tbuckley/cabot-search huggingface dataset:
Tissue advanced glycation end products are associated with diastolic function and aerobic exercise capacity in diabetic heart failure patients
Authors: Suzan Willemsen, Jasper W.L. Hartog, Yoran M. Hummel, Marieke H.I. van Ruijven, Iwan C.C. van der Horst, Dirk J. van Veldhuisen, Adriaan A. Voors
Journal: European Journal of Heart Failure (2010)
Localization of gene for familial hypertrophic cardiomyopathy to chromosome 14q1 in a diverse US population.
Authors: J F Hejtmancik, P A Brink, J Towbin, R Hill, L Brink, T Tapscott, A Trakhtenbroit, R Roberts
Journal: Circulation (1991)

Familial hypertrophic cardiomyopathy, an inherited primary cardiac abnormality characterized by ventricular hypertrophy, is the leading cause of sudden death in the young. Recent application of restriction fragment length polymorphism markers has provided provocative results, with localization to chromosome 18 (Japanese studies), 16 (Italian studies), 14 (US and French-Canadian studies), and two (National Institutes of Health studies) indicating genetic heterogeneity. Interpretation remains speculative until at least one of these loci is confirmed in unrelated pedigrees by independent investigators.We studied eight unrelated families of varied ethnic origins across the United States. DNA from each individual was digested with restriction enzymes TaqI or BamHI and analyzed by Southern blots followed by hybridization with probes T cell receptor alpha (TCRA), myosin heavy chain beta, D14S25, and D14S26. Multipoint linkage analysis showed a maximum lod score of 4.3, placing the locus 10 cM from D14S26 between D14S26 and TCRA, with an odds ratio of 20,000:1 and 90% confidence limits of 12 cM proximal to D14S25 to 4 cM distal to TCRA. The probability of linkage to 14q1 was more than 99%.These results indicate that the loci for familial hypertrophic cardiomyopathy in our families is primarily 14q1 but does not exclude other loci in a small proportion of the families. Thus, 14q1 appears to be the locus for familial hypertrophic cardiomyopathy in a significant proportion of the US population.
A critical role for TNFα in the selective attachment of mononuclear leukocytes to angiotensin-II-stimulated arterioles
Authors: Teresa Mateo, Yafa Naim Abu Nabah, Mercedes Losada, Rossana Estellés, Chantal Company, Begoña Bedrina, Jose Miguel Cerdá-Nicolás, Stephen Poole, Peter J. Jose, Julio Cortijo, Esteban J. Morcillo, Maria-Jesus Sanz
Journal: Blood (2007)
Promising Drug Combination for Sickle Cell Anemia
Authors: Beverly Merz
Journal: JAMA (1989)

TEAMWORK between an anticancer agent and a hematopoietic growth factor may provide the first effective treatment for sickle cell anemia. Promising data from a small study in which the drug hydroxyurea was used to treat patients with sickle cell anemia have prompted the expansion of trials to six centers. Pediatrician George J. Dover, MD, and internist Samuel Charache, MD, who have been using hydroxyurea to treat 2 patients since 1983, have expanded treatment to 38 patients in the enlarged study. In a pilot study involving six patients, three of whom were treated at Johns Hopkins, three patients demonstrated marked clinical improvement. However, it was pathological rather than clinical findings that stimulated enthusiasm for hydroxyurea. The drug appeared to turn on the gene responsible for the production of the gamma protein chain, which in turn can combine with the alpha protein chain to form the fetal hemoglobin molecule. The gene for
Scintigraphic Evaluation of a Patient With Hemangiosarcoma Labeled Red Blood Cell Imaging is Nondiagnostic
Authors: RUTH HARDOFF, ESTHER AGHAI, HAIM BITTERMAN
Journal: Clinical Nuclear Medicine (1993)

