tbuckley/cabot-search huggingface dataset:
Abstract 2596: Identification and characteration of IKBKE kinase inhibitor selectively inhibits tumor growth in cancer cells
Authors: Jianping Guo, Donghwa Kim, Jin Q. Cheng
Journal: Cancer Research (2011)

Abstract The serine/threonine kinase IKBKE is frequently altered in human cancer. Ectopic expression of IKBKE induces malignant transformation, cell migration, invasion and chemoresistance. Thus, IKBKE is an attractive target for anti-cancer drug discovery. By screening a small molecule compound library, we identified an IKBKE inhibitor, MCCK1. It inhibits IKBKE kinase as well as downstream targets of IKBKE including phosphorylation such as Iκ-Bα, P65 and IRF3. MCCK1 is highly selective for IKBKE and does not inhibit the activation of IKKβ, STAT3, Erk-1/2, p38 or JNK. The inhibition of IKBKE by MCCK1 results in induction of cell growth arrest and apoptosis selectively in human cancer cells that harbor aberrant expression IKBKE. Further, MCCK1 inhibits tumor growth in nude mice of human cancer cells in which IKBKE is elevated but not of those cancer cells in which it is not. These data indicate that MCCK1 is an IKBKE inhibitor with anti-tumor activity in vitro and in vivo and could be a potential anti-cancer agent for patients whose tumors express elevated IKBKE. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2596. doi:10.1158/1538-7445.AM2011-2596
Examination of the Hand
Authors: Richard A. Silver
Journal: JAMA (1972)

<i>Examination of the Hand</i>represents the author's years of clinical experience dealing with hand injuries and their resultant sequelae. The text is divided into three convenient sections: "Acute Injury," "Evaluation of Reconstructive Problems," and "Disability Evaluation," in each of which the author details his methodical approach to the patient presenting with a hand problem. The hand is thoroughly evaluated by individual assessment of the skin, circulation, sensation, tendon and bone integrity. Xrays and special studies are utilized when necessary. Chapters in the second section, "Evaluation of Reconstructive Problems," merit particular praise—for this section details for the interested physician an awareness of the anatomical variations and a logical approach for the care of an injured hand. The making of an accurate diagnosis is stressed. The recent advances in hand surgery have shown that the optimum situation for both patient and surgeon alike is for the patient to come under the care
Author's reply to Witham and colleagues
Authors: L. Targownik
Journal: BMJ (2012)

Witham and colleagues express concern about my recommendation to consider co-prescribing proton pump inhibitors (PPIs) for patients using concomitant aspirin and clopidogrel for prevention of cardiovascular complications because of the associated medical complications.1 2 They go on to state that the increased risk of serious gastrointestinal complications associated with dual antiplatelet treatment has been shown only …
Oliver St John Gogarty, MD, FRCSI (1878-1957)
Authors: J.B. Lyons
Journal: JAMA (1979)

Writing to a Boston friend in 1934, Oliver St John Gogarty, MD, aviator, archer, and former cycling champion, said: I, for my poor part, have chosen the sock and not the Miltonian buskin. My spirit is God given? Very well: why does it prefer Aristophanes to Aeschylus?... Because the first does not usurp the metier of the Gods: and we are not thronged with destiny. In his youth (he was born on Aug 17, 1878, the eldest son of Henry Gogarty, FRCSI), when attending Trinity College, Dublin, his wit, levity, and irreverence made him an apt companion for James Joyce. He is Buck Mulligan in<i>Ulysses</i>—"Buck Mulligan, panamahelmeted, went step by step, iambing, trolling"—but when the novel was published, Gogarty was a member of the Irish Free State Senate and a leading ear, nose, and throat surgeon. Understandably, he resented the overstated characterization. He was more sensitive and less
Harvard students protest over closure of primary care programme
Authors: J. Lenzer
Journal: BMJ (2009)

Medical students at Harvard University have sent a petition to the dean of the Harvard Medical School protesting against the termination of a primary care programme at the medical school. By the end of last week more than 500 Harvard medical students, doctors, and others had signed the online petition.

