tbuckley/cabot-search huggingface dataset:
Glucose Turnover in Type I Diabetic Subjects During Exercise: Effect of selective and nonselective β-blockade and insulin withdrawal
Authors: Jonathan J Benn, Philip M Brown, Lucy J Beckwith, Martin Farebrother, Peter H Sönksen
Journal: Diabetes Care (1992)

To assess the effect of selective beta 1-blockade (atenolol and betaxolol) and nonselective beta-blockade (propranolol) on glucose turnover in subjects with insulin-dependent (type I) diabetes mellitus during moderate exercise.Five subjects with type I diabetes were infused with insulin and then exercised for 1 h, after pretreatment with each of the three drugs or saline and, on a separate day, after withdrawal of insulin. Glucose turnover was measured using tritiated glucose.Plasma glucose, initially 9.2 +/- 0.5 mmol/L (mean +/- SE) when insulin infused and 14.0 +/- 0.8 when insulin was withdrawn, fell on exercise by 3.4 +/- 1.1 mmol/L (P < 0.05) saline, 4.0 +/- 0.8 mmol/L (P < 0.01) with betaxolol, 3.8 +/- 0.7 mmol/L (P < 0.01) with atenolol, 5.0 +/- 0.6 mmol/L (P < 0.005) with propranolol, and 1.7 +/- 1.0 mmol/L (NS) when insulin was withdrawn. Propranolol, but not the other beta-blockers, caused a significantly greater fall in glucose on exercise than during the control study. Glucose appearance rate (Ra) was similar basally and rose to an almost identical level in all five groups during exercise. Glucose disappearance rate (Rd) rose similarly during exercise, except after propranolol when the rise was significantly greater than with saline (P < 0.01). Failure of glucose to change significantly during exercise when insulin had been withdrawn was associated with the smallest rise in Rd and the highest nonesterified fatty acid concentrations. Propranolol and betaxolol, but not atenolol, reduced nonesterified fatty acids.We conclude that the greater fall in glucose on exercise after beta-blocking drugs is probably largely a direct effect of beta 2-blockade on muscle, increasing the exercise-induced rise in Rd glucose. This offers support to the use of beta 1-specific drugs, where beta-blockade is necessary in type I diabetes.
Double blind controlled study of treatment of atopic eczema with a preparation of hydrocortisone in a new drug delivery system versus betamethasone 17-valerate
Authors: JOHN ALMEYDA, B. W. BURT
Journal: British Journal of Dermatology (1974)

A double blind study has shown that topical treatment with a new preparation of I% hydrocortisone in a stabilized carbamide drug delivery system effectively controls atopic eczema without the hazards of potent fluorinated corticosteroids. Clinical evaluation confirms that it is at least as effective as 0·1% betamethasone 17-valerate. The preparation has the physical properties of both a cream and an ointment and can be used in place of either. It has a high level of patient acceptance and can be used in fissured eczemas without causing any sensations of stinging or smarting.
Functions of AP1 (Fos/Jun) in bone development
Authors: E F Wagner
Journal: Annals of the Rheumatic Diseases (2002)

Genetically modified mice and cells have provided important insights into the biological functions of the dimeric transcription factor complex AP1, in particular into its role in skeletal development. Data obtained from knockout mice revealed that some components, such as c-Fos are key regulators of bone cell differentiation, whereas others, like c-Jun, JunB and Fra-1 are essential in embryonic and/or postnatal development. Apart from identifying the specific roles of AP1 proteins in developmental processes, researchers are beginning to obtain a better molecular understanding of their cell-context dependent functions, their downstream target genes and how they regulate bone cell proliferation, differentiation, and apoptosis.
Wide Complex Tachycardia Recorded With a Smartphone Cardiac Rhythm Monitor
Authors: Jonathan W. Waks, Adam S. Fein, Saumya Das
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Lithium Response in Unipolar Versus Bipolar Depression
Authors: FREDERICK K. GOODWIN, DENNIS L. MURPHY, DAVID L. DUNNER, WILLIAM E. BUNNEY
Journal: American Journal of Psychiatry (1972)

