tbuckley/cabot-search huggingface dataset:
Differential modulation of keratinocyte intercellular adhesion molecule-i expression by gamma interferon and phorbol ester: evidence for involvement of protein kinase C signal transduction
Authors: C.E.M. GRIFFITHS, J. ESMANN, G.J. FISHER, J.J. VOORHEES, B.J. NICKOLOFF
Journal: British Journal of Dermatology (1990)

There is growing evidence that keratinocytc (KC) intercellular adhesion molecule-i (ICAM-i) expression is involved in the epidermal trafficking øf T lymphocytes. To further characterize the molecular basis of KC ICAM-i expression, the detailed kinetics of induction by gamma interferon (IFN-γ)) as well as the phorbol ester, 12-O tetradecanoylphorbol-13-acetate (TPA), were studied. This study reports that KCs express both the class II major histocompatibility antigen (HLA-DR) and ICAM-i in response to IFN-γ, although the response is distinctive for each molecule. Also, TPA induces ICAM-i, but not HLA-DR expression, whilst the protein kinase inhibitor, H7, blocks the TPA, but not the IFN-γ-mediated response. The results provide a molecular basis whereby non-cytokine-mediated stimuli (e.g. TPA) alter KC signal transduction events involving protein kinase-C (PK-C) and thereby generate such immunologically relevant events as ICAM-i expression. Thus, KCs may be targets for both T-cell derived cytokines (e.g. IFN-γ), and non-cytokine TPA-like molecules which stimulate PK-C. Induction of ICAM-i by either mechanism would be capable of instigating intraepidermal T-cell trafficking.
Learning from cerebellar lesions about the temporal and spatial aspects of saccadic control
Authors: Alain Guillaume, Laurent Goffart, Denis Pélisson
Journal: Behavioral and Brain Sciences (1999)

In the model proposed by Findlay &amp; Walker, the programming of saccadic eye movements is achieved by two parallel processes, one dedicated to the coding of saccade metrics (Where) and the other controlling saccade initiation (When). One outcome of the “winner-take-all” characteristics of the salience map, the main node of the model, is an independence between the metrics and the latency of saccades. We report on some observations, made in the head-unrestrained cat under pathological conditions, of a correlation between accuracy and latency of saccadic gaze shifts. To account for such a correlation, the link between metrics specification (Where) and saccade triggering (When) should be amended in the model.
Suppression of Androgen-Independent Prostate Cancer Cell Aggressiveness by FTY720: Validating Runx2 as a Potential Antimetastatic Drug Screening Platform
Authors: Chee-Wai Chua, Yung-Tuen Chiu, Hiu-Fung Yuen, Kwok-Wah Chan, Kwan Man, Xianghong Wang, Ming-Tat Ling, Yong-Chuan Wong
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Previously, FTY720 was found to possess potent anticancer effects on various types of cancer. In the present study, we aimed to first verify the role of Runx2 in prostate cancer progression and metastasis, and, subsequently, assessed if FTY720 could modulate Runx2 expression, thus interfering downstream events regulated by this protein. Experimental Design: First, the association between Runx2 and prostate cancer progression was assessed using localized prostate cancer specimens and mechanistic investigation of Runx2-induced cancer aggressiveness was then carried out. Subsequently, the effect of FTY720 on Runx2 expression and transcriptional activity was investigated using PC-3 cells, which highly expressed Runx2 protein. Last, the involvement of Runx2 in FTY720-induced anticancer effects was evaluated by modulating Runx2 expression in various prostate cancer cell lines. Results: Runx2 nuclear expression was found to be up-regulated in prostate cancer and its expression could be used as a predictor of metastasis in prostate cancer. Further mechanistic studies indicated that Runx2 accelerated prostate cancer aggressiveness through promotion of cadherin switching, invasion toward collagen I, and Akt activation. Subsequently, we found that FTY720 treatment down-regulated Runx2 expression and its transcriptional activity, as well as inhibited its regulated downstream events. More importantly, silencing Runx2 in PC-3 enhanced FTY720-induced anticancer effects as well as cell viability inhibition, whereas overexpressing Runx2 in 22Rv1 that expressed very low endogenous Runx2 protein conferred resistance in the same events. Conclusion: This study provided a novel mechanism for the anticancer effect of FTY720 on advanced prostate cancer, thus highlighting the therapeutic potential of this drug in treating this disease.
Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS.
Authors: Zhuowei Li, Jacqueline D Carter, Lisa A Dailey, Yuh-Chin T Huang
Journal: Environmental Health Perspectives (2003)

