tbuckley/cabot-search huggingface dataset:
Abstract 2120: Cdk5 involves in interleukin-6 induces AR activation through phosphorylation of serine 727 Stat3 and serine 81 AR in prostate cancer cells
Authors: Jo-Hsin Wang, Pei-Chi Li, Li-Chiung Lin, Fu-Ning Hsu, Mei-Chih Chen, Ho Lin
Journal: Cancer Research (2014)

Abstract Signal transducer and activator of transcription 3 (Stat3), a common transcription factor, has been reported to regulate cancer development, including prostate cancer. Stat3 has also been suggested that its transcriptional activity is initiated by phosphorylation. The tyrosine 705 (Y705) and serine 727 (S727) phosphorylation of Stat3 were documented to Stat3 activation. Androgen receptor (AR) is a ligand-activated transcription factor that mediates the biological responses of androgens. Cyclin-dependent kinase 5 (Cdk5), which belongs to Cdk family, is a proline-directed serine/threonine kinase. Our previous results indicate that Cdk5 may phosphorylate AR at serine 81 site (S81) and increase AR stabilization and transactivation. On the other hand, previous studies have shown that Interleukin-6 (IL-6), which is a cytokine, activates androgen receptor (AR) via MAPK and Stat3-related pathway. Therefore, the aim of this study is to investigate if Cdk5 regulates S81 phosphorylation-related AR activation through S727 Stat3 phosphorylation under IL-6 treatment. First we observed IL-6 enhanced S727 phosphorylation of Stat3 and S81 phosphorylation of AR as well as AR protein level. Next, IL-6 increased AR biochemical interaction with Stat3 and AR stabilization, nuclear localization, and transactivation, which is correlated to S727 phosphorylation of Stat3. Subsequently, we found that IL-6 induced tyrosine 15 (Y15) phosphorylation of Cdk5, which is an indicator of Cdk5 activation, and this phosphorylation was inhibited by AG490 (JAK inhibitor). We also found that Y15-Cdk5 mutant (Y15F) decreased IL-6-induced phosphorylation of AR S81 and Stat3 S727 and the biochemical interaction between AR and Stat3 was also affected. In summary, these results suggest that IL-6 activated AR by S81 phosphorylation via S727 phosphorylation of Stat3 and Cdk5 might be an upstream regulator in the pathway. Citation Format: Jo-Hsin Wang, Pei-Chi Li, Li-Chiung Lin, Fu-Ning Hsu, Mei-Chih Chen, Ho Lin. Cdk5 involves in interleukin-6 induces AR activation through phosphorylation of serine 727 Stat3 and serine 81 AR in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2120. doi:10.1158/1538-7445.AM2014-2120
Influenza Immunization
Authors: Henry A. Cromwell
Journal: JAMA (1969)

The 437 residents (average age 78.3 years) and 203 employees (average age 40.0 years) of a retirement community were the subjects in a clinical study comparing immunological effectiveness and reactogenicity of two monovalent Hong Kong influenza vaccines—one a conventional, intact virus vaccine and the other a vaccine prepared from ethyl ether extracted influenza virus antigens. Vaccine pyrogenicity was virtually eliminated by ether treatment, and local and systemic subjective reactions in the antigen vaccinees were one-half to one-fourth as frequent as in the conventional vaccine group. The vaccines were of equal immunogenicity in both populations; however, resident serologic response greatly exceeded employee response presumably because of a youthful experience with a Hong Kong-like virus. Although the community members mingled freely with the general population during the Hong Kong epidemic, no influenzalike disease was observed.
Prevalence, Acquisition, and Clearance of Cervical Human Papillomavirus Infection among Women with Normal Cytology: Hawaii Human Papillomavirus Cohort Study
Authors: Marc T. Goodman, Yurii B. Shvetsov, Katharine McDuffie, Lynne R. Wilkens, Xuemei Zhu, Pamela J. Thompson, Lily Ning, Jeffrey Killeen, Lori Kamemoto, Brenda Y. Hernandez
Journal: Cancer Research (2008)

