tbuckley/cabot-search huggingface dataset:
Epinephrine plasma thresholds for lipolytic effects in man: measurements of fatty acid transport with [l-13C]palmitic acid.
Authors: A D Galster, W E Clutter, P E Cryer, J A Collins, D M Bier
Journal: Journal of Clinical Investigation (1981)

To determine the plasma epinephrine thresholds for its lipolytic effect, 60-min epinephrine infusions at nominal rates of 0.1, 0.5, 1.0, 2.5, and 5.0 micrograms/min were performed in each of four normal young adult men while they also received a simultaneous infusion of [1-13C]palmitic acid to estimate inflow transport of plasma free fatty acids. These 20 infusions resulted in steady-state plasma epinephrine concentrations ranging from 12 to 870 pg/ml. Plasma epinephrine thresholds for changes in blood glucose, lactate, and beta-hydroxybutyrate were in the 150--200-pg/ml range reported by us previously (Clutter, W. E., D. M. Bier, S. D. Shah, and P. E. Cryer. 1980. J. Clin. Invest. 66: 94--101.). Increments in plasma glycerol and free fatty acids and in the inflow and outflow transport of palmitate, however, occurred at lower plasma epinephrine thresholds in the range of 75 to 125 pg/ml. Palmitate clearance was unaffected at any steady-state epinephrine level produced. These data indicate that (a) the lipolytic effects of epinephrine occur at plasma levels approximately threefold basal values and (b) lipolysis is more sensitive than glycogenolysis to increments in plasma epinephrine.
Novel Therapies Focused on the High-Density Lipoprotein Particle
Authors: Julian C. van Capelleveen, H. Bryan Brewer, John J.P. Kastelein, G. Kees Hovingh
Journal: Circulation Research (2014)

Cardiovascular disease (CVD) remains a major burden for morbidity and mortality in the general population, despite current efficacious low-density lipoprotein-cholesterol–lowering therapies. Consequently, novel therapies are required to reduce this residual risk. Prospective epidemiological studies have shown that high-density lipoprotein-cholesterol (HDL-C) levels are inversely correlated with cardiovascular disease risk, and this initiated the quest for HDL-C–increasing therapies. Consequently, several different targets in HDL metabolism have been identified. Initial studies addressing the effect of cholesteryl ester transfer protein inhibition on cardiovascular disease outcome have been discontinued for reasons of futility or increased mortality. As of yet, 2 cholesteryl ester transfer protein inhibitors are still in phase III studies. Other HDL-based interventions, such as apolipoprotein A1–based compounds, ABC-transporter upregulators, selective peroxisome proliferator–activated receptor modulators and lecithin-cholesterol acyltransferase–based therapy, hold great promise for the future. The aim of this review is to provide a comprehensive overview of HDL-targeted pharmaceutical strategies in humans, both in early development as well as in late stage clinical trials.
Abstract 4655: Aplidin induces a non-canonical ER stress response in HeLa cells response in HeLa cells
Authors: Alejandro Losada, Alberto Bejarano, Marta Palafox, David Moreno-Mateos, Victoria Moneo, Antonio Jimenez-Ruiz, Federico Gago, Carmen Cuevas, Luis F. Garcia-Fernandez, Juan FM Leal, Carlos M. Galmarini
Journal: Cancer Research (2012)

