tbuckley/cabot-search huggingface dataset:
Phosphoproteome Analysis of Cardiomyocytes Subjected to β-Adrenergic Stimulation
Authors: Guoxiang Chu, Gregory F. Egnaczyk, Wen Zhao, Su-Hyun Jo, Guo-Chang Fan, John E. Maggio, Rui-Ping Xiao, Evangelia G. Kranias
Journal: Circulation Research (2003)

Posttranslational modification of target substrates underlies biological processes through activation/inactivation of signaling cascades. To concurrently identify the phosphoprotein substrates associated with cardiac β-adrenergic signaling, the mouse myocyte phosphoproteome was analyzed using 2-D gel electrophoresis in combination with 32 P autoradiography. Phosphoprotein spots, detected by silver staining, were identified using MALDI-TOF mass spectrometry in conjunction with computer-assisted protein spot matching. Stimulation with isoproterenol (1 μmol/L for 5 minutes) was associated with maximal increases in myocyte contractile parameters, and significant stimulation of the phosphorylation of troponin I (190±23%) and succinyl CoA synthetase (160±16%), whereas the phosphorylation of pyruvate dehydrogenase (48±10%), NADH-ubiquinone oxidoreductase (46±6%), heat shock protein 27 (18±3%), αB-crystallin (20±3%), and an unidentified 26-kDa protein (29±7%) was significantly decreased, compared with unstimulated cells (100%). After sustained (30 minutes) stimulation with isoproterenol, only the alterations in the phosphorylation levels of troponin I and NADH-ubiquinone oxidoreductase were maintained and de novo phosphorylation of a phosphoprotein (≈20 kDa and pI 5.5) was observed. The tryptic peptide fragments of this phosphoprotein were sequenced using postsource decay mass spectrometry, and the protein was subsequently cloned and designated as p20, based on its high sequence homology with rat and human skeletal p20. The mouse cardiac p20 contains the conserved domain sequences for heat shock proteins, and the RRAS consensus sequence for cAMP-PKA substrates. LC-MS/MS phosphorylation mapping confirmed phosphorylation of Ser 16 in p20 on β-agonist stimulation. Adenoviral gene transfer of p20 was associated with significant increases in contractility and Ca transient peak in adult rat cardiomyocytes, suggesting an important role of p20 in cardiac function. These findings suggest that cardiomyocytes undergo significant posttranslational modification via phosphorylation in a multitude of proteins to dynamically fine-tune cardiac responses to β-adrenergic signaling.
The <i>MBL2</i> ‘LYQA Secretor’ Haplotype Is an Independent Predictor of Postoperative Myocardial Infarction in Whites Undergoing Coronary Artery Bypass Graft Surgery
Authors: Charles D. Collard, Stanton K. Shernan, Amanda A. Fox, Toralf Bernig, Stephen J. Chanock, William K. Vaughn, Kazue Takahashi, Alan B. Ezekowitz, Petr Jarolim, Simon C. Body
Journal: Circulation (2007)

Mannose-binding lectin (MBL) is an important component of innate immunity and activator of the lectin complement pathway. Within the MBL2 gene are seven 5' "secretor" haplotypes that code for altered serum MBL levels and complement activation. However, recent evidence suggests that 3' MBL2 haplotypes may also modify MBL function and circulating levels. Because MBL and the lectin complement pathway have been implicated in cardiovascular injury, we investigated whether MBL2 haplotypes are independently associated with an increased risk of postoperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery.Genotyping of 18 polymorphic sites within the MBL2 gene was performed in a prospective, longitudinal multi-institutional study of 978 patients undergoing primary coronary artery bypass graft-only surgery with cardiopulmonary bypass between August 2001 and May 2005. After adjustment for multiple comparisons by permutation testing, multivariate, stepwise logistic regression, including a score test, was performed controlling for patient demographics, preoperative risk factors, medications, and intraoperative variables to determine if MBL2 secretor haplotypes are independent predictors of PMI in whites undergoing primary coronary artery bypass graft surgery. Neither the 5' nor 3' MBL2 haplotypes alone were associated with an increased incidence of PMI. However, the incidence of PMI in whites (n=843) expressing the combined MBL2 5' LYQA secretor haplotype (CGTCGG) and 3' haplotype (CGGGT) was significantly higher than in whites not expressing the haplotype (38% versus 10%; P<0.007). Moreover, the combined MBL2 LYQA secretor haplotype was an independent predictor of PMI in whites after primary coronary artery bypass graft surgery after adjustment for other covariates (P<0.02; adjusted OR: 3.97; 95% CI: 1.30 to 12.07). The combined MBL2 LYQA secretor haplotype in whites was also an independent predictor of postoperative CKMB levels exceeding 60 ng/mL (P<0.02; adjusted OR: 4.48; 95% CI: 1.95 to 16.80). Inclusion of the combined MBL2 LYQA secretor haplotype improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.715 versus 0.705).The combined MBL2 LYQA secretor haplotype is a novel independent predictor of PMI and may aid in preoperative risk stratification of whites undergoing primary coronary artery bypass graft surgery.
Stop Alcohol Abuse
Authors: Donald W. Goodwin
Journal: JAMA (1984)

