tbuckley/cabot-search huggingface dataset:
458. Efficient Transduction of Human and Murine Cells and Circumvention of Preexisting Human Adenoviral Immunity by Porcine Adenoviral Vectors
Authors: Takako Miyamae, Anthony D. Marinov, Sylvie Fabre, David C. Wilson, Tomoyuki Imagawa, Bruce C. Trapnell, Gregory P. Boivin, Raphael Hirsch
Journal: Molecular Therapy (2004)

Adenovirus is a well-known vector for delivering therapeutic genes to tissues. However, it induces an immune response against viral antigens, which results in loss of transgene expression. This has limited the utility of adenovirus in applications in which long-term transgene expression is desired. Fibronectin (FN) is an extracellular matrix glycoprotein that interacts with a variety of cells through integrin and non-integrin receptors. These interactions play a role in cell adhesion and migration during an inflammatory response. In previous studies, we showed that a 33-KD carboxyl-terminal heparin-binding fragment of fibronection (FN-C/H-II) inhibited leukocyte recruitment in mouse arthritis. The present study was designed to determine whether FN-C/H-II could also blunt the inflammatory response to adenovirus. An adenoviral vector (1 × 109 particles) encoding murine IL-10 (AdmIL10) was co-injected with an equal titer of either an adenovirus encoding FN-C/H-II (AdFN) or a control backbone adenovirus (AdBglII) into knee joints of normal C57BL/6 mice. Expression of mIL-10 was significantly higher in the knees co-injected with AdFN over a 2 week observation period. Histological evaluation revealed a marked reduction in infiltration of both neutrophils and lymphocytes in the synovium of mice co-injected with the AdFN vector. These results suggest that adenoviral expression of FN-C/H-II peptide can reduce adenovirus-associated inflammation and enhance the efficacy of adenovirus as a gene transfer vector.
The predictive values of combined assessment of preoperative plasma levels of OPN and ICAM-1 for prognosis of patients with hepatocellular carcinoma:retrospective and prospective validations
Authors: Lun-Xiu Qin, Hong-Hai Wang, Hui Zhang, Qing-Hai Ye, Ning Ren, Zhao-You Tang
Journal: Clinical Cancer Research (2006)

B55   Objective In our previous studies, osteopontin (OPN) and intercellular adhesion molecule-1 (ICAM-1) were found to be related to invasion and metastasis of human hepatocellular carcinoma (HCC). In this study, we aimed to investigate the prognostic value of combined assessment of preoperative plasma levels of OPN and ICAM-1 for patients with HCC. Methods A total of 204 patients underwent liver resection for HCC were enrolled. Among them, 75 patients treated in 2001 were studied retrospectively, the other 129 patients treated in 2004 were used for prospective study. Levels of OPN and ICAM-1 were detected by ELISA, and their association with HCC recurrence and patients9 survival was analyzed. Results Significant higher levels of OPN and ICAM-1 were found in patients with postoperative HCC recurrence compared with those without recurrence (210.4 vs. 154.9 ng/ml,  P =0.001; 1011.2 vs. 747.5ng/ml,  P =0.027). The patients with higher and lower plasma levels of OPN (>200 ng/ml) and ICAM-1 (>900 ng/ml) had a higher 2-year recurrence rate (87.5% vs. 28.0%  P  P =0.001), and lower 2-year disease-free survival (DFS) rate (12.5%, vs. 76.0,  P =0.001). Prospectively, patients with higher levels were defined as high-risk recurrence group, which was found to have a higher 1 year recurrent rate (60% vs. 10%), a lower 1 year OS rate (75.0% vs. 100%) and DFS rate (40.0% vs. 90.0%). The specificity and sensitivity were 0.939 and 0.220, positive and negative predictive values were 0.643 and 0.706, respectively. Conclusions: The combined assessment of the preoperative plasma levels of OPN and ICAM-1 could be used in the prediction of postoperative recurrence of HCC and patients9 prognosis.
THE CULTIVATION OF PHYSIOLOGICAL RELAXATION
Authors: Edmund Jacobson
Journal: Annals of Internal Medicine (1943)