Abstract Aplidin (APL), a marine cyclic depsipeptide originally found in the Mediterranean tunicate Aplidium albicans, is currently under phase II/III clinical investigation for cancer therapy. The mechanism of action of the compound includes the oxidative-stress mediated activation of Rac1 and JNK1, which rapidly trigger the mitochondrial apoptotic pathway. Comparing the protein expression profiles of HeLa wt cells and an APL-resistant subclone previously generated in our lab (HeLa-APL), we identified a subset of differentially expressed proteins the function of which was related to the unfolded protein response (UPR). HeLa-APL resistant cells showed reduced levels of BiP (GRP78) and relatively higher levels of Ero1α and phospho-eIF2α, indicating a higher basal endoplasmic reticulum (ER) stress. To investigate whether APL was inducing a bona fide ER stress response in HeLa cells and whether this process was essential in the mechanism of action of this compound, we compared the molecular and cellular effects elicited by APL with those induced by two well-known ER-stress inducing agents, thapsigargin and tunicamycin. Basically, while these agents elicited a complete canonical UPR response, APL only triggered part of the stress signaling cascade, including the phosphorylation of eIF2α and JNK1 and a rapid inhibition of protein synthesis. By contrast, CHOP, a transcription factor involved in launching apoptosis by the UPR, was not induced by APL. Rather, it seemed to be slightly reduced in treated cells. Similarly, while tunicamycin induced the alternative splicing of XBP1 by IRE1 and the activation of the ER-related caspase-4, APL failed to induce the same response in HeLa cells. At present, the precise connection between the partial activation of the ER stress signaling pathway and the rapid induction of apoptosis by APL remains poorly understood, although it could represent a new, aberrant UPR response Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4655. doi:1538-7445.AM2012-4655
The Unique Association Between Salivary Gland Cancer and Breast Cancer
Authors: John W. Berg
Journal: JAMA (1968)

In a group of 396 patients with known cancers of the major salivary glands there were seven in whom breast cancers later developed. This represents an eightfold increase in risk beyond the statistical expectation. The probability that these patients with salivary gland cancers later had breast cancer only by chance is about 0.004%; indicating the possibility of common causal factors. We believe that it is important to alert the clinician to the observed but not yet explained significantly high risk for patients with salivary gland cancers to later have breast cancers. We hope that awareness of this risk will direct attention to careful examination of the breasts, since the detection of localized cancer increases the likelihood of cure.
Flavopiridol Blocks Integrin-Mediated Survival in Dormant Breast Cancer Cells
Authors: Saltanat Najmi, Reju Korah, Rachna Chandra, Maha Abdellatif, Robert Wieder
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Breast cancer micrometastases in the bone marrow are resistant to chemotherapy. They can remain dormant for years before some begin to proliferate. We seek to understand survival mechanisms and develop targeted approaches to eliminating these cells. Experimental Design: In an in vitro model of dormancy, basic fibroblast growth factor 2 (FGF-2), abundant in the bone marrow, inhibits the growth of well-differentiated cells in the 2- to 10-cell stage and up-regulates integrin α5β1. Through this integrin, cells bind fibronectin, spread out, and acquire a survival advantage, partly through activation of the phosphatidylinositol 3-kinase/Akt pathway. We investigated the effects of Taxotere, flavopiridol, and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase and p38 inhibitors on survival of dormant clones and that of flavopiridol on expression of integrins, adhesion strength, and phosphorylation of Akt, ERK 1/2, and p38. Results: Dormant MCF-7 and T-47D cell clones were resistant to Taxotere concentrations 10-fold higher than needed to eliminate growing clones but were almost completely eradicated by 200 nmol/L flavopiridol. Flavopiridol caused a decrease in FGF-2–induced expression of integrins, including α5 and β1, and decreased FGF-2–induced specific adhesion to fibronectin. It diminished Akt phosphorylation, but reexpression of active Akt was not sufficient to reverse dormant clone inhibition. Flavopiridol did not affect phosphorylation of ERK 1/2 and p38 but diminished total protein levels. Chemical inhibition of these pathways partially abrogated dormant clone survival. Conclusions: Flavopiridol has pleiotropic effects on key targets involved with survival of dormant breast cancer cells and may represent a useful approach to eliminating cells dependent on multiple signal pathways for survival.
Leukemia in the proximity of a German boiling-water nuclear reactor: evidence of population exposure by chromosome studies and environmental radioactivity.
Authors: I Schmitz-Feuerhake, B Dannheim, A Heimers, B Oberheitmann, H Schröder, H Ziggel
Journal: Environmental Health Perspectives (1997)