The antidepressant effects of lithium carbonate were evaluated in a group of 52 hospitalized depressed patients, using a longitudinal double-blind design that involved alternating drug and placebo periods in the same patient. Thirty-six of the 52 patients showed some improvement on lithium, including 15 who had complete remission of symptoms. Virtually all of the antidepressant responses occurred in patients with a past history of mania or hypomania (the bipolar group).
Comorbidity of Severe Psychotic Disorders With Measures of Substance Use
Authors: Sarah M. Hartz, Carlos N. Pato, Helena Medeiros, Patricia Cavazos-Rehg, Janet L. Sobell, James A. Knowles, Laura J. Bierut, Michele T. Pato
Journal: JAMA Psychiatry (2014)

Although early mortality in severe psychiatric illness is linked to smoking and alcohol, to our knowledge, no studies have comprehensively characterized substance use behavior in severe psychotic illness. In particular, recent assessments of substance use in individuals with mental illness are based on population surveys that do not include individuals with severe psychotic illness.To compare substance use in individuals with severe psychotic illness with substance use in the general population.We assessed comorbidity between substance use and severe psychotic disorders in the Genomic Psychiatry Cohort. The Genomic Psychiatry Cohort is a clinically assessed, multiethnic sample consisting of 9142 individuals with the diagnosis of schizophrenia, bipolar disorder with psychotic features, or schizoaffective disorder, and 10,195 population control individuals.Smoking (smoked >100 cigarettes in a lifetime), heavy alcohol use (>4 drinks/day), heavy marijuana use (>21 times of marijuana use/year), and recreational drug use.Relative to the general population, individuals with severe psychotic disorders have increased risks for smoking (odds ratio, 4.6; 95% CI, 4.3-4.9), heavy alcohol use (odds ratio, 4.0; 95% CI, 3.6-4.4), heavy marijuana use (odds ratio, 3.5; 95% CI, 3.2-3.7), and recreational drug use (odds ratio, 4.6; 95% CI, 4.3-5.0). All races/ethnicities (African American, Asian, European American, and Hispanic) and both sexes have greatly elevated risks for smoking and alcohol, marijuana, and drug use. Of specific concern, recent public health efforts that have successfully decreased smoking among individuals younger than age 30 years appear to have been ineffective among individuals with severe psychotic illness (interaction effect between age and severe mental illness on smoking initiation, P = 4.5 × 105).In the largest assessment of substance use among individuals with severe psychotic illness to date, we found the odds of smoking and alcohol and other substance use to be dramatically higher than recent estimates of substance use in mild mental illness.
Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia
Authors: Rongqing Pan, Leah J. Hogdal, Juliana M. Benito, Donna Bucci, Lina Han, Gautam Borthakur, Jorge Cortes, Daniel J. DeAngelo, LaKeisha Debose, Hong Mu, Hartmut Döhner, Verena I. Gaidzik, Ilene Galinsky, Leonard S. Golfman, Torsten Haferlach, Karine G. Harutyunyan, Jianhua Hu, Joel D. Leverson, Guido Marcucci, Markus Müschen, Rachel Newman, Eugene Park, Peter P. Ruvolo, Vivian Ruvolo, Jeremy Ryan, Sonja Schindela, Patrick Zweidler-McKay, Richard M. Stone, Hagop Kantarjian, Michael Andreeff, Marina Konopleva, Anthony G. Letai
Journal: Cancer Discovery (2013)

Abstract B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here, we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nmol/L, and cell death occurred within 2 hours. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia, a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on-target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML. Significance: Although targeting BCL-2 has largely been investigated in lymphoid cancers, we present preclinical results of targeting BCL-2 in AML. These results support clinical testing of the small-molecule BCL-2 antagonist ABT-199 in AML, accompanied by testing of predictive biomarkers used in this study. Cancer Discov; 4(3); 362–75. ©2013 AACR. See related commentary by Hockenbery, p. 278 This article is highlighted in the In This Issue feature, p. 259
A Three-Gene Model to Robustly Identify Breast Cancer Molecular Subtypes
Authors: Benjamin Haibe-Kains, Christine Desmedt, Sherene Loi, Aedin C. Culhane, Gianluca Bontempi, John Quackenbush, Christos Sotiriou
Journal: JNCI Journal of the National Cancer Institute (2012)

