tbuckley/cabot-search huggingface dataset:
Abstract 1270: Identification and functional analysis of Pim-1 kinase substrates in prostate cancer
Authors: Nicole Barkley, Xiang Li, Charles Bieberich
Journal: Cancer Research (2012)

Abstract Protein kinases constitute one of the largest and most pleiotropic families of proteins. Mutations leading to activation of protein kinases and loss of function of phosphatases can have deleterious consequences that lead to disease. Pim-1, a serine/threonine kinase, is one of many kinases that may play a role in the etiology of malignant diseases including lymphoma and prostate cancer. Recent studies indicate Pim-1 is overexpressed in prostate cancer and is a highly plausible therapeutic target. Paradoxically, a decrease in Pim-1 expression in later stages of prostate cancer correlates with poor prognosis. Pim-1 has been known to be an oncogene for more than two decades, however, our understanding of how it functions is incomplete. A key underlying factor in this lack of knowledge is that, to date, fewer than fifteen Pim-1 substrates have been identified. The identification and validation of novel Pim-1 substrates could elucidate biomarkers of Pim-1 activity and provide insight into the molecular basis of Pim-1 function. A recent, innovative kinase-substrate profiling method termed the Reverse In-gel Kinase Assay (RIKA) reverses the role of kinase and substrate in a traditional in-gel kinase assay. The assay involves the partial immobilization of an active kinase in a denaturing polyacrylamide gel to determine which substrates from cell lysates can be phosphorylated by the kinase within the gel. The potential substrates are excised from the gel and identified using mass spectrometry. Using a Pim-1 RIKA approach, 40S Ribosomal Protein 7 (RPS7) was identified as a potential novel Pim-1 substrate. RPS7 was expressed in E.coli to conduct preliminary in vitro studies. These in vitro studies demonstrated that Pim-1 robustly phosphorylates RPS7. Further studies were performed to identify sites of phosphorylation on RPS7, and alanine-substitution mutants were generated that completely abolished phosphorylation of RPS7 by Pim-1. These data indicated that RPS7 may be a novel Pim-1 substrate. Studies to validate RPS7 as a direct target of Pim-1 in vivo, and to determine the functional consequences of Pim-1 phosphorylation of RPS7 are in progress. 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 1270. doi:1538-7445.AM2012-1270
Contact sensitivity to Candida albicans—comparative studies in man and animal (guinea-pig)
Authors: H. TAGAMI, S. URANO-SUEHISA, N. HATCHOME
Journal: British Journal of Dermatology (1985)

We studied the elicitation of contact sensitivity to Candida albicans antigen in guinea-pigs with experimental cutaneous candidiasis and in humans, using commercially available potent 1: 100 C. albicans antigen (Torii) by patch testing on abraded skin. In guinea-pigs, non-immune animals became patch test-reactive 4–5 days after topical application of viable C. albicans, either under occlusion or without occlusive dressings, concurrently with the demonstrability of delayed responses to intradermally injected 1: 10 000 Candida antigen. In humans, all healthy adults who showed delayed hypersensitivity reactions to intradermally injected 1:10 000 C albicans antigen demonstrated positive patch-test reactions to 1:100 C. albicans antigen. There was a significant correlation between the magnitude of responses to these tests. In contrast, no positive patch test reactions were elicited to the 1: 100 C. albicans antigen on neonatal skin, emphasizing the lack of irritability of this test agent. These results also indicate that in humans contact sensitivity to Candida antigen occurs during later life because C. albicans is a ubiquitous organism. The practical value of this Candida patch test for evaluation of patients' immune function was assessed by a prospective study in patients with various skin disorders. The results obtained suggested some potential value of the test for evaluation of cell-mediated immune function of patients with regard to ubiquitous recall antigens.
Standardized Treatment of Active Tuberculosis in Patients with Previous Treatment and/or with Mono-resistance to Isoniazid: A Systematic Review and Meta-analysis
Authors: Dick Menzies, Andrea Benedetti, Anita Paydar, Sarah Royce, Madhukar Pai, William Burman, Andrew Vernon, Christian Lienhardt
Journal: PLoS Medicine (2009)

