tbuckley/cabot-search huggingface dataset:
Sex-specific expression of alternative transcripts in Drosophila
Authors: Lauren M McIntyre, Lisa M Bono, Anne Genissel, Rick Westerman, Damion Junk, Marina Telonis-Scott, Larry Harshman, Marta L Wayne, Artyom Kopp, Sergey V Nuzhdin
Journal: Genome biology (2006)

Abstract Background Many genes produce multiple transcripts due to alternative splicing or utilization of alternative transcription initiation/termination sites. This 'transcriptome expansion' is thought to increase phenotypic complexity by allowing a single locus to produce several functionally distinct proteins. However, sex, genetic and developmental variation in the representation of alternative transcripts has never been examined systematically. Here, we describe a genome-wide analysis of sex-specific expression of alternative transcripts in Drosophila melanogaster . Results We compared transcript profiles in males and females from eight Drosophila lines ( OregonR and 2b , and 6 RIL) using a newly designed 60-mer oligonucleotide microarray that allows us to distinguish a large proportion of alternative transcripts. The new microarray incorporates 7,207 oligonucleotides, satisfying stringent binding and specificity criteria that target both the common and the unique regions of 2,768 multi-transcript genes, as well as 12,912 oligonucleotides that target genes with a single known transcript. We estimate that up to 22% of genes that produce multiple transcripts show a sex-specific bias in the representation of alternative transcripts. Sexual dimorphism in overall transcript abundance was evident for 53% of genes. The X chromosome contains a significantly higher proportion of genes with female-biased transcription than the autosomes. However, genes on the X chromosome are no more likely to have a sexual bias in alternative transcript representation than autosomal genes. Conclusion Widespread sex-specific expression of alternative transcripts in Drosophila suggests that a new level of sexual dimorphism at the molecular level exists.
Ron Kinase Transphosphorylation Sustains <i>MET</i> Oncogene Addiction
Authors: Silvia Benvenuti, Luca Lazzari, Addolorata Arnesano, Giulia Li Chiavi, Alessandra Gentile, Paolo M. Comoglio
Journal: Cancer Research (2011)

Receptors for the scatter factors HGF and MSP that are encoded by the MET and RON oncogenes are key players in invasive growth. Receptor cross-talk between Met and Ron occurs. Amplification of the MET oncogene results in kinase activation, deregulated expression of an invasive growth phenotype, and addiction to MET oncogene signaling (i.e., dependency on sustained Met signaling for survival and proliferation). Here we show that cancer cells addicted to MET also display constitutive activation of the Ron kinase. In human cancer cell lines coexpressing the 2 oncogenes, Ron is specifically transphosphorylated by activated Met. In contrast, Ron phosphorylation is not triggered in cells harboring constitutively active kinase receptors other than Met, including Egfr or Her2. Furthermore, Ron phosphorylation is suppressed by Met-specific kinase inhibitors (PHA-665752 or JNJ-38877605). Last, Ron phosphorylation is quenched by reducing cell surface expression of Met proteins by antibody-induced shedding. In MET-addicted cancer cells, short hairpin RNA-mediated silencing of RON expression resulted in decreased proliferation and clonogenic activity in vitro and tumorigenicity in vivo. Our findings establish that oncogene addiction to MET involves Ron transactivation, pointing to Ron kinase as a target for combinatorial cancer therapy.
Intracellular and extracellular sulphydryl levels in rheumatoid arthritis.
Authors: J F Koster, P Biemond, A J Swaak
Journal: Annals of the Rheumatic Diseases (1986)

We detected no difference in the reduced glutathione content of erythrocytes obtained from patients with rheumatoid arthritis (RA) and controls. The stability of glutathione to oxidative stress (cumene hydroperoxide) was also the same. Although measured in the erythrocyte, our results indicate that changes in intracellular reduced glutathione are not involved in the aetiology of RA. Serum from patients with RA had a significantly reduced (p less than 0.01) sulphydryl (SH) concentration (415 +/- 89 (SD) mumol/l) compared with controls (583 +/- 74 mumol/l). This was also valid if the SH groups were expressed per gram of protein. Serum and synovial fluid from RA patients contained similar levels of SH groups (mumol/g protein).
Gestational Diabetes Mellitus Alone in the Absence of Subsequent Diabetes Is Associated With Microalbuminuria
Authors: Andrew S. Bomback, Yelena Rekhtman, Adam T. Whaley-Connell, Abhijit V. Kshirsagar, James R. Sowers, Shu-Cheng Chen, Suying Li, Kavitha M. Chinnaiyan, George L. Bakris, Peter A. McCullough
Journal: Diabetes Care (2010)