Perfusion vascularity mismatch is characteristic of liver cavernous hemangiomas. The large blood volume and slow perfusion are responsible for this pattern. Often a large lesion demonstrate “cold” areas within the hemangioma, which are explained by slow or absent perfusion due to localized thrombosis. The authors present a polyvinyl- chloride worker with a large liver lesion whose Tc-99m RBC scintigraphy was consistent with cavernous hemangioma with a “cold” area. The lesion was diagnosed at surgery as hemangiosarcoma. It is concluded that malignant vascular lesions of the liver cannot be differentiated from the benign lesions by RBC imaging alone, because they may demonstrate similar patterns.
Prosthetic Valve Replacement in Active Bacterial Endocarditis.
Authors: Don W. Chapman
Journal: Annals of Internal Medicine (1969)

s1 May 1969Prosthetic Valve Replacement in Active Bacterial Endocarditis.Don W. Chapman, M.D., F.A.C.P., William L. Winters Jr., M.D., F.A.C.P., H. Liston Beazley, M.D., F.A.C.P., Paul K. Peterson, M.D., Temple W. Williams, M.D., F.A.C.P., Jimmy F. Howell, M.D.Don W. Chapman, M.D., F.A.C.P.Search for more papers by this author, William L. Winters Jr., M.D., F.A.C.P.Search for more papers by this author, H. Liston Beazley, M.D., F.A.C.P.Search for more papers by this author, Paul K. Peterson, M.D.Search for more papers by this author, Temple W. Williams, M.D., F.A.C.P.Search for more papers by this author, Jimmy F. Howell, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1074_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn 19 cases of active bacterial endocarditis terminal heart failure necessitated prosthetic valve replacement. The organisms included five due to alpha streptococci; two, gamma streptococci; three, pneumococci; and four due to staphylococci; in five the organism was undetermined. Hemodynamic studies revealed predominently severely regurgitating valves, elevated right-sided pressures, and low cardiac output. There were ten patients with aortic insufficiency who survived, both of the mitral valve patients lived, and one of the three combined mitral and aortic valve patients survived. Vegetations and leaflet perforation were constant findings, and abscess at the base of the valve made it difficult to suture... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Houston, Texas PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPreparation of Carborane-Siloxane Polymers 1 May 1969Volume 70, Issue 5Page: 1074-1074KeywordsAbscessesAortic valveCardiac outputEndocarditisHeart failureHemodynamicsValve replacement Issue Published: 1 May 1969 PDF DownloadLoading ...
Mcl‐1 and Bcl‐2/Bax ratio are associated with treatment response but not with Rai stage in B‐cell chronic lymphocytic leukemia
Authors: Anurag Saxena, Sathiyanarayanan Viswanathan, Oksana Moshynska, Puneeta Tandon, Koravangattu Sankaran, David P. Sheridan
Journal: American Journal of Hematology (2003)

Abstract Although both Bcl‐2/Bax ratio and Mcl‐1 have been identified to be of clinical relevance in B‐cell chronic lymphocytic leukemia (CLL), there is controversy regarding their role; further, their relative importance is not well delineated. Expression of Bcl‐2, Bax, the Bcl‐2/Bax ratio, and Mcl‐1 in 51 consecutive previously untreated CLL patients and 16 controls was determined by Western blotting. Only 37 patients were treated, all with chlorambucil and prednisone initially. Six patients achieved complete response (CR), 14 were non‐responders (NR), and 17 had a partial response (PR), as defined by NCI criteria. There was considerable inter‐patient variability in protein expression and overlap with healthy volunteers ( P &gt; 0.05). All patients with CR had low Mcl‐1 levels compared to the PR + NR group (0.07 ± 0.02 vs. 0.14 ± 0.07, P = 0.043). Higher Mcl‐1 expression as determined by dichotomizing the data was associated with a failure to achieve CR ( P = 0.021). The Bcl‐2/Bax ratio was significantly associated with treatment response only when CR and PR were considered together (0.89 ± 0.53 [CR + PR] vs. 3.38 ± 4.47 [NR], P = 0.0118). There was no association with Rai stage. Low Mcl‐1 appears to be a requirement for CR, while low Bcl‐2/Bax ratio is indicative of some response to conventional treatment. Am. J. Hematol. 75:22–33, 2004. © 2003 Wiley‐Liss, Inc.
DILATATION OF THE STOMACH.
Authors: HENRY M. LYMAN
Journal: JAMA (1897)

