tbuckley/cabot-search huggingface dataset:
Phosphorylation of the Mutant K303R Estrogen Receptor α at Serine 305 Impacts Aromatase Inhibitor Sensitivity.
Authors: I. Barone, A. Beyer, K. Covington, A. Tsimelzon, S. Ando', S. Fuqua
Journal: Cancer Research (2009)

Abstract Aromatase inhibitors (AIs) are challenging tamoxifen as the treatment of choice for both early and advanced breast cancer in postmenopausal women with estrogen receptor (ER) α-positive diseases. However, resistance frequently occurs. Previously, we identified a lysine to arginine transition at residue 303 (K303R) in ERα in premalignant breast lesions and invasive breast cancers, which confers estrogen hypersensitivity and resistance to the AI Anastrozole (Ana) when transfected in MCF-7 breast cancer cells. To identify genes whose expression was associated with the development of aromatase inhibitor resistance (AIR), we performed microarray analysis, and found a marked increase in the gene expression of different IGF family members in the mutant cells. Immunoblot analysis also revealed elevated constitutive phosphorylation of the IGF-1R/IRS-1/Akt pathway in K303R-expressing cells. Treatment with IGF-1R and Akt inhibitors drastically inhibited proliferation of the K303R-mutant expressing cells, while wild-type ERα-expressing clones showed little reduction of growth by these inhibitors, confirming the increased IGF signaling activation in the mutant cells.Post-translational modifications of ERα, such as phosphorylation, tightly regulate its function, and the K303R mutation resides at a major post-translational modification site, serine (S) residue 305. We found that the mutant was more efficiently phosphorylated than the WT receptor by Akt in vitro, and that the mutant cells exhibited enhanced S305 phosphorylation in vivo. Mutation of S305 to alanine (A) to destroy this phosphorylation site prevented in vitro and in vivo Akt-mediated phosphorylation.The ERα S305 residue is an important site that modifies response to tamoxifen; thus, we questioned whether the S305 site could also influence AI response. To address the role of S305 phosphorylation on AIR, we generated pools of stable transfectants expressing exogenous WT, K303R, or K303R/S305A mutant receptors, and then evaluated for the effects of Ana in soft agar assays. Expression of the K303R/S305A mutant resulted in a significant reduction in the basal non-stimulated growth and sensitivity to Ana compared to K303R ERα-expressing pools, thus mimicking the same response profile of wild-type ERα clones. A selective blocking peptide (S305 peptide, residues 298-308) able to antagonize this phosphorylation reversed AIR. Blockade of S305 phosphorylation also resulted in a specific inhibition of IGF-1R/IRS-1/Akt activation, but only in the mutant cells.Our data suggest that the K303/S305 residues of the ERα mutation may be a novel determinant of aromatase inhibitor response in breast cancer, and blockade of S305 ERα phosphorylation represents a new therapeutic strategy to overcome resistance to hormonal therapies in tumors with the ERα mutation. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5053.
SOME STUDIES ON THE NATURALLY OCCURRING LEUCOCYTE AGGLUTININS 12
Authors: John J. Butler
Journal: Journal of Clinical Investigation (1956)

The purpose of this report is to describe some investigations which attempt to define the nature and incidence of naturally occurring leucocyte agglutinins.Agglutinins have been demonstrated in the sera of patients with acquired hemolytic anemia (1) and thrombocytopenic purpura (2, 3) and these have been distinguished from naturally occurring anti-red cell (4) and anti-platelet (5) agglutinins.Leucocyte agglutinins have been demonstrated in various clinical conditions including lupus erythematosus (6), aleukemic leukemia (6), pancyto- penia (6, 7), agranulocytosis due to pyramidon (8) and chronic neutropenia (9).Some have implicated these agglutinins as the causative fac- tors for the leukopenia in these diseases.Goudsmit and van Loghem (6) tested the sera of 100 healthy donors against type 0 white cells.They found weakly positive clumping reactions in 10 instances.Dausset, Nenna, and Brecy (10) studied the sera of 300 normal donors for the presence of agglutinins to compatible leucocyte suspensions and failed to demonstrate any.Daus- set (11) cited some unpublished experiments in collaboration with van Loghem in which combina- tions of 50 normal sera and 50 corresponding va- rieties of white cells were tested for leucocyte ag- glutination.They observed frequent but incon- stant agglutinations in the combinations which were incompatible for the ABO blood groups.Moeschlin and Schmid (12) tested blood samples of 30 persons in 380 leucocyte serum combinations without regard for A, B and 0 blood groups.They noted leucocyte agglutination in 60 cases of
Points: Patient misinformation
Authors: G B Carter
Journal: BMJ (1984)

known inhibitors of the enzyme-for example, isoniazide.Isoniazide interferes with the ALA- synthase coenzyme, pyridoxal phosphate, and, chronically administered, has a potent inhibitory effect on the hepatic enzyme in guinea pigS.2 3 I know of no trial concerning the effect of the drug in acute porphyria, either clinical or experimental.
New Strains of Bacteria and Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Sanjay Sethi, Nancy Evans, Brydon J.B. Grant, Timothy F. Murphy
Journal: New England Journal of Medicine (2002)

