tbuckley/cabot-search huggingface dataset:
Wild-Type H- and N-Ras Promote Mutant K-Ras-Driven Tumorigenesis by Modulating the DNA Damage Response
Authors: Elda Grabocka, Yuliya Pylayeva-Gupta, Mathew J.K. Jones, Veronica Lubkov, Eyoel Yemanaberhan, Laura Taylor, Hao Hsuan Jeng, Dafna Bar-Sagi
Journal: Cancer Cell (2014)
EFFECTS OF AN INTENSIVE GLYCEMIC CONTROL WITH INSULIN ON PLATELET AGGREGATION PROFILE IN PATIENTS WITH ACUTE CORONARY SYNDROME: THE CHIPS (CONTROL DE LA HIPERGLUCEMIA Y FUNCIÓN PLAQUETARIA EN LOS SÍNDROMES CORONARIOS AGUDOS) STUDY
Authors: David Vivas, Esther Bernardo, Juan Carlos Garcia-Rubira, Dominick J. Angiolillo, Patricia Martin Rojas-Marco, Alfonso Calle, Carlos Macaya, Antonio Fernandez-Ortiz
Journal: Journal of the American College of Cardiology (2010)
STUDIES OF THE RATE OF DISAPPEARANCE OF LABELED THYROXINE FROM THE INTRAVASCULAR COMPARTMENT*
Authors: Edward J. Lennon, Norman H. Engbring, William W. Engstrom
Journal: Journal of Clinical Investigation (1961)

Each subject was evaluated by one or more of the authors and a clinical impression of the state of thyroidal function was made without reference to laboratory stud- ies.Impressions were confirmed by serum protein-bound iodine (PBI) determinations and, in some instances, by measuring the thyroidal 24-hour uptake of P131.The 996
Less Hazardous Cigarette Debated-Reply
Authors: Cornelius J. Lynch
Journal: JAMA (1979)

<h3>In Reply.—</h3> Most of the issues raised by Drs Miller and Schumaker have been addressed in separate letters, three of which appeared inThe Journal(240:2005; 2142; 2143, 1978) and one that will appear in<i>Science</i>. We welcome the opportunity to summarize our responses here. Miller and Schumaker state that the assumptions for "critical values" have been criticized by a number of prominent statisticians. They support this statement by reference to a single letter by two statisticians, which Science declined to publish. However, a subsequent letter by these same statisticians is to be published in Science, with a rejoinder that refutes each criticism made. Basically, the rejoinder describes fundamental epidemiologic realities of which the critics may not have been aware. Since the rejoinder is to be published in its entirety, it is not repeated here. In any case, our article inThe Journaluses only one statistic from the
Complete Transposition of the Great Vessels: Importance of Septal Defects and Patent Ductus Arteriosus
Authors: IB BOESEN
Journal: Circulation (1963)

In 1,145 autopsies performed on children with congenital heart disease who died before the age of 4, 180 were found to have a completely transposed aorta and pulmonary artery. Of these, 35 were excluded from the analysis because of other severe congenital cardiac malformations (among which were six with pulmonary stenosis); 11 who died from noncardiac disorders and two mongoloid idiots were also excluded. The remaining 132 were analyzed with reference to the relationship between the time of death and the presence of veno-arterial communications. Fortytwo per cent of the children died within 1 month and 73 per cent within the first 3 months of life. Therefore, diagnostic and therapeutic problems chiefly arise during the first months of life in patients with complete transposition of the great vessels.
Clinical Diagnosis by Whole-Genome Sequencing of a Prenatal Sample
Authors: Michael E. Talkowski, Zehra Ordulu, Vamsee Pillalamarri, Carol B. Benson, Ian Blumenthal, Susan Connolly, Carrie Hanscom, Naveed Hussain, Shahrin Pereira, Jonathan Picker, Jill A. Rosenfeld, Lisa G. Shaffer, Louise E. Wilkins-Haug, James F. Gusella, Cynthia C. Morton
Journal: New England Journal of Medicine (2012)