Performing a systematic review of studies evaluating retreatment of tuberculosis or treatment of isoniazid mono-resistant infection, Dick Menzies and colleagues find a paucity of evidence to support the WHO-recommended regimen.
Acute Dissecting Aortic Aneurysm
Authors: Robert S. Shaw
Journal: New England Journal of Medicine (1955)

DISSECTING aneurysm of the aorta is a well described clinical and pathological entity, and yet nearly all the considerable literature on this disease is descriptive and analytical, with very little discussion of therapy. There is an incentive to attempts at surgical treatment of this disorder since it is mechanical and since the results of nonspecific treatment are poor.Gurin et al.,1 in 1935, reported surgical treatment of a case of dissecting aortic aneurysm in which the presenting picture was acute arterial insufficiency in one leg. Excision of the internal wall of the aneurysm at the furthermost point of its advance . . .
Correlation between High Vascular Endothelial Growth Factor-A Serum Levels and Treatment Outcome in Patients with Standard-Risk Acute Lymphoblastic Leukemia: A Report from Children's Oncology Group Study CCG-1962
Authors: Ioannis A. Avramis, Eduard H. Panosyan, Fred Dorey, John S. Holcenberg, Vassilios I. Avramis
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Many molecular pathways, including cell cycle control, angiogenesis, and drug resistance, mediate tumor growth and survival. Vascular endothelial growth factor-A (VEGF-A) serum levels &amp;lt;40 and &amp;gt;100 pg/mL have been associated with good and poor prognoses, respectively. Experimental Design: The hypothesis was that serum VEGF-A levels in standard-risk acute lymphoblastic leukemia pediatric patients at induction are predictive of event-free survival (EFS). One hundred seventeen patients were entered in CCG-1962 study and randomized into the native and polyethylene glycolated asparaginase arms. VEGF-A levels were quantified by an ELISA assay. Results: All patients had a decrease in VEGF-A levels by day 14 of induction, but they later dichotomized; EFS group levels remained low and event group levels increased. A correlation exists between high VEGF-A levels at entry to induction and time to event. Moreover, 6-year EFS patients have lower end of induction VEGF-A levels (28 ± 6 pg/mL) than event patients (&amp;gt;100 pg/mL; P &amp;lt; 0.01). Kaplan-Meier curves using various VEGF-A values were produced; with ≤30 at entry into induction (day 0) and ≤60 pg/mL at the end of induction (day 28), patients with low VEGF-A levels had superior EFS (P &amp;lt; 1e−4). Furthermore, patients who had an increase in VEGF-A during induction (ΔVEGF-positive, days 0-28) were more likely to have an event (P &amp;lt; 1e−4). Bifurcation by asparaginase treatment arm did not alter these results. Conclusions: These observations strongly support that high VEGF-A levels in induction are an asparaginase treatment–independent predictive marker for EFS. Hence, an anti-VEGF-A therapy should be tested in acute lymphoblastic leukemia.
220 Effects of lamivudine on disease progression and development of liver cancer in advanced chronic hepatitis B: a prospective double-blind placebo-controlled clinical trial
Authors: Y LIAW, J SUNG, W CHENCHOW, K SHUE, G FARRELL
Journal: Hepatology (2003)

