tbuckley/cabot-search huggingface dataset:
Isotretinoin increases skin-surface levels of neutrophil gelatinase-associated lipocalin in patients treated for severe acne
Authors: K.R. Lumsden, A.M. Nelson, M.C. Dispenza, K.L. Gilliland, Z. Cong, A.L. Zaenglein, D.M. Thiboutot
Journal: British Journal of Dermatology (2011)

A clear-cut need exists for safe and effective alternatives to the use of isotretinoin in severe acne. Lack of data regarding the specifics of isotretinoin's mechanism of action has hampered progress in this area. Recently, the protein neutrophil gelatinase-associated lipocalin (NGAL) has been identified as a mediator of the apoptotic effect of isotretinoin on sebocytes.To establish further the clinical relevance of NGAL and to elucidate the factors that induce NGAL expression in sebocytes.Methods were developed to isolate and quantify skin-surface levels of NGAL from normal subjects and patients with acne undergoing treatment with isotretinoin.Patients with acne were found to have higher skin levels of NGAL compared with normal subjects. Studies in SEB-1 sebocytes indicate that NGAL expression is increased in response to Propionibacterium acnes and interleukin (IL)-1β. In patients, isotretinoin increases NGAL levels by 2·4-fold on the skin surface and this increase precedes decreases in sebum and P. acnes counts.These data support the hypothesis that NGAL is an important mediator of the early effects of isotretinoin on the sebaceous glands and provide insights into the mechanisms that regulate NGAL expression in the skin.
Infectious disease surveillance during emergency relief to Bhutanese refugees in Nepal
Authors: A. A. Marfin
Journal: JAMA (1994)

To implement simplified infectious disease surveillance and epidemic disease control during the relocation of Bhutanese refugees to Nepal.Longitudinal observation study of mortality and morbidity.Refugee health units in six refugee camps housing 73,500 Bhutanese refugees in the eastern tropical lowland between Nepal and India.Infectious disease surveillance and community-based programs to promote vitamin A supplementation, measles vaccination, oral rehydration therapy, and early use of antibiotics to treat acute respiratory infection.Crude mortality rate, mortality rate for children younger than 5 years, and cause-specific mortality.Crude mortality rates up to 1.15 deaths per 10,000 persons per day were reported during the first 6 months of surveillance. The leading causes of death were measles, diarrhea, and acute respiratory infections. Surveillance data were used to institute changes in public health management including measles vaccination, vitamin A supplementation, and control programs for diarrhea and acute respiratory infections and to ensure rapid responses to cholera, Shigella dysentery, and meningoencephalitis. Within 4 months of establishing disease control interventions, crude mortality rates were reduced by 75% and were below emergency levels.Simple, sustainable disease surveillance in refugee populations is essential during emergency relief efforts. Data can be used to direct community-based public health interventions to control common infectious diseases and reduce high mortality rates among refugees while placing a minimal burden on health workers.
Translational research in Huntington’s disease: opening up for disease modifying treatment
Authors: Jean-Marc Burgunder
Journal: Translational Neurodegeneration (2013)

Research on the molecular mechanisms involved in Huntington's disease, a monogenic disorder with a complex phenotype including motor, behaviour, and cognitive impairments, is advancing at a rapid path. Knowledge on several of the multimodal pathways has now lead to the establishment of rational strategies to prepare trials of several compounds in affected people. Furthermore, improved understanding of the phenotype and on ways of assessing it, as well as the process of developing biomarkers, allows setting the frame for such studies. In this brief review, the present status of some of these aspects is examined.
Varicocele--the most common cause of male factor infertility?
Authors: J. B. Redmon
Journal: Human Reproduction Update (2002)

Varicocele is often cited as the most common cause of male factor infertility. Arguments in support of this statement include reports of increased prevalence of varicocele in populations of infertile men compared with fertile or otherwise unselected men, association of varicocele with abnormal semen parameters, and improvements in semen parameters and/or pregnancy rates after varicocele repair. Logically, there would appear to be three possibilities regarding the relationship between varicocele and fertility: (i) varicocele has no association with or effect on male fertility; (ii) varicocele may be associated with, but is not the cause of, male subfertility; and (iii) varicocele is a direct cause of male subfertility. In the following, we review evidence from the literature for and against these three possibilities: at the current time, available evidence appears inadequate to confirm or deny any of these three possibilities. Since the ultimate goal of infertile couples is to conceive, it seem logical that future varicocele research should focus primarily on adequately powered, controlled clinical trials in well-characterized infertile couples, randomized to intervention or appropriate controlled observation, with pregnancy as the primary outcome.
Genomic neighborhoods for Arabidopsis retrotransposons: a role for targeted integration in the distribution of the Metaviridae.
Authors: Brooke D Peterson-Burch, Dan Nettleton, Daniel F Voytas
Journal: Genome biology (2004)