Exposure to excessive vanadium occurs in some occupations and with consumption of some dietary regimens for weight reduction and body building. Because vanadium is vasoactive, individuals exposed to excessive vanadium may develop adverse vascular effects. We have previously shown that vanadyl sulfate causes acute pulmonary vasoconstriction, which could be attributed in part to inhibition of nitric oxide production. In the present study we investigated whether NO inhibition was related to phosphorylation of endothelial nitric oxide synthase (eNOS). VOSO4 produced dose-dependent constriction of pulmonary arteries in isolated perfused lungs and pulmonary arterial rings and a right shift of the acetylcholine-dependent vasorelaxation curve. VOSO4 inhibited constitutive as well as A23187-stimulated NO production. Constitutive NO inhibition was accompanied by increased Thr495 (threonine at codon 495) phosphorylation of eNOS, which would inhibit eNOS activity. Thr495 phosphorylation of eNOS and inhibition of NO were partially reversed by pretreatment with calphostin C, a protein kinase C (PKC) inhibitor. There were no changes in Ser1177 (serine at codon 1177) or tyrosine phosphorylation of eNOS. These results indicate that VOSO4 induced acute pulmonary vasoconstriction that was mediated in part by the inhibition of endothelial NO production via PKC-dependent phosphorylation of Thr495 of eNOS. Exposure to excessive vanadium may contribute to pulmonary vascular diseases.
Maintenance of Functional Capacity
Authors: Michael M. Dacso
Journal: JAMA (1961)

Recent reports of the National Health Survey support the belief that the rapidly growing number of elderly persons is, to a great extent, responsible for the increasing incidence of disabling chronic diseases in the total population. Restorative medicine, or—as it is more popularly known—rehabilitation is commonly accepted as being responsible for the restoration and maintenance of functional capacity in those patients who suffer from an established disability. The role of restorative medicine in the prevention of crippling complications in the chronically ill is not sufficiently utilized. This article deals with some of the clinical principles upon which prevention of the more commonly encountered crippling complications rests. The practical application of simple procedures could considerably reduce the the number and severity of crippling in the elderly and chronically ill population.
Efficacy of longterm interferon treatment in chronic liver disease evaluated by sensitive polymerase chain reaction assay for hepatitis C virus RNA.
Authors: O Yokosuka, N Kato, K Hosoda, Y Ito, F Imazeki, M Ohto, M Omata
Journal: Gut (1995)

Effects of interferon treatment on hepatitis C virus were examined by investigating the presence of hepatitis C virus ribonucleic acid and anti-hepatitis C virus antibody in 70 patients with non-A, non-B chronic liver diseases. Twenty one patients were treated with three million units of interferon alfa 2a three times a week for 52 weeks, 24 patients were treated similarly for eight weeks, and 25 patients were given a placebo for eight weeks and served as control. Sixty six of 70 patients (94%) were positive for both hepatitis C virus RNA and second generation anti-hepatitis C virus antibody. Fourteen of 21 (67%) receiving the longterm treatment had a normalised alanine aminotransferase (ALT) activity, and in 12 of these hepatitis C virus ribonucleic acid became undetectable by the end of treatment and remained so during the three year follow up after the treatment. Anti-hepatitis C virus antibody determined by first generation assay became negative in one case at the end of the 52 week treatment, and in four cases at the end of the one year follow up. In contrast, only one of 24 (4%) who received the eight week treatment and only one of 25 (4%) who received the placebo had normalised ALT activities. Hepatitis C virus ribonucleic acid became negative in two patients undergoing short-term treatment and in none receiving the placebo. Thus, longterm interferon treatment seems effective in clearing hepatitis C virus from serum of patients with chronic liver disease.
B-type natriuretic peptide in the emergency diagnosis of diastolic dysfunction heart failure
Authors: Alan S. Maisel, Patricia Hlavin, James McCord, Richard M. Nowak, Judd E. Hollander, Phillippe Duc, Gabriel Steg, Torbjorn Omland, Arne Westhelm, William T. Abraham, Alan B. Storrow, Charles A. McKay, Alan H. Wu, Peter A. McCullough
Journal: Journal of the American College of Cardiology (2002)
Catalytic Life of Activated Factor XIII in Thrombi
Authors: Brian R. Robinson, Aiilyan K. Houng, Guy L. Reed
Journal: Circulation (2000)