Abstract Few natural history studies of cervical human papillomavirus (HPV) incidence and duration have been conducted among older women, especially from multiethnic populations. Viral and nonviral determinants of HPV acquisition and clearance were examined among 972 sexually active women, ages 18 to 85 years, recruited from clinics on Oahu, Hawaii, and followed for a mean duration of 15 months (range, 2–56 months). Interviews and cervical cell specimens for cytology and HPV DNA detection by PCR, using the PGMY09/PGMY11 primer system, were obtained at baseline and at 4-month intervals. The prevalence of cervical HPV infection was 25.6% at study entry. A total of 476 incident genotype-specific infections were observed during the follow-up period. The incidence of high-risk (HR) HPV types (9.26 per 1,000 woman-months) was similar to low-risk (LR) HPV types (8.24 per 1,000 woman-months). The most commonly acquired HR-HPV types were HPV-52, HPV-16, and HPV-31; and their incidence was increased significantly with a coexisting cervical HPV infection. Cervical HPV acquisition decreased with age, income, and long-term use of oral contraceptives and increased with number of sexual partners, use of hormonal creams, alcohol drinking, and condom use by a sexual partner. Cohort participants cleared 265 of the 476 incident infections during follow-up. LR-HPV infections cleared more rapidly than did HR-HPV infections (median, 180 days versus 224 days). Clearance times were enhanced among older women and women with multiple infections. Our data suggest several viral and nonviral determinants of cervical HPV acquisition and clearance that might be used in cervical cancer prevention programs. [Cancer Res 2008;68(21):8813–24]
Myoedema and vitamins.
Authors: A. N. Patel
Journal: BMJ (1969)

MMICAJOUNALfour thugs, and having had a chair broken over his head at three o'clock in the morning, is back at work functioning efficiently by about 9 a.m.?The only logical explanation is that being beaten unconscious really does very little harm to anyone.Let us have less violence and a more realistic presentation of the after-effects of trauma -I am, etc.,
Judging a Confession
Authors: Sheila Feit
Journal: Annals of Internal Medicine (2004)

Letters6 April 2004Judging a ConfessionSheila Feit, MDSheila Feit, MDFrom Syosset, NY 11791.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-7-200404060-00040 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The story told in “Confession” (1)—of an army doctor who destroys the medical record of a wife's miscarriage to shield it from her cuckolded husband—was troubling. The incident seems to date from decades ago, when a perhaps more paternalistic brand of medicine existed. But it was still wrong.The problem seems to have arisen because the doctor identified more with the husband than with the patient, his wife. But the doctor's obligation was still to her. Moral issues aside, the record could have become relevant, in case of complications or future gynecologic problems, for example. And, in ...Reference1. Confession. Ann Intern Med. 2003;139:229-30. [PMID: 12899591] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Syosset, NY 11791. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoConfession H. James Merchant Judging a Confession H. James Merchant Metrics 6 April 2004Volume 140, Issue 7Page: 585-586KeywordsForecastingMiscarriage ePublished: 6 April 2004 Issue Published: 6 April 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Proposal to stop bad doctors setting up elsewhere
Authors: T. Sheldon
Journal: BMJ (1997)

Proposals to protect patients against doctors who move to another country in the European Union after being found guilty of professional misconduct have been launched at an Amsterdam symposium this week. They include setting up a computerised European databank with details on qualifications and disciplinary matters that would be mandatory for any host country to check.

As part of its six month presidency of the EU the Netherlands is seeking to strengthen EU directive 93/16 EEC, which regulates …
Helicobacter pylori secretes a chemotactic factor for monocytes and neutrophils.
Authors: P M Craig, M C Territo, W E Karnes, J H Walsh
Journal: Gut (1992)

Helicobacter pylori is associated with an inflammatory reaction in the stomach and duodenum, yet the mechanism of this inflammatory infiltrate is unknown. The ability of Helicobacter pylori to secrete a factor that attracts leucocytes is investigated. Helicobacter pylori conditioned supernatant attracted neutrophils and monocytes with 50-100% of the activity of control chemotactic factor, 10(-8) M formyl-methionine-leucine-phenylalanine. Strains derived from individuals with ulcer or non-ulcer associated H pylori infections displayed similar chemotactic activity. Preliminary characterisation shows that the factor has a molecular weight of less than 3000, is heat stable, is acid resistant, and can be diluted at least 10-fold. Checkerboard analysis confirmed that the activity was chemotactic rather than chemokinetic. This chemotactic activity could play a role in the pathogenesis of Helicobacter pylori gastritis.
M28 From NEWS to CREWS: The chronic respiratory early warning score for patients with chronic hypoxaemia: Abstract M28 Table 1.
Authors: SR Eccles, C Subbe, D Hancock, N Thompson
Journal: Thorax (2013)