Exceptional elevation of children's leukemia appearing 5 years after the 1983 startup of the Krümmel nuclear power plant, accompanied by a significant increase of adult leukemia cases, led to investigations of radiation exposures of the population living near the plant. The rate of dicentric chromosomes in peripheral lymphocytes of seven parents of children with leukemia and in 14 other inhabitants near the plant was significantly elevated and indicated ongoing exposures over the years of its operation. These findings led to the hypothesis that chronic reactor leakages had occurred. This assumption is support by identification of artificial radioactivity in air, rainwater, soil and vegetation by the environmental monitoring program at the nuclear power plant. Calculations of the corresponding source terms show that emissions must have been well above authorized annual limits. Bone marrow doses supposedly result primarily through incorporation of bone-seeking beta- and alpha-emitters.
Load detection in subjects with sleep-induced upper airway obstruction.
Authors: A A Clerk, S R Dunan, C Guilleminault
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Respiratory flow-resistive load detection in obese patients has been shown to be impaired. We tested the hypothesis that there is no difference in inspiratory flow-resistive load detection measured in nonobese obstructive sleep apnea patients, nonobese snorers, and normal control subjects. Eleven male obstructive sleep apnea patients and seven male snorers were investigated and compared with 10 normal male control subjects. Severely obese patients (body mass index, BMI > 35 kg/m2) were excluded. Patients were investigated by nocturnal polysomnography with measurement of esophageal pressure (Pes). Awake pulmonary function tests were performed before the investigation. Airway resistance (Raw) and lung volumes were measured with plethysmography. Resistive loads were investigated according to Tapper and associates (13) and Killian and associates (12). Resistances were applied for the duration of one inspiratory cycle and a minimum of two breaths allowed between each resistive load. Six different resistances plus background shams were presented 10 times in random order. Flow, pressure, and subject response were recorded with a calibrated multichannel recorder. Subjects signaled detected changes of inspiratory resistance with a hand-held signaling device. The probability of detecting a particular resistance was calculated as the ratio of correct identification to the number of presentations (i.e., 10). The resistance corresponding to a 0.5 probability of detection was determined. The Weber fraction (wf) calculated as delta R/R(apparatus) +Raw. There were no differences between nonobese subjects and controls in terms of resistive load detection.
Congenital defect of the hard palate
Authors: S. Tanaka, H. Fujita, M. Iwamuro, J. Kubota, M. Goubaru, T. Ohta
Journal: Endoscopy (2006)

Endoscopists are not generally familiar with diseases of the oral cavity. We present here a unique image of the oral cavity in an 83-year-old man who presented with dysarthria. He had been well all his life and never been under the care of a doctor. Computed tomography (CT) of the head revealed a hemorrhage in the left temporal lobe, but this did not enlarge following admission, and the clinical course was uneventful. Fourteen days later, an upper gastrointestinal endoscopy examination was carried out, as anemia was also noted on admission. A large lumen in the oral cavity was observed (Figure [1 a]). Careful observation identified turbinates at the back of the lumen (Figure [1 b]). It was therefore considered that the lumen was a large fistula into the nasal cavity. The patient had no history of trauma or infection associated with otorhinolaryngological diseases. The head CT on admission did not suggest any tumor invasion or chronic inflammation in the nasal cavity (Figure [2]). The disease was thought possibly to be an anomaly. Ultimately, the condition was diagnosed as a congenital defect of the hard palate. As the patient had been well and lived a normal life, nobody had noticed the congenital defect before. After rehabilitation, the patient was able to eat and drink again, and moved to another hospital.
LAW AND MEDICINE
Authors: Veronica M. O'Hern
Journal: JAMA (1968)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hypoplastic Left Heart Syndrome
Authors: Carolyn A. Bondy
Journal: New England Journal of Medicine (2010)