Single sample predictors (SSPs) and Subtype classification models (SCMs) are gene expression–based classifiers used to identify the four primary molecular subtypes of breast cancer (basal-like, HER2-enriched, luminal A, and luminal B). SSPs use hierarchical clustering, followed by nearest centroid classification, based on large sets of tumor-intrinsic genes. SCMs use a mixture of Gaussian distributions based on sets of genes with expression specifically correlated with three key breast cancer genes (estrogen receptor [ER], HER2, and aurora kinase A [AURKA]). The aim of this study was to compare the robustness, classification concordance, and prognostic value of these classifiers with those of a simplified three-gene SCM in a large compendium of microarray datasets. Thirty-six publicly available breast cancer datasets (n = 5715) were subjected to molecular subtyping using five published classifiers (three SSPs and two SCMs) and SCMGENE, the new three-gene (ER, HER2, and AURKA) SCM. We used the prediction strength statistic to estimate robustness of the classification models, defined as the capacity of a classifier to assign the same tumors to the same subtypes independently of the dataset used to fit it. We used Cohen κ and Cramer V coefficients to assess concordance between the subtype classifiers and association with clinical variables, respectively. We used Kaplan–Meier survival curves and cross-validated partial likelihood to compare prognostic value of the resulting classifications. All statistical tests were two-sided. SCMs were statistically significantly more robust than SSPs, with SCMGENE being the most robust because of its simplicity. SCMGENE was statistically significantly concordant with published SCMs (κ = 0.65–0.70) and SSPs (κ = 0.34–0.59), statistically significantly associated with ER (V = 0.64), HER2 (V = 0.52) status, and histological grade (V = 0.55), and yielded similar strong prognostic value. Our results suggest that adequate classification of the major and clinically relevant molecular subtypes of breast cancer can be robustly achieved with quantitative measurements of three key genes.
Nicotinamide Adenine Dinucleotide (Phosphate) Reduced:Quinone Oxidoreductase and Glutathione S-Transferase M1 Polymorphisms and Childhood Asthma
Authors: Gloria L. David, Isabelle Romieu, Juan Jose Sienra-Monge, William J. Collins, Matiana Ramirez-Aguilar, Blanca Estela del Rio-Navarro, Norma Isabel Reyes-Ruiz, Richard W. Morris, Jacqueline M. Marzec, Stephanie J. London
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) M1 are phase II enzymes important in response to oxidative stress, such as occurs during exposure to ozone. We examined the relationship between functionally significant polymorphisms in NQO1 (Pro187Ser) and GSTM1 (homozygous deletion) and asthma risk in children with high lifetime exposure to ozone. We enrolled children with asthma from the allergy referral clinic at a public pediatric hospital in Mexico City, together with their parents. We assayed for the Pro187Ser polymorphism in NQO1 using a polymerase chain reaction–restriction fragment length polymorphism assay and for the presence of GSTM1 by polymerase chain reaction among 218 case–parent triads. We did not find strong evidence of an association between NQO1 genotype alone and asthma risk. However, among subjects with homozygous deletion of GSTM1, carriers of a serine allele were at significantly reduced risk of asthma compared with Pro/Pro homozygotes (relative risk = 0.4; 95% confidence interval, 0.2–0.8). The p value for difference in relative risk for NQO1 by GSTM1 genotype = 0.013. These data are consistent with a protective effect of the NQO1 Ser allele in this population of GSTM1-null children with high ozone exposure.
Comparative Genomic Analysis of Fruiting Body Formation in Myxococcales
Authors: S. Huntley, N. Hamann, S. Wegener-Feldbrugge, A. Treuner-Lange, M. Kube, R. Reinhardt, S. Klages, R. Muller, C. M. Ronning, W. C. Nierman, L. Sogaard-Andersen
Journal: Molecular Biology and Evolution (2010)