The high rate of relapse after cessation of nucleos(t)ide analogues (NUCs) treatment in chronic hepatitis B (CHB) patients leads us to reassess the feasibility for off-therapy, but long-term follow-up data are scarce. We assessed the feasibility for off-therapy by a long-term observation of relapse in response to lamivudine (LAM) and telbivudine (LdT). Eighty-six NUC-naive CHB patients, treated with LAM (n = 46) or LdT (n = 40) who reached the guidelines recommended for off-therapy, were followed for up to 10 years. Hepatitis B virus (HBV), viral serology and biochemistries were periodically determined. COX model was used to predict the risk of relapse. A total of 52.3% of patients experienced relapse within a median of 115 months (range, 61–122 months). A total of 93.3% of relapses occurred within 48 months. Relapse rates in hepatitis B e antigen (HBeAg)-positive (n = 56) and HBeAg-negative (n = 30) patients were 39.3% and 76.7%, respectively (p < 0.01). HBeAg-positive patients who achieved an early viral response (EVR), defined as undetectable HBV DNA within 6 months, had a lower relapse rate compared to non-EVR patients (21.4% vs. 59.2%, p < 0.01). EVR patients who had both lower HBV DNA (<106 copies/mL) at baseline and lower hepatitis B surface antigen (HBsAg) at end of treatment had a relapse rate of 10.7%. The high relapse rates in CHB patients over this 10-year follow-up make LAM or LdT off therapy infeasible in most of the cases, except in the case of HBsAg loss and/or seroconversion. HBeAg-positive patients with EVR, lower HBV DNA and HBsAg had lower relapse rates and could be good candidates for off-therapy. Long-term monitoring, especially during the first 4 years, is critical for patients off-therapy.
Confidentiality of Records in PSRO's
Authors: William J. Curran
Journal: New England Journal of Medicine (1978)

ONE of the most important experiments in medical-care regulation of this country in the 1970's is the group of organizations called PSRO's, or Professional Standards Review Organizations. These organizations were designed by the United States Congress to allow the medical profession the opportunity to monitor the quality and appropriateness of the medical care rendered to hospital patients covered by federally financed health care, mainly Medicare and Medicaid.PSRO's are organized all across the country as nonprofit, private corporations. They generally view themselves as nongovernmental. The Department of Health, Education, and Welfare seems to agree with this view. However, it is . . .
Response of Malabsorption of Tropical Sprue to Antibiotics.
Authors: Ricardo Guerra, Munsey S. Wheby, Barbara Baggs, Theodore M. Bayless
Journal: Annals of Internal Medicine (1964)

s1 April 1964Response of Malabsorption of Tropical Sprue to Antibiotics.Ricardo Guerra, M.D., Munsey S. Wheby, Barbara Baggs, Theodore M. BaylessRicardo Guerra, M.D.Search for more papers by this author, Munsey S. WhebySearch for more papers by this author, Barbara BaggsSearch for more papers by this author, Theodore M. BaylessSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-725_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPatients with tropical sprue treated with folic acid or vitamin B12usually show general improvement, although frequently, malabsorption persists. Altered bacterial flora has been implicated in other malabsorption states. Somewhat conflicting evidence has been reported regarding the effect of antibiotics in tropical sprue. The efficacy of long-term antibiotic therapy in alleviating malabsorption was evaluated in ten patients with persistent symptoms and malabsorption despite treatment with folic acid, vitamin B12and gluten free diet (Group I), and in eight untreated patients with sprue (Group II). After baseline hematologic and absorptive studies including fecal fat excretion, D-xylose excretion, serum carotene, and jejunal... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: San Juan, PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1964Volume 60, Issue 4Page: 725-725KeywordsAntibioticsCarotenoidsDietExcretionFatsFolic acidGlutenXylose Issue Published: 1 April 1964 PDF DownloadLoading ...
Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications.
Authors: M A Pfeffer, E Braunwald
Journal: Circulation (1990)