Background —Because the increased fibrinolytic resistance of older thrombi may be caused by the continuous cross-linking action of fibrin-bound activated factor XIII (FXIIIa), we examined the persistence of FXIIIa catalytic activity in clots of various ages. Methods and Results —The time-related changes in FXIIIa activity in clots was measured with (1) α 2 -antiplasmin (α 2 AP), a physiological glutamine substrate; (2) α 2 AP 13–24 , a peptide; and (3) pentylamine, a nonspecific lysine substrate. The cross-linking of α 2 AP, α 2 AP 13–24 , and pentylamine into fibrin by clot-bound FXIIIa declined rapidly with half-lives of 19, 21, and 26 minutes, respectively. Mutational studies showed that glutamine 14 (but not glutamine 3 or 16) and valine 17 of α 2 AP 13–24 were required for efficient cross-linking to fibrin. The loss of activity was not due primarily to FXIIIa proteolysis and was partially restored by reducing agents, suggesting that oxidation contributes to the loss of the enzyme’s activity in clots. In vivo, the ability of thrombus-bound FXIIIa to cross-link an infused α 2 AP 13–24 peptide into existing pulmonary emboli also declined significantly over time. Conclusions —FXIIIa cross-links α 2 AP and an α 2 AP peptide, in a sequence-specific manner, into formed clots with a catalytic half-life of ≈20 minutes. This indicates that FXIIIa activity is a hallmark of new thrombi and that the antifibrinolytic cross-linking effects of FXIIIa are achieved more rapidly in thrombi than previously believed.
Quarter of GPs want to quit, BMA survey shows
Authors: Z. Kmietowicz
Journal: BMJ (2001)

General practice is no longer the stable, lifelong career it once was, according to a survey showing that the level of disillusionment among GPs is so widespread that a quarter want to leave the profession and many more plan to retire sooner than they had anticipated.

Results from the biggest consultation of UK GPs in a decade show that GPs (mainly from England) are more dissatisfied than ever with their working conditions. More than two thirds described their morale as either “fairly low” or “very low,” with most of them admitting it was worse than five years ago.

Only a third of the 23521 GPs who completed a questionnaire (55% of those who had been sent one from the BMA's General Practitioners Committee (GPC) a month ago) said they would recommend a career in general practice to a newly qualified doctor or a medical student.

With most …
Hip resurfacing offers no benefits over total hip replacement in some patients, finds study
Authors: Z. Kmietowicz
Journal: BMJ (2012)

An analysis of more than 400 000 hip replacement operations carried out in England and Wales since 2003 has called into question the value of resurfacing after it was found that this type of procedure is more likely to fail within five years than a total hip replacement.

The likelihood of needing a second operation is especially high among women, but revision rates after resurfacing are also raised in those men who have smaller devices fitted, show the findings.1 Resurfacing should be avoided in both these groups of patients, say the authors.

In February a joint investigation by the BMJ and the BBC's Newsnight programme found that metal on metal devices had a failure rate of 11.8% for resurfacing and 13.6% for total hip replacements after seven years, much higher than the 3.3% to 4.9% for hip implants made of other materials.2 The findings, which were based on data from the …
V/Q SPECT: the primary imaging test for suspected pulmonary embolism
Authors: P. Roach
Journal: BMJ (2013)

Wiener and colleagues raise important questions about the overuse of computed tomography (CT) pulmonary angiography, the relevance of incidental findings, and whether subsegmental emboli should be treated.1 However, their assertion that V/Q scanning is inferior to CT pulmonary angiography is incorrect.