Women with gestational diabetes mellitus (GDM) maintain a higher risk for recurrent GDM and overt diabetes. Overt diabetes is a risk factor for development of chronic kidney disease (CKD), but GDM alone, without subsequent development of overt diabetes, may also pose a risk for CKD.This cross-sectional analysis included Kidney Early Evaluation Program (KEEP) participants from 2000 to 2009. Patient characteristics and kidney function among three categories (GDM alone, overt diabetes, and no history of diabetes) were compared. The prevalence of microalbuminuria, macroalbuminuria, and CKD stages 1-2 and 3-5 was assessed using logistic regression.Of 37,716 KEEP female participants, 571 (1.5%) had GDM alone and 12,100 (32.1%) had overt diabetes. Women with GDM had a higher rate of microalbuminuria but not macroalbuminuria than their nondiabetic peers (10.0 vs. 7.7%) that was substantially lower than the 13.6% prevalence in diabetic women. In multivariate analysis, women with GDM alone, compared with nondiabetic women, demonstrated increased odds of CKD stages 1-2 (multivariate odds ratio 1.54 [95% CI 1.16-2.05]) similar to the odds for women with overt diabetes (1.68 [1.55-1.82]). In stratified analyses, age, race, BMI, and hypertension modified the odds for CKD stages 1-2 but not CKD stages 3-5 among women with GDM.Women with GDM alone have a higher prevalence of microalbuminuria than women without any history of diabetes, translating to higher rates of CKD stages 1-2. These results suggest that GDM, even in the absence of subsequent overt diabetes, may increase the risk for future cardiovascular and kidney disease.
Mary Theresa Brennan (née Rahill)
Journal: BMJ (2004)

Former community physician Bury (b Dublin 1927; q Dublin 1952), died from ovarian cancer on 4 April 2004.​2004.




Figure 1




After graduation Mary moved to Manchester, where she completed her preregistration posts at Ancoats Hospital. She then spent one year in anaesthetics at Crumpsall Hospital. After bringing up four children she worked in the emergency department at Bury General Hospital and also in the community. Her devoted family and Catholic faith sustained her during her last short illness. Predeceased by her husband, Tony, she leaves four children and 10 grandchildren.
β-Adrenergic Stimulation Induces Acetylcholine to Activate ATP-Sensitive K <sup>+</sup> Current in Cat Atrial Myocytes
Authors: Yong Gao Wang, Stephen L. Lipsius
Journal: Circulation Research (1995)

Abstract Our previous work on atrial myocytes suggested that the effect of acetylcholine (ACh) to increase K + conductance can be potentiated by prior loading of the sarcoplasmic reticulum (SR) with Ca 2+ . The present study, therefore, sought to determine whether prior exposure to isoproterenol (ISO) potentiates ACh-induced increases in K + conductance and the underlying mechanisms. A nystatin–perforated patch whole-cell configuration was used to record from cat atrial myocytes. Voltage-clamp ramps (40 mV/s) were used to assess total membrane conductance. The experimental protocol consisted of two consecutive 30-second ACh exposures (ACh 1 and ACh 2 ) separated by a 6-minute recovery period in ACh-free solution. In general, experimental interventions, such as exposure to ISO, were imposed during the period between ACh 1 and ACh 2 to determine their effects on the response to ACh 2 in relation to ACh 1 . Under control conditions, K + conductances induced by ACh 1 and ACh 2 were not different from one another with or without activation of L-type Ca 2+ current (I Ca,L ) during the recovery period. When 1 μmol/L ISO plus I Ca,L activation was imposed during the recovery period, ACh 2 induced a significantly larger increase in K + conductance than ACh 1 . The ACh 2 -induced K + current potentiated by ISO was time independent and selectively blocked by 10 μmol/L glibenclamide and therefore identified as ATP-sensitive K + current (I K,ATP ). The effect of ISO to induce ACh 2 -activated I K,ATP was mimicked by 1 μmol/L forskolin or 200 μmol/L 8-(4-chlorophenylthio)-cAMP, but not by 0.5 μmol/L BAY K 8644, and was selectively abolished by (1) 5 μmol/L thapsigargin or 1 μmol/L ryanodine, agents that prevent accumulation of SR Ca 2+ , (2) inhibition of L-type Ca 2+ current (I Ca,L ) by 1 μmol/L nisoldipine or zero external Ca 2+ , (3) 50 μmol/L Rp-cAMPs, an inhibitor of cAMP-dependent protein kinase A, or (4) 2 μmol/L propranolol. Atropine (1 μmol/L) abolished all ACh-induced currents. Moreover, ACh 2 -activated I K,ATP was selectively blocked by 0.2 μmol/L pirenzepine, an M 1 muscarinic receptor antagonist, or 0.1 μmol/L calphostin C, a selective inhibitor of protein kinase C. AFDX116 (100 μmol/L), an M 2 muscarinic receptor antagonist, blocked the conventional ACh-activated K + current and revealed ACh 2 -activated I K,ATP . These results indicate that prior exposure to ISO potentiates ACh-induced increases in K + current via ACh-activated I K,ATP . ISO acts via β-adrenergic receptors and cAMP to enhance both Ca 2+ influx via I Ca,L and SR Ca 2+ uptake. By loading SR Ca 2+ , ISO facilitates ACh-induced stimulation of the M 1 receptor/phosphoinositol signaling pathway to activate I K,ATP . These findings suggest that prior β-adrenergic stimulation accentuates subsequent cholinergic inhibition of atrial function via ACh-induced activation of ATP-sensitive K + channels.
Isolated Valvular Pulmonic Stenosis
Authors: S. GILBERT BLOUNT, MALCOLM C. MCCORD, HELMUT MUELLER, HENRY SWAN
Journal: Circulation (1954)