Genetic programs underlying multicellular morphogenesis and cellular differentiation are most often associated with eukaryotic organisms, but examples also exist in bacteria such as the formation of multicellular, spore-filled fruiting bodies in the order Myxococcales. Most members of the Myxococcales undergo a multicellular developmental program culminating in the formation of spore-filled fruiting bodies in response to starvation. To gain insight into the evolutionary history of fruiting body formation in Myxococcales, we performed a comparative analysis of the genomes and transcriptomes of five Myxococcales species, four of these undergo fruiting body formation (Myxococcus xanthus, Stigmatella aurantiaca, Sorangium cellulosum, and Haliangium ochraceum) and one does not (Anaeromyxobacter dehalogenans). Our analyses show that a set of 95 known M. xanthus development-specific genes—although suffering from a sampling bias—are overrepresented and occur more frequently than an average M. xanthus gene in S. aurantiaca, whereas they occur at the same frequency as an average M. xanthus gene in S. cellulosum and in H. ochraceum and are underrepresented in A. dehalogenans. Moreover, genes for entire signal transduction pathways important for fruiting body formation in M. xanthus are conserved in S. aurantiaca, whereas only a minority of these genes are conserved in A. dehalogenans, S. cellulosum, and H. ochraceum. Likewise, global gene expression profiling of developmentally regulated genes showed that genes that upregulated during development in M. xanthus are overrepresented in S. aurantiaca and slightly underrepresented in A. dehalogenans, S. cellulosum, and H. ochraceum. These comparative analyses strongly indicate that the genetic programs for fruiting body formation in M. xanthus and S. aurantiaca are highly similar and significantly different from the genetic program directing fruiting body formation in S. cellulosum and H. ochraceum. Thus, our analyses reveal an unexpected level of plasticity in the genetic programs for fruiting body formation in the Myxococcales and strongly suggest that the genetic program underlying fruiting body formation in different Myxococcales is not conserved. The evolutionary implications of this finding are discussed.
The Influence of Blood on In Vivo Adenovirus Bio-distribution and Transduction
Authors: Andrew H Baker, John H Mcvey, Simon N Waddington, Nelson C Di Paolo, Dmitry M Shayakhmetov
Journal: Molecular Therapy (2007)

Intravascular delivery of adenovirus (Ad) vectors is being developed for liver-directed gene therapy for targeting disseminated disease in cancer therapeutics and for targeting non-hepatic tissues and organs through vector engineering strategies. The utility of Ad vectors is not limited to serotype 5 (Ad5), and many alternate human serotypes and non-human serotypes of Ad are currently being investigated. Critical to intravascular delivery of Ad is the interaction of the virus with host blood cells and plasma proteins, because immediate contact is observed following injection. Although incompletely understood, recent studies suggest that these interactions are critical in dictating the particle bio-distribution and resulting transduction properties of Ad in vivo. For example, plasma proteins-in particular, vitamin K-dependent coagulation zymogens-are able to directly bind to Ad, and "bridge" the virus to receptors in the liver. Unraveling and characterizing these mechanisms will be of fundamental importance both for understanding basic Ad biology in vivo and for refinement and optimization of Ad vectors for human gene therapy.
Reducing Heart Rate of the Dog by Electrical Stimulation
Authors: JOSE F. LOPEZ, ARYEH EDELIST, LOUIS N. KATZ, Eugene Boyd
Journal: Circulation Research (1964)