Conventional cytogenetic testing offers low-resolution detection of balanced karyotypic abnormalities but cannot provide the precise, gene-level knowledge required to predict outcomes. The use of high-resolution whole-genome deep sequencing is currently impractical for the purpose of routine clinical care. We show here that whole-genome "jumping libraries" can offer an immediately applicable, nucleotide-level complement to conventional genetic diagnostics within a time frame that allows for clinical action. We performed large-insert sequencing of DNA extracted from amniotic-fluid cells with a balanced de novo translocation. The amniotic-fluid sample was from a patient in the third trimester of pregnancy who underwent amniocentesis because of severe polyhydramnios after multiple fetal anomalies had been detected on ultrasonography. Using a 13-day sequence and analysis pipeline, we discovered direct disruption of CHD7, a causal locus in the CHARGE syndrome (coloboma of the eye, heart anomaly, atresia of the choanae, retardation, and genital and ear anomalies). Clinical findings at birth were consistent with the CHARGE syndrome, a diagnosis that could not have been reliably inferred from the cytogenetic breakpoint. This case study illustrates the potential power of customized whole-genome jumping libraries when used to augment prenatal karyotyping.
Transient Receptor Potential Melastatin 7–like Current in Human Head and Neck Carcinoma Cells: Role in Cell Proliferation
Authors: Jie Jiang, Ming-Hua Li, Koichi Inoue, Xiang-Ping Chu, Joshua Seeds, Zhi-Gang Xiong
Journal: Cancer Research (2007)

Abstract Ion channels are involved in normal physiologic processes and in the pathology of various diseases. In this study, we investigated the presence and potential function of transient receptor potential melastatin 7 (TRPM7) channels in the growth and proliferation of FaDu and SCC25 cells, two common human head and neck squamous carcinoma cell lines, using a combination of patch-clamp recording, Western blotting, immunocytochemistry, small interfering RNA (siRNA), fluorescent Ca2+ imaging, and cell counting techniques. Although voltage-gated K+ currents were recorded in all cells, none of FaDu cells express voltage-gated Na+ or Ca2+ currents. Perfusion of cells with NMDA or acidic solution did not activate inward currents, indicating a lack of NMDA receptor and acid-sensing channels. Lowering extracellular Ca2+, however, induced a large nondesensitizing current reminiscent of Ca2+-sensing cation current or TRPM7 current previously described in other cells. This Ca2+-sensing current can be inhibited by Gd3+, 2-aminoethoxydiphenyl borate (2-APB), or intracellular Mg2+, consistent with the TRPM7 current being activated. Immunocytochemistry, Western blot, and reverse transcription-PCR detected the expression of TRPM7 protein and mRNA in these cells. Transfection of FaDu cells with TRPM7 siRNA significantly reduced the expression of TRPM7 mRNA and protein as well as the amplitude of the Ca2+-sensing current. Furthermore, we found that Ca2+ is critical for the growth and proliferation of FaDu cells. Blockade of TRPM7 channels by Gd3+ and 2-APB or suppression of TRPM7 expression by siRNA inhibited the growth and proliferation of these cells. Similar to FaDu cells, SCC25 cells also express TRPM7-like channels. Suppressing the function of these channels inhibited the proliferation of SCC25 cells. [Cancer Res 2007;67(22):10929–38]
Adenosine Diphosphate–Induced Platelet Aggregation Is Associated With <i> P2Y <sub>12</sub> </i> Gene Sequence Variations in Healthy Subjects
Authors: Pierre Fontana, Annabelle Dupont, Sophie Gandrille, Christilla Bachelot-Loza, Jean-Luc Reny, Martine Aiach, Pascale Gaussem
Journal: Circulation (2003)