Article1 December 1943THE CULTIVATION OF PHYSIOLOGICAL RELAXATIONEDMUND JACOBSON, M.D., F.A.C.P.EDMUND JACOBSON, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-19-6-965 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA perusal of medical journals today, as compared with a decade ago, indicates a growing recognition of the problems of relaxation. Most commonly it is linked with the discussion of hyperemotional states, noted when the patient is excitable, fatigued or hypochondriac; the need of "calmness and poise" is being stressed in a variety of disorders so wide as to include not only essential hypertension, coronary occlusion, bronchial asthma and neuropsychiatric states but also spastic colitis and even common forms of constipation.1Knowledge of the problem of relaxation would seem to be spread wide, but extremely thin, in the sense that...Bibliography1. WAKEFIELD EG: Etiologic considerations of functional disorders of the colon, Proc. Staff Meet. Mayo Clin., 1937, xii, 193. Google Scholar2. JACOBSON E: Electrical measurements concerning muscular contraction (tonus) and the cultivation of relaxation in man. The effects of daily rests without training to relax on muscular tonus, Am. Jr. Psychol., 1942, lv, 248. CrossrefGoogle Scholar3. JACOBSON E: Treatment of nervous irritability and excitement, Ill. Med. Jr., 1920. Google Scholar4. JACOBSON E: Progressive relaxation, Rev. Ed., 1938, Univ. of Chicago Press, Chicago. Google Scholar5. JACOBSON E: An integrating voltmeter for the study of nerve and muscle potentials, Rev. Sci. Instr., 1940, xi, 415-418. CrossrefGoogle Scholar6. JACOBSON E: Differential relaxation during reading, writing and other activities as tested by the knee-jerk, Am. Jr. Physiol., 1928, cxxxvi, 675. CrossrefGoogle Scholar7. Editorial: Differential relaxation, Jr. Am. Med. Assoc., 1928, xci, 1465. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois*Received for publication June 12, 1942.From the Laboratory for Clinical Physiology, Chicago. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDysponesis: A Neurophysiologic Factor in Functional DisordersElectrophysiology of Mental Activities and Introduction to The Psychological Process of ThinkingDysponesis: A neurophysiology factor in functional disorders 1 December 1943Volume 19, Issue 6Page: 965-972KeywordsAsthmaClinical laboratoriesColitisHypertensionResearch laboratories ePublished: 1 December 2008 Issue Published: 1 December 1943 PDF downloadLoading ...
Abstract P297: Alcohol Consumption and Cardiac Biomarkers
Authors: Mariana Lazo, Yuan Chen, John W McEvoy, Chiadi Ndumele, Suma Konety, A. Richey Sharrett, Christie M Ballantyne, Elizabeth Selvin
Journal: Circulation (2015)

Background:  Excess alcohol consumption can lead to myocardial dysfunction. However, whether novel cardiac biomarkers tests can detect subclinical myocardial damage and wall stress in asymptomatic populations exposed to alcohol is currently unknown.   Objective:  To characterize the association of alcohol consumption with subclinical myocardial damage, as assessed by a novel highly sensitive assay for cardiac troponin T (hs-cTnT) and wall stress, as assessed by N-terminal pro-brain natriuretic peptide (NT-proBNP).   Methods:  Using data from the community-based ARIC Study we examined the cross-sectional association of categories of self-reported alcohol consumption with cardiac biomarkers among 10,381 individuals without cardiovascular disease (1990-92). We also examined the prospective association of alcohol consumption with 6-year change in cardiac biomarkers in a subset of participants (n=8,972 for hs-cTnT and n=9,060 for NT-proBNP), who had each biomarker measured at two time points. Incident elevated NT-proBNP was defined as ≥300 pg/mL.   Results:  Cross-sectionally, compared to those drinking ≤ 1 drink/week, those drinking moderately (2-7 drinks/wk) and high (8+ drinks/wk) amounts of alcohol had significantly lower levels of hs-TnT (Figure). We found no significant association in the prospective analyses of alcohol and hs-cTnT. In contrast, high alcohol consumption was associated with elevated NT-proBNP (Figure). Prospectively, compared to those drinking ≤ 1 drink/week, those drinking 8-14 drinks/week and 15+ drinks/week had increased risk of incident elevation of NT-proBNP RRR=1.77(95%CI 1.19-2.63) and RRR=2.83 (95%1.66-4.85), respectively.   Conclusions:  We found a weak protective effect of moderate and high alcohol consumption on myocardial damage. In contrast, opposite effect was observed for subclinical wall stress. These findings are consistent with the observed elevated risk of hypertension and stroke with alcohol consumption.
A memorable incident: When is a spade not a spade
Authors: P J Tomlin
Journal: BMJ (1999)

