tbuckley/cabot-search huggingface dataset:
Neuroprotective effect of a new DJ-1-binding compound against neurodegeneration in Parkinson's disease and stroke model rats
Authors: Yoshihisa Kitamura, Shotaro Watanabe, Masanobu Taguchi, Kentaro Takagi, Takuya Kawata, Kazuko Takahashi-Niki, Hiroyuki Yasui, Hiroshi Maita, Sanae MM Iguchi-Ariga, Hiroyoshi Ariga
Journal: Molecular Neurodegeneration (2011)

Abstract Background Parkinson's disease (PD) and cerebral ischemia are chronic and acute neurodegenerative diseases, respectively, and onsets of these diseases are thought to be induced at least by oxidative stress. PD is caused by decreased dopamine levels in the substantia nigra and striatum, and cerebral ischemia occurs as a result of local reduction or arrest of blood supply. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy and an anti-oxidant have been used for cerebral ischemia therapy, cell death progresses during treatment. Reagents that prevent oxidative stress-induced cell death are therefore necessary for fundamental therapies for PD and cerebral ischemia. DJ-1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ-1 renders DJ-1 inactive, and such oxidized DJ-1 has been observed in patients with the sporadic form of PD. Results In this study, a compound, comp-23, that binds to DJ-1 was isolated by virtual screening. Comp-23 prevented oxidative stress-induced death of SH-SY5Y cells and primary neuronal cells of the ventral mesencephalon but not that of DJ-1-knockdown SH-SY5Y cells, indicating that the effect of the compound is specific to DJ-1. Comp-23 inhibited the production of reactive oxygen species (ROS) induced by oxidative stress and prevented excess oxidation of DJ-1. Furthermore, comp-23 prevented dopaminergic cell death in the substantia nigra and restored movement abnormality in 6-hydroxyldopamine-injected and rotenone-treated PD model rats and mice. Comp-23 also reduced infarct size of cerebral ischemia in rats that had been induced by middle cerebral artery occlusion. Protective activity of comp-23 seemed to be stronger than that of previously identified compound B. Conclusions The results indicate that comp-23 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that comp-23 becomes a lead compound for PD and ischemic neurodegeneration therapies.
Role of Extent of Resection in the Long-Term Outcome of Low-Grade Hemispheric Gliomas
Authors: Justin S. Smith, Edward F. Chang, Kathleen R. Lamborn, Susan M. Chang, Michael D. Prados, Soonmee Cha, Tarik Tihan, Scott VandenBerg, Michael W. McDermott, Mitchel S. Berger
Journal: Journal of Clinical Oncology (2008)

Purpose The prognostic role of extent of resection (EOR) of low-grade gliomas (LGGs) is a major controversy. We designed a retrospective study to assess the influence of EOR on long-term outcomes of LGGs. Patients and Methods The study population (N = 216) included adults undergoing initial resection of hemispheric LGG. Region-of-interest analysis was performed to measure tumor volumes based on fluid-attenuated inversion-recovery (FLAIR) imaging. Results Median preoperative and postoperative tumor volumes and EOR were 36.6 cm 3 (range, 0.7 to 246.1 cm 3 ), 3.7 cm 3 (range, 0 to 197.8 cm 3 ) and 88.0% (range, 5% to 100%), respectively. There was no operative mortality. New postoperative deficits were noted in 36 patients (17%); however, all but four had complete recovery. There were 34 deaths (16%; median follow-up, 4.4 years). Progression and malignant progression were identified in 95 (44%) and 44 (20%) cases, respectively. Patients with at least 90% EOR had 5- and 8-year overall survival (OS) rates of 97% and 91%, respectively, whereas patients with less than 90% EOR had 5- and 8-year OS rates of 76% and 60%, respectively. After adjusting each measure of tumor burden for age, Karnofsky performance score (KPS), tumor location, and tumor subtype, OS was predicted by EOR (hazard ratio [HR] = 0.972; 95% CI, 0.960 to 0.983; P &lt; .001), log preoperative tumor volume (HR = 4.442; 95% CI, 1.601 to 12.320; P = .004), and postoperative tumor volume (HR = 1.010; 95% CI, 1.001 to 1.019; P = .03), progression-free survival was predicted by log preoperative tumor volume (HR = 2.711; 95% CI, 1.590 to 4.623; P ≤ .001) and postoperative tumor volume (HR = 1.007; 95% CI, 1.001 to 1.014; P = .035), and malignant progression-free survival was predicted by EOR (HR = 0.983; 95% CI, 0.972 to 0.995; P = .005) and log preoperative tumor volume (HR = 3.826; 95% CI, 1.632 to 8.969; P = .002). Conclusion Improved outcome among adult patients with hemispheric LGG is predicted by greater EOR.
Cell cycle regulation therapy combined with cytokine blockade enhances antiarthritic effects without increasing immune suppression
Authors: Tadashi Hosoya, Hideyuki Iwai, Yu Yamaguchi, Kimito Kawahata, Nobuyuki Miyasaka, Hitoshi Kohsaka
Journal: Annals of the Rheumatic Diseases (2014)