Background— The adenosine diphosphate (ADP) receptor P2Y 12 plays a pivotal role in platelet aggregation, as demonstrated by the benefit conferred by its blockade in patients with cardiovascular disease. Some studies have shown interindividual differences in ADP-induced platelet aggregation responses ex vivo, but the mechanisms underlying this variability are unknown. Methods and Results— We examined ADP-induced platelet aggregation responses in 98 healthy volunteers, and we identified 2 phenotypic groups of subjects with high and low responsiveness to 2 μmol/L ADP. This prompted us to screen the recently identified G i -coupled ADP receptor gene P2Y 12 for sequence variations. Among the 5 frequent polymorphisms thus identified, 4 were in total linkage disequilibrium, determining haplotypes H1 and H2, with respective allelic frequencies of 0.86 and 0.14. The number of H2 alleles was associated with the maximal aggregation response to ADP in the overall study population ( P =0.007). Downregulation of the platelet cAMP concentration by ADP was more marked in 10 selected H2 carriers than in 10 noncarriers. Conclusions— In healthy subjects, ADP-induced platelet aggregation is associated with a haplotype of the P2Y 12 receptor gene. Given the crucial role of the P2Y 12 receptor in platelet functions, carriers of the H2 haplotype may have an increased risk of atherothrombosis and/or a lesser clinical response to drugs inhibiting platelet function.
Pituitary-Ovarian Endocrinology
Authors: Nathan Kase
Journal: JAMA (1964)

The present volume compactly records the transactions of a symposium on gynecologic endocrinology. This, sponsored by the Portuguese Cancer Institute, took place in Lisbon in the summer of 1962. The American and English participants are among the major figures in this field and in each instance their stature is reflected in the quality of the reviews presented at this meeting. Each chapter of the transactions deals with a major area of current clinical interest. These include among others, gonadal steroid biosynthesis and detection, ovulation stimulation and inhibition, and the management of functional uterine bleeding and menopause. A group of articles by Loraine and his Edinburgh associates, dealing with the basic issues of gonadotropin-ovarian interactions, are particularly noteworthy for their concise and intelligible treatment of important material. In general the clinical formulations projected by the contributors are based on well-substantiated experimental data which have suffered little attrition in the two years
Tamoxifen — Panacea or Pandora's Box?
Authors: Nancy E. Davidson
Journal: New England Journal of Medicine (1992)

TAMOXIFEN, a nonsteroidal compound that has both antiestrogen and estrogen-agonist activity, has been used to treat women with breast cancer for nearly 20 years, and many clinical trials have documented its efficacy in the palliative care of patients with metastatic disease. Its use is associated with a significant reduction in the rates of disease recurrence and death among women over 50 years of age who have early-stage breast cancer, although its benefits in younger women are less well established. Moreover, the adjuvant use of tamoxifen may reduce the risk of cancer in the other breast.1 Data emerging from trials of . . .
Hemodynamic Monitoring in the Critically Ill Patient
Authors: James A. Shaver
Journal: New England Journal of Medicine (1983)