The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial. In older studies, the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease. However, these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time. We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease.
Higher Triglycerides, Lower High-Density Lipoprotein Cholesterol, and Higher Systolic Blood Pressure in Lipoprotein Lipase–Deficient Heterozygotes
Authors: Dennis L. Sprecher, Betsy V. Harris, Evan A. Stein, Paul S. Bellet, Leonard M. Keilson, Loretta A. Simbartl
Journal: Circulation (1996)

Background Heterozygous lipoprotein lipase (LPL) deficiency has been associated with familial hypertriglyceridemia and familial combined hyperlipidemia. Studies of heterozygotes with LPL gene defects at amino acid residues 188 and 207 showed higher triglycerides (TG) and lower HDL cholesterol (HDL-C), with no elevation in LDL cholesterol (LDL-C). Other LPL defects may reveal alternate clinical phenotypes. Methods and Results We evaluated three families with defects at amino acid residues 64, 194, and 188. Thirty-eight heterozygotes (8 with defect 64, 14 with defect 194, and 16 with defect 188) and 95 family members without defects were studied. Plasma lipid, lipoprotein, and apolipoprotein (apo) values were measured, as well as blood pressure. Pooled carriers demonstrated higher systolic blood pressure (SBP) (127 versus 116 mm Hg, P &lt;.0001) and TG (160 versus 125 mg/dL, P =.004) and lower HDL-C (44 versus 52 mg/dL, P =.001) than did noncarriers. A comparison of the 188 carriers and noncarriers revealed the most striking phenotypic characteristics, with lower HDL-C (36 versus 51 mg/dL, P &lt;.0001) and HDL-C/(apo A-I + apo A-II) (0.21 versus 0.24, P =.002) and higher TG (206 versus 123 mg/dL, P =.0003), SBP (132 versus 116 mm Hg, P =.0004), and apo B/LDL-C (1.12 versus 0.93, P &lt;.0001). Conclusions These data confirm past observations that LPL deficient heterozygotes trend toward lower HDL-C and higher TG levels while potentially expressing higher SBP. These data also implicate the specific LPL gene defect as a contributing factor to the variable expression of HDL-C, TG, and SBP.
Valaciclovir as a single dose during prodrome of herpes facialis: a pilot randomized double-blind clinical trial
Authors: O. Chosidow, Y. Drouault, R. Garraffo, P. Veyssier
Journal: British Journal of Dermatology (2003)

Journal Article Valaciclovir as a single dose during prodrome of herpes facialis: a pilot randomized double‐blind clinical trial Get access O. Chosidow, O. Chosidow Department of Internal Medicine, Assistance Publique‐Hôpitaux de Paris, Groupe Hospitalier Pitié‐Salpêtrière, Université Paris VI, 47‐83 boulevard de l'Hôpital, 75 651 Paris cedex 13, France O.Chosidow. E‐mail: olivier.chosidow@psl.ap‐hop‐paris.fr Search for other works by this author on: Oxford Academic Google Scholar Y. Drouault, Y. Drouault Department of Dermatology, Hôpital Tarnier‐Cochin, Paris, France Search for other works by this author on: Oxford Academic Google Scholar R. Garraffo, R. Garraffo Department of Pharmacology, Hôpital Pasteur, Nice, France Search for other works by this author on: Oxford Academic Google Scholar P. Veyssier, P. Veyssier Department of Internal Medicine, Centre Hospitalier, Compiègne, France Search for other works by this author on: Oxford Academic Google Scholar For the Valaciclovir Herpes Facialis Study Group For the Valaciclovir Herpes Facialis Study Group Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 1, 1 January 2003, Pages 142–146, https://doi.org/10.1046/j.1365-2133.2003.05062.x Published: 01 January 2003 Article history Accepted: 18 July 2002 Published: 01 January 2003
Fibrinolytic Therapy of Acute Myocardial Infarction
Authors: Jay M. Sullivan
Journal: New England Journal of Medicine (1972)