Biological disease-modifying antirheumatic drugs (DMARDs) that inhibit aberrant immune reactions in rheumatoid arthritis (RA) cannot induce complete remission in all patients. Combination therapies using two biological DMARDs have failed to exert additive effects and increased serious infections. We have found that cell cycle inhibition of synovial fibroblasts with cyclin-dependent kinase (CDK) inhibitors ameliorated the disease in animal models of RA without attenuating acquired immunity. The objective of this study was to determine whether a clinically well-tolerated selective CDK 4/6 inhibitor (CDKI), palbociclib, is effective and whether combination with cytokine blockers acts additively without enhancing immune suppression.The effects of CDKI on haematopoiesis and physical and behavioural findings in mice were evaluated. Mice with collagen-induced arthritis (CIA) were treated with CDKI, etanercept or anti-interleukin (IL)-6 receptor antibody (MR16-1) alone or with a combination of CDKI with etanercept or MR16-1. Their clinical, histological and radiographic scores, serum anti-(type II collagen (CII)) antibody levels and proliferative responses of lymph node cells to CII were determined.Although CDKI induced marginal myelosuppression, it was well tolerated and ameliorated CIA dose-dependently. The combinations of low-dose CDKI and either tumour necrosis factor-α or IL-6 blocker enhanced the antiarthritic effects additively. The addition of CDKI to either cytokine blocker did not affect the levels of anti-CII antibodies and proliferative responses of lymphocytes to CII.A clinically well-tolerated CDK4/6 inhibitor exerted antiarthritic effects in this mouse model. By combining therapeutic agents targeting immune reaction and synovial proliferation, we have demonstrated for the first time that two molecular targeting treatments act additively and may not increase immune suppression.
Exercising with reserve: evidence that the central nervous system regulates prolonged exercise performance
Authors: J Swart, R P Lamberts, M I Lambert, A St Clair Gibson, E V Lambert, J Skowno, T D Noakes
Journal: British Journal of Sports Medicine (2008)

Objective: The purpose of this study was to measure the effects of an amphetamine (methylphenidate) on exercise performance at a fixed rating of perceived exertion of 16. Methods: Eight elite cyclists ingested 10 mg methylphenidate in a randomised, placebo-controlled crossover trial. Results: Compared with placebo, subjects receiving methylphenidate cycled for approximately 32% longer before power output fell to 70% of the starting value. At the equivalent time at which the placebo trial terminated, subjects receiving methylphenidate had significantly higher power outputs, oxygen consumptions, heart rates, ventilatory volumes and blood lactate concentrations although electromyographic activity remained unchanged. The ingestion of a centrally acting stimulant thus allowed subjects to exercise for longer at higher cardiorespiratory and metabolic stress indicating the presence of a muscular reserve in the natural state. Conclusions: This suggests that endurance performance is not only “limited” by mechanical failure of the exercising muscles (“peripheral fatigue”). Rather performance during prolonged endurance exercise under normal conditions is highly regulated by the central nervous system to ensure that whole-body homeostasis is protected and an emergency reserve is always present.
Analysis of Immunoglobulin (Ig) Isotype Diversity and Igm/D Memory in the Response to Phenyl-Oxazolone
Authors: Harry White, David Gray
Journal: The Journal of Experimental Medicine (2000)