Almost 13 years have passed since Swan and associates reported their experience with the flow-directed catheter for right-heart catheterization at the bedside.1 This procedure is now accepted worldwide and used routinely in the care of the critically ill patient. There is no longer any question that the precise physiologic data obtained by right-heart catheterization are essential in the evaluation and management of many critically ill patients and therefore justify the risks of this invasive procedure.2 , 3 However, the same information can often be obtained through careful physical examination and noninvasive laboratory evaluation. It is therefore incumbent on the clinician to assess . . .
Treatment of Colon and Lung Cancer Patients with<b><i>ex Vivo</i></b>Heat Shock Protein 70-Peptide-Activated, Autologous Natural Killer Cells
Authors: Stefan W. Krause, Robert Gastpar, Reinhard Andreesen, Catharina Gross, Heidrun Ullrich, Gerald Thonigs, Karin Pfister, Gabriele Multhoff
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The 14 amino acid sequence (aa450–463) TKDNNLLGRFELSG (TKD) of heat shock protein 70 (Hsp70) was identified as a tumor-selective recognition structure for natural killer (NK) cells. Incubation of peripheral blood lymphocyte cells with TKD plus low-dose interleukin 2 (IL-2) enhances the cytolytic activity of NK cells against Hsp70 membrane-positive tumors, in vitro and in vivo. These data encouraged us to test tolerability, feasibility, and safety of TKD-activated NK cells in a clinical Phase I trial. Experimental Design: Patients with metastatic colorectal cancer (n = 11) and non-small cell lung cancer (n = 1) who had failed standard therapies were enrolled. After ex vivo stimulation of autologous peripheral blood lymphocytes with Hsp70-peptide TKD (2 μg/ml) plus low-dose IL-2 (100 units/ml), TKD was removed by extensive washing, and activated cells were reinfused i.v. The procedure was repeated for up to six cycles, applying a dose escalation schedule in 4 patients. Results: The percentage of activated NK cells in the reinfused leukapheresis products ranged between 8 and 20% of total lymphocytes, corresponding to total NK cell counts of 0.1 up to 1.5 × 109. Apart from restless feeling in 1 patient and itching in 2 patients, no negative side effects were observed. Concomitant with an enhanced CD94 cell surface density, the cytolytic activity of NK cells against Hsp70 membrane-positive colon carcinoma cells was enhanced after TKD/IL-2 stimulation in 10 of 12 patients. Concerning tumor response, 1 patient was in stable disease during therapy by formal staging criteria and another patient showed stable disease in one metastases and progression in another. Conclusions: Reinfusion of Hsp70-activated autologous NK cells is safe. Immunological results warrant additional studies in patients with lower tumor burden.
Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines.
Authors: R D Feldman, L E Limbird, J Nadeau, G A FitzGerald, D Robertson, A J Wood
Journal: Journal of Clinical Investigation (1983)