They quote results from planar V/Q scanning, a two dimensional technique still …
Getting the Lead out
Authors: Herbert L. Needleman, John Scanlon
Journal: New England Journal of Medicine (1973)

On December 27, 1972, Mr. William Ruckelshaus, administrator of the Environmental Protection Agency, announced a 60-day delay in the implementation of regulations that, over the next five years, would reduce the content of lead in gasoline by approximately 1/2. During this delay, which ends March 11, 1973, the administrator is seeking further comment from the public and the scientific community on the hazards to health from airborne lead. This issue is said to be the most controversial to face the agency in its young career, and the nature of its resolution will be critical to the public welfare.Each year . . .
Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2
Authors: Elke Heiss, Kristina Masson, Christina Sundberg, Malin Pedersen, Jianmin Sun, Susanne Bengtsson, Lars Rönnstrand
Journal: Blood (2006)
Effect of hypoxia and reoxygenation on the isolated rabbit heart determined by monoclonal antimyosin antibody uptake
Authors: K. S Kilgore, B. R Lucchesi
Journal: Cardiovascular Research (1993)

The aim was to examine the effect of hypoxia and reoxygenation upon the isolated rabbit heart, and to determine whether or not irreversible tissue injury develops in association with the reintroduction of molecular oxygen to the previously hypoxic heart.Isolated rabbit hearts suspended on a Langendorff apparatus and perfused with a modified Krebs-Henseleit buffer were subjected to either 5 or 30 min hypoxia and, when applicable, followed by 45 min reoxygenation. The effect of hypoxia and reoxygenation upon the isolated heart was determined with a 125labelled monoclonal antibody to the intracellular protein myosin. Determination of tissue creatine kinase release and morphological analysis, using lanthanum chloride as a marker of vessel damage, were also performed to document the uptake of antimyosin with myocardial tissue injury.Hearts subjected to 30 min hypoxia followed by 45 min reoxygenation showed a significant increase in antimyosin uptake when compared to hearts exposed to 30 min hypoxia. Creatine kinase release and morphological analysis showed an increase in intracellular damage in hearts receiving 30 min hypoxia and 45 min reoxygenation when compared to hearts receiving 30 min hypoxia without subsequent reoxygenation. Hearts subjected to 5 min hypoxia followed by reoxygenation did not show a significant increase in antimyosin uptake as compared to continuously oxygenated control hearts or hearts made hypoxic for 5 min without subsequent reoxygenation.Antimyosin antibody binding increased in hearts subjected to hypoxia and reoxygenation compared to hearts subjected to hypoxia without reoxygenation. The data provide compelling evidence that reoxygenation of hypoxic tissue exacerbates the extension of cellular damage. The ability of superoxide dismutase and catalase to decrease antimyosin uptake suggests that reactive oxygen species play a role in reoxygenation induced myocardial damage. This study also provides evidence that the labelled antimyosin antibody provides a convenient approach to quantitate the extent of damage induced by hypoxia with and without subsequent reoxygenation.
Ankle brachial pressure index
Authors: R. Price
Journal: Journal of the Royal Society of Medicine (2007)

Smith calls for a coordinated campaign to instigate change and asks who will take the lead. 4Among medical students, this position is being taken up by Medsin's Global Health Advocacy Project (www.medsin.org/ghap). 5 This student group, whose annual conference last month attracted some 400 student delegates and included Lancet editor Richard Horton as a guest lecturer, forms a strong body of internationally aware future health professionals.GHAP members at various medical schools are writing to their course lecturers and authors of popular undergraduate
User fees would both yield money and encourage more responsible use of NHS
Authors: J. Reggler
Journal: BMJ (1998)

Editor—Creese attacks user fees but fails to make a proper case against them in Britain, basing his arguments predominantly on evidence from countries in the second and third worlds.1 Creese's statements about the disadvantages of user fees may be true for underdeveloped nations, where absolute poverty is common and the main diseases are infections and illnesses associated with real deprivation. The situation in first world nations is different. Both the media and politicians have encouraged what …
P1-08-05: Age and Survival in Women with Early Stage Breast Cancer: An Analysis Controlling for Tumor Subtype.
Authors: AH Partridge, ME Hughes, R Ottesen, Y-N Wong, SB Edge, RL Theriault, DW Blayney, JC Niland, EP Winer, JC Weeks, RM Tamimi
Journal: Cancer Research (2011)

