tbuckley/cabot-search huggingface dataset:
The High-Mobility Group A1 Gene Up-Regulates Cyclooxygenase 2 Expression in Uterine Tumorigenesis
Authors: Abeba Tesfaye, Francescopaolo Di Cello, Joelle Hillion, Brigitte M. Ronnett, Ossama Elbahloul, Raheela Ashfaq, Surajit Dhara, Edward Prochownik, Kathryn Tworkoski, Raymond Reeves, Richard Roden, Lora Hedrick Ellenson, David L. Huso, Linda M. S. Resar
Journal: Cancer Research (2007)

Abstract Uterine cancer is the most common cancer of the female genital tract and is the fourth most frequent cause of cancer death in women in the U.S. Despite the high prevalence of uterine cancers, the molecular events that lead to neoplastic transformation in the uterus are poorly understood. Moreover, there are limited mouse models to study these malignancies. We generated transgenic mice with high-mobility group A1 gene (HMGA1a) expression targeted to uterine tissue and all female mice developed tumors by 9 months of age. Histopathologically, the tumors resemble human uterine adenosarcoma and are transplantable. To determine whether these findings are relevant to human disease, we evaluated primary human uterine neoplasms and found that HMGA1a mRNA and protein levels are increased in most high-grade neoplasms but not in normal uterine tissue, benign tumors, or most low-grade neoplasms. We also found that HMGA1a up-regulates cyclooxygenase 2 (COX-2) expression in transgenic tumors. Moreover, both HMGA1a and COX-2 expression are up-regulated in high-grade human leiomyosarcomas. Using chromatin immunoprecipitation, HMGA1a binds directly to the COX-2 promoter in human uterine cancer cells in vivo and activates its expression in transfection experiments. We also show that blocking either HMGA1a or COX-2 in high-grade human uterine cancer cells blocks anchorage-independent cell growth in methylcellulose. These findings show that HMGA1a functions as an oncogene when overexpressed in the uterus and contributes to the pathogenesis of human uterine cancer by activating COX-2 expression. Although a larger study is needed to confirm these results, HMGA1a may be a useful marker for aggressive human uterine cancers. [Cancer Res 2007;67(9):3998–4004]
Serum Digoxin and Thyroid Hormones
Authors: T. P. NIELSEN
Journal: Annals of Internal Medicine (1974)

Comments1 July 1974Serum Digoxin and Thyroid HormonesT. P. NIELSEN, M.A., R. E. BODFISH, M.D., F.A.C.P., A. KABOK, M.D.T. P. NIELSEN, M.A.Search for more papers by this author, R. E. BODFISH, M.D., F.A.C.P.Search for more papers by this author, A. KABOK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-1-126 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The article, "Digoxin Metabolism in Hypoand Hyperthyroidism. Studies with Tritiated Digoxin," by Doherty and Perkins (Ann Intern Med 64:489-507, 1966) reported that hyperthyroid subjects have lower serum digoxin levels and hypothyroid subjects have higher levels than euthyroid subjects.With the development of radioimmunoassays for blood levels of the thyroid hormones and digoxin, relations between these hormones and digoxin may be examined in eumetabolic men; we have done this in 30 male hospitalized patients.Patients were admitted to this study if they: [1] had heart failure compensated by maintenance digoxin; [2] had received daily doses of 0.25 mg...References1. HOGANRILEY EW: Radioimmunoassay of plasma digoxin, with use of iodinated tracer. Clin Chem 19:187-190, 1973 CrossrefMedlineGoogle Scholar2. CHOPRAHOLAM IRR: An improved radioimmunoassay of triiodothyronine in serum: its application to clinical and physiological studies. J Lab Clin Med 80:729-739, 1972 MedlineGoogle Scholar3. CHOPRA I: A radioimmunoassay for measurement of thyroxine in unextracted sera. J Clin Endocrinol Metab 34:938-947, 1972 CrossrefMedlineGoogle Scholar4. MURPHYPATTEE BC: Determination of thyroxine utilizing the property of protein binding. J Clin Endocrinol Metab 24:187-196, 1964 CrossrefMedlineGoogle Scholar5. SCHWARTZSURKSOPPENHEIMER HMJ: Quantitation of extrathyroidal conversion of L-thyroxine to 3,5,3'-triiodo-L-thyronine in the rat. J Clin Invest 50:1124-1130, 1971 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Nuclear Medicine Service and Medical Research Programs Veterans Administration Hospital Long Beach, California University of Southern California School of Medicine Los Angeles, California Rancho Los Amigos Hospital Downey, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAmiodarone-Associated Hypothyroidism — A Possible Cause of Digoxin IntoxicationThyroid Hormone Effects on the HeartÄnderung der Glykosidtoleranz durch hormonelle FaktorenThe Kinetics of Propylthiouracil in Hyperthyroidism 1 July 1974Volume 81, Issue 1Page: 126-127KeywordsBloodHeart failureHyperthyroidismLongitudinal studiesRadioimmunoassaysThyroid hormones Issue Published: 1 July 1974 PDF downloadLoading ...
S31 Variation at GLCCI1: Association with Increased Steroid Dose But Not Adrenal Suppression in Asthmatic Children
Authors: B Thompson, DB Hawcutt, DF Carr, AL Jorgensen, RL Smyth, M Pirmohamed
Journal: Thorax (2012)