beta-Adrenergic receptors on human mononuclear leukocytes were assessed using [125I]iodohydroxybenzylpindolol binding. Subjects were studied supine and after being ambulatory, a maneuver that increases plasma catecholamines approximately two-fold. beta-Receptor affinity for agonists, measured by the competition of [125I]iodohydroxybenzylpindolol binding by (-)isoproterenol was significantly reduced with ambulation and this reduction was associated with a reduction in the proportion of beta-receptors binding agonist with a high affinity from a mean (+/- SEM) of 42 +/- 5 to 24 +/- 2% (P less than 0.01). In a parallel series, beta-adrenergic-stimulated adenylate cyclase activity was also reduced with postural change from 4.6 +/- 1.1 to 2.4 +/- 0.6 pmol [32P]cAMP/min per mg protein (P less than 0.05) after ambulation. Similar reductions in the proportion of receptors binding agonist with a high affinity were seen after infusion of norepinephrine. We conclude that the maneuver of ambulation reduces leukocyte beta-receptor responsiveness and affinity for agonists, probably by the effect of increased plasma catecholamines mediating an uncoupling of the beta-receptor-adenylate cyclase complex.
Nitrite Treatment for Hydrogen Sulfide Poisoning
Authors: ROGER P. SMITH
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 December 1981Nitrite Treatment for Hydrogen Sulfide PoisoningROGER P. SMITH, PH.D.ROGER P. SMITH, PH.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-6-782_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The September issue carries accounts of two remarkably similar tragedies. Three deaths and a serious nonfatal poisoning occurred in a liquid manure storage facility (1), and three deaths and two nonfatal poisonings occurred in an abandoned cesspool (2). I suggest that the similarities go beyond coincidence. The first accident was ascribed to hydrogen sulfide poisoning, but the second seems more likely to have been due to the same cause instead of to simple hypoxia. Putrifying fecal material has been associated with the evolution of hydrogen sulfide for centuries (3), and the rapid "knock-down" in both cases is...References1. OSBERNCRAPO LR. Dung lung: a report of toxic exposure to liquid manure. Ann Intern Med. 1981;95:312-4. LinkGoogle Scholar2. BERLIN C. Death from anoxia in an abandoned cesspool. Ann Intern Med. 1981;95:387. Letter. LinkGoogle Scholar3. . Hydrogen Sulfide. Baltimore: University Park Press; 1979:141-53. Google Scholar4. SMITHGOSSELIN RR. Hydrogen sulfide poisoning. J Occup Med. 1979;21:93-7. CrossrefMedlineGoogle Scholar5. PETERS J. Hydrogen sulfide poisoning in a hospital setting. JAMA. 1981;246:1588-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Dartmouth Medical School Hanover, NH 03755 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByMethylene Blue Administration During and After Life-Threatening Intoxication by Hydrogen Sulfide: Efficacy Studies in Adult Sheep and Mechanisms of ActionEffects of infusion of human methemoglobin solution following hydrogen sulfide poisoningHigh-dose hydroxocobalamin administered after H 2 S exposure counteracts sulfide-poisoning-induced cardiac depression in sheepHydrogen sulfide intoxicationIn Vivo Interactions Between Cobalt or Ferric Compounds and the Pools of Sulphide in the Blood During and After H2S PoisoningInhibitory effects of hyperoxia and methemoglobinemia on H2S induced ventilatory stimulation in the ratHypoxia-induced arterial chemoreceptor stimulation and Hydrogen sulfide: Too much or too little?Hydrogen sulfide oxidation and the arterial chemoreflex: Effect of methemoglobinHydrogen Sulfide 1 December 1981Volume 95, Issue 6Page: 782-782KeywordsHypoxia Issue Published: 1 December 1981 PDF DownloadLoading ...
Validation of the Contemporary Epstein Criteria for Insignificant Prostate Cancer in European Men
Authors: Claudio Jeldres, Nazareno Suardi, Jochen Walz, Georg C. Hutterer, Sascha Ahyai, Jean-Baptiste Lattouf, Alexander Haese, Markus Graefen, Andreas Erbersdobler, Hans Heinzer, Hartwig Huland, Pierre I. Karakiewicz
Journal: European Urology (2007)
A mutation in CFTR produces different phenotypes depending on chromosomal background
Authors: S. Kiesewetter, M. Macek, C. Davis, S. M. Curristin, C.-S. Chu, C. Graham, A. E. Shrimpton, S. M. Cashman, L.-C. Tsui, J. Mickle, J. Amos, W. E. Highsmith, A. Shuber, D. R. Witt, R. G. Crystal, G. R. Cutting
Journal: Nature Genetics (1993)
Apoptosis in chronic myeloid leukemia cells transiently treated with imatinib or dasatinib is caused by residual BCR–ABL kinase inhibition
Authors: Pavel Simara, Stanislav Stejskal, Irena Koutna, David Potesil, Lenka Tesarova, Michaela Potesilova, Zbynek Zdrahal, Jiri Mayer
Journal: American Journal of Hematology (2013)

Transient, potent BCR-ABL inhibition with tyrosine kinase inhibitors (TKIs) was recently demonstrated to be sufficient to commit chronic myeloid leukemia (CML) cells to apoptosis irreversibly. This mechanism explains the clinical efficacy of once-daily dasatinib treatment, despite the rapid clearance of the drug from the plasma. However, our in vitro data suggest that apoptosis induction after transient TKI treatment, observed in the BCR-ABL-positive cell lines K562, KYO-1, and LAMA-84 and progenitor cells from chronic phase CML patients, is instead caused by a residual kinase inhibition that persists in the cells as a consequence of intracellular drug retention. High intracellular concentrations of imatinib and dasatinib residues were measured in transiently treated cells. Furthermore, the apoptosis induced by residual imatinib or dasatinib from transient treatment could be rescued by washing out the intracellularly retained drugs. The residual kinase inhibition was also undetectable by the phospho-CRKL assay. These findings confirm that continuous target inhibition is required for the optimal efficacy of kinase inhibitors.
Gonorrhoea and Other Venereal Diseases
Authors: A. J. King
Journal: BMJ (1959)