An acute myocardial infarction, particularly one that is large and transmural, can produce alterations in the topography of both the infarcted and noninfarcted regions of the ventricle. This remodeling can importantly affect the function of the ventricle and the prognosis for survival. In the early period, infarct expansion has been recognized by echocardiography as a lengthening of the noncontractile region. The noninfarcted region also undergoes an important lengthening that is consistent with a secondary volume-overload hypertrophy and that can be progressive. The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival. The process of ventricular enlargement can be influenced by three interdependent factors, that is, infarct size, infarct healing, and ventricular wall stresses. A most effective way to prevent or minimize the increase in ventricular size after infarction and the consequent adverse effect on prognosis is to limit the initial insult. Acute reperfusion therapy has been consistently shown to result in a reduction in ventricular volume. The reestablishment of blood flow to the infarcted region, even beyond the time frame for myocyte salvage, has beneficial effects in attenuating ventricular enlargement. The process of scarification can be interfered with during the acute infarct period by the administration of glucocorticosteroids and nonsteroidal antiinflammatory agents, which result in thinner infarcts and greater degrees of infarct expansion. Modification of distending or deforming forces can importantly influence ventricular enlargement. Even short-term augmentations in afterload have deleterious long-term effects on ventricular topography. Conversely, judicious use of nitroglycerin seems to be associated with an attenuation of infarct expansion and long-term improvement in clinical outcome. Long-term therapy with an angiotensin converting enzyme inhibitor can favorably alter the loading conditions on the left ventricle and reduce progressive ventricular enlargement as demonstrated in both experimental and clinical studies. With the former therapy, this attenuation of ventricular enlargement was associated with a prolongation in survival. The long-term clinical consequences of long-term angiotensin converting enzyme inhibitor therapy after myocardial infarction is currently being evaluated. Although studies directed at attenuating left ventricular remodeling after infarction are in the early stages, it does seem that this will be an important area in which future research might improve long-term outcome after infarction.
Is Pregnancy Outcome Worse in Type 2 Than in Type 1 Diabetic Women?
Authors: Natalia Hillman, Lucrecia Herranz, Pilar M. Vaquero, Africa Villarroel, Alberto Fernandez, Luis F. Pallardo
Journal: Diabetes Care (2006)

Most research on pregestational diabetes has focused on type 1 diabetes, and surprisingly little knowledge exists concerning outcomes of pregnancies of women with type 2 diabetes. A dearth of published data suggest outcomes similar to those of type 1 diabetic women (1,2), although recent studies report poorer outcomes in women with type 2 diabetes (3–7).

We retrospectively compared maternal and perinatal outcomes of 93 consecutive singleton pregnancies in women with type 2 diabetes and 532 consecutive singleton pregnancies in women with type 1 diabetes referred to the Diabetes and Pregnancy Unit at University Hospital La Paz from 1984 to 2004.

Women with type 2 diabetes were significantly older ([means ± SD] 31.8 ± 5.5 …
Apolipoprotein(a) Attenuates Endogenous Fibrinolysis in the Rabbit Jugular Vein Thrombosis Model In Vivo
Authors: Bart J. Biemond, Philip W. Friederich, Marlys L. Koschinsky, Marcel Levi, Waheed Sangrar, Jiazhi Xia, Harry R. Büller, Jan W. ten Cate
Journal: Circulation (1997)

Background In many case-control as well as epidemiological studies, increased lipoprotein(a) [Lp(a)] levels are considered to constitute an independent risk factor for premature coronary artery and cerebrovascular disease. Lp(a) resembles an LDL particle with an additional linked protein [apolipoprotein(a), apo(a)], whose molecular structure has been demonstrated to be homologous to the fibrinolytic proenzyme plasminogen. Because of the high similarity between plasminogen and apo(a), apo(a) may potentially interfere in the fibrinolytic system by competing with plasminogen for fibrin binding sites. In vitro studies have demonstrated that Lp(a) indeed competes with plasminogen binding to fibrin and inhibits tissue plasminogen activator (TPA)-mediated activation of plasminogen. No direct in vivo studies to test this hypothesis have been performed. Methods and Results To test this hypothesis, we studied the effect of a recombinant form of apo(a) on endogenous and TPA-mediated thrombolysis in an in vivo model of experimental venous thrombosis. Thrombi containing either 16 μg r-apo(a), 8 μg r-apo(a), or vehicle (HEPES-buffered saline, control) were formed in the jugular veins of a rabbit and showed significantly reduced endogenous thrombolysis after 60 minutes in a dose-dependent fashion, ID 2.7±0.9% and 4.6±1.8%, respectively, versus 7.4±1.6% of that of the control. High concentrations of incorporated apo(a) significantly reduced TPA-induced thrombolysis (12.2±2.5% versus 22.2±2.6% in the control thrombi), but no effect of lower concentrations of incorporated r-apo(a) was demonstrated on the exogenous TPA-induced thrombolysis. Conclusions The present study demonstrates the attenuation of endogenous fibrinolysis by apo(a) in an in vivo model of experimental venous thrombosis, lending support to the proposed mechanism of impaired fibrinolysis by which Lp(a) may contribute to atherothrombotic disorders.
The endoplasmic reticular heat shock protein gp96 is transcriptionally upregulated in interferon-treated cells.
Authors: S L Anderson, T Shen, J Lou, L Xing, N E Blachere, P K Srivastava, B Y Rubin
Journal: The Journal of Experimental Medicine (1994)