<h3>Introduction</h3> Corticosteroids are the main stay of preventative therapy for asthma-related symptoms. There is a wide range of inter-patient variability both in terms of response to therapy, and suppression of the HPA axis leading to potentially fatal adrenal suppression. A recently undertaken GWAS identified the GLCCI1 variant rs37973 as a biomarker for corticosteroid efficacy using FEV<sub>1</sub> response as the outcome measure. The aim of this study was two-fold: (a) to replicate the association with corticosteroid efficacy (using steroid dose and an increase in asthma exacerbations as surrogate measures) and (b) to determine whether the same variant is associated with adrenal suppression in asthmatic patients on inhaled corticosteroids. <h3>Methods</h3> The study included data on 402 asthmatic children (age 5–18yrs), who were recruited to the Pharmacogenetics of Adrenal Suppression with inhaled Steroids (PASS) study, all of whom were on long term corticosteroid therapy (&gt;6 months), and had a clinically indicated low dose short Synacthen test (LDSST). Detailed history of their medication use and exacerbations were recorded for the 6 months prior to LDSST. Regression models, adjusted for significant clinical factors, were used to test for association between the SNP and each outcome. <h3>Results</h3> The rs37973 variant was associated with an increase in prescribed total inhaled/intranasal corticosteroid doses both before and after adjustment for body surface area. This association was significant when assuming both an additive mode of inheritance (p-value=0.020 for BSA adjusted total) as previously reported, and a recessive model (p-value =0.006 for BSA adjusted total). The variant was also associated with increased hospital admissions over the 6 month period (OR 2.16, 95% CI:1.10–4.33 when comparing homozygous states). There was no association with adrenal suppression (baseline or peak) or the number of rescue oral steroid courses. <h3>Conclusion</h3> In the first replication study in a European population, we have shown that the rs37973 SNP is associated with increased corticosteroid dose and an increase in asthma-related hospital admissions, further supporting the evidence that GLCCI1 is a determinant of steroid efficacy in asthma. However, this SNP was not associated with steroid-induced adrenal suppression, divorcing efficacy from toxicity, at least with respect to this gene.
Screening for T-Groups: The Myth of Healthy Candidates
Authors: WALTER N. STONE, MURRAY E. TIEGER
Journal: American Journal of Psychiatry (1971)

The authors screened 105 applicants for attendance at a week-long T-group conducted by nonprofessionals. The psychological evaluation and screening procedures included a written application, psychological tests, and a small group experience. Fifteen applicants were not permitted to attend the T-group; six additional applicants chose not to attend. The authors describe the diagnostic groupings of those who were rejected and present vignettes of several applicants. They also discuss the need for screening procedures for any group experience and the current lack of established guidelines for such screening.
THE 15-MINUTE HOUR: BRIEF THERAPY IN A MILITARY SETTING
Authors: HARVEY H. BARTEN
Journal: American Journal of Psychiatry (1965)

The usefulness of very brief psychiatric appointments in treating many different kinds of patients is reported. It is suggested that the 15-minute interview is entirely sufficient for many patients who are relatively poor candidates for exploratory psychotherapy. Moreover, it is also an acceptable though limited alternative for some of the patients who ideally would receive more lengthy treatment. A few mornings of 15-minute appointments enable the psychiatrist to expand his practice considerably, while still preserving the great majority of his time for other, more exhaustive psychotherapeutic techniques.
THE ASSOCIATION OF PYLOROSPASM AND THYMIC ENLARGEMENT IN CHILDREN
Authors: MITCHELL I. RUBIN
Journal: JAMA (1928)