Every treatment needs a name. A good name for these cassetterecorded exercises for overcoming alcoholism would be the "Yuk! Scram! Wet Spaghetti!" treatment. The tape-instructed patient imagines looking into a vomit-filled toilet. His hands are hanging weakly onto the rim of the bowl. His booze sits on the back rim. A repulsive sight. "Yuk!" (For those of little imagination, a picture of the bowl is provided with the cassettes.) He then screams (silently) "Scram!" to whatever thought prompted him to want to drink (called "thought-stopping"). He pictures a dish of wet spaghetti. He lifts up the spaghetti with a fork, intoning: "I am as<i>limp</i>, as<i>loose</i>, as<i>relaxed</i>as wet spaghetti." Instant relaxation occurs (if you can picture wet spaghetti). McDowell's approach to alcoholism, in short, is behavioristic. He believes alcoholics have a chemical vulnerability to alcohol and are born that way; it is their "natural endowment." They shouldn't
A 17-yr old boy with productive cough and progressive dyspnoea
Authors: JE Tulleken, CA van Minnen, TJ Waterbolk, HJ Groen, TS van der Werf, JJ Ligtenberg, JG Zijlstra
Journal: European Respiratory Journal (2000)

Case historyA 17-yr old boy presented with productive cough andprogressive shortness of breath. His medical historystarted four months earlier with successful surgical repairof a longitudinal airway rupture extending from the carinainto the left main bronchus following a blunt chest trauma.A follow-up bronchoscopy after one month revealed anarrowing of the left main bronchus by endoluminalgranulation tissue formation around the intraluminal nylonstitches. Neodymium/yttrium-aluminium-garnet (Nd/YAG)thermal laser vapourisation with the rigid bronchoscopewas attempted twice in three weeks. Although initiallysuccessful, the symptoms worsened. The chest radio-graph on hospital admission suggested complete atelec-tasis of the left lung (fig. 1). On endoscopy purulentsecretions were seen while excessive granulation tissue atthe site of bronchial repair narrowed the lumen by >50%.To limit recurrence, stent placement was performed afterapplication of a third Nd/YAG laser treatment. Airwaypatency was reached. On the distal part of the stentgranulation tissue was still present. Following the proce-dure, oral corticosteroids and nebulized beta-adrenergicagonist therapy were started.His shortness of breath did not subside and on the day ofadmission to the intensive care unit (ICU) he had anonproductive cough and was more dyspnoeic. He waseating and had vomited once. His temperature was 37.38C,pulse rate was 110 beats.min
An Apology for Socratic Bioethics
Authors: Franklin G. Miller, Robert D. Truog
Journal: The American Journal of Bioethics (2008)

Bioethics is a hybrid discipline. As a theoretical enterprise it stands for untrammeled inquiry and argument. Yet it aims to influence medical practice and policy. In this article we explore tensions between these two dimensions of bioethics and examine the merits and perils of a "Socratic" approach to bioethics that challenges "the conventional wisdom."
Abstract 470: Motility of human colorectal cancer cells is promoted by H1047R kinase mutation of PI3K p110-alpha
Authors: Guanghua Wan, Melanie Ongchin, Essence Hand, Ashwani Rajput
Journal: Cancer Research (2012)