I was visiting professor of anaesthetics in a hospital outside Britain when I was asked to see an emergency admission with a severe haematemesis. The patient was elderly, wasted, disoriented, somewhat dehydrated, hypotensive, and tachycardic. He had a chronic gastric ulcer. He had been an inmate of the local mental hospital for the previous 20years. He was a Jehovah's Witness. His medical superintendent left the decision about blood transfusion to his wife who was on her way in. The surgeon would accept my decision about whether to operate or not.

I telephoned the chief administrator. He would not give permission but would consult the minister of health (it was that sort of country) as the state was legally responsible for the patient's welfare. Within 10minutes (it really was that sort of country), …
The Ungifted Physician
Authors: S J Koven
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
I Have a Girl Child
Authors: S Nagy-Agren
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
571. Expression of IL-27 in Murine Carcinoma Cells Produces T Cell-Dependent and -Independent Antitumor Effects
Authors: Masatoshi Tagawa, Masako Chiyo, Osamu Shimozato, Ling Yu, Takehiko Fujisawa
Journal: Molecular Therapy (2004)

Interleukin (IL)-27 is a recently identified heterodimeric cytokine and is composed of p28, a newly identified IL-12p35-related protein, and Epstein-Barr virus-induced gene 3 (EBI3), an IL-12p40-related protein. IL-27 is produced primarily from activated dendritic cells and induces proliferation of naive but not memory CD4-positive T cells. It also synergizes with IL-12 in interferon (IFN)-γ production from naive T and natural killer (NK) cells. WSX-1/TCCR, one of the IL-27 receptor (R) molecules, is highly expressed in lymphoid organs particularly in naive CD4-positive T and NK cells, and the IL-27/WSX-1 signaling induces the T-bet transcription factor and IL-12Rβ2 expression. These data suggest that IL-27 play a crucial role in the initiation of type 1 helper T cell differentiation before the IL-12/IL-12R system and can augment cell-mediated immunity. We constructed p28-internal ribosomal entry site-EBI3 cDNA (IL-27) and found that IL-27 secreted from COS-7 cells induced both IL-12Rβ1 and IL-12Rβ2 expression, and production of IFN-γ from naive spleen cells. We then examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the IL-27 gene (Colon 26/IL-27) could produce antitumor effects in inoculated mice. Although proliferation in vitro of Colon 26/IL-27 cells was not different from that of parent cells, syngeneic BALB/c mice rejected Colon 26/IL-27 tumors inoculated and subsequently acquired tumor-specific protective immunity. The antitumor effects were dependent on the amounts of IL-27 secreted. In contrast, mice inoculated with Colon 26 cells transduced with either the p28 or EBI3 gene developed tumors and survival of the mice remained the same as that of the mice inoculated with parent cells. Syngeneic nude mice developed Colon 26/IL-27 tumors but the growth was retarded compared with that of parent tumors. Depletion of NK cells from nude mice with anti-asialo GM1 Ab diminished the growth retardation of Colon 26/IL-27 tumors. Survival of severe combined immunodeficiency (SCID) mice that received subcutaneous inoculation of Colon 26/IL-27 cells was not different from that of the SCID mice inoculated with parent cells. Antibody-mediated depletion showed that IFN-γ was produced from CD4-positive and CD8-positive T, and NK cells of the mice that rejected Colon 26/IL-27 tumors. Cytotoxic activity against Colon 26 cells but not irrelevant tumor cells was also detected from the mice. These data collectively suggest that expressed IL-27 in tumors produces T cell-dependent and -independent antitumor effects and is a possible therapeutic strategy for cancer.
Abstract 1798: Mechanistic study of NVP-CGM097: a potent, selective and species specific inhibitor of p53-Mdm2
Authors: Thérèse Valat, Keiichi Masuya, Frédéric Baysang, Geneviève Albrecht, Nicole Buschmann, Dirk Erdmann, Pascal Furet, Tobias Gabriel, François Gessier, Francesco Hofmann, Philipp Holzer, Joerg Kallen, Carole Pissot-Solderman, Stefan Stutz, Patrick Chène, Sébastien Jeay
Journal: Cancer Research (2014)