Just 30 years ago, the newborn with hypoplastic left heart syndrome faced certain death. This congenital defect involves a rudimentary mitral valve and left ventricle, coupled with a hypoplastic aortic valve and ascending aorta.1 Multistage surgical remediation of hypoplastic left heart syndrome, introduced in the 1980s, has led to survival rates that exceed 60%, and in this issue of the Journal, Ohye et al. report a further survival benefit with the use of a newly developed shunt.2 The fetus with hypoplastic left heart is able to survive until birth because of the unique fetal circulatory pattern. In the fetus with . . .
Gelatinous transformation of bone marrow from a starch‐free diet
Authors: Chen Wang, Dominick Amato, Bernard Fernandes
Journal: American Journal of Hematology (2001)

Abstract Gelatinous marrow transformation is characterized by marrow hypoplasia, fat atrophy, and gelatinous material deposition, and usually develops as a hematologic complication of chronic wasting disorders. Most of the cases associated with severe nutritional deficiency were seen in anorexia nervosa due to a depletion of protein or fat. This report describes a case of gelatinous transformation attributed to a specific restriction of carbohydrates in diet. The hematologic deficiency was eventually recovered after the patient resumed a regular starch‐containing diet. This brief report illustrates the potential side effect of the compulsive dietary behavior on the hematologic system. Am. J. Hematol. 68:58–59, 2001. © 2001 Wiley‐Liss, Inc.
Predictive Factors of Gefitinib Antitumor Activity in East Asian Advanced Non-small Cell Lung Cancer Patients
Authors: Gee-Chen Chang, Chun-Ming Tsai, Kun-Chieh Chen, Chong-Jen Yu, Jin-Yuan Shih, Tsung-Ying Yang, Ching-Pei Lin, Jeng-Yuan Hsu, Chao-Hua Chiu, Reury-Perng Perng, Pan-Chyr Yang, Chih-Hsin Yang
Journal: Journal of Thoracic Oncology (2006)
Ivo John Carré
Authors: Desmond Creery
Journal: BMJ (2008)

Ivo John Carre received his early training in paediatrics in London and Birmingham, and was later a research fellow in Melbourne. In 1956 he became senior lecturer in child health in Belfast, and subsequently (1963) professor in that department, retiring in 1984.

He had a most distinguished career in paediatrics, and he …
Correlative Imaging in Crowned Dens Syndrome
Authors: Frank De Geeter, Lode Goethals, Yves Piette, Jan De Neve, Johan Ghekiere
Journal: Clinical Nuclear Medicine (2007)

Bone scintigraphy with Tc-99m oxidronate in a 51-year-old woman with subacute neck pain and inflammatory markers showed a hot spot in the area of the upper cervical spine. Correlative imaging with CT and MRI suggested calcification of the transverse axial ligament and inflammation at the atlantoaxial joint as the cause of these findings. Symptomatic cases of calcifications surrounding the odontoid process in a crown-like distribution have been termed “crowned dens syndrome.” In patients with neck pain and an inflammatory syndrome, this should be included in the differential diagnosis of upper cervical hot spots on bone scanning.
DISORDERS OF MOTILITY OF THE IRIS
Authors: F. H. LEE
Journal: JAMA (1933)

A knowledge of the disorders of motility of the iris is frequently of considerable help in pointing to, if not determining, many abnormal conditions of the body as functional and organic disturbances, especially toxic and central nervous system diseases. The knowledge should be used by all, but it is of greater help to those who have not ready access to many of the more intricate or special methods of diagnosis, particularly laboratory or technical procedures. To understand the disorders of motility of the iris it is desirable to consider its structure and its normal function. Within the anterior segment of the eye the iris forms a diaphragm which contracts or dilates to permit the entrance into the eye of the amount of light most favorable to satisfactory vision. To accomplish this there are two sets of muscle fibers, each having a different source and type of nerve supply. The contracting
Stoichiometry of Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex.
Authors: M Soleimani, S M Grassi, P S Aronson
Journal: Journal of Clinical Investigation (1987)