The distribution of immunoglobulin (Ig) isotypes within specific B cell clones in vivo after immunization is not well defined. Using an IgVH/CDR3- and isotype-specific reverse transcription polymerase chain reaction method, we have carried out a survey of the diversification of the isotype in a splenic response to phenyl-oxazolone (phOx) on a chicken serum albumin carrier. The phOx-specific VH (VHOx-1 with specific CDR3 motif) is associated with all of the heavy chains (μ, δ, α, γ, and ε) after simple immunization with antigen in alum. The kinetics of expression of each isotype are distinct and reproducible. Focusing mainly on the expression of secretory Ig transcripts, IgM, IgG1, and IgE are found after priming, whereas IgD and IgA appear after boosting. Secretory IgD transcripts are found reproducibly at moderate levels and may, therefore, contribute significantly to the secreted Ig response in mice. Most crucially, we find enhanced levels of secretory IgM/VHOx-1 transcripts (with ‘phOx-specific’ CDR3) after boosting, strongly indicating the existence of IgM memory cells that give rise to an enhanced specific IgM secretion in the secondary response.
IMAGING OF THE BRAIN BY NUCLEAR MAGNETIC RESONANCE
Authors: F.H. Doyle, J.M. Pennock, J.S. Orr, J.C. Gore, G.M. Bydder, R.E. Steiner, I.R. Young, H. Clow, D.R. Bailes, M. Burl, D.J. Gilderdale, P.E. Walters
Journal: The Lancet (1981)
Empathic Relationship Therapy Utilizing Student Nurses: A Five-Year Pilot Study
Authors: SELIG M. KORSON, WINIFRED L. HAYES
Journal: American Journal of Psychiatry (1966)

An educational-therapeutic approach to patient care has been demonstrated in an affiliate psychiatric nursing program in a state hospital. The rewards of this integrated interpersonal relationship approach are two-fold: 1. For the student nurse—a more meaningful learning process which has resulted in better understanding of the psychiatric patient; and 2. For the patient—more "tender, loving care," which after all is the basic ingredient so necessary to any psychotherapeutic process leading to improvement or recovery of the mentally ill.
Substitution of coagulation factor XIII partially restores scar healing after myocardial infarction in factor XIII knockout mice
Authors: Matthias Nahrendorf, Kai Hu, Karl-Heinz Hiller, Christiane Waller, Stefan Gattenlöhner, Gerhard Dickneite, Axel Haase, Wolfgang R. Bauer, Georg Ertl
Journal: Journal of the American College of Cardiology (2003)
Hemodynamic effects of ventricular defibrillation
Authors: Donald G. Pansegrau, François M. Abboud
Journal: Journal of Clinical Investigation (1970)