The cutbacks and the protest come amid a national debate over a shortage of primary care practitioners in the United States, a problem that is expected to worsen if President Barack Obama’s planned insurance coverage is extended to the 40 million to 50 million people who are currently …
Don't ignore preventive message of baby Jayden's case
Authors: P. J. Lucas, T. Jessiman, A. Cameron
Journal: BMJ (2012)

We read the judgement of the prosecution of the parents of baby Jayden with sadness and interest. 1 It is accepted that Jayden had congenital rickets-he was born with it, probably because his mother was vitamin D deficient during pregnancy.He was entirely breast fed; one of the sad facts is that, unbeknown to his mother or those advising her, this contributed to his vitamin D deficiency.
Acute exacerbations of asthma in adults: role of Chlamydia pneumoniae infection
Authors: L Allegra, F Blasi, S Centanni, R Cosentini, F Denti, R Raccanelli, P Tarsia, V Valenti
Journal: European Respiratory Journal (1994)

Respiratory infections precipitate wheezing in many asthmatic patients and may be involved in the aetiopathogenesis of asthma. Several studies have demonstrated that viral infections may provoke asthma. Bacterial infections seem to play a minor role. However, Chlamydia pneumoniae has been recently reported as a possible cause of asthma. The aim of the present study was to evaluate the role of C. pneumoniae infection in acute exacerbations of asthma in adults. Seventy four adult out-patients with a diagnosis of acute exacerbation of asthma were studied. Acute and convalescent (&gt; or = 3 weeks) serological determination of antibodies to cytomegalovirus, respiratory syncytial virus, adenovirus, influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae and Legionella pneumophila were performed by means of immunofluorescence tests. C. pneumoniae specific antibodies were detected by two microimmunofluorescence tests using a specific antigen (TW-183) and a kit with three chlamydial antigens. Pharyngeal swab specimens were also obtained for C. pneumoniae identification. Samples for bacterial culture were obtained in patients with productive cough (15 out of 74 patients). Fifteen patients (20%) presented seroconversion to at least one of the studied pathogens. Seven were found to be infected by virus, six by C. pneumoniae alone, and one by M. pneumoniae. One more patient showed seroconversion to C. pneumoniae and cytomegalovirus.(ABSTRACT TRUNCATED AT 250 WORDS)
TAP1 and TAP2 polymorphisms analysis in northwestern Colombian patients with systemic lupus erythematosus
Authors: P A Correa
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To determine the influence of TAP1 and TAP2 alleles in northwestern Colombian patients with systemic lupus erythematosus (SLE). <b>Methods:</b> Unselected patients with SLE (n=140) and controls (n=120) matched for sex, age, and ethnicity were analysed. Clinical manifestations, clinical activity, and severity of disease were recorded. Autoantibodies were detected by enzyme linked immunosorbent assay (ELISA). TAP1 and TAP2 polymorphisms were determined by amplification refractory mutation system-polymerase chain reaction. A Hardy-Weinberg equilibrium test, microdifferentiation analysis, linkage disequilibrium analysis, and haplotype and allele frequency comparisons were performed. <b>Results:</b> The TAP2 variant Val379/Ala565/Ala665 (allele TAP2*0201) was associated with SLE (56% <i>v</i> 39%; odds ratio=2, 95% confidence interval 1.22 to 3.30, p<sub>c</sub>=0.03). There was no stratification between patient and control samples. Linkage disequilibrium between TAP1 and TAP2 loci was found in controls but not in patients. An excess in the number of heterozygotes in the TAP2 locus was found in patients. No association between TAP1 and TAP2 variants and the presence of autoantibodies, clinical expression, or severity of disease was found. <b>Conclusions:</b> The TAP2 locus influences susceptibility to SLE in our patient group; however, it has no significant effect on the immune response or on the clinical course of the disease.
A PORTABLE APPARATUS FOR STOMACH DOUCHE.
Authors: R. M. HARBIN
Journal: JAMA (1907)

A simple and at the same time efficient means for irrigating the stomach can be made by bisecting the tube of an ordinary fountain syringe and inserting a glass T tube to which an ordinary stomach tube may be attached. The stomach tube may be first introduced and then the attachment is made. While the left hand steadies the stomach tube the fingers of the right hand alternately compress at A and B. By having the stomach tube and a glass T the ordinary household fountain syringe may be made available in less than a minute in emergency cases. The whole apparatus may be sterilized and wrapped in paper so as to be carried in the coat pocket. Recovery After Carbolic Acid Poisoning.—The<i>Gaz. méd. Beige</i>, xix, 208, relates that d'Hotel was able to save two patients who had taken carbolic acid by prolonged rinsing out of the stomach, although
Prostatic Acid Phosphatase Is an Ectonucleotidase and Suppresses Pain by Generating Adenosine
Authors: Mark J. Zylka, Nathaniel A. Sowa, Bonnie Taylor-Blake, Margaret A. Twomey, Annakaisa Herrala, Vootele Voikar, Pirkko Vihko
Journal: Neuron (2008)
Troponin I isoform expression in human heart.
Authors: N M Hunkeler, J Kullman, A M Murphy
Journal: Circulation Research (1991)