A cDNA clone complementary to an interferon (IFN)-induced mRNA approximately 3 kb in length was identified and sequenced revealing homology with the endoplasmic reticular heat shock protein/ATPase gp96. Both IFN-alpha and -gamma transcriptionally upregulate expression of this gene. gp96 transcripts, protein, and ATPase activity are shown to be enhanced as a result of IFN treatment in two human cell lines and this effect requires de novo protein synthesis. gp96 molecules have recently been implicated in the presentation of endogenous antigens. A number of the key elements in this pathway, the transporter proteins, the major histocompatibility complex (MHC)-linked units of the proteasomes and the MHC class I molecules are known to be IFN inducible. Our results show that yet another molecule suggested to play an accessory role in the endogenous presentation pathway is IFN inducible. Further, our studies represent the first demonstration of modulation of expression of a heat shock protein by a cytokine and identify a new enzymatic activity upregulated in IFN-treated cells.
Pure Politics and Impure Science: The Swine Flu Affair
Authors: Arnold S. Monto
Journal: JAMA (1982)

In this small volume, Dr Silverstein broadly reviews the Swine Influenza Immunization Program. The author's background uniquely qualifies him for this review. He was on Capitol Hill in 1976 as the first Congressional Science Fellow of the Federation of American Societies for Experimental Biology and saw the event unfold firsthand; he also is an immunologist and has worked with the influenza virus. As described in the preface, he decided to write this book when he read other accounts of the program and its aftermath, especially that of Professors Neustadt and Fineberg of Harvard (<i>The Swine Flu Affair</i>, Government Printing Office, 1978) and said to himself, "That's not what really happened." On further consideration, Silverstein concluded that the problem was not of fact, but rather of interpretation. In his view, the event unfolded like a Greek tragedy, in which no one was at fault, and if there was a culprit it
Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma
Authors: Oscar W.H. Yeung, Chung-Mau Lo, Chang-Chun Ling, Xiang Qi, Wei Geng, Chang-Xian Li, Kevin T.P. Ng, Stuart J. Forbes, Xin-Yuan Guan, Ronnie T.P. Poon, Sheung-Tat Fan, Kwan Man
Journal: Journal of Hepatology (2014)
Sudden, Unexpected and Unexplained Death in Infancy — A Status Report — 1973
Authors: Marie A. Valdes-Dapena
Journal: New England Journal of Medicine (1973)

In 1953 the subject of sudden death in infancy lay dormant. Little related research was under way, and pertinent scientific publications were few. Twenty years later, on the contrary, there are numerous relevant articles and myriads of applications for the support of research in this field. Multiple factors participated in this change, not the least of which was the strength of organized parent groups. Physicians and governmental representatives have become aware and are taking appropriate action. The National Institute of Child Health and Human Development has responded with a comprehensive program for the stimulation and support of research and the . . .
HORMONE CONTROL OF CONNECTIVE TISSUE*
Authors: Gustav Asboe-Hansen
Journal: British Journal of Dermatology (1969)

Journal Article HORMONE CONTROL OF CONNECTIVE TISSUE Get access GUSTAV ASBOE‐HANSEN GUSTAV ASBOE‐HANSEN Department of Dermatology with Connective‐Tissue Research Laboratories, University of Copenhagen, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue s2, 1 March 1969, Pages 2–8, https://doi.org/10.1111/j.1365-2133.1969.tb12838.x Published: 01 March 1969