The preoperative and postoperative clinical and physiologic data are presented in 10 patients with isolated valvular pulmonic stenosis. The valvulotomy was performed in five patients by the generally accepted blind ventricular approach, while in the remaining five patients the valvular surgery was accomplished by a direct pulmonary arterial approach. The physiologic data revealed uniform obliteration of the systolic pressure gradient from the right ventricle to the pulmonary artery in the patients operated by the direct technic in striking contrast to the inadequate and variable relief of stenosis by the transventricular approach.
Point mutation in the beta-spectrin gene associated with alpha I/74 hereditary elliptocytosis. Implications for the mechanism of spectrin dimer self-association.
Authors: W T Tse, M C Lecomte, F F Costa, M Garbarz, C Feo, P Boivin, D Dhermy, B G Forget
Journal: Journal of Clinical Investigation (1990)

alpha I/74 hereditary elliptocytosis (HE) is a subgroup of HE in which patients exhibit an impaired self-association of spectrin dimers and an abnormal proteolytic cleavage of the alpha I domain of spectrin. We studied a family in which the proband presented with a severe neonatal hemolytic anemia with poikilocytosis. Biochemical analysis of erythrocytes from the proband and his family members allowed us to ascertain a diagnosis of homozygosity for alpha I/74 HE in the proband and heterozygosity in his parents and several of their offspring. Results of polymorphism linkage analysis suggested that the defect in this family was located in beta rather than alpha spectrin. We analyzed the 3' end of the beta-spectrin gene of the proband and detected a mutation that changes a codon for alanine to one for proline. Allele-specific oligomer hybridization on slot blots of DNA from other family members confirmed the presence of the mutation only in members heterozygous for the disorder. This is the first example of a point mutation in the beta-spectrin chain that is associated with defective spectrin dimer self-association and an abnormal proteolytic cleavage of the alpha chain. Based on this finding, we propose a model for the mechanism of interaction between the alpha- and beta-spectrin chains.
Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel
Authors: Sima Halevy, Pierre-Dominique Ghislain, Maja Mockenhaupt, Jean-Paul Fagot, Jan Nico Bouwes Bavinck, Alexis Sidoroff, Luigi Naldi, Ariane Dunant, Cecile Viboud, Jean-Claude Roujeau
Journal: Journal of the American Academy of Dermatology (2007)
Soft Tissue Sarcoma and Exposure to Phenoxyherbicides and Chlorophenols in New Zealand&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A H Smith, N E Pearce, D O Fisher, H J Giles, C A Teague, J K Howard
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Soft Tissue Sarcoma and Exposure to Phenoxyherbicides and Chlorophenols in New Zealand Get access Allan H. Smith, Allan H. Smith 5 5Address reprint requests to Dr. Smith at his present address: Department of Biomedical and Environmental Health Sciences, School of Public Health, University of California, Berkeley, Calif. 94720. Search for other works by this author on: Oxford Academic PubMed Google Scholar Neil E. Pearce, Neil E. Pearce Search for other works by this author on: Oxford Academic PubMed Google Scholar David O. Fisher, David O. Fisher Search for other works by this author on: Oxford Academic PubMed Google Scholar Heather J. Giles, Heather J. Giles Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinton A. Teague, Clinton A. Teague Search for other works by this author on: Oxford Academic PubMed Google Scholar James K. Howard James K. Howard Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 73, Issue 5, November 1984, Pages 1111–1117, https://doi.org/10.1093/jnci/73.5.1111 Published: 01 November 1984 Article history Received: 12 June 1984 Accepted: 31 July 1984 Published: 01 November 1984
Thai doctors say they won't treat police who attack demonstrators
Authors: B. Bland
Journal: BMJ (2008)