Abstract INTRODUCTION: Mutations in the catalytic subunit p110α of Class 1A phosphatidyinositol 3-kinase (PI3K) occur in nearly 1/3 human colorectal cancer (CRC). In vivo studies have demonstrated that cell lines bearing the p110α mutation are more metastatic than wild type PI3K cells. The most frequent cancer-specific mutations in p110α are the kinase domain mutation H1047R and the helical domain mutation E542K/E545K. Our group has previously shown that the two hotspot mutations in PI3K in either the helical or kinase domains have a significantly different metastatic potential in an orthotopic murine model. The aim of this study was to compare the difference in cell motility between the helical and kinase domain mutation bearing human CRC cell lines. METHODS: Wound healing Assay was used to determine the motility of human CRC cells in vitro. Effect of PI3K inhibition on cell motility was tested under the treatments with 0.1 and 1.0 µM of wortmannin, which is a class 1 PI3K inhibitor, and PIK75, which is the specific inhibitor of p110α. RESULTS: Our data indicate that H1047R-p110α increases cell motility more than E545K-p110α and the inhibition of PI3K significantly delayed or abrogated the migration of CRC cells. Immuno-blotting analysis showed increased downstream survival signaling pathway activation of PI3K in the cells bearing H1047R-p110α knase domain mutation compared to the cells which have E545K-p110α helical domain mutation. CONCLUSION: The PI3K-p110α kinase mutation bearing CRC cells were more motile as compared to the helical domain mutation bearing cells. This data supports our previous in vivo data that kinase domain mutations have a greater metastatic capability than helical domain bearing mutants. Cell motility was abrogated by both nonspecific and p110α directed PI3K inhibition suggesting that the activation of PI3K is necessary for CRC cell motility. This data supports the efforts to target the PI3K pathway in patients with advanced CRC. 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 470. doi:1538-7445.AM2012-470
190 GRAFT DYSFUNCTION (GD) IN HBV RECURRENCEFREE RECIPIENTS IS ASSOCIATED WITH SERUM AUTOANTIBODIES REACTIVITY
Authors: M.F. Donato, E. Arosio, F. Agnelli, C. Rigamonti, M. Vigano, L. Caccamo, P. Lampertico, G. Rossi, M. Colombo
Journal: Journal of Hepatology (2008)
Cardioscience enters into history
Authors: P. Harris
Journal: Cardiovascular Research (1995)

Cardioscience enters into history Get access Peter Harris Peter Harris Venice, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 3, September 1995, Page 317, https://doi.org/10.1016/S0008-6363(95)90137-X Published: 01 September 1995
Dual Radionuclide Study of Acute Myocardial Infarction
Authors: HARVEY J. BERGER
Journal: Annals of Internal Medicine (1978)

We evaluated dual imaging with thallium-201 (201TI) and technetium-99m (99mTc) pyrophosphate in 80 patients with documented acute myocardial infarction (55 transmural, 25 nontransmural infarction). Color-coded isocount display of 201TI images was essential for interpretation in 16 patients. Combined 201TI and 99mTc-pyrophosphate imaging for infarct detection was 100% sensitive; however, either was falsely negative in 12 of 80 patients. False-negative individual 201TI or 99mTc-pyrophosphate infarct images were most common in patients with small infarcts or left ventricular hypertrophy. Thallium-201 images correctly localized the site of acute transmural infarction in all 51 patients with a positive image, while 99mTc-pyrophosphate localized the site of infarction in49 of 53 with an abnormal image. Comparison of the size of the imaged infarct region revealed size discordance in 25 of 49 patients, with 99mTc-pyrophosphate larger in 21 of 49 and201TI larger in only four of 49. Thus dual radionuclide imagingprovides definition of the presence and location of acute myocardial infarction.
Doctors involved in South Africa's biological warfare programme
Authors: P. Sidley
Journal: BMJ (1998)

South Africa has been rocked by a series of disclosures at the Truth and Reconciliation Commission concerning the previous government's biological and chemical warfare programme.

The programme, which was a military operation, was designed, run, staffed, and researched by doctors, scientists, a dentist, and at least one veterinarian. Leading the programme was Dr Wouter Basson, the private physician of the former president, P W Botha.

