacco smoke, with men being more prone to an emphysematous phenotype and women an airway predominant phenotype. Inasmuch as COPD is a disease of inflammation, it is also possible that sexual dimorphism of the human immune response may also be responsible for gender differences in the disease. More data are still needed on what the implications of these findings are on therapy. In this clinical commentary, we present current knowledge regarding how gender influences the epidemiology, diagnosis, and presentation of COPD in addition to physiologic and psychologic impairments and we attempt to offer insight into why these differences might exist and how this may influence therapeutic management.
Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse.
Authors: R P Oude Elferink, R Ottenhoff, M van Wijland, J J Smit, A H Schinkel, A K Groen
Journal: Journal of Clinical Investigation (1995)

Disruption of the mdr2 gene in mice leads to a complete absence of phospholipid from bile (Smit, J. J. M., et al. 1993. Cell. 75:451-462). We have investigated the control of both mdr2 P-glycoprotein (Pgp) expression and bile salt secretion on biliary lipid secretion in the mouse. Lipid secretion was monitored at various bile salt output rates in wild-type mice (+/+), heterozygotes (+/-), and homozygotes (-/-) for mdr2 gene disruption. In (-/-) mice, phospholipid secretion was negligible at all bile salt output rates. In (+/-) mice, a curvilinear relation between bile salt and phospholipid secretion was observed similar to that in (+/+) mice; however, at all bile salt secretion rates phospholipid secretion was reduced compared to (+/+) mice, indicating that mdr2 Pgp exerts a strong control over secretion. Infusion of increasing amounts of taurocholate up to maximal secretory rate led to a decline in the phospholipid and cholesterol secretion in both (+/+) and (+/-) mice in accordance to what has been observed in other species. In contrast, in (-/-) mice cholesterol secretion increased under these conditions while phospholipid output remained extremely low. The increased cholesterol secretion may represent extraction of cholesterol from the canalicular plasma membrane by taurocholate micelles as opposed to the concomitant secretion of both phospholipid and cholesterol in the presence of a functional mdr2 Pgp. Increased bile flow in (-/-) mice could be attributed completely to an increase in the bile salt-independent fraction and may therefore be caused by the bile duct proliferation in these mice.
Patterns of Institutional Review of Percutaneous Coronary Intervention Appropriateness and the Effect on Quality of Care and Clinical Outcomes
Authors: Nihar R. Desai, Craig S. Parzynski, Harlan M. Krumholz, Karl E. Minges, John C. Messenger, Brahmajee K. Nallamothu, Jeptha P. Curtis
Journal: JAMA Internal Medicine (2015)

This Research Letter reports heterogeneity in institutional review of percutaneous coronary intervention appropriateness and calls for the identification of effective strategies to improve institutional review.
Inflammatory Breast Carcinoma: The Sphinx of Breast Cancer Research
Authors: Massimo Cristofanilli, Eva S. Singletary, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2004)