I place before you, this morning, a patient whose sallow complexion and expression of distress declare him to be a sufferer from chronic disease. He is about 50 years of age, though his whitened locks and bald crown seem to indicate a greater number of years. He is quite thin; his muscles are flaccid, and readily discernible through the dry and inelastic skin. In the left side of the scrotum hangs a considerable varicocele; the veins of the lower extremities are enlarged and tortuous; he is constipated and has long been a sufferer with internal piles. During the winter he complains of a hacking cough, but his thorax is everywhere extremely resonant; he has a chronic bronchitis with some degree of vesicular emphysema. The heart is not enlarged; there are no valvular murmurs, but the second sound is decidedly accentuated over the right ventricle. The liver is of normal size,
Promoting sexual health.
Authors: G. T. Gardner
Journal: BMJ (1992)

gastric motility as observed in states of reduced dietary intake such as anorexia nervosa.' Un- fortunately, Chua and colleagues do not report dietary data or body mass indices.All functional diseases must ultimately be explicable in terms of biochemical phenomena.Do patients benefit more, however, from the comfortable assertion that they have a "neuro- transmitter problem" and the pharmacological treatments that this inevitably suggests or by doctors addressing the psychosocial stressors that underlie or exacerbate the diseases?Evidence suggests that accepting a medicalising label and its attendant invalid role may be associated with delayed recovery in patients without demonstrable organic disease.'
Tests for Carotid Artery Disease
Authors: GARY G. WINZELBERG
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 April 1983Tests for Carotid Artery DiseaseGARY G. WINZELBERG, M.D.GARY G. WINZELBERG, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-4-556_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The article by Cebul and Ginsberg (1) describes digital subtraction intravenous angiography as a noninvasive method. Initial studies with this method used a 16 gauge catheter (2) in the antecubital vein for contrast injection. However, most investigators have found this method suboptimal and many now use a 5 or 6 French catheter placed in the superior vena cava or right atrium. This method cannot be labeled noninvasive. Although the method does not carry the risks of selective carotid angiography, it is an invasive procedure with some inherent risk from venous catheterization and contrast injection. Nevertheless, digital subtraction...References1. CEBUL R and GINSBERG M. Noninvasive neurovascular tests for carotid artery disease. Ann Intern Med. 1982;97:867-72. LinkGoogle Scholar2. MISTRETTA C, CRUMMY A, and STROTHER C. Digital angiography: a perspective. Radiology. 1981;139:273-6. CrossrefMedlineGoogle Scholar3. CHILCOTE W, MODIC M, PAVLICHEK W, LITTLE J, FURLAN A, DUCHESNEAU P, and WEINSTEIN M. Digital subtraction angiography of the carotid arteries: a comparative study in 100 patients. Radiology. 1981;139:287-95. CrossrefMedlineGoogle Scholar1. CEBUL R and GINSBERG M. Noninvasive neurovascular tests for carotid artery disease. Ann Intern Med. 1982;97:867-72. LinkGoogle Scholar2. FORBES G, ERNEST F, KISPERT D, FOLGER W, and SUNDT T. Digital angiography: introducing digital techniques to clinical cerebral angiography practice. Mayo Clin Proc. 1982;57:683-93. MedlineGoogle Scholar3. LITTLE J, FURLAN A, MODIC M, and WEINSTEIN M. Digital subtraction angiography in cerebrovascular disease. Stroke. 1982;13:557-66. CrossrefMedlineGoogle Scholar4. GINSBERG M and CEBUL R. Noninvasive diagnosis of carotid artery disease. In: HARRISON MJG, DYKEN ML, eds. Neurology, Cerebral Vascular Disease. Kent, England: Butterworth and Co., Ltd.; 1983. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: GARY G. WINZELBERG, M.D.Affiliations: Shadyside Hospital Pittsburgh, PA 15232 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1983Volume 98, Issue 4Page: 556-556KeywordsAngiographyCarotid arteriesCatheterizationCathetersVeins ePublished: 1 December 2008 Issue Published: 1 April 1983 PDF downloadLoading ...
Thyroid Hormone Action in the Heart
Authors: George J. Kahaly, Wolfgang H. Dillmann
Journal: Endocrine Reviews (2005)