Retrotransposons are an abundant component of eukaryotic genomes. The high quality of the Arabidopsis thaliana genome sequence makes it possible to comprehensively characterize retroelement populations and explore factors that contribute to their genomic distribution.We identified the full complement of A. thaliana long terminal repeat (LTR) retroelements using RetroMap, a software tool that iteratively searches genome sequences for reverse transcriptases and then defines retroelement insertions. Relative ages of full-length elements were estimated by assessing sequence divergence between LTRs: the Pseudoviridae were significantly younger than the Metaviridae. All retroelement insertions were mapped onto the genome sequence and their distribution was distinctly non-uniform. Although both Pseudoviridae and Metaviridae tend to cluster within pericentromeric heterochromatin, this association is significantly more pronounced for all three Metaviridae sublineages (Metavirus, Tat and Athila). Among these, Tat and Athila are strictly associated with pericentromeric heterochromatin.The non-uniform genomic distribution of the Pseudoviridae and the Metaviridae can be explained by a variety of factors including target-site bias, selection against integration into euchromatin and pericentromeric accumulation of elements as a result of suppression of recombination. However, comparisons based on the age of elements and their chromosomal location indicate that integration-site specificity is likely to be the primary factor determining distribution of the Athila and Tat sublineages of the Metaviridae. We predict that, like retroelements in yeast, the Athila and Tat elements target integration to pericentromeric regions by recognizing a specific feature of pericentromeric heterochromatin.
Positron-Emission Tomography Reporter Gene Expression Imaging in Rat Myocardium
Authors: Masayuki Inubushi, Joseph C. Wu, Sanjiv S. Gambhir, Gobalakrishnan Sundaresan, Nagichettiar Satyamurthy, Mohammad Namavari, Simon Yee, Jorge R. Barrio, David Stout, Arion F. Chatziioannou, Lily Wu, Heinrich R. Schelbert
Journal: Circulation (2003)

Background— This study examines the quantitative accuracy, detection sensitivity, and time course of imaging the expression of a mutant herpes simplex type-1 virus thymidine kinase (HSV1-sr39tk) PET reporter gene in rat myocardium by using the PET reporter probe 9-(4-[ 18 F]-Fluoro-3-Hydroxymethylbutyl)-Guanine ([ 18 F]-FHBG) and a small-animal PET (microPET). Methods and Results— In 40 rats, adenovirus expressing HSV1-sr39tk driven by a cytomegalovirus promoter (Ad-CMV-HSV1-sr39tk, 1×10 6 to 1×10 9 pfu) was injected through a thoracotomy directly into the left ventricular myocardium. After 3 days, myocardial perfusion was imaged with [ 13 N]-ammonia for delineating the left ventricular myocardium, followed by imaging the expression of the reporter gene with intravenous [ 18 F]-FHBG. The total myocardial [ 18 F]-FHBG accumulation was quantified in percent of injected dose (%ID). Immunohistochemistry and autoradiography demonstrated HSV1-sr39tk enzyme (HSV1-sr39TK) and accumulation of [ 18 F]-FHBG in the inoculated myocardium in 3 rats each. In 24 rats with various viral titers, the %ID was correlated with ex vivo well counting ( r 2 =0.981, P &lt;0.0001) and myocardial HSV1-sr39TK activity by tissue enzyme activity assay ( r 2 =0.790, P &lt;0.0001). Myocardial [ 18 F]-FHBG accumulation was identified at viral titers down to 1×10 7 pfu. In 6 rats serially imaged up to day 17, myocardial [ 18 F]-FHBG accumulation on microPET peaked on days 3 to 5 and was no longer identified on days 10 to 17. Conclusions— HSV1-sr39tk reporter gene expression can be monitored with [ 18 F]-FHBG and microPET in rat myocardium quantitatively and serially with high detection sensitivity. Cardiac PET reporter gene imaging offers the potential of monitoring the expression of therapeutic genes in cardiac gene therapy.
Operant contingencies and “near-money”
Authors: Simon Kemp, Randolph C. Grace
Journal: Behavioral and Brain Sciences (2006)