The Medical Council of Thailand has launched an investigation after a group of doctors at Bangkok’s leading university hospital said they would not treat police officers hurt in violent clashes with antigovernment protestors last week.

The group of around 50 doctors at Chulalongkorn Hospital said that as a protest against the government’s use of violence on demonstrators they would deny treatment to injured police.

But Suthep Kolchanwit, the group’s leader, later apologised for having announced the boycott, insisting that he had not, in practice, denied treatment …
Lung deposition of inhaled 1-proteinase inhibitor in cystic fibrosis and 1-antitrypsin deficiency
Authors: P. Brand, M. Schulte, M. Wencker, C. H. Herpich, G. Klein, K. Hanna, T. Meyer
Journal: European Respiratory Journal (2009)

Individuals with α 1 -antitrypsin (AAT) deficiency and cystic fibrosis (CF) have a protease–antiprotease imbalance in their lungs, which leads to early onset progressive lung disease. Inhalation of AAT may restore protective levels in the lungs. This study aimed to determine the efficiency of delivering AAT using a novel inhalation device in subjects with AAT deficiency and CF compared with healthy subjects. In total, 20 subjects (six healthy, seven with AAT deficiency and seven with CF) inhaled ∼70 mg of radiolabelled active AAT, with controlled breathing patterns adjusted to lung function. Post-inhalation, total and regional lung deposition and extrathoracic deposition of radiolabelled AAT were measured. Total lung deposition of AAT was ∼70% of the filling dose. The magnitude of deposition was similar in all treatment groups, with no adverse effect on lung function or any influence of disease severity on total lung deposition. Inhalation with controlled breathing patterns using the AKITA 2 device (lung function adapted) leads to high total lung deposition regardless of the degree of lung function impairment. Delivery of large amounts of AAT was achieved in a short period of time. This device may be an ideal option for aerosol therapy.
Progressive Attenuation of Myocardial Vascular Endothelial Growth Factor Expression Is a Seminal Event in Diabetic Cardiomyopathy
Authors: Young-sup Yoon, Shigeki Uchida, Osamu Masuo, Manfred Cejna, Jong-Seon Park, Hyeon-cheol Gwon, Rudolf Kirchmair, Ferdinand Bahlman, Dirk Walter, Cynthia Curry, Allison Hanley, Jeffrey M. Isner, Douglas W. Losordo
Journal: Circulation (2005)

Diabetic cardiomyopathy (DCM) is characterized by microvascular pathology and interstitial fibrosis, which leads to progressive heart failure; however, the pathogenesis of DCM remains uncertain.Using the streptozotocin-induced diabetic rat model, we evaluated the natural course of DCM over a period of 1 year by serial echocardiography, Western blot analysis for vascular endothelial growth factor (VEGF), endothelial progenitor cell assays, myocardial blood flow measurements, and histopathologic analysis that included terminal dUTP nick end-labeling (TUNEL), capillary and cardiomyocyte density, and fibrosis area. Downregulation of myocardial VEGF expression preceded all other features of DCM and was followed by increased apoptosis of endothelial cells, decreased numbers of circulating endothelial progenitor cells, decreased capillary density, and impaired myocardial perfusion. Apoptosis and necrosis of cardiomyocytes ensued, along with fibrosis and progressive diastolic and then systolic dysfunction. To provide further evidence of the central role of VEGF in the pathophysiology of DCM, we replenished myocardial VEGF expression using naked DNA gene therapy via direct intramyocardial injection of plasmid DNA encoding VEGF (phVEGF165). VEGF-replenished rats showed increased capillary density, decreased endothelial cell and cardiomyocyte apoptosis, and in situ differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells. These anatomic findings were accompanied by significant improvements in cardiac function.These findings suggest that downregulation of VEGF may compromise microvascular homeostasis in the myocardium and thereby play a central role in the pathogenesis of DCM.
An enantiomer-enantiomer interaction of (S)- and (R)-propafenone modifies the effect of racemic drug therapy.
Authors: H K Kroemer, M F Fromm, K Bühl, H Terefe, G Blaschke, M Eichelbaum
Journal: Circulation (1994)