The major pathway for HCO3- transport across the basolateral membrane of the proximal tubule cell is electrogenic Na+-HCO3- cotransport. In this study, we have determined the stoichiometry of the Na+-HCO3- cotransport system in basolateral membrane vesicles that were isolated from rabbit renal cortex by Percoll gradient centrifugation. When the membrane potential is approximated by the Nernst potential for K+, as in the presence of the K+ ionophore valinomycin, equilibrium thermodynamics predicts that the Na+-HCO3- cotransport system should come to equilibrium and mediate no net flux when (Na)i/(Na)o = [(HCO3)o/(HCO3)i]n[(K)o/(K)i]n-1, where n is the HCO3-:Na+ stoichiometry. Our experimental approach was to impose transmembrane Na+, HCO3-, and K+ gradients of varying magnitude and direction, and then to measure the net flux of Na+ over the subsequent 3-s period. In this way, we could determine the conditions for equilibrium of the transport system and thereby calculate n. The results of these experiments indicate that the value of n is greater than 2.6 and less than 3.5, consistent with a stoichiometry of 3 HCO3-:1 Na+, or a thermodynamically equivalent process. Based on reported intracellular potentials and ion activities, this value for the stoichiometry indicates that the inside-negative membrane potential is sufficient to drive HCO3- exit against the inward concentration gradients of HCO3- and Na+ that are present across the basolateral membrane of the intact proximal tubule cell under physiologic conditions.
Fundamentals of Clinical Hematology
Authors: William R. Best
Journal: JAMA (1972)

There are now available a number of good texts in hematology. In reviewing this new edition of one such, I ask myself, For whom is it particularly suited? What is unique about this? It is quite satisfactory—readable, balanced, soundly based, and well documented. It covers the field from the clinical standpoint, is well organized and indexed. Selected case histories give the flavor of clinical practice and insights into decisions of workup and treatment. Morphologic illustrations are minimal but good. There are selected references to slides in commercially available filmstrips on morphologic hematology. This volume can be recommended for student, resident, or practitioner. There is little on laboratory methodology, however, so it is of less appeal to the technician. Hematology has shown continued strides, and it is a real chore for an author to update from edition to edition—there is usually a five- or six-year gap between. Perhaps the thing which
Legalized Physician-Assisted Suicide in Oregon — The First Year's Experience
Authors: Arthur E. Chin, Katrina Hedberg, Grant K. Higginson, David W. Fleming
Journal: New England Journal of Medicine (1999)

On October 27, 1997, Oregon legalized physician-assisted suicide. We collected data on all terminally ill Oregon residents who received prescriptions for lethal medications under the Oregon Death with Dignity Act and who died in 1998. The data were obtained from physicians' reports, death certificates, and interviews with physicians. We compared persons who took lethal medications prescribed under the act with those who died from similar illnesses but did not receive prescriptions for lethal medications.Information on 23 persons who received prescriptions for lethal medications was reported to the Oregon Health Division; 15 died after taking the lethal medications, 6 died from underlying illnesses, and 2 were alive as of January 1, 1999. The median age of the 15 patients who died after taking lethal medications was 69 years; 8 were male, and all 15 were white. Thirteen of the 15 patients had cancer. The case patients and controls were similar with regard to sex, race, urban or rural residence, level of education, health insurance coverage, and hospice enrollment. No case patients or controls expressed concern about the financial impact of their illness. One case patient and 15 controls expressed concern about inadequate control of pain (P=0.10). The case patients were more likely than the controls to have never married (P=0.04) and were more likely to be concerned about loss of autonomy due to illness (P=0.01) and loss of control of bodily functions (P=0.02). At death, 21 percent of the case patients and 84 percent of the controls were completely disabled (P<0.001).During the first year of legalized physician-assisted suicide in Oregon, the decision to request and use a prescription for lethal medication was associated with concern about loss of autonomy or control of bodily functions, not with fear of intractable pain or concern about financial loss. In addition, we found that the choice of physician-assisted suicide was not associated with level of education or health insurance coverage.
Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions
Authors: David Yao, Yuanshuai Huang, Xiaoran Huang, Weihuan Wang, Quanjian Yan, Lebing Wei, Wei Xin, Stanton Gerson, Pamela Stanley, John B. Lowe, Lan Zhou
Journal: Blood (2011)