Hemodynamic responses to ventricular defibrillation were studied in anesthetized dogs. Observations were made on arterial, right atrial and left ventricular end-diastolic pressures, on cardiac output (dye dilution), heart rate, and right atrial electrocardiogram. Ventricular fibrillation was induced electrically with a bipolar electrode catheter placed in the right ventricle. Fibrillation was maintained for 15 or 30 sec and terminated with a 400 w sec capacitor discharge across the thoracic cage. Responses lasted 1-10 min after conversion and included a cholinergic and an adrenergic component. The cholinergic component was characterized by sinus bradycardia, periods of sinus arrest, atrioventricular block, and ventricular premature beats. The adrenergic component included increases in arterial pressure, in cardiac output, and in left ventricular stroke work at a time when left ventricular end-diastolic pressure was normal; there was no change in total peripheral resistance. The pH of arterial blood decreased slightly and pCO(2) increased but pO(2) and the concentration of lactate were unchanged. Bilateral vagotomy and intravenous administration of atropine blocked the cholinergic component, unmasked a sinus tachycardia, and accentuated the adrenergic component of the response. The latter was blocked by intravenous administration of propranolol and phenoxybenzamine.THESE RESPONSES WERE RELATED PRIMARILY TO CONVERSION OF VENTRICULAR FIBRILLATION RATHER THAN TO THE ELECTRICAL DISCHARGE OF COUNTERSHOCK BECAUSE COUNTERSHOCK WITHOUT VENTRICULAR FIBRILLATION CAUSED MORE TRANSIENT AND SMALLER RESPONSES THAN THOSE OBSERVED WITH DEFIBRILLATION: furthermore, the hemodynamic effects of defibrillation were augmented by prolongation of the duration of fibrillation. The results suggest that the cholinergic component of the response may be detrimental in that it favors spontaneous recurrence of fibrillation; on the other hand, the adrenergic component may be essential for conversion since only one of six dogs depleted of endogenous catecholamines with reserpine survived ventricular defibrillation.
HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity
Authors: Mitsumasa Kurita, Terrell Holloway, Aintzane García-Bea, Alexey Kozlenkov, Allyson K Friedman, José L Moreno, Mitra Heshmati, Sam A Golden, Pamela J Kennedy, Nagahide Takahashi, David M Dietz, Giuseppe Mocci, Ane M Gabilondo, James Hanks, Adrienne Umali, Luis F Callado, Amelia L Gallitano, Rachael L Neve, Li Shen, Joseph D Buxbaum, Ming-Hu Han, Eric J Nestler, J Javier Meana, Scott J Russo, Javier González-Maeso
Journal: Nature Neuroscience (2012)
Physician-Assisted Suicide
Authors: G. Kevin Donovan
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Ms Alpers and Dr Lo<sup>1</sup>have correctly identified Oregon's effort to legalize physician-assisted suicide as a "bold experiment." However, their analysis fails to adequately address the issue on two counts: does suicide assistance constitute health care and is it rightly seen as a benefit? The first question begs for an answer, perhaps because it seems self-evident. Why should suicide assistance come through a physician's involvement? In truth, the medical expertise required to successfully poison someone is not so great as to require a medical degree. A physician's involvement seems desirable because of the trust placed in the profession, a trust that will be severely undermined if the profession takes it upon itself to bring about patients' deaths. As the authors point out, this assistance would not even require a long-term relationship with the patient, but could commence at the first visit. To their credit, the authors
Number of agents being developed to combat drug resistant bacteria is "alarmingly low," warns report
Authors: M. McCarthy
Journal: BMJ (2013)

Little progress is being made to develop new drugs to combat the growing threat of drug resistant bacteria, a new report from the Infectious Diseases Society of America has said.

In the report a society panel focused on systemic drugs for the treatment of multidrug resistant Gram negative bacilli, pathogens that are responsible for a substantial proportion of serious infections in US hospitals.1