Abstract An effective strategy to restore p53 activity in cancer cells containing wild type p53 is to inhibit the Mdm2-p53 protein-protein interaction (PPI). NVP-CGM097 is a novel PPI inhibitor under evaluation in a Phase I clinical trial. It binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction between both proteins, leading to an activation of the p53 pathway. The main biophysical and biochemical inhibitory characteristics of NVP-CGM097 are presented here. These include an affinity constant for Mdm2 in the nanomolar range and a selectivity of 3 orders of magnitude vs. Mdm4. The binding kinetics of NVP-CGM097 to Mdm2 are characterized by a high association rate constant (Kon =37 x 106 M-1.s-1) and a moderate dissociation rate constant (Koff =0.071 s-1). Additionally, NVP-CGM097 exhibits an 8-fold greater affinity for Mdm2 over Nutlin-3 due to a longer residence time of the Mdm2-inhibitor complex. Moreover, biochemical studies have revealed the species specificity of NVP-CGM097 with human Mdm2 being inhibited more strongly than the dog, mouse or rat forms of the protein. This was confirmed in cellular assays where NVP-CGM097 treatment resulted in induction of p53 target gene expression (p21, PUMA and Mdm2) only in human, but not in dog, mouse or rat cell lines. Citation Format: Thérèse Valat, Keiichi Masuya, Frédéric Baysang, Geneviève Albrecht, Nicole Buschmann, Dirk Erdmann, Pascal Furet, Tobias Gabriel, François Gessier, Francesco Hofmann, Philipp Holzer, Joerg Kallen, Carole Pissot-Solderman, Stefan Stutz, Patrick Chène, Sébastien Jeay. Mechanistic study of NVP-CGM097: a potent, selective and species specific inhibitor of p53-Mdm2. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1798. doi:10.1158/1538-7445.AM2014-1798
Norway recruits Hungarian doctors
Authors: Carl Kovac
Journal: BMJ (2000)

Faced with planned government cuts in hospital facilities and staff, scores of Hungarian doctors may soon be heading north to Norway, which is offering 50 Hungarian specialists contracts and incomes considerably higher than they could hope to earn in Hungary.

The Norwegian labour office has informed its counterpart in Budapest that there currently is a need for general practitioners, anaesthesiologists, radiologists, gynaecologists, and pathologists.