1) The frequency of effective ventricular contractions could be reduced by almost 50% in dogs by stimulating the ventricles (or atria) with electrical impulses of long duration (2 volts, 200 to 350 msec). 2) A similar result was obtained when pairs of impulses (2 volts), each 3 msec in duration, were used, with the time interval between the two impulses of the pair similar to that between the make and break of the long impulses (noted above). 3) The dogs were under general anesthesia and positive pressure breathing was maintained. After thoracotomy, platinum electrodes were implanted in the epicardial surface of the right ventricle or atrium. Pressures were measured in all heart chambers and the unipolar electrocardiogram was recorded from the right atrium with a catheter electrode. Several frequencies of stimulation, below the inherent sinus rate, were tested and at each frequency the time interval between pairs of stimuli was progressively increased from 100 to 350 msec. 4) In all dogs reduction of the frequency of the effective ventricular contractions could be obtained with pairs of stimuli 200 and 350 msec apart. Only the make of the long impulse or the first of the pair of short impulses produced an effective ventricular contraction, while the break of the long impulse or the second short impulse stimulated the ventricles so early in the cycle that no effective mechanical contraction followed. However, the refractory period produced by the break prevented the sinus impulse from reaching the ventricles. The several mechanisms involved are discussed. 5) In one dog the reduction of the frequency of the effective ventricular contractions could be maintained during the 24 hours of survival. 6) The method was applied to a patient being treated for Stokes-Adams attacks. Right atrial stimulation produced a noticeable reduction in ventricular frequency. This involved a reduction in the frequency of electrical responses of the ventricles as well, ensuring a reduction of the per minute energy cost and oxygen consumption of the heart. Such a reduction of the frequency of electrical responses of the ventricles could not be accomplished, so far, in the dog by atrial stimulation. 7) Reduction of the frequency of effective ventricular responses was obtained in one dog with induced atrial flutter and in another with a pacemaker induced "parasystolic" ventricular tachycardia by employing an artificial ventricular pacemaker similar to that used with sinus rhythm. 8) The significance of the findings is discussed. This experimental approach suggests a possible method of slowing the heart rate in clinical cases of ventricular or atrial tachycardia refractory to other methods of treatment. 9) Finally, this approach offers a means of studying certain properties of the heart in the dog which may give insight into the mechanisms involved in some of the more complex arrhythmias encountered in man.
New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition
Authors: R Chaligné, C Tonetti, R Besancenot, L Roy, C Marty, P Mossuz, J-J Kiladjian, G Socié, D Bordessoule, M-C Le Bousse-Kerdilès, W Vainchenker, S Giraudier
Journal: Leukemia (2008)
Growth Inhibition of Multiple Myeloma Cells by a Novel IκB Kinase Inhibitor
Authors: Takaomi Sanda, Shinsuke Iida, Hiroka Ogura, Kaori Asamitsu, Toshiki Murata, Kevin B. Bacon, Ryuzo Ueda, Takashi Okamoto
Journal: Clinical Cancer Research (2005)

Abstract Involvement of nuclear factor-κB (NF-κB) in cell survival and proliferation of multiple myeloma has been well established. In this study we observed that NF-κB is constitutively activated in all human myeloma cell lines, thus confirming the previous studies. In addition, we found the phosphorylation of p65 subunit of NF-κB in addition to the phosphorylation of IκBα and the activation of NF-κB DNA binding and that various target genes of NF-κB including bcl-xL, XIAP, c-IAP1, cyclin D1, and IL-6 are up-regulated. We then examined the effect of a novel IκB kinase inhibitor, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile (ACHP). When myeloma cells were treated with ACHP, the cell growth was efficiently inhibited with IC50 values ranging from 18 to 35 μmol/L concomitantly with inhibition of the phosphorylation of IκBα/p65 and NF-κB DNA-binding, down-regulation of the NF-κB target genes, and induction of apoptosis. In addition, we observed the treatment of ACHP augmented the cytotoxic effects of vincristine and melphalan (l-phenylalanine mustard), conventional antimyeloma drugs. These findings indicate that IκB kinase inhibitors such as ACHP can sensitize myeloma cells to the cytotoxic effects of chemotherapeutic agents by blocking the antiapoptotic nature of myeloma cells endowed by the constitutive activation of NF-κB.