Troponin I is the inhibitory component of troponin, the thin filament regulatory complex in striated muscle. Separate genes encode cardiac-specific fast and slow skeletal-specific isoforms of this protein. We have previously described gene switching from the slow skeletal to the cardiac troponin I mRNA expression in developing rat heart. The purpose of this work was to characterize the expression of the different troponin isoforms in the human heart. Human cardiac and slow skeletal troponin I cDNA probes were obtained by screening an adult cardiac cDNA library and by Taq polymerase amplification of RNA from an infant's heart, respectively. We found that the cardiac troponin I isoform is tissue-specific in its expression in normal adult tissues. RNA blot analysis of cardiac ventricular RNA from infants with congenital heart disease and from an adult with cardiomyopathy revealed expression of human cardiac troponin I in all analyzed specimens. In addition, we found expression of slow skeletal troponin I mRNA and protein in infant hearts but no detectable mRNA expression in the adult heart. We conclude that troponin I isoforms are developmentally regulated in the human heart by a mechanism similar to that in the rat heart.
Explaining socioeconomic differences in sickness absence: the Whitehall II Study.
Authors: F North, S L Syme, A Feeney, J Head, M J Shipley, M G Marmot
Journal: BMJ (1993)

To describe and explain the socioeconomic gradient in sickness absence.Analysis of questionnaire and sickness absence data collected from the first phase of the Whitehall II study. Grade of employment was used as a measure of socioeconomic status.20 civil service departments in London.6900 male and 3414 female civil servants aged 35-55 years.Rates of short spells (< or = 7 days) and long spells (> 7 days) of sickness absence.A strong inverse relation between grade of employment and sickness absence was evident. Men in the lowest grade had rates of short and long spells of absence 6.1 (95% confidence interval 5.3 to 6.9) and 6.1 (4.8 to 7.9) times higher than those in the highest grade. For women the corresponding rate ratios were 3.0 (2.3 to 3.9) and 4.2 (2.5 to 6.8) respectively. Several risk factors were identified, including health related behaviours (smoking and frequent alcohol consumption), work characteristics (low levels of control, variety and use of skills, work pace, and support at work), low levels of job satisfaction, and adverse social circumstances outside work (financial difficulties and negative support). These risk factors accounted for about one third of the grade differences in sickness absence.Large grade differences in sickness absence parallel socioeconomic differences in morbidity and mortality found in other studies. Identified risk factors accounted for a small proportion of the grade differences in sickness absence. More accurate measurement of the risk factors may explain some of the remaining differences in sickness absence but other factors, as yet unrecognised, are likely to be important.
Pharmacologic Treatment of Acute Traumatic Brain Injury
Authors: Alan I. Faden
Journal: JAMA (1996)

During the past several years, results of clinical trials have generated considerable optimism about the prospects for effective treatment of acute central nervous system (CNS) injuries. A multicenter trial demonstrated the effectiveness of methylprednisolone, as well as naloxone hydrochloride, in improving neurologic recovery after spinal cord injury.<sup>1</sup>In ischemic stroke, early treatment with tissue plasminogen activator<sup>2</sup>or treatment with low-molecular-weight heparin<sup>3</sup>led to improved outcome for some patients. To date, however, no effective pharmacotherapy has been developed for head injury. One of the more promising experimental strategies for treatment of acute CNS injury has been the use of antioxidants or free-radical scavengers. This approach is based on the concept that oxygen free radicals are generated in response to the insult, thereby overwhelming endogenous antioxidant or free radical-scavenging systems such as superoxide dismutase (SOD), catalase, glutathione, ascorbic acid, and α-tocopherol.<sup>4,5</sup>Free radicals are believed to contribute to
Mitochondria Are the Major Targets in Albumin-Induced Apoptosis in Proximal Tubule Cells
Authors: Elif Erkan, Prasad Devarajan, George J. Schwartz
Journal: Journal of the American Society of Nephrology (2007)