The heart is a major target organ for thyroid hormone action, and marked changes occur in cardiac function in patients with hypo- or hyperthyroidism. T3-induced changes in cardiac function can result from direct or indirect T3 effects. Direct effects result from T3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T3 effects, which occur independent of nuclear T3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T3 effects are mediated by the binding of T3 to specific nuclear receptor proteins, which results in increased transcription of T3-responsive cardiac genes. The T3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. T3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum. This T3 effect results from T3-induced increases in the level of the mRNA coding for the sarcoplasmic reticulum calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the sarcoplasmic reticulum.
Abstract 1719: Significance of thymidylate synthase copy numbers for resistance to pemetrexed in lung cancer
Authors: Daishi Kasai, Tetsuya Oguri, Hiroaki Ozasa, Takehiro Uemura, Eiji Kunii, Osamu Takakuwa, Hirotsugu Ohkubo, Mikinori Miyazaki, Ken Maeno, Shigeki Sato
Journal: Cancer Research (2012)

Abstract Pemetrexed is a multitargeted antifolate with promising clinical activity in non-squamous lung cancer. It targets the folate-dependent enzymes thymidylate synthase (TS), reduced folate carrier, and folylpolygamma-glutamate synthetas, all of which are involved in the de novo biosynthesis of thymidine and purine nucleotides.The primary mechanism of the action of pemetrexed is inhibition of TS, which results in a decrease in the available thymidine necessary for DNA synthesis. We have previously established pemetrexed -resistant lung cancer cell line, and have shown that overexpression of TS resulted in increased pemetrexed resistance. We have also examined that TS copy numbers by quantitative real-time PCR, were increased in pemetrexed-resistant cells. Therefore we investigated TS copy numbers in lung cancer cell lines and clinical samples to examine whether TS copy numbers are the biomarker for pemetrexed sensitivity. First, we examined the correlation of TS copy numbers and 50% cell survival of pemetrexed for 14 lung adenocarcinoma cell lines, and a meaningful relationship was accepted. In addition, we examined TS copy number in 20 bronchoscopic specimens of non-squamous lung cancers, and found that the correlation was also confirmed between TS copy numbers and clinical response. Our study suggests that TS copy number may be a predictive marker for pemetrexed sensitivity in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1719. doi:1538-7445.AM2012-1719
Rational Responses to Graduate Education of Physicians
Authors: L. S. McKittrick
Journal: JAMA (1967)

My role in this program is clearly limited to a discussion of the report of the Millis Commission on Graduate Education (except that section on family practice) and specifically to present what might be a reasonable response to a study and its recommendations, which if followed, would alter greatly our present concept of education beyond medical school and would require drastic changes in its overall structure. I begin with the assumption that those responsibile for education at this level recognize a need for and welcome a study in depth of graduate education, hopeful that from a better understanding of its weaknesses as well as its strength will come more coordinated and efficient educational opportunities for all of the recent medical school graduates. Before proceeding to the report itself, I would like to comment briefly on the commission which developed it. There are undoubtedly many who believe that those selected to
Long term effects of deprivation increase health's sensitivity to current policies
Authors: R. G Wilkinson
Journal: BMJ (1998)

EDITOR—Gabbay spreads a dangerously widespread misunderstanding in his editorial on the government's green paper Our Healthier Nation . 1 2 He says that “even if new policies have favourable results, they are unlikely to show much effect by the year 2010.” Both the influences of early life on later health and the long term cumulative health effects …
Abortion and the Internist
Authors: Roberta B. Ness
Journal: Annals of Internal Medicine (1997)