Recently my attention was called to the fact that, following the taking of a series of roentgenograms in cases of vomiting with suspected pyloric stenosis, the vomiting frequently stopped. This, and the fact that in these cases of vomiting there was frequently a history of disturbances of respiration, led me to investigate the relation of vomiting to the disturbances of respiration and to the result of roentgen-ray exposure. The type of disturbances of respiration complained of in these patients consisted of attacks of breath holding and cyanosis. These attacks of breath holding are not to be confused with those usually seen in children during the second year of life, since they were not in relation to crying or temper tantrums but came on without apparent cause. This type of disturbance of respiration has frequently been considered by many observers as evidence of an enlarged thymus. With this in mind, chest
Massive pulmonary haemorrhage in the newborn associated with Coxsackie B virus infection.
Authors: R. Hurley, A. P. Norman, J. Pryse-Davies
Journal: BMJ (1969)

BRITISHand Mukherjee (1968), it may further have a teratogenic effect, which is also indicated from animal studies by Alexander et al. (1967), Auerbach and Rugowski (1967), and Geber (1967).A comparatively low frequency of chromosome abnormalities, such as gaps and breaks, may have no deleterious effect on the organism or on the offspring.On the other hand, a higher frequency of breaks with fragments, dicentric chromosomes, ring chromosomes, translocations, and aneuploid cells may be associated with mutations and probably predispose to malignant disorders and an increased risk of abortions, chromosome abnormalities, and congenital abnormalities in the offspring.If certain drugs induce quite extensive chromosome abnor- malities like perphenazine and lysergide, and if other drugs with a similar therapeutic effect have a considerably less toxic effect on chromosomes, then it would seem advisable not to use the more toxic drugs until further studies concerning the risks of such toxic chromosome abnormalities as found in patients treated with lysergide and perphenazine have been made.
Psychological Factors and the Relationship between Perceptual Style and Pain Tolerance
Authors: R. Adler, F. Lomazzi
Journal: Psychotherapy and Psychosomatics (1973)

Among many other factors, an individual's perceptual style is said to contribute to his Pain Tolerance (1, 2). Our study aimed at confirming the positive correlation (2) between Perceptual Style and Pain Tolerance, Perception being assessed by means of measuring a subject's Field-Orientation with the Embedded Figures Test (3) and Pain being inducted by the Submaximum Effort Tourniquet Technique (4), a modified ischaemic muscle pain test. The expected positive correlation between Field-Orientation and Pain Tolerance was designated Hypothesis A.
Managing urinary tract infection.
Authors: R R Bailey
Journal: BMJ (1993)

was also considerably less, with 37 of 40 (93%) patients having no postoperative discomfort and being able to return to school soon after surgery compared with 16 of 35 (46%) who were circum- cised.Twenty eight of 40 responding parents whose son had had preputial plasty thought that the final appearance of their son's penis was normal.Only two patients were unable to retract their foreskins, and in both there had been no effort at early mobilisation.Preputial plasty is a well recognised procedure in Europe,4 and we think that it is a reliable option for selected patients with tight but unscarred and uninfected foreskins.It certainly enables many more foreskins to be saved.
The nutritional management of hepatic encephalopathy in patients with cirrhosis: International society for hepatic encephalopathy and nitrogen metabolism consensus
Authors: Piero Amodio, Chantal Bemeur, Roger Butterworth, Juan Cordoba, Akinobu Kato, Sara Montagnese, Misael Uribe, Hendrik Vilstrup, Marsha Y. Morgan
Journal: Hepatology (2013)