We make two major comments. First, negative reinforcement contingencies may generate some apparent “drug-like” aspects of money motivation, and the operant account, properly construed, is both a tool and drug theory. Second, according to Lea &amp; Webley (L&amp;W), one might expect that “near-money,” such as frequent-flyer miles, should have a stronger drug and a weaker tool aspect than regular money. Available evidence agrees with this prediction.
Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study
Authors: Eva Havrdova, Steven Galetta, Michael Hutchinson, Dusan Stefoski, David Bates, Chris H Polman, Paul W O'Connor, Gavin Giovannoni, J Theodore Phillips, Fred D Lublin, Amy Pace, Richard Kim, Robert Hyde
Journal: The Lancet Neurology (2009)
Lung epithelial apoptosis in influenza virus pneumonia: the role of macrophage-expressed TNF-related apoptosis-inducing ligand
Authors: Susanne Herold, Mirko Steinmueller, Werner von Wulffen, Lidija Cakarova, Ruth Pinto, Stephan Pleschka, Matthias Mack, William A. Kuziel, Nadia Corazza, Thomas Brunner, Werner Seeger, Juergen Lohmeyer
Journal: The Journal of Experimental Medicine (2008)

Mononuclear phagocytes have been attributed a crucial role in the host defense toward influenza virus (IV), but their contribution to influenza-induced lung failure is incompletely understood. We demonstrate for the first time that lung-recruited "exudate" macrophages significantly contribute to alveolar epithelial cell (AEC) apoptosis by the release of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a murine model of influenza-induced pneumonia. Using CC-chemokine receptor 2-deficient (CCR2(-/-)) mice characterized by defective inflammatory macrophage recruitment, and blocking anti-CCR2 antibodies, we show that exudate macrophage accumulation in the lungs of influenza-infected mice is associated with pronounced AEC apoptosis and increased lung leakage and mortality. Among several proapoptotic mediators analyzed, TRAIL messenger RNA was found to be markedly up-regulated in alveolar exudate macrophages as compared with peripheral blood monocytes. Moreover, among the different alveolar-recruited leukocyte subsets, TRAIL protein was predominantly expressed on macrophages. Finally, abrogation of TRAIL signaling in exudate macrophages resulted in significantly reduced AEC apoptosis, attenuated lung leakage, and increased survival upon IV infection. Collectively, these findings demonstrate a key role for exudate macrophages in the induction of alveolar leakage and mortality in IV pneumonia. Epithelial cell apoptosis induced by TRAIL-expressing macrophages is identified as a major underlying mechanism.
Venous thromboembolism and cancer
Authors: John A Baron, Gloria Gridley, Elisabete Weiderpass, Olof Nyren, Martha Linet
Journal: The Lancet (1998)

Although cancer has been clearly associated with venous thromboembolism (VTE), many aspects of this relation are poorly understood, including the cancer sites most affected and the cancer risk during long-term follow-up. To clarify these relations, we carried out a large, population-based analysis of VTE and cancer risk.Using the Swedish Inpatient Register and linkage to the nationwide Cancer Registry, we assessed cancer incidence during 1989 among 61,998 patients without a previous cancer diagnosis admitted to hospital between 1965 and 1983 for VTE. To measure possible increases in cancer risk, we computed standardised incidence ratios (SIRs) using Swedish national cancer rates for the period of the study.At the time of thromboembolic admission or during the first year of follow-up, 2509 cancers were diagnosed (SIR 4.4, 95% CI 4.2-4.6) [corrected]. The SIR for polycythaemia vera was 12.9 (8.6-18.7), and the SIRs for cancers of the liver, pancreas, ovary, and brain, and for Hodgkin lymphoma also exceeded 5.0. Patients aged less than 65 years had higher SIRs than those who were older. In subsequent years, 6081 cancers were diagnosed (1.3, 1.3-1.3). Even 10 years or more after admission to hospital with VTE, cancer incidence had increased (1.3, 1.3-1.4).At the time of VTE or in the first year afterwards, we found a large increase in the risk for diagnosis of virtually all cancers. In subsequent years, a persistent 30% increase in risk remains. Either premalignant change promotes thrombosis, or cancer and thrombosis share common risk factors.
Modulation of endothelial cell hemostatic properties by tumor necrosis factor.
Authors: P P Nawroth, D M Stern
Journal: The Journal of Experimental Medicine (1986)