Half a century after Herrick,1 a disturbing number of basic questions about myocardial infarction remain unanswered. Pending the discovery of methods to prevent atherosclerosis and myocardial infarction or the discovery of widely effective therapy, it appears that we must continue to chip away at the problem. One advance has been the coronary-care unit, where early recognition and treatment of cardiac arrhythmias has reduced mortality by 1/3 as compared to patients managed on general hospital wards. This improvement appears to be limited to deaths from arrhythmia, deaths from congestive heart failure and cardiogenic shock remaining relatively unaffected. A more aggressive approach, . . .
Heart Failure With Recovered Ejection Fraction
Authors: Anupam Basuray, Benjamin French, Bonnie Ky, Esther Vorovich, Caroline Olt, Nancy K. Sweitzer, Thomas P. Cappola, James C. Fang
Journal: Circulation (2014)

Background— We hypothesized that patients with heart failure (HF) who recover left ventricular function (HF-Recovered) have a distinct clinical phenotype, biology, and prognosis compared with patients with HF with reduced ejection fraction (HF-REF) and those with HF with preserved ejection fraction (HF-PEF). Methods and Results— The Penn Heart Failure Study (PHFS) is a prospective cohort of 1821 chronic HF patients recruited from tertiary HF clinics. Participants were divided into 3 categories based on echocardiograms: HF-REF if EF was &lt;50%, HF-PEF if EF was consistently ≥50%, and HF-Recovered if EF on enrollment in PHFS was ≥50% but prior EF was &lt;50%. A significant portion of HF-Recovered patients had an abnormal biomarker profile at baseline, including 44% with detectable troponin I, although in comparison, median levels of brain natriuretic factor, soluble fms-like tyrosine kinase receptor-1, troponin I, and creatinine were greater in HF-REF and HF-PEF patients. In unadjusted Cox models over a maximum follow-up of 8.9 years, the hazard ratio for death, transplantation, or ventricular assist device placement in HF-REF patients was 4.1 (95% confidence interval, 2.4–6.8; P &lt;0.001) and in HF-PEF patients was 2.3 (95% confidence interval, 1.2–4.5; P =0.013) compared with HF-Recovered patients. The unadjusted hazard ratio for cardiac hospitalization in HF-REF patients was 2.0 (95% confidence interval, 1.5–2.7; P &lt;0.001) and in HF-PEF patients was 1.3 (95% confidence interval, 0.90–2.0; P =0.15) compared with HF-Recovered patients. Results were similar in adjusted models. Conclusions— HF-Recovered is associated with a better biomarker profile and event-free survival than HF-REF and HF-PEF. However, these patients still have abnormalities in biomarkers and experience a significant number of HF hospitalizations, suggesting persistent HF risk.
Research on the Fetus
Authors: Lin Richter
Journal: JAMA (1974)

To the Editor.—  The Dykes-Czapek article supporting the right of physicians to do legitimate, humane, and well-planned research on human beings deserves applause. It was a reasonable and mature statement pointing out some of the problems in this area. I was especially pleased to seeThe Journalsupporting our besieged Boston physicians, who are, after all, doing precisely what they should be doing—searching for more scientific, more efficient ways to combat disease.
Hyperparathyroidism Secondary to Vitamin D Deficiency
Authors: MOHAMMED AHMED, ABDULRAOF ALMAHFOUZ, ABDULLAH ALARIFI, TARIQ NASSER, NOURA ALKAHTANI, FOUAD AL DAYEL
Journal: Clinical Nuclear Medicine (2003)

AHMED, MOHAMMED M.D., F.A.C.P., F.A.C.E.*; ALMAHFOUZ, ABDULRAOF*; ALARIFI, ABDULLAH*; NASSER, TARIQ*; ALKAHTANI, NOURA*; AL DAYEL, FOUAD† Author Information
Acquired Hypersensitivity to Sodium P.A.S., Streptomycin, and Penicillin
Authors: B. Jeffery, P. Borrie, N. Macdonald
Journal: BMJ (1952)

STREPTOMYCIN FOR CHRONIC TUBERCULOSISBe 647to his family or colleagues.With this in view, there is considerable scope for chemotherapy in certain types of more chronic patients whose only real disability is an in- fectious sputum, and this series of cases has shown that the sputum can be converted without interfering with the ordinary day's work.Summary Streptomycin and P.A.S. have been used for certain types of patient whose only adverse clinical sign was a positive sputum.Twenty-four patients, in four cate- gories, whose sputum was consistently positive, were treated without interfering with their work or ordinary life.In 23 cases the sputum was converted; in 14 of them it has remained negative up to two years.Five patients have since had an isolated positive sputum, and four have-reverted to positive sputa after being sputum- negative for a period.The value of such results is discussed when applied to the problem of employable chronic patients, so com- monly attending chest clinics.I am grateful to Dr. R. R. Trail and Dr. L. B.
Drug Delivery: pH-Responsive Reversible PEGylation Improves Performance of Antineoplastic Agent (Adv. Healthcare Mater. 6/2015)
Authors: Diankui Sun, Jianxun Ding, Chunsheng Xiao, Jinjin Chen, Xiuli Zhuang, Xuesi Chen
Journal: Advanced Healthcare Materials (2015)