reference standard for indium-111-capromab pendetide radioimmunoscintigraphy.Therefore, the best test of Inmab scan accuracy is assiduous clinical follow-up to improve the classification of In-mab scan findings [8].The prostate-specific antigen (PSA) level is a debated end point in the evaluation of new treatment methods or modalities [9][10][11].Large multicenter and prospective analyses are needed to test whether PSA control after salvage radiation therapy leads to prolonged prostate cancer specific survival.Nevertheless, a favorable PSA profile after salvage radiation therapy is currently the best short-term surrogate for posttreatment prostate cancer survival and in turn success of salvage radiation therapy.Regarding the advocacy of image fusion, registering the In-mab scan to the negative computed tomography scan for each cohort may or may not change the results.Midline abdominal positivity by In-mab imaging may demonstrate mesenteric lymph nodes, but image registration likely will not compensate for normal physiological bowel movement.Image registration is an established and valuable imaging tool.It is not unequivocal and requires its own careful assessment [12,13].We noted a recent press release entitled "Cytogen, Siemens and University Hospitals of Cleveland Join Forces to Promote Breakthroughs in Prostate Cancer Imaging" (http://www.cytogen.com/pr/nr_06_23_03.html), in which Dr Sodee describes his technique.It is possible that his technique will improve image results.We wish him success in his efforts and look forward to peer-reviewed publication of his work.Our investigation did not test the use of capromab pendetide imaging for radiation therapy treatment planning or prostate cancer staging.There was never an assertion that future applications with advanced versions of capromab penditide have no value.However, for postprostatectomy PSA relapse, indium-111-capromab pendetide imaging results were not prognostic of postsalvage radiation therapy PSA outcome.The results are relevant for the imaging method used and stand on their own merit.
Delta Opioid Receptors Presynaptically Regulate Cutaneous Mechanosensory Neuron Input to the Spinal Cord Dorsal Horn
Authors: Rita Bardoni, Vivianne L. Tawfik, Dong Wang, Amaury François, Carlos Solorzano, Scott A. Shuster, Papiya Choudhury, Chiara Betelli, Colleen Cassidy, Kristen Smith, Joriene C. de Nooij, Françoise Mennicken, Dajan O’Donnell, Brigitte L. Kieffer, C. Jeffrey Woodbury, Allan I. Basbaum, Amy B. MacDermott, Grégory Scherrer
Journal: Neuron (2014)
Preventive effects of pravastatin on thrombin-triggered vascular responses via Akt/eNOS and RhoA/Rac1 pathways in vivo
Authors: H. Ohkawara, T. Ishibashi, S.-i. Saitoh, N. Inoue, K. Sugimoto, M. Kamioka, H. Uekita, T. Kaneshiro, K. Ando, Y. Takuwa, Y. Maruyama, Y. Takeishi
Journal: Cardiovascular Research (2010)

AimsSmall GTPases RhoA and Rac1 play crucial roles in endothelial dysfunction and reactive oxygen species (ROS) generation. We reported evidence that in thrombin-stimulated endothelial cells, rapid geranylgeranylation is an essential process for full activation of unprocessed RhoA, which is blocked by statin. In this study, we examined the effects of intravenous administration of pravastatin on thrombin-triggered vascular responses in vivo, as well as on the lipid modification of unprocessed forms of RhoA and Rac1 and their activation induced by thrombin.
Review of respiratory physician inpatient pleural ultrasound service
Authors: Burhan Khan, Majid Mushtaq
Journal: European Respiratory Journal (2011)

Introduction:  The appropriate and timely investigation, interventions and management of pleural effusions remains discrepant with variable practices and pathways, possible impacting upon quality of care.   Aims:  To ascertain the qualitative and quantitative outcomes of running a Respiratory physician led inpatient pleural ultrasound service.   Methods:  A prospective analysis of 12-18 month experience in a district general hospital of providing an inpatient pleural service by chest physicians with thoracic ultrasound.   Results:  From May 2010 to date (10 months) 111 patients were included. We compare the pleural disease activity level pre and post establishing of this service.  The remit and breadth of inpatient pleural service and interventions undertaken are as follows.   Conclusion:  Provision of an inpatient pleural service does require work planning and resources but results in qualitative and quantitative improvements in patient care including: improved clinical practices by avoiding “X” marks the spot; pleural interventions done quicker and safely with no complications to date; and improved pathways for patients with pleural disease.
Heme Iron, Zinc, Alcohol Consumption, and Colon Cancer: Iowa Women's Health Study
Authors: D.-H. Lee, K. E. Anderson, L. J. Harnack, A. R. Folsom, D. R. Jacobs
Journal: JNCI Journal of the National Cancer Institute (2004)

We examined associations among colon cancer incidence and dietary intake of heme iron, a possible prooxidant, zinc, a possible antioxidant, and alcohol, a disruptor of iron homeostasis. During 15 years of follow-up, 34 708 postmenopausal women, aged 55–69 years at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for incident colon cancer. After adjusting for each micronutrient, the relative risks for proximal colon cancer increased more than twofold across categories of heme iron intake (Ptrend = .01) and the corresponding relative risks decreased more than 50% across categories for zinc intake (Ptrend = .01). The positive association with heme iron and the inverse association with zinc intake were stronger among women who consumed alcohol than among those who did not. Zinc intake was also associated with a decreased risk of distal colon cancer (Ptrend = .03), regardless of alcohol or heme iron consumption. Our results suggest that intake of dietary heme iron is associated with an increased risk of proximal colon cancer, especially among women who drink, but that intake of dietary zinc is associated with a decreased risk of both proximal and distal colon cancer.