Tumor necrosis factor/cachectin (TNF) is a mediator of the septic state, which involves diffuse abnormalities of coagulation throughout the vasculature. Since previous studies have shown that endothelial cells can play an active role in coagulation, we wished to determine whether TNF could modulate endothelial cell hemostatic properties. Incubation of purified recombinant TNF with cultured endothelial cells resulted in a time- and dose-dependent acquisition of tissue factor procoagulant activity. Concomitant with enhanced procoagulant activity, TNF also suppressed endothelial cell cofactor activity for the anticoagulant protein C pathway; both thrombin-mediated protein C activation and formation of functional activated protein C-protein S complex on the cell surface were considerably attenuated. Comparable concentrations of TNF (half-maximal affect at approximately 50 pM) and incubation times (half-maximal affect by 4 h after addition to cultures) were required for each of these changes in endothelial cell coagulant properties. This unidirectional shift in cell surface hemostatic properties favoring promotion of clot formation indicates that, in addition to leukocyte procoagulants, endothelium can potentially be instrumental in the pathogenesis of the thrombotic state associated with inflammatory and malignant disorders.
Class I MHC can present an endogenous peptide to cytotoxic T lymphocytes.
Authors: J L Whitton, M B Oldstone
Journal: The Journal of Experimental Medicine (1989)

Since class I MHC glycoproteins may function by "screening and selecting" degraded proteins, we wished to determine whether very short peptides made within a cell were detected and bound by MHC, and presented for T cell perusal. We show that a 22 amino acid viral sequence containing a Db-restricted nonameric CTL epitope is sufficient to direct CTL recognition/lysis of H2b target cells. The mechanism of epitope presentation is by the "natural" endogenous route, and appears to direct lysis as effectively as wild-type virus infection, in which the epitope is part of a 236 residue glycoprotein.
Resorption kinetics of osseous substitute: natural coral and synthetic hydroxyapatite
Authors: F. Braye, J.L. Irigaray, E. Jallot, H. Oudadesse, G. Weber, N. Deschamps, C. Deschamps, P. Frayssinet, P. Tourenne, H. Tixier, S. Terver, J. Lefaivre, A. Amirabaldi
Journal: Biomaterials (1996)
Socialization in patients with chronic respiratory failure (CRF), undergoing long-term oxygen therapy (LTOT), as assessed by Lubben social networking scales-6 (LSNS-6)
Authors: Hiroo Wada, Yoko Akiyama, Hirotaka Takeda, Masuo Nakamura, Rina Nishinono, Hajime Takizawa, Hajime Goto
Journal: European Respiratory Journal (2013)

INTRODUCTION  Chronic respiratory failure (CRF) and utilization of LTOT impair patients9 socialization. To address this, socialization of CRF patients was evaluated, using Lubben Social Networking Scale-6 (LSNS-6), a questionnaire to estimate social isolation in the elderly individuals, in which higher scores indicate better socialization and scores less than 12 indicate social isolation.   METHODS  38 out-patients in our hospital (Pt-Krn) and 13 members of a local patients’ association for LTOT, “Chofu Sanso no Kai” (Pt-Ch), were enrolled and their clinical information as well as LSNS-6 scores were analyzed. All the participants suffered CRF, undergoing LTOT.   RESULTS  CRF resulted mostly from COPD (50%) and interstitial lung disease (42%) in Pt-Km, while COPD (54%) and sequale of tuberculosis (15%) in Pt-Ch. Prescribed oxygen volumes in Pt-Km were similar level with those in Pt-Ch. 19 patients of Pt-Km (50.0%) and 4 of Pt-Ch (30.1%) had LSNS-6 scores less than 12. Total scores of LSNS-6 were 12.5+/-7.1 in Pt-Krn, lower in treand than that in Pt-Ch, 16.0+/-8.2 (p=0.08). This trend was accounted for by friends9 components of LSNS-6, which were 4.6+/-4.8 in Pt-Krn, significantly lower than those in Pt-Ch, 7.6+/-4.9 (p    DISCUSSIONS AND CONCLUSIONS  Compared to a Japanese population-based survey, i.e. 19.4% had LSNS-6 scores less than 12 and LSNS-6 scores were 16.2+/-5.1 (Kurimoto A et al.,  Jpn J Geriatr Med  2009), our study demonstrated that socialization was deteriorated in CRF patients undergoing LTOT. However, deteriorated socialization in CRF patients was restored by joining a local patients’ organization.
Accuracy of Predictions of Survival in Later Stages of Cancer
Authors: C. M. Parkes
Journal: BMJ (1972)