<h3>Introduction</h3> In patients with respiratory conditions associated with chronic hypoxaemia such as COPD, use of the National Early Warning Score (NEWS)[1] leads to a high number of triggers. We designed a simple variant of NEWS for patients with chronic hypoxaemia. <h3>Methods</h3> Data was collected from respiratory wards at two hospitals in North Wales over a three-month period. Patients were categorised into those with chronic hypoxaemia (CH, target oxygen saturations 88–92%) and others (O, target saturations 94–98%). Vital signs were recorded on admission to hospital, at the peak NEWS score during admission, and during a period of stability/at discharge. <h3>Results</h3> 196 admissions were included in the analysis. 98 (50%) were male, 91 had COPD, 26 received long-term oxygen therapy. Mean age was 70 (range 19–102). 78 patients had target saturations of 88–92% (CH patients). The mean NEWS for all patients on admission was 5 (SD 3), mean peak NEWS was 7 (SD 3), and median hospital length of stay was 10 days (IQR 6:17). 23 patients died within 30 days; 12 with CH. Of these, all patients with CH scored 6 + using NEWS compared to 9/11 O patients. When stable/at discharge, 32% of CH patients scored 6 + using NEWS (Welsh trigger) and 50% scored 5 + (RCP trigger). By using a recalibrated scoring system (CREWS, table 1), patients triggering during stability/at discharge were reduced to 14% (5 + trigger) and 8% (6 + trigger). All patients who subsequently died still triggered at peak CREWS scores. <h3>Conclusion</h3> Patients with chronic respiratory conditions have altered baseline parameters that lead to a high number of NEWS triggers. CREWS reduces triggers, which may reduce unnecessary reviews and alarm fatigue, without compromising safety. <h3>Reference</h3> Royal College of Physicians. National Early Warning Score (NEWS): Standardising the assessment of acute illness severity in the NHS. Report of a working party. London: RCP, 2012.
Doctors in Japan oppose government plans to reform universal healthcare system
Authors: G. Blair
Journal: BMJ (2013)

The Japan Medical Association (JMA), the largest doctors’ group in the country, which represents most private practices and local clinics, is opposing reforms of the universal healthcare system proposed by the government as part of its attempts to deregulate the economy. 

Prime Minister Shinzo Abe, who took power in December 2012, has included healthcare reform as a central pillar of the “third arrow” of his economic plans, which have been dubbed “Abenomics.”

The issue of most concern to doctors is an end to the current ban on mixed public and private treatments, which is seen as vital in maintaining the universal nature of the health insurance and care system, established in 1961. The ban means that, …
Improved inflammatory activity with peginterferon alfa-2b maintenance therapy in non-cirrhotic prior non-responders: A randomized study
Authors: Thierry Poynard, Jordi Bruix, Eugene R. Schiff, Moises Diago, Thomas Berg, Ricardo Moreno-Otero, Andre C. Lyra, Flair Carrilho, Louis H. Griffel, Navdeep Boparai, Ruiyun Jiang, Margaret Burroughs, Clifford A. Brass, Janice K. Albrecht
Journal: Journal of Hepatology (2012)
Letters: CD4+ Lymphocytopenia in Systemic Lupus Erythematosus
Authors: Jeffrey Laurence
Journal: Annals of Internal Medicine (1994)