In their review the authors were able to identify only seven new systemic antibiotics targeting drug resistant Gram negative bacilli that had reached phase II or III trials, …
Incidence of fires and related injuries after giving out free smoke alarms: cluster randomised controlled trial
Authors: C. DiGuiseppi
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To measure the effect of giving out free smoke alarms on rates of fires and rates of fire related injury in a deprived multiethnic urban population. <b>Design:</b>Cluster randomised controlled trial. <b>Setting:</b> Forty electoral wards in two boroughs of inner London, United Kingdom. <b>Participants:</b> Primarily households including elderly people or children and households that are in housing rented from the borough council. <b>Intervention:</b> 20 050 smoke alarms, fittings, and educational brochures distributed free and installed on request. <b>Main outcome measures:</b> Rates of fires and related injuries during two years after the distribution; alarm ownership, installation, andfunction. <b>Results:</b> Giving out free smoke alarms did not reduce injuries related to fire (rate ratio 1.3; 95% confidence interval 0.9 to 1.9), admissions to hospital and deaths (1.3; 0.7 to 2.3), or fires attended by the fire brigade (1.1; 0.96 to 1.3). Similar proportions of intervention and control households had installed alarms (36/119 (30%) <i>v</i> 35/109 (32%); odds ratio 0.9; 95% confidence interval 0.5 to 1.7) and working alarms (19/118 (16%) <i>v</i> 18/108 (17%); 0.9; 0.4 to 1.8). <b>Conclusions:</b> Giving out free smoke alarms in a deprived, multiethnic, urban community did not reduce injuries related to fire, mostly because few alarms had been installed or were maintained. <h3>What is already known on this topic</h3> In the United Kingdom, residential fires caused 466 deaths and 14 600 non-fatal injuries in 1999 The risk of death from fire is associated with socioeconomic class One study reported an 80% decline in hospitalisations and deaths from residential fires after free smoke alarms were distributed in an area at high risk, but these results may not apply in other settings, and evidence from randomised controlled trials is lacking <h3>What this study adds</h3> Giving out free smoke alarms in a multiethnic poor urban population did not reduce injuries related to fire or fires Giving smoke alarms away may be a waste of resources and of little benefit unless alarm installation and maintenance is assured
Proteasomal and Genetic Inactivation of the NF1 Tumor Suppressor in Gliomagenesis
Authors: Lauren T. McGillicuddy, Jody A. Fromm, Pablo E. Hollstein, Sara Kubek, Rameen Beroukhim, Thomas De Raedt, Bryan W. Johnson, Sybil M.G. Williams, Phioanh Nghiemphu, Linda M. Liau, Tim F. Cloughesy, Paul S. Mischel, Annabel Parret, Jeanette Seiler, Gerd Moldenhauer, Klaus Scheffzek, Anat O. Stemmer-Rachamimov, Charles L. Sawyers, Cameron Brennan, Ludwine Messiaen, Ingo K. Mellinghoff, Karen Cichowski
Journal: Cancer Cell (2009)
Chordin-like 1 and Twisted Gastrulation 1 Regulate BMP Signaling following Kidney Injury
Authors: Barry W. Larman, Michele J. Karolak, Derek C. Adams, Leif Oxburgh
Journal: Journal of the American Society of Nephrology (2009)

Stimulation of the bone morphogenetic protein (BMP) pathway protects the kidney from acute and chronic injury. Numerous regulators in the kidney control BMP signaling, offering many targets for therapeutic manipulation. Here, we screened for modulators of BMP signaling in the ischemia-sensitive S3 segment and found that Chordin-like 1 is expressed in this segment of both the mouse and human nephron. Chordin-like 1 specifically antagonizes BMP7, which is expressed in the neighboring distal nephron, and this depends on the presence of the protein Twisted gastrulation. Upon ischemia-induced degeneration of the S3 segment, we observed a reduction in Chordin-like 1 expression coincident with intense BMP signaling in tubules of the recovering kidney. Restored expression accompanied proximal tubule epithelia redifferentiation, again coincident with decreased BMP signaling. We propose that Chordin-like 1 reduces BMP7 signaling in healthy proximal tubules, and the loss of this activity upon sloughing of injured epithelia promotes BMP7 signaling in repopulating, dedifferentiated epithelia. As regenerating epithelia differentiate, Chordin-like 1 is again expressed, antagonizing BMP7. These data suggest a mechanism for dynamic regulation of renoprotective BMP7 signaling in the S3 segment of the proximal tubule.
P31 Disease targeted therapies and effect on survival in idiopathic, heritable and anorexigen-associated pulmonary arterial hypertension (PAH)
Authors: Y. Ling, M. Johnson, A. Peacock
Journal: Thorax (2010)