As with syphilis, so the treatment of the other venereal diseases has been revolutionized by the introduction of new remedies, particularly the antibiotics.From the patient's point of view the benefits have been considerable, but the new methods of treatment bring their own problems, not the least of which is the ready assumption by the patient, and sometimes by the doctor, that rapid subsidence of symptoms means cure. GONORRHOEA Resistance to AntibioticsThe gonococcus proved itmarkably susceptible in vitro to most antibiotics.Penicillin has been the remedy of choice, and, until recently, there was no convincing evi- dence, in vitro or in vivo, that strains of gonococci were becoming resistant to it.A single small intramuscular dose of a long-acting preparation of penicillin, such as 300,000 units of the procaine salt in watery suspension or in oily suspension with 2% aluminium monostearate proved effective in well over 90% of the cases.Since 1956, however, a small but increasing number of patients with
Meta-Analysis: Outcomes in Patients with Suspected Pulmonary Embolism Managed with Computed Tomographic Pulmonary Angiography
Authors: Lisa K. Moores, William L. Jackson, Andrew F. Shorr, Jeffrey L. Jackson
Journal: Annals of Internal Medicine (2004)

Background: Spiral computed tomographic pulmonary angiography (CTPA) is increasingly being used in the evaluation of patients with clinically suspected pulmonary embolism (PE). However, CTPA as a definitive diagnostic test may be limited by inadequate sensitivity, especially in instances of isolated subsegmental emboli. Purpose: To assess the safety of withholding anticoagulation in patients with suspected PE and negative results on CTPA. Data Sources: All relevant studies identified in MEDLINE (1966 to March 2004) and EMBASE (1974 to 2004) and in bibliographies of key articles. The search was not limited to the English language. Study Selection: The authors selected all published studies that used CTPA to evaluate suspected PE and reported at least 3 months of follow-up in patients not receiving anticoagulation on the basis of a negative CTPA result. Data Extraction: Two reviewers independently rated study quality on the basis of predetermined criteria. Data were extracted on participants, CTPA technique, diagnostic studies performed, prevalence of PE, number of patients with negative or indeterminate CTPA results who were followed, and subsequent rates of venous thromboembolism and fatal PE. Data Synthesis: Twenty-three studies reported on 4657 patients with negative CTPA results who did not receive anticoagulation. The 3-month rate of subsequent venous thromboembolic events was 1.4% (95% CI, 1.1% to 1.8%), and the 3-month rate of fatal PE was 0.51% (CI, 0.33% to 0.76%). Limitations: The CTPA technology used varied across studies and was not applied uniformly in the same step of diagnostic algorithms. Only 1 study used CTPA as the sole diagnostic test. Conclusion: The rate of subsequent venous thromboembolism after negative results on CTPA is similar to that seen after negative results on conventional pulmonary angiography. It appears to be safe to withhold anticoagulation after negative CTPA results.
172 RISK FACTORS AND MANAGEMENT OF BILIARY TRACT COMPLICATIONS POST LIVER TRANSPLANTATION
Authors: A.A. Negm, T.J. Weismueller, S. Pischke, A.S. Schneider, T.O. Lankisch, C.P. Strassburg, J. Klempnauer, J. Wedemeyer, M.P. Manns
Journal: Journal of Hepatology (2013)
Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy
Authors: F J Giles, E Abruzzese, G Rosti, D-W Kim, R Bhatia, A Bosly, S Goldberg, G L S Kam, M Jagasia, W Mendrek, T Fischer, T Facon, U Dünzinger, D Marin, M C Mueller, Y Shou, N J Gallagher, R A Larson, F-X Mahon, M Baccarani, J Cortes, H M Kantarjian
Journal: Leukemia (2010)