A reversible PEGylated prodrug integrates the advantages of PEGylation and responsiveness. J. Ding and colleagues reveal on page 844 that the prodrug exhibits acid-accelerated drug release, improved cellular internalization and cytotoxicity in vitro, and upregulated intratumoral accumulation, antitumor efficacy, and security in vivo.
Protein biomarkers in vernix with potential to predict the development of atopic eczema in early childhood
Authors: T. Holm, D. Rutishauser, Y. Kai‐Larsen, Y. Lyutvinskiy, F. Stenius, R. A. Zubarev, B. Agerberth, J. Alm, A. Scheynius
Journal: Allergy (2013)

Abstract Background Atopic eczema ( AE ) is a chronic inflammatory skin disease, which has increased in prevalence. Evidence points toward lifestyle as a major risk factor. AE is often the first symptom early in life later followed by food allergy, asthma, and allergic rhinitis. Thus, there is a great need to find early, preferentially noninvasive, biomarkers to identify individuals that are predisposed to AE with the goal to prevent disease development. Objective To investigate whether the protein abundances in vernix can predict later development of AE . Methods Vernix collected at birth from 34 newborns within the Assessment of Lifestyle and Allergic Disease During INfancy ( ALADDIN ) birth cohort was included in the study. At 2 years of age, 18 children had developed AE . Vernix proteins were identified and quantified with liquid chromatography coupled to tandem mass spectrometry. Results We identified and quantified 203 proteins in all vernix samples. An orthogonal projections to latent structures‐discriminant analysis ( OPLS ‐ DA ) model was found with R 2 = 0.85, Q 2 = 0.39, and discrimination power between the AE and healthy group of 73.5%. Polyubiquitin‐C and calmodulin‐like protein 5 showed strong negative correlation to the AE group, with a correlation coefficient of 0.73 and 0.68, respectively, and a P ‐value of 8.2 E‐7 and 1.8 E‐5, respectively. For these two proteins, the OPLS ‐ DA model showed a prediction accuracy of 91.2%. Conclusion The protein abundances in vernix, and particularly that of polyubiquitin‐C and calmodulin‐like protein 5, are promising candidates as biomarkers for the identification of newborns predisposed to develop AE .
Why patients need leaders: introducing a ward safety checklist
Authors: Yogen Amin, Dave Grewcock, Steve Andrews, Aidan Halligan
Journal: Journal of the Royal Society of Medicine (2012)

The safety and consistency of the care given to hospital inpatients has recently become a particular political and public concern. The traditional ‘ward round’ presents an obvious opportunity for systematically and collectively ensuring that proper standards of care are being achieved for individual patients. This paper describes the design and implementation of a ‘ward safety checklist’ that defines a set of potential risk factors that should be checked on a daily basis, and offers multidisciplinary teams a number of prompts for sharing and clarifying information between themselves, and with the patient, during a round. The concept of the checklist and the desire to improve ward rounds were well received in many teams, but the barriers to adoption were informative about the current culture on many inpatient wards. Although the ‘multidisciplinary ward round’ is widely accepted as good practice, the medical and nursing staff in many teams are failing to coordinate their workloads well enough to make multidisciplinary rounds a working reality. ‘Nursing’ and ‘medical’ care on the ward have become ‘de-coupled’ and the potential consequences for patient safety and good communication are largely self-evident. This problem is further complicated by a medical culture which values the primacy of clinical autonomy and as a result can be resistant to perceived attempts to ‘systematize’ medical care through instruments such as checklists.
Lymphocytic infiltrates as a presenting feature of Sweet's syndrome with myelodysplasia and response to cyclophosphamide
Authors: A.V. Evans, R.A. Sabroe, K. Liddell, R. Russell-Jones
Journal: British Journal of Dermatology (2002)