Nephrotic-range proteinuria is considered a poor prognostic factor. A correlation between tubulointerstitial injury and the degree of proteinuria is well established. In an attempt to explain the tubular atrophy that is observed in advanced glomerulonephritides, this study investigated apoptotic mechanisms in cultured human proximal tubule cells (HKC-8) that were exposed to endotoxin-free albumin (5, 10, and 20 mg/ml). Apoptosis was detected by Hoechst 33342; annexin staining; and assays for caspases 3, 8, and 9. The apoptotic effect of albumin was maximal at 10 mg/ml albumin, and necrosis prevailed in cells that were incubated with 20 mg/ml. Increase in caspase-9 and -3 activity was observed starting at 6 and maximally at 16 to 24 h. The proapoptotic Bcl-2 protein Bax was upregulated at 6 h, associated with translocation of cytochrome-c from mitochondria to cytosol and alteration in the mitochondrial membrane potential. Production of reactive oxygen species (ROS) was significant at 6 h but declined at 16 and 24 h. Treatment with ROS scavenger dimethylthiourea or antioxidant N-acetylcysteine did not alleviate caspase-3 production. Pan protein kinase C inhibitor bisindolylmaleimide-1 protected the cells from apoptosis. It is concluded that albumin induces apoptosis in human proximal tubule cells by stimulating mitochondrial apoptotic pathway independent of ROS production.
Myelodysplastic syndrome with trisomy 8 in an adolescent with fanconi anaemia and selective igA deficiency
Authors: Graham R. Standen, Leuan A. Hughes, A. Denise Geddes, Brian M. Jones, Charles A. J. Wardrop
Journal: American Journal of Hematology (1989)

Abstract We describe a patient with growth failure and multiple congenital anomalies characteristic of Fanconi anaemia, but without the classical feature of progressive bone marrow hypoplasia. Following treatment with growth hormone for a period of 8 years, he presented with myelodysplastic syndrome and a karyotypically abnormal clone in the bone marrow (47,XY, + 8). The diagnosis of Fanconi anaemia was supported by the induction of abnormally high levels of characteristic chromosome aberrations in peripheral lymphocytes following exposure in vitro to the bifunctional alkylating agent mitomycin C. Immune function studies also identified a selective IgA deficiency. The relative importance of interacting constitutional and exogenous factors involved in the development of preleukaemia in this patient is discussed.
Update on primary sclerosing cholangitis
Authors: Tom H. Karlsen, Kirsten Muri Boberg
Journal: Journal of Hepatology (2013)

Primary sclerosing cholangitis (PSC) remains one of the most challenging conditions of clinical hepatology. There has been a steady growth in research to overcome this fact and the present review aims at summarizing the most recently published literature. The main emphasis will be put on the link of recent pathogenetic insights to clinical characteristics and patient management. With regard to pathogenesis, there is no consensus yet as to whether immune mediated injury or factors related to bile acid physiology are the most important. It also remains to be clarified whether PSC is a mixed bag of various secondary etiologies yet to be defined, or a disease entity predominantly represented by sclerosing cholangitis in the context of inflammatory bowel disease. Most important, there is no available medical therapy with proven influence on clinical end points, and timing of liver transplantation and patient follow-up are challenging due to the unpredictable and high risk of cholangiocarcinoma.
Unicef warns of “epidemic” of childhood malnutrition
Authors: Peter Moszynski
Journal: BMJ (2006)

B lymphocytes are important players of the adaptive immune system. However, not just activation of B cells but also regulation of B cell signaling is important to prevent hyperactivity and dysregulation of the immune response. Different mechanisms and proteins contribute to this balance. One of these is CD22, a member of the Siglec family. It is an inhibitory coreceptor of the BCR and inhibits B cell activation. Upon BCR stimulation, CD22-dependent inhibition of BCR signaling results in a decreased calcium mobilization. Although some CD22 binding partners have already been identified, the knowledge about the CD22 interactome is still incomplete. In this study, quantitative affinity purification–mass spectrometry enabled the delineation of the CD22 interactome in the B cell line DT40. These data will clarify molecular mechanisms and CD22 signaling events after BCR activation and revealed several new CD22-associated proteins. One new identified interaction partner is the E3 ubiquitin ligase cullin 3, which was revealed to regulate CD22 surface expression and clathrin-dependent CD22 internalization after BCR stimulation. Furthermore cullin 3 was identified to be important for B lymphocytes in general. B cell–specific cullin 3-deficient mice show reduced developing B cells in the bone marrow and a severe pro-B cell proliferation defect. Mature B cells in the periphery are also reduced and characterized by increased CD22 expression and additionally by preactivated and apoptotic phenotypes. The findings reveal novel functions of cullin 3 in B lymphocytes, namely regulating CD22 surface expression and internalization after B cell activation, as well as promoting proliferation of pro-B cells.
Pathomechanisms in rheumatoid arthritis -- time for a string theory?
Authors: Cornelia M. Weyand, Jörg J. Goronzy
Journal: Journal of Clinical Investigation (2006)