Therapy with racemic compounds produces effects that can be attributed to both (S)- and (R)-enantiomers. Here we have tested the hypothesis that an enantiomer-enantiomer interaction would modulate the effects of treatment with a racemate, the antiarrhythmic propafenone. Previous studies have shown that while the enantiomers of propafenone exert similar sodium channel-blocking (QRS widening) effects, it is the (S)-enantiomer that produces beta-blockade; moreover, we have demonstrated recently that (R)-propafenone inhibits the metabolism of (S)-propafenone in vitro.This single-blind, randomized study compared the effects of (R/S)-, (S)-, (R)-propafenone (150 mg q 6 hours for 4 days) and placebo on QRS duration (delta QRS) and on maximum exercise heart rate (delta HRmax), an index of beta-blockade. The clearance of (S)-propafenone was significantly lower (-55 +/- 24%, P < .001) during treatment with (R/S)-propafenone than with the (S)-enantiomer alone, and delta HRmax was significantly altered during (R/S)-propafenone (-8.8 +/- 6.6 beats per minute; P < .01) and during (S)-propafenone (-4.3 +/- 4.8 beats per minute; P < .01) but not during (R)-propafenone (-1.8 +/- 6.4 beats per minute) or placebo (0.3 +/- 7.1 beats per minute). In contrast, (R/S)-, (S)-, and (R)-propafenone all prolonged QRS compared with placebo.These data indicate that (R)-propafenone impairs the disposition of (S)-propafenone in humans. As a result, the beta-blocking effects of 150 mg of racemic propafenone (75 mg of the [S]-enantiomer) were more pronounced than those of 150 mg of (S)-propafenone alone. Thus, the effects of racemic drug therapy are not necessarily those predicted by summation of the effects of the individual enantiomers.
Effect of the AutoPulse™ automated band chest compression device on hemodynamics in out-of-hospital cardiac arrest resuscitation
Authors: François-Xavier Duchateau, Papa Gueye, Sonja Curac, Florence Tubach, Claire Broche, Patrick Plaisance, Didier Payen, Jean Mantz, Agnès Ricard-Hibon
Journal: Intensive Care Medicine (2010)
Effect of Diet and Lactobacillus acidophilus Supplements on Human Fecal Bacterial Enzymes23
Authors: Barry R. Goldin, Linda Swenson, Johanna Dwyer, Margaret Sexton, Sherwood L. Gorbach
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Effect of Diet and Lactobacillus acidophilus Supplements on Human Fecal Bacterial Enzymes Get access Barry R. Goldin, Ph.D., Barry R. Goldin, Ph.D. 4Department of Medicine, Infectious Disease Service, New England Medical Center Hospital and Tufts University School of Medicine, 171 Harrison Ave., Boston, Mass. 02111. Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda Swenson, M.S., Linda Swenson, M.S. 5Frances Stern Nutrition Center, New England Medical Center Hospital. Search for other works by this author on: Oxford Academic PubMed Google Scholar Johanna Dwyer, D.Sc., Johanna Dwyer, D.Sc. 5Frances Stern Nutrition Center, New England Medical Center Hospital. 6Recipient of PHS Career Development Award K04-AM00272 from the National Institute of Arthritis, Metabolism, and Digestive Diseases. Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret Sexton, M.S., Margaret Sexton, M.S. 5Frances Stern Nutrition Center, New England Medical Center Hospital. 7Present address: Nutritionist Health Maintenance Unit, 530 N. Main St., Providence, R.I. 02904. Search for other works by this author on: Oxford Academic PubMed Google Scholar Sherwood L. Gorbach, M.D. Sherwood L. Gorbach, M.D. 4Department of Medicine, Infectious Disease Service, New England Medical Center Hospital and Tufts University School of Medicine, 171 Harrison Ave., Boston, Mass. 02111. 8We acknowledge the excellent technical assistance of Mr. Wayne Gordon and Ms. Eugenie Boutin. We also thank Dr. R. Ernst Clarke and Mrs. Marion Wu-Lee for their statistical analysis of these data. We are grateful to Mr. Kovacks, President of Vitamins, Inc., for supplying the bran supplements used in this study. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 2, February 1980, Pages 255–261, https://doi.org/10.1093/jnci/64.2.255 Published: 01 February 1980 Article history Received: 16 February 1979 Accepted: 23 July 1979 Published: 01 February 1980