<h3>Introduction</h3> The median survival of idiopathic PAH was 2.8 years before the availability of modern therapies. Substantial progress has been made over the past 20 years. Currently available disease targeted therapies have been shown in clinical trials to improve symptoms, exercise capacity and survival. Combination therapies should also be considered in patients with inadequate clinical response to monotherapy (ESC/ERS 2009). We aim to assess the use of modern advance treatments in ‘real-life’ patients and their impact on survival. <h3>Methods</h3> A retrospective review of all incident cases of idiopathic, heritable and anorexigen-associated PAH diagnosed between 1st January 2001 and 31st December 2009 in our unit. Baseline and follow-up data were collected from case notes and local pulmonary hypertension database. <h3>Results</h3> 94 incident cases were diagnosed (62% female) with median age of 63 years. 36% (n=34) of patients were on combination therapy. All except one patient were started on monotherapy, with second agent added at later stage. The median time from initiation of monotherapy to introduction of the second agent was 244 days. 25% had prostanoids; 51% endothelin receptor antagonists and 81% phosphodiesterase type-5 inhibitor at some point of their treatment. The median survival is 5.63 years. We performed further analysis on the 28 patients who have died by censor date. Only seven patients were on prostanoids and eight patients on combination therapy. Possible explanations for low proportions of dead patients on prostanoids and/or combination therapy are outlined in Abstract P31 Table 1. <h3>Conclusion</h3> Our results demonstrate improved survival compared to pre-advance therapy era. Apart from proven efficacy of various PAH specific treatment, several other factors may also influence the treatment decision for individual patient.
Atypical Spitz tumors in patients younger than 18 years
Authors: Daniela Massi, Carlo Tomasini, Rebecca Senetta, Milena Paglierani, Francesca Salvianti, Maria Elena Errico, Vittoria Donofrio, Paola Collini, Gabrina Tragni, Angela Rita Sementa, Franco Rongioletti, Renata Boldrini, Andrea Ferrari, Claudio Gambini, Maria Cristina Montesco
Journal: Journal of the American Academy of Dermatology (2014)
Proinflammatory Homeobox Gene, <i>ISX</i>, Regulates Tumor Growth and Survival in Hepatocellular Carcinoma
Authors: Shih-Hsien Hsu, Li-Ting Wang, King-Teh Lee, Yao-Li Chen, Kwei-Yan Liu, Jau-Ling Suen, Chee-Yin Chai, Shen-Nien Wang
Journal: Cancer Research (2012)

Abstract Chronic inflammation drives initiation of hepatocellular carcinoma (HCC), but the underlying mechanisms linking inflammation and tumor formation remain obscure. In this study, we compared the expression of interleukin (IL)-6 and cyclin D1 (CCND1) with the IL-6–induced homeobox gene ISX (intestine-specific homeobox) in 119 paired specimens of HCCs and adjacent normal tissues and also in paired specimens from 11 patients with non-HCCs. In pathologic analysis, ISX exhibited a tumor-specific expression pattern and a high correlation to patient survival time, tumor size, tumor number, and progression stage. Enforced expression of ISX accelerated cell proliferation and tumorigenic activity in hepatoma cells through CCND1 induction. In contrast, short hairpin RNA–mediated attenuation of ISX in hepatoma cells decreased cell proliferation and malignant transformation in vitro and in vivo. A high positive correlation existed in human hepatoma tumors between ISX and CCND1 expression. Together, our results highlight ISX as an important regulator in hepatoma progression with significant potential as a prognostic and therapeutic target in HCCs. Cancer Res; 73(2); 508–18. ©2012 AACR.