Abstract Nitrogen metabolism plays a major role in the development of hepatic encephalopathy (HE) in patients with cirrhosis. Modulation of this relationship is key to the management of HE, but is not the only nutritional issue that needs to be addressed. The assessment of nutritional status in patients with cirrhosis is problematic. In addition, there are significant sex-related differences in body composition and in the characteristics of tissue loss, which limit the usefulness of techniques based on measures of muscle mass and function in women. Techniques that combine subjective and objective variables provide reasonably accurate information and are recommended. Energy and nitrogen requirements in patients with HE are unlikely to differ substantially from those recommended in patients with cirrhosis per se viz. 35-45 kcal/g and 1.2-1.5g/kg protein daily. Small meals evenly distributed throughout the day and a late-night snack of complex carbohydrates will help minimize protein utilization. Compliance is, however, likely to be a problem. Diets rich in vegetables and dairy protein may be beneficial and are therefore recommended, but tolerance varies considerably in relation to the nature of the staple diet. Branched chain amino acid supplements may be of value in the occasional patient intolerant of dietary protein. Increasing dietary fiber may be of value, but the utility of probiotics is, as yet, unclear. Short-term multivitamin supplementation should be considered in patients admitted with decompensated cirrhosis. Hyponatremia may worsen HE; it should be prevented as far as possible and should always be corrected slowly. Conclusion : Effective management of these patients requires an integrated multidimensional approach. However, further research is needed to fill the gaps in the current evidence base to optimize the nutritional management of patients with cirrhosis and HE. (Hepatology 2013)
The New Medicine and the Old Ethics
Authors: Roger J. Bulger
Journal: JAMA (1991)

This short, interesting, provocative book by a self-proclaimed doctor-watcher (or medical ethicist) is about modern medicine and the predicaments in which it finds itself. Built upon the George Gay Lectures delivered at Harvard Medical School in 1988, it represents an attempt of one of the leading figures in the modern movement in medical and biomedical ethics to paint a picture of the dynamism and tensions that surround and suffuse the modern medical interchange between patient and would-be healer, the latter armed with a dazzling technical armamentarium of interventions and watched over by a host of critics, lawyers, payers, and policymakers. This is a book in which one of medicine's most learned, perceptive, and friendly observers attempts a three-dimensional look at a profession under strain, placing it in a historical context as he describes its central ethical tensions. This is not a book on ethics, although it contains much of substantive
Normal aminotransferase concentrations in patients with antibodies to hepatitis C virus
Authors: S Bruno, S Rossi, M L Petroni, E Villa, M Zuin, M Podda
Journal: BMJ (1994)

Two studies have recently reported normal aminotransferase concentrations in patients with antibodies to hepatitis C virus and histologically proved chronic liver disease.1,2 These studies, however, disagreed about the predictive values of concentrations of hepatitis C virus RNA in detecting liver disease.

Tests for hepatitis C virus are now included in screening tests for blood donors and in health check ups in Italy, and the number of patients with antibodies to hepatitis C virus and normal aminotransferase concentrations referred to outpatient clinics is rising sharply. We conducted a study to determine the prevalence of histological liver disease in these patients and its relation …
Abstract P3-15-03: Prospective Evaluation of the Drug-Metabolizing Enzyme Polymorphisms and Toxicity Profile of Docetaxel in Korean Patients with Early-Stage Breast Cancer Receiving Adjuvant Chemotherapy
Authors: K-p Kim, J-H Ahn, K-H Jung, S-B Kim, H-S. Lim
Journal: Cancer Research (2010)

Abstract Background Interindividual variability of pharmacokinetics may account for unpredictable toxicity of docetaxel. Pharmacogenetic analysis on the metabolic pathway of docetaxel has been performed in hopes of identifying predicting factors related to docetaxel-related toxicities. Methods From March 2007 to June 2008, female patients with early-stage breast cancer receiving docetaxel-containing adjuvant chemotherapy were included in this study. The 4 cycles of planned dose of docetaxel (100 mg/m2) was performed as adjuvant chemotherapy, following 4 cycles of adriamycin and cyclophosphamide. We evaluated toxicity profile of docetaxel according to the drug-metabolizing enzyme or transporter polymorphisms reported to affect the pharmacokinetics of docetaxel. The single nucleotide polymorphisms (SNPs) of CYP3A5 gene (6986 A&amp;gt;G), ABCB1 gene (1236 C&amp;gt;T, 3435 C&amp;gt;T, 2677 G&amp;gt;T(A)), ABCC2 gene (-24C&amp;gt;T, 1249 G&amp;gt;A, 3972 C&amp;gt;T, rs1276549) and SCLO1B3 gene (334 T&amp;gt;G, 699 G&amp;gt;A, rs11045585) were sequenced from individuals. Toxicities including neutropenia was evaluated for the 1st cycle of docetaxel and defined according to the NCI CTCAE version 3.0. Results Pharmacogenetic analysis was performed in 218 Korean women who had received the planned chemotherapy. With regard to ABCB1 3435 C&amp;gt;T, ABCB1 3435 T/T had significantly higher risks of neutropenia (P=0.015). Meanwhile, allele frequencies for CYP3A5 6986 G and ABCB1 3435 T revealed a trend for neutropenia (P=0.107 and 0.068). We could not find any other association between genotypes and other toxicities. Discussion Although ABCB1 3435 T/T was significantly associated with docetaxel-related neutropenia in our study population, polymorphism of pharmacogenetic genes related to docetaxel metabolism did not appear to be evidently associated with docetaxel-related adverse events. Further external validation of these genes may be required to allow them to enter clinical practice. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-15-03.
Delay in Renal Perfusion Due to Elongated Vascular Graft
Authors: FERRIS GINSBERG, JOHN J. SZIKLAS, RICHARD P. SPENCER, HENRY B C LOW
Journal: Clinical Nuclear Medicine (1987)