Letters15 January 1994Letters: CD4+ Lymphocytopenia in Systemic Lupus ErythematosusJeffrey Laurence, MDJeffrey Laurence, MDLaboratory for AIDS Virus Research; Cornell University Medical College; New York, NY 10021Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-2-199401150-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Cytotoxic antilymphocyte antibodies, particularly those restricted to the CD4+ subpopulation of T lymphocytes, may be a factor in idiopathic T-cell depletion, as I briefly noted [1]. They also arise in HIV infection [2], although the lack of a consistent relation between antilymphocyte antibodies titer and the extent of CD4+ or CD8 (+) T-cell depletion or both [3] mitigates their clinical relevance. Disorders with an autoimmune component, such as systemic lupus erythematosus, similarly manifest antilymphocytic antibody [4]. Lymphocytopenia occurs in less than 80% of patients with systemic lupus erythematosus during the acute clinical phase and is often accompanied by ...References1. Laurence J. T-cell subsets in health, infectious disease, and idiopathic CD4+ T lymphocytopenia. Ann Intern Med. 1993; 119:55-62. Google Scholar2. Stricker RB, McHugh TM, Moody DJ, Morrow WJ, Stites DP, Shuman MA, et al. An AIDS-related cytotoxic autoantibody reacts with a specific antigen on stimulated CD4+ T cells. Nature. 1987; 327: 710-3. Google Scholar3. Schattner E, Laurence J. HIV induced T-lymphocyte depletion. Clin Lab Med. 1993; (In press). Google Scholar4. Laurence J, Wong JE, Nachman R. The cellular hematology of systemic lupus erythematosus. In: Lahita RG, ed. Systemic Lupus Erythematosus. Second edition. New York:Churchill Livingstone; 1992:771-806. Google Scholar5. Stohl W, Crow MK, Kunkel HG. Systemic lupus erythematosus with deficiency of the T4 epitope on T helpher/inducer cells. N Engl J Med. 1985; 312:1671-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: Laboratory for AIDS Virus Research; Cornell University Medical College; New York, NY 10021 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAntibodies to CD4 in primary Sjögren's syndrome 15 January 1994Volume 120, Issue 2Page: 168-169KeywordsAntibodiesAntibody productionHIV infectionsHIV-1Human leukocyte antigenLupus erythematosusLymphocytesLymphopeniaMonoclonal antibodies Issue Published: 15 January 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Cusp degeneration in frame-supported autologous fascia lata mitral valves: Clinical results in 67 patients
Authors: M. T. McEnany, D. N. Ross, A. K. Yates
Journal: Thorax (1972)

Sixty-seven metal-frame-supported autologous fascia lata mitral valves were placed in 67 patients. There was an operative mortality of 25% and an overall mortality of 40% within 20 months. Most of the late deaths were due to valve malfunction which occurred in 50% of survivors. Female patients demonstrated a much higher rate of valve dysfunction than did men. This mal-function of the fascial valves in the mitral position, which has not been observed in the aortic position, may be due to inappropriate design for the mitral position. The fascia is not exposed to the continued and reproducible mechanical stimulation in the atrioventricular position that it has when used as an aortic valve substitute. The mechanical properties of fascia may make it suitable for human valve substitutes but it is clear that an inverted three-cusped semilunar fascial valve will not be adequate for mitral or tricuspid valve replacements because of the haemodynamic characteristics of the atrioventricular position.
Arsenic Exposure and Motor Function among Children in Bangladesh
Authors: Faruque Parvez, Gail A. Wasserman, Pam Factor-Litvak, Xinhua Liu, Vesna Slavkovich, Abu B. Siddique, Rebeka Sultana, Ruksana Sultana, Tariqul Islam, Diane Levy, Jacob L. Mey, Alexander van Geen, Khalid Khan, Jennie Kline, Habibul Ahsan, Joseph H. Graziano
Journal: Environmental Health Perspectives (2011)

Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children's intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function.
On Probability and Possibility
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1974)

STATISTICALLY, the probability of any one of us being here is so small that you'd think the mere fact of existing would keep us all in a contented dazzlement of surprise. We are alive against the stupendous odds of genetics, infinitely outnumbered by all the alternates who might, except for luck, be in our places.Even more astounding is our statistical improbability in physical terms. The normal, predictable state of matter throughout the universe is randomness, a relaxed sort of equilibrium, with atoms and their particles scattered around in an amorphous muddle. We, in brilliant contrast, are completely organized structures, . . .
Sinusitis in the common cold
Authors: Tuomo Puhakka, Mika J. Mäkelä, Anu Alanen, Timo Kallio, Leo Korsoff, Pertti Arstila, Maija Leinonen, Markku Pulkkinen, Jouko Suonpää, Jussi Mertsola, Olli Ruuskanen
Journal: Journal of Allergy and Clinical Immunology (1998)
Who Teaches Physiological Chemistry?
Authors: John W. Mehl
Journal: JAMA (1966)