Abstract Background: Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death in women with early stage breast cancer. However, young women are more likely to have aggressive subtypes of breast cancer. No prior studies have adequately controlled for tumor phenotype, including HER-2/neu (HER2) status, in particular. Recent evidence has suggested that the prognostic effect of young age varies by tumor subtype. Methods: We examined data from women with newly diagnosed Stage 1–3 breast cancer presenting to one of 8 NCCN centers between January 2000 and December 2007. Multivariate Cox proportional hazards models were used to assess the relationship between age and breast cancer specific survival, controlling for known prognostic factors and treatment. In addition, we conducted stratified analyses by estrogen receptor (ER) and HER2 status. Results: 19,633 women with Stage 1–3 breast cancer eligible for analysis including 2,177 (11%) who were age 40 years or younger at diagnosis. Younger women were more likely to be non-white or Hispanic, more educated, employed, and to have higher stage, high grade, ER-negative, progesterone receptor (PR) negative, and HER2−positive disease, and treated with chemotherapy and trastuzumab (all variables P&amp;lt; 0.0001 by Chi-Square test). 5-year survival among younger women was 94.1 (95% Confidence Interval [CI] 92.9−95.3) and 96.3 (95% CI 95.9−96.6) for older women. In a multivariate Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women age &amp;lt; 40 or younger at diagnosis had increased mortality compared to older women (Hazard Ratio [HR] 1.26, 95% CI 1.02−1.56). In stratified analyses, age 40 or less was associated with increased mortality among women with ER-positive disease (HR 1.44, 95% CI 1.01−2.05), but was not among those with ER-negative disease (HR 1.15, 95% CI 0.85−1.55). Younger age was associated with a statistically significant increase in mortality among women with HER2−negative disease (HR 1.29, 95% CI 1.00−1.68), but this difference did not reach statistical significance among those with HER2−positive disease (HR 1.30, 95% CI 0.82−2.09). Conclusions: The effect of age on short-term survival of women with early breast cancer appears to vary by breast cancer subtype, particularly ER status. Further research to elucidate differences in breast cancer biology and efficacy of therapy within tumor types by age is warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-05.
Diabetic Neuropathy
Authors: Christopher H. Gibbons, Roy Freeman, Aristidis Veves
Journal: Diabetes Care (2010)

OBJECTIVE To determine the relationships among large, small, and autonomic fiber neurophysiological measures in a cross-sectional study of patients with diabetes. RESEARCH DESIGN AND METHODS We assessed 130 individuals: 25 healthy subjects and 105 subjects with diabetes. Subjects were classified by the presence or absence of neuropathy by physical examination. All subjects underwent autonomic testing, nerve conduction studies, quantitative sensory testing, and nerve-axon reflex vasodilation in addition to quantifiable neurological examination and symptom scores. Correlation and cluster analysis were used to determine relationships between and among different neurophysiological testing parameters. RESULTS Results of neurophysiological tests were abnormal in patients with clinical evidence of diabetic neuropathy compared with results in healthy control subjects and in those without neuropathy (P &amp;lt; 0.01, all tests). The correlations among individual tests varied widely, both within (r range &amp;lt;0.5–&amp;gt;0.9, NS to &amp;lt;0.001) and between test groups (r range &amp;lt;0.2–&amp;gt;0.5, NS to &amp;lt;0.01). A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical “small,” “large,” or “autonomic” nerve fiber subtypes. CONCLUSIONS The modest correlation coefficients seen between the different testing modalities suggest that these techniques measure different neurophysiological parameters and are therefore not interchangeable. However, the data suggest that only a small number of neurophysiological tests are actually required to clinically differentiate individuals with neuropathy from those without. The natural clustering of both patients and healthy control subjects suggests that variations in the population will need to be considered in future studies of diabetic neuropathy.