Though 83% of 168 cancer patients admitted for "terminal care" died within 12 weeks of admission predictions of the probable length of survival showed little relation to the actual length of survival. A total of 83% of all "errors" were in an "optimistic" direction, the patient being expected to survive longer than he actually did. No significant differences were found between the accuracy of predictions made at referral by general practitioners, by doctors at other hospitals, by hospice physicians on the day of admission, or by ward sisters and senior nurses at the same time. A week after admission predicted and actual survival correlated more closely but predictions were still optimistic. It is concluded that predictions of the length of time which a cancer patient who is at the end of active treatment can be expected to survive should be made and interpreted with the greatest caution.
Exercise-induced ST elevation in patients without myocardial infarction.
Authors: J C Longhurst, W L Kraus
Journal: Circulation (1979)

A review of 6040 consecutive exercise tests yielded 106 patients without previous myocardial infarction (MI) who had exercise-induced ST elevation (greater than or equal to 0.5 mm in a 15-lead ECG system). In 46, ST elevation was correlated with left ventriculography and coronary angiography. Coronary artery disease (CAD) (greater than or equal to 70% narrowing) was detected in 40 of 46 patients: 12 patients had one-vessel disease, 13 had two-vessel disease, and 15 had three-vessel disease. Resting ventriculograms were normal in 36 of 40 patients. Of 21 patients with anterior (V1-V3) ST elevation, 86% had a left anterior descending (LAD) obstruction and 78% had obstruction proximal to the first diagonal branch. LAD disease occurred significantly more frequently than right and circumflex CAD. There was no anatomic correlation of three persons with lateral (leads V4--6, I or aVL) or 27 patients with inferior-posterior (leads II, III, aVF, Y or Z) exercise-induced ST elevation. Therefore, exercise-induced ST elevation is strongly correlated with CAD but not resting wall motion abnormalities. Further, anterior exercise-induced ST elevation in patients without a previous MI often predicts a significant proximal LAD obstruction.
Sustained Human Factor VIII Expression in Hemophilia A Mice Following Systemic Delivery of a Gutless Adenoviral Vector
Authors: P.Seshidhar Reddy, Kiran Sakhuja, Shanthi Ganesh, Lijuan Yang, Dawn Kayda, Terrence Brann, Scott Pattison, Doug Golightly, Neeraja Idamakanti, Anne Pinkstaff, Michele Kaloss, Catherine Barjot, Jeffrey S. Chamberlain, Michael Kaleko, Sheila Connelly
Journal: Molecular Therapy (2002)

Gutless adenoviral vectors are devoid of all viral coding regions and display reduced cytotoxicity, diminished immunogenicity, and an increased coding capacity compared with early generation vectors. Using hemophilia A, a deficiency in clotting factor VIII (FVIII), as a model disease, we generated and evaluated a gutless vector encoding human FVIII. The FVIII gutless vector grew to high titer and was reproducibly scaled-up from vector seed lots. Extensive viral DNA analyses revealed no rearrangements of the vector genome. A quantitative PCR assay demonstrated helper virus contamination levels of <2%, with the best preparation containing 0.3% helper virus. We compared the gutless vector with an E1/E2a/E3-deficient (Av3) early generation vector encoding an identical FVIII expression cassette following intravenous administration to hemophilia A mice. Gutless vector-treated mice displayed 10-fold higher FVIII expression levels that were sustained for at least 9 months. In contrast, mice treated with the Av3 vector displayed FVIII levels below the limit of sensitivity of the assay at 3 months. Assessment of hepatotoxicity by measuring the serum levels of liver enzymes demonstrated that the gutless vector was significantly less toxic than the Av3 vector at time points later than 7 days. At the highest dose used, both vectors caused a transient 10-fold increase in liver enzymes 1 day after vector administration, suggesting that this increase was caused by direct toxicity of the input capsid proteins. These data demonstrate that the gutless vector displayed increased duration and levels of FVIII expression, and was significantly less toxic than an analogous early generation vector.