Letters1 March 1997Abortion and the InternistRoberta B. Ness, MD, MPH and Jeane Ann Grisso, MD, MScRoberta B. Ness, MD, MPHUniversity of Pittsburgh, Pittsburgh, PA 15261University of Pennsylvania, Philadelphia, PA 19104Search for more papers by this author and Jeane Ann Grisso, MD, MScUniversity of Pittsburgh, Pittsburgh, PA 15261University of Pennsylvania, Philadelphia, PA 19104Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-5-199703010-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Abortion has been a divisive issue in our culture since before Roe v. Wade, and entrenched ethical arguments exist on both sides of the issue. Dr. Simcic eloquently presents one side of the abortion debate. It was not, and is not, our intention to argue the other side. Nevertheless, it is a fact that some physicians choose to perform abortions. Each physician makes this very personal choice on the basis of deeply held beliefs that we feel are unlikely to be altered by our review. The portion of our discussion of women's health devoted to medical abortion was ... Author, Article, and Disclosure InformationAffiliations: University of Pittsburgh, Pittsburgh, PA 15261University of Pennsylvania, Philadelphia, PA 19104 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1997Volume 126, Issue 5Page: 411KeywordsClinical epidemiologyObstetrics and gynecologySafety Issue Published: 1 March 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract 5454: Novel STAT3:STAT3 small-molecule inhibitors as potential anticancer agents
Authors: Mohammad R. Haque, Giovanna Zinzalla, Samantha L. Kaye, Shozeb Haider, B. Piku Basu, John Anderson, Khondaker M. Rahman, Dyeison Antonow, Samantha Essex, Jonathan Palmer, Edwin Nkansah, Fyeza Hasan, Daniel Morgenstern, Andrew F. Wilderspin, Stephen Neidle, David E. Thurston
Journal: Cancer Research (2010)

Abstract Transcription factors are important targets for cancer therapy. The inhibition of protein-protein interactions (PPIs) within signalling pathways known to be key regulators of transcriptional activity is a viable approach to novel chemotherapeutic strategies. Proof-of-concept studies in cell-culture and animal models have validated the potential of small-molecule inhibitors of STAT3 signalling in cancer therapy. In particular, the protein-protein interaction between two STAT3 monomers (i.e., the dimerisation event in the signalling cascade) has been identified as a valid target to inhibit DNA-binding and the resultant transcriptional activation. Of the approximately 20 small-molecule STAT3 inhibitors reported in the literature to date, only three are described as potential STAT3:STAT3 dimerisation inhibitors, and these have IC50 values in STAT3-expressing cell lines of between 10-90 μM. Using in silico and medicinal chemistry-based approaches based on a published X-Ray structure of STAT3 (PDB: ID-1BG1) to identify “hit” inhibitors, a focussed library (approx. 50 members) was designed around one such “hit” and synthesized employing an efficient 4-step linear approach. Library members were then entered into a screening cascade involving initial evaluation of their ability to inhibit STAT3:STAT3 interaction in a Fluorescent Polarisation (FP)-based primary PPI binding assay. “Hit” molecules from this primary assay were then studied in two cell-based assays designed to test for STAT3 selectivity. The first was a comparative MTS assay between STAT3-expressing MDA MB231 breast cancer cells and STAT3-null colon A4 cells. The second was a luciferase reporter assay designed to measure transcription inhibition in STAT3-Luc-transformed Hela cells compared to SV40-Luc-transformed Hela control cells. A potential “lead” molecule, RH06, emerged from this screening cascade with potentially selective STAT3 inhibitory activity in the low micromolar (i.e., ∼1 µM) region. RH06 is currently being studied for its effect on STAT3 and pSTAT3 signal activation, and its potentially differential effect on upstream and downstream mediators (i.e., JAK2, Bcl-xl, Cyclin D1 and pSTAT1). Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5454.