The doctors would be employed in …
A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis
Authors: Omer T. Njajou, Norbert Vaessen, Marijke Joosse, Bianca Berghuis, Jeroen W.F. van Dongen, Martijn H. Breuning, Pieter J.L.M. Snijders, Wim P.F. Rutten, Lodewijk A. Sandkuijl, Ben A. Oostra, Cornelia M. van Duijn, Peter Heutink
Journal: Nature Genetics (2001)
Aberrant expression of complement regulatory proteins, membrane cofactor protein and decay accelerating factor, in the involved epidermis of patients with vitiligo
Authors: R.M.J.G.J. Van Den Wijngaard, S.S. Asghar, A.C.L.M. Pijnenborg, A.J. Tigges, W. Westerhof, P.K. Das
Journal: British Journal of Dermatology (2002)

Summary Background Vitiligo is a pigmentary disorder of the skin characterized by the complete absence of melanocytes from the lesion. Complement‐activating antimelanocyte antibodies have been implicated in vitiligo pathogenesis. As membrane regulators of complement activation, membrane cofactor protein, decay accelerating factor and CD59 protect cells from elimination by autologous complement, their absence or downregulation on melanocytes may be associated with autoantibody and complement‐mediated melanocyte destruction in vitiligo. Objectives We studied the expression of these regulatory proteins in non‐lesional, perilesional and lesional vitiligo skin compared with those of control specimens. Methods We used immunohistochemistry to study the expression of the regulatory proteins, and flow cytometric analysis of cultured melanocytes to investigate possible constitutive changes in the expression levels of these molecules. We also investigated whether melanocytes can influence keratinocyte susceptibility to autologous complement by regulating keratinocytic decay accelerating factor and membrane cofactor protein expression levels. Results Immunohistochemical data showed that expression of membrane cofactor protein and decay accelerating factor in whole epidermis was lower in lesional and perilesional skin in comparison with non‐lesional skin. The reduced in situ expression appeared to be specific to vitiligo. However, coculture experiments indicated that melanocytes do not influence keratinocyte susceptibility to autologous complement. Further, flow cytometric analysis of cultured melanocytes convincingly demonstrated that non‐lesional vitiligo and control melanocytes have comparable decay accelerating factor, membrane cofactor protein and CD59 expression levels. Conclusions It is therefore concluded that there is no constitutive melanocyte defect per se that could be related to the in vivo expression of these molecules in vitiligo. Nevertheless, the present data suggest that both keratinocytes and melanocytes in the involved vitiliginous whole epidermis express lower levels of decay accelerating factor and membrane cofactor protein compared with controls that could render them more vulnerable to autologous complement attack.
Abstract 12797: Temporal Changes in Mortality Risk Post-Discharge After Hospitalization for Heart Failure
Authors: Thomas D Cook, Andreas P Kalogeropoulos, Gregg C Fonarow, Ryan Zea, Karl Swedberg, Faiez Zannad, Hassan Khan, Aldo P Maggioni, Marvin A Konstam, Mihai Gheorghiade, Javed Butler
Journal: Circulation (2014)

Importance: In observational studies, the risk for adverse events among patients admitted for heart failure (HF) is highest immediately post-discharge and declines over time. This ‘vulnerable phase’ concept has led to research and quality of care initiatives focusing primarily on early post-discharge period. However, whether this risk trajectory represents lowering of individual patient risk or changes in the population risk profile is not known. Methods: Survival and longitudinal models were used to assess temporal changes in mortality risk post-discharge in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. Post hoc analysis of EVEREST included 4017 patients &gt;18 years old discharged alive after hospitalization for HF with an ejection fraction of &lt;40% at 359 sites from 2003-2006 and randomized to receive oral tolvaptan or placebo. Results: After a median of 9.8 months, 971 patients died (24.2%). Mortality at 1 year was 24.2%. Cumulative mortality rate declined from 15.9/100 patient-years immediately post-discharge to 13.4 at 30 days and 12.8 at 90 days; it rose steadily thereafter. The risk variation between quintiles of baseline risk was considerably larger than the temporal variation within risk strata. In a longitudinal model assessing updated mortality risk after each follow up visit, mortality risk increased during the 90 days preceding readmission and then followed a trajectory similar to the index admission. The net increase in mortality attributable to readmission was ~37%. Conclusions and Relevance: Among hospitalized HF patients, although there is a transiently elevated risk in 90 days before and after discharge, the patient’s clinical risk profile rather than temporal change remains the main determinant of mortality risk.