Although Dr Basson is required to testify before the Truth Commission (which is empowered by …
Anaphylactoid Reactions Associated With the Clinical Use of Dextran 70
Authors: Ronald Brisman
Journal: JAMA (1968)

Two of four new cases of anaphylactoid reactions associated with the use of dextran 70 occurred in a consecutive series of 84 hemodynamically stable patients, an incidence of 2.4%. These reactions developed immediately after intravenous infusion of small amounts of dextran 70. The reactions were characterized by generalized subjective discomforts rapidly followed by severe gastrointestinal disturbances and hypotension. The true nature of these reactions and the role and source of prior sensitization in unknown. The infusion of dextran 70 may provoke life-threatening reactions, especially in unconscious patients and in those with preexisting hypotension or intraabdominal pathological conditions.
Gastritis staging in clinical practice: the OLGA staging system
Authors: M. Rugge, A. Meggio, G. Pennelli, F. Piscioli, L. Giacomelli, G. De Pretis, D. Y Graham
Journal: Gut (2006)

The available classifications of gastritis are inconsistently used, possibly because none provides immediate prognostic/therapeutic information to clinicians. As histology reporting of hepatitis in terms of stage is clinically useful and widely accepted, an international group (Operative Link on Gastritis Assessment (OLGA)) proposed an equivalent staging system for reporting gastric histology. Gastritis staging integrates the atrophy score (obtained by biopsy) and the atrophy topography (achieved through directed biopsy mapping).To test in a prospective cross-sectional study whether OLGA staging consistently stratified patients according to their cancer risk and provided clear prognostic/therapeutic information.OLGA staging for gastric cancer risk (0-IV) and gastritis grading (overall score of the inflammatory infiltrate, grade 1-4) were applied in 439 prospectively enrolled, consecutive, dyspeptic outpatients who underwent endoscopy with standardised biopsy sampling. Incidental neoplastic lesions and coexisting peptic ulcers were recorded. Results were presented as stage (including antral (A) and corpus (C) atrophy scores) and H pylori status (eg, A = 3; C = 2: stage IV; Hp+ve).Benign conditions (including duodenal ulcers; p<0.001) consistently clustered in stages 0-II, whereas all neoplastic (invasive and non-invasive) lesions clustered in stages III-IV (p<0.001).Gastritis staging, combined with H pylori status, provided clinically relevant information on the overall status of the gastric mucosa with implications for prognosis, therapy and management.
Different S/M Checkpoint Responses of Tumor and Non–Tumor Cell Lines to DNA Replication Inhibition
Authors: Verónica Rodríguez-Bravo, Sandra Guaita-Esteruelas, Noelia Salvador, Oriol Bachs, Neus Agell
Journal: Cancer Research (2007)

Abstract Cell cycle checkpoint abrogation, especially the inhibition of Chk1 in combination with DNA-damaging treatments, has been proposed as a promising way of sensitizing cancer cells. However, less is known about the possibility to selectively affect tumor cells when they are treated with agents that block DNA synthesis in combination with replication checkpoint inhibitors. Here, we present clear insights in the different responses of tumor and non-transformed cells to the inhibition of DNA replication with hydroxyurea in combination with checkpoint abrogation via inhibition of Ataxia telangiectasia–mutated– (ATM) and Rad3-related/ATM (ATR/ATM) and Chk1 kinases. Interestingly, we find that non-transformed cell lines activate ATR/ATM- and Chk1-independent pathways in response to replication inhibition to prevent mitotic entry with unreplicated DNA. In contrast, tumor cell lines such as HCT116 and HeLa cells rely entirely on Chk1 activity for a proper response to replication inhibitors. Our results show that p38 is activated in response to hydroxyurea treatment and collaborates with Chk1 to prevent mitotic entry in non-transformed cell lines by maintaining cyclin B1/Cdk1 complexes inactive. Furthermore, DNA replication arrest down-regulates cyclin B1 promoter activity in non-transformed cells, but not in tumor cells in a Chk1- and p38-independent way. Thus, our data show that non-transformed cells present a more robust DNA replication checkpoint response compared with tumor cells that involves activation of the p38 pathway. We show that some of these responses to replication block can be lost in tumor cells, causing a defective checkpoint and providing a rationale for tumor-selective effects of combined therapies. [Cancer Res 2007;67(24):11648–56]
NRC Report on Diet and Health: An Ounce of Prevention...
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article NRC Report on Diet and Health: An Ounce of Prevention… Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 7, 5 April 1989, Pages 476–478, https://doi.org/10.1093/jnci/81.7.476 Published: 05 April 1989
How to learn scepticism
Authors: C. Brewer
Journal: BMJ (2013)