Following resection of an abdominal aortic aneurysm, a man had a marked difference between initial perfusion of the two kidneys. This was found to be due to a disparity of the path length of blood from the aorta to each kidney. While one kidney had blood coming directly from the aorta, the other was nourished by a graft originating just below the aortic bifurcation.
Measurement of trypsin and chymotrypsin activity in stools to detect chronic pancreatic disease
Authors: J. G. Banwell, P. J. Leonard, R. M. F. Lobo
Journal: Gut (1965)

EDITORIAL SYNOPSIS Trypsin and chymotrypsin activity per gram of stool varies inversely with the weight of the sample in control African subjects.The total daily output of both enzymes in patients with pancreatic calcification does not differ significantly from the output of control subjects.The lower mean concentration of the enzymes in chronic pancreatic disease can be accounted for by the weightier stool found in these patients.
1274 MEF2 regulates hepatic stellate cell activation and growth
Authors: X WANG, X TANG, X GONG, J WANDS, S FRIEDMAN, Z MAO
Journal: Hepatology (2003)

Hypersecretion of mucin plays an important role in the pathophysiology of many inflammatory airway diseases, including asthma, chronic bronchitis, and cystic fibrosis. Myristoylated alanine-rich C-kinase substrate (MARCKS) protein has been shown to play an important role in regulation of airway mucin secretion, as peptides analogous to the amino (N)-terminus of MARCKS attenuate mucin secretion by airway epithelium in vitro and in vivo. Here, we investigated a potential role for the protease Calpain, a calcium-dependent cysteine protease that can cleave MARCKS, in the MARCKS-related secretory mechanism. We theorized that Calpain might cleave MARCKS near the N-terminus, thereby attenuating the ability of MARCKS to bind to membranes and/or creating a small N-terminal peptide that could act as a competitive intracellular inhibitor to remaining endogenous full-length MARCKS molecules. Primary normal human bronchial epithelial (NHBE) cells and the virally-transformed human bronchial epithelial HBE1 cell line were exposed to phorbol-12-myristate-13-acetate (PMA) to stimulate the Protein Kinase C (PKC) pathway, leading to enhanced mucin secretion, and Calpain activity within the cells was measured with a fluorescent cleavage assay. Calpain activity was increased by PMA, and pretreatment of the cells with Calpain inhibitors reduced both Calpain activity and mucin secretion in a concentration-dependent manner. Thus, as opposed to the original hypothesis, inactivating Calpain caused a decrease rather than an increase in secretion. HBE1 cells transfected with DNA constructs encoding a MARCKS-YFP fusion protein showed cleavage at a putative site near the N-terminus in response to PMA. Cleavage of MARCKS by Calpain may have an important role in regulation of the PKC/MARCKS pathway regulating airway mucin secretion.
Aid may make roads more dangerous than landmines
Authors: Gregory Rose
Journal: BMJ (2004)

EDITOR—Roberts and Abbasi highlight disproportionately low spending on preventing road injuries compared with more popular investment areas.1 Perel et al address gaps in road safety in developing countries where risks are high since protective clothing, road rules, driver training, and speed limits are often absent.2

Annual injuries and deaths from road traffic crashes overtook those …