<h3>To the Editor:—</h3> With his recent article, "Who Teaches Physiological Chemistry?" (<b>197</b>:409, 1966), Samuel P. Bessman, MD, will undoubtedly have succeeded in raising the hackles of his fellow American biochemists. My initial reaction was one of less than unqualified acceptance, but after thinking more about the situation I would certainly have to agree that there is a serious problem, and that to some degree the conclusions which he reaches as to possible solutions are correct. His argument suffers, however, from what appear to me to be some historical inaccuracies and some defects in logic. The Flexner Report certainly had a most important effect in making possible the tremendous developments in basic biochemistry. It assured biochemistry of an increased number of academic homes in which biochemists could make their own choice of areas of research which they believed would be most fruitful in developing an understanding of biochemical mechanisms. Through
Postoperative diabetes insipidus
Authors: J P Monson, M I Mccarthy, G C Toms
Journal: BMJ (1989)

stores and that those patients with the greatest aluminium burden had an increased mortality after infection.4As most aluminium given to patients with acute renal failure is taken up by soft tissues, including the liver and spleen, but not by bone' and thus enters the reticuloendothelial system it is not surprising that aluminium may have an immunomodulatory role.Although this may be of benefit to the recipient of a renal transplant, aluminium accumulation should be avoided in patients with acute renal failure, in whom sepsis remains a major cause of both morbidity and mortality.
Abstract 230: Connectivity-map analyses identify FDA-approved drugs targeting breast cancer stem cells.
Authors: Poornima Bhat-Nakshatri, Chirayu Goswami, Sunil Badve, George W. Sledge, Harikrishna Nakshatri
Journal: Cancer Research (2013)

Abstract Recently developed genomics-based tools are allowing repositioning of established drugs as cancer treatments. This approach has not been employed extensively to identify drugs that may target cancer stem cells (CSCs) of solid tumors. CD44+/CD24- cancer cells are the first described CSCs for breast cancer, which are enriched in mesenchymal stem-like (MSL) and mesenchymal-like (ML) subtypes of triple negative (TNBCs) and in anti-estrogen resistant breast cancers. We subjected gene expression array datasets containing list of genes differentially expressed in CD44+/CD24- CSCs compared to non-CSCs as well as in cells enriched for other markers of CSCs including CD271 and GD3S (six datasets in total) to connectivity map (CMAP) to identify drugs that may reverse gene expression patterns unique to CSCs. All trans retinoic acid (ATRA) was negatively connected with gene expression in CD44+/CD24-, CD271+, and GD3S+ CSCs as well as in ML and MSL subtypes of TNBCs. Independently, ATRA was found to modulate the expression of several genes in the recently described CSC-enriched Yes-Associated Protein (YAP) signature. ATRA-inducible genes of the YAP signature were associated with good prognosis, whereas ATRA-repressible genes were associated with poor prognosis, depending on the subtype of breast cancer. ATRA reduced mammosphere forming ability of breast cancer cells including acquired anti-estrogen resistant cells, which correlated with ATRA-mediated reduction of the critical stemness-associated gene SOX2 and induction of SOX21, which functions as a differentiation factor depending on the cell type. CD44+/CD24- breast cancer cell line with K-ras mutation was resistant to ATRA, which was reversed by MAP kinase inhibitors. From these results, we propose ATRA as a potential therapy for specific subtypes of breast cancers enriched for CSCs. A biomarker-driven patient selection may help to identify patients who may benefit from ATRA therapy. Citation Format: Poornima Bhat-Nakshatri, Chirayu Goswami, Sunil Badve, George W. Sledge, Harikrishna Nakshatri. Connectivity-map analyses identify FDA-approved drugs targeting breast cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 230. doi:10.1158/1538-7445.AM2013-230
BRADYCARDIA IN APPENDICITIS.
Authors: MAURICE KAHN
Journal: JAMA (1906)

A careful research of the literature at my command has failed to reveal any mention of bradycardia in appendicitis, the nearest approach thereto being the statement that the pulse and temperature are not to be relied on to too great a degree, as they are both, at times, capricious, even rarely being normal in the presence of a virulent condition. It is generally acknowledged that the symptoms of gangrenous appendicitis may be latent and exceedingly deceptive, and every surgeon realizes that early recognition and prompt interference is the only harbor of safety in this malignant form of appendicitis; and, conversely, that danger reposes on the rocks of tardy enlightenment and delayed operation, which has wrecked many surgical mariners, and still continues to augment our mortality rate in this disease. Hence the great importance attaching to any new symptom which may project further light on a given case prior to the