Journal Article Lymphocytic infiltrates as a presenting feature of Sweet's syndrome with myelodysplasia and response to cyclophosphamide Get access A.V. Evans, A.V. Evans St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K Alun V.Evans. E‐mail: alun@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R.A. Sabroe, R.A. Sabroe Greenwich District Hospital, London SE10 9HE, U.K Search for other works by this author on: Oxford Academic Google Scholar K. Liddell, K. Liddell Eastbourne District General Hospital, Eastbourne BN21 2UD, U.K Search for other works by this author on: Oxford Academic Google Scholar R. Russell‐Jones R. Russell‐Jones St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 6, 1 June 2002, Pages 1087–1090, https://doi.org/10.1046/j.1365-2133.2002.04701.x Published: 01 June 2002 Article history Accepted: 22 November 2001 Published: 01 June 2002
Bereavement and Psychiatric Symptoms: an Item Analysis
Authors: R.G. Priest, A.H. Crisp
Journal: Psychotherapy and Psychosomatics (1973)

The Middlesex Hospital Questionnaire (MHQ) is a brief self-rating inventory that is intended to cover the full clinical range of neurotic illness. The subjects selected for investigation were persons aged between 40 and 65 years. It was found that there were few associations between positive responses and bereavement. This was true whether one analyzed all bereavements, bereavements of members of the nuclear family, or bereavement of individual relationships. The last insignificant findings were related to loss of a husband.
Identification of rDNA-Specific Non-LTR Retrotransposons in Cnidaria
Authors: Kenji K. Kojima, Kei-ichi Kuma, Hiroyuki Toh, Haruhiko Fujiwara
Journal: Molecular Biology and Evolution (2006)

Ribosomal RNA genes are abundant repetitive sequences in most eukaryotes. Ribosomal DNA (rDNA) contains many insertions derived from mobile elements including non–long terminal repeat (non-LTR) retrotransposons. R2 is the well-characterized 28S rDNA–specific non-LTR retrotransposon family that is distributed over at least 4 bilaterian phyla. R2 is a large family sharing the same insertion specificity and classified into 4 clades (R2-A, -B, -C, and -D) based on the N-terminal domain structure and the phylogeny. There is no observation of horizontal transfer of R2; therefore, the origin of R2 dates back to before the split between protostomes and deuterostomes. Here, we in silico identified 1 R2 element from the sea anemone Nematostella vectensis and 2 R2-like retrotransposons from the hydrozoan Hydra magnipapillata. R2 from N. vectensis was inserted into the 28S rDNA like other R2, but the R2-like elements from H. magnipapillata were inserted into the specific sequence in the highly conserved region of the 18S rDNA. We designated the Hydra R2–like elements R8. R8 is inserted at 37 bp upstream from R7, another 18S rDNA–specific retrotransposon family. There is no obvious sequence similarity between targets of R2 and R8, probably because they recognize long DNA sequences. Domain structure and phylogeny indicate that R2 from N. vectensis is the member of the R2-D clade, and R8 from H. magnipapillata belongs to the R2-A clade despite its different sequence specificity. These results suggest that R2 had been generated before the split between cnidarians and bilaterians and that R8 is a retrotransposon family that changed its target from the 28S rDNA to the 18S rDNA.
MITOCHONDRIAL NA+/CA2+ EXCHANGER INHIBITION DURING REPERFUSION EXHIBITS POTENTIAL CARDIOPROTECTIVE EFFECT, IN A PORCINE ISCHEMIA-REPERFUSION MODEL
Authors: John Terrovitis, Stefania Sventzouri, Lampros Katsaros, Vasilios Sousonis, Nickolaos Michelinakis, Chris Kapelios, Titika Sfakianaki, Argyrios Ntalianis, Apostolos Papalois, John Nanas
Journal: Journal of the American College of Cardiology (2013)
THE BROAD TAPEWORM IN MINNESOTA, WITH THE REPORT OF A CASE OF INFECTION ACQUIRED IN THE STATE.
Authors: W. S. NICKERSON
Journal: JAMA (1906)

<h3>MINNEAPOLIS.</h3> In the last edition<sup>1</sup>of his text-book Osler says concerning the broad tapeworm of man (<i>Dibothriocephalus latus</i>). "So far as I know it has not been found in the United States except in a few imported cases." Max Braun,<sup>2</sup>in describing the distribution of this species throughout the world, quotes one case as having been reported from North America (Philadelphia). Ward<sup>3</sup>puts it also among the species "recorded from man in N. America, but probably acquired elsewhere." These citations give a fair epitome of the opinion of the best authorities in both medicine and helminthology on the occurrence of this species in America. I believe, however, that in this part of the country, which has a considerable Scandinavian, Finnish, Polish and German population, the worm is very much less rare than is indicated by the opinions quoted. Three cases in Minnesota have come to my knowledge