RA is a quintessential autoimmune disease with a growing number of cells, mediators, and pathways implicated in this tissue-injurious inflammation. Now Kuhn and colleagues have provided convincing evidence that autoantibodies reacting with citrullinated proteins, known for their sensitivity and specificity as biomarkers in RA, enhance tissue damage in collagen-induced arthritis (see the related article beginning on page 961). This study adds yet another soldier to the growing army of autoaggressive mechanisms that underlie RA. With great success researchers have dismantled the pathogenic subunits of RA, adding gene to gene, molecule to molecule, and pathway to pathway in an ever more complex scheme of dysfunction. The complexity of the emerging disease model leaves us speechless. It seems that with this wealth of data available, we need to develop a new theory for this disease. We may want to seek guidance from our colleagues in physics and mathematics who have successfully integrated their knowledge of elementary particles and the complexity of their interacting forces by formulating the string theory.
Incidence and size of erosions in the wrist and hand of rheumatoid patients: a quantitative microfocal radiographic study.
Authors: J C Buckland-Wright, S R Walker
Journal: Annals of the Rheumatic Diseases (1987)

Quantitative macroradiographic examination of a group of early to moderately advanced rheumatoid patients showed the wrist and hand to have an average of 75 (SD 26) erosions out of 142 possible sites. Joint involvement was greatest in the wrist followed by the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints respectively. In the wrist erosion distribution was concentrated in the radiocarpal and medial carpometacarpal complex, in the hand it tended to be located at the second and third MCP and third PIP joints. No difference was observed in erosion number and area between the right and left extremities. The distribution of the lesions is discussed in relation to the intra-articular pressures on normal hand function. The similarity of erosion development, across the joints at the different regions of the hand, suggests the presence of factors other than mechanical pressure. In general, erosions were widespread, and the largest erosions occurred in the larger bones of the wrist and hand.
An Address ON THE CARE OF THE HEALTH OF MARRIED WOMEN MISSIONARIES
Authors: M. Scharlieb
Journal: BMJ (1915)

A RESOLUTION has recently been discussed by tIme associa-tioIn to the effect that women missionaries slhall not marry until they lhave beeni in their proposed field of service for at least a year.The proposed rule appears likely to be of real value.It is quite itnpossible for anyone to lknow lhow far the climate is likelv to prove suitable, anid should it prove tllat the worker is uinable to mailntaini lher hlealtlh in the climiiate in wlhichl her fuiture husband h1-as to worlk, it is evident that miiuclh annoyance, disappointinelt, and eveln wreckage of lhealtlh and happiness iw ill en su1e.U'ndoubtedly tlle rnle can be followed in tlle case of w-olmeni wlho lhave gone out, unmarried and unibetrotlhel, to work as missionaries.If suclh a lady meets her destined lhu.sband in thle field there is relatively little lhardslhip, anld thtere is miuch wisdom in asking thlem-l botlh to wait until tlle waoman haas had-time to find out howv far slhe is able to adapt heirself to the climate.On the otlher hand.diffictulty appears likely to arise when the couple meet at lhome, the womian never lhaving been in the field.They may beconme enogaged and wislh to go out as b-ide and bridegroom, or the ma-an miay go to lis miiission stationi, or return to it, expecting his Ji(VeCe to folloWv him.In the two latter cases tlle womani arrives oni the mission field as a -bride, without any experie-ice of the climiiate.How is slhe in this case to obey the rLule of waiting the prescribed year?Thiere miiay be lno othier European wom-oian in the stationi, or at any rate tlhere.ray be no sutitable liome in vhliell slhc can live duiing the probationary period.