Sadly, routine scepticism—rather than routine willingness to believe what we wish to be true—still seems a rare commodity, even in science departments. It is, of course, even rarer in places where they teach alternative medicine and the infallibility of sacred texts, whether religious or homeopathic. Ten years after I qualified, Richard Feynman, Nobel laureate in physics, complained that “this long history of learning how not to fool ourselves, of having utter scientific integrity is, I’m sorry to say, something that we haven’t specifically included in any particular course that I know of. …
Comparison of the Effect of Plasmapheresis and Penicillamine on the Level of Circulating Rheumatoid Factor
Authors: I. A. Jaffe
Journal: Annals of the Rheumatic Diseases (1963)

Peniilamine.-Oneweek after return to control, DL-penicillamine was begun in a dosage of 0 5 g.four times daily.Precipitin curves were determined at
Response of psoriasis to sunbed treatment: comparison of conventional ultraviolet A lamps with new higher ultraviolet B-emitting lamps
Authors: S. Das, J.J. Lloyd, D. Walshaw, B.L. Diffey, P.M. Farr
Journal: British Journal of Dermatology (2002)

Summary Background Sunbeds fitted with conventional ultraviolet (UV) A lamps that have about 0·7% UVB emission are widely used by patients with psoriasis even though they are minimally effective. A new fluorescent sunbed lamp has been developed that emits a higher proportion of UVB (4·6%) than conventional lamps and also requires shorter exposure times to achieve equivalent erythema. Objectives To perform a randomized, within‐patient comparison of conventional sunbed lamps (Cleo Performance) with the new lamps (Cleo Natural) in the treatment of psoriasis. Methods A sunbed and canopy unit were modified to allow exposure to Cleo Performance lamps on one side of the body (front and back) and Cleo Natural lamps to the other side of the body. Two studies were done. In study 1, equal erythemal doses were given from the two lamp types. In study 2, equal exposure times were given. We treated 34 patients with psoriasis, giving 12 exposures over a period of 4 weeks. Assessment was made using a modified Psoriasis Area and Severity Index (PASI) score, individual plaque assessment and patient questionnaire. Results Fourteen patients completed each study. In study 1, there was no significant difference in median improvement in half‐body PASI score for the two lamp types. In study 2, there was a significant difference in PASI score improvement between the two lamps (median Cleo Performance change minus median Cleo Natural change was − 2·20; 95% confidence interval − 3·75 to − 0·65; P = 0·006). Conclusions That no difference in response was found when equal erythemal doses were given suggests that the spectral emission of the Cleo Natural lamp is of no greater advantage for clearance of psoriasis than conventional lamps. However, the Cleo Natural lamps are more erythemally powerful, and exposure times similar to those used in conventional sunbeds result in a significant improvement of psoriasis. The risk of non‐melanoma skin cancer from different patterns of exposure to Cleo Natural lamps can be estimated using established numerical models.
Isolated Antibody to Hepatitis B Core Antigen and the Immune Response to Hepatitis B Vaccination,-Reply
Authors: Ron B. Schifman
Journal: JAMA (1988)

<h3>In Reply.—</h3> In the majority of adults with acute hepatitis B infection, HBsAg and hepatitis B e antigen disappear after a short time, followed by seroconversion to anti-HBe, anti-HBc, and ultimately antibody to hepatitis B surface antigen. This pattern indicates a recovery phase. Conversely, chronic infection generally is marked by failure to develop antibody to hepatitis B surface antigen and persistance of HBsAg, anti-HBc, and either anti-HBe or hepatitis B e antigen. Anti-HBc and anti-HBe, when present as the only serological markers of hepatitis B infection, can signify past infection, with recovery and loss of antibody to hepatitis B surface antigen; or as in the case described by Drs Howell and Barbara, occult chronic infection with loss of HBsAg. Therefore, testing for anti-HBe to determine the significance of an isolated anti-HBc result would not help differentiate between these two diagnostic possibilities. Isolated low-titer anti-HBc also may represent a nonspecific false-positive
From Culture to Vaccine — Salk and Sabin
Authors: Samuel L. Katz
Journal: New England Journal of Medicine (2004)

The Nobel Prize–winning demonstration by John Enders, Frederick Robbins, and Thomas Weller that polioviruses could be propagated successfully in nonneural cell cultures paved the way for two brilliant, ambitious scientists to reorient and accelerate their development of poliovirus vaccines. The backgrounds of Jonas Salk (Figure) and Albert Sabin (Figure) were similar in many ways. Salk was born in New York City, the eldest son of an Orthodox Jewish designer of blouses in Manhattan's garment district. He was a superb student who made his way through a special high school for honors students, on to City College where he . . .