tbuckley/cabot-search huggingface dataset:
Pathways Mediating the Expansion and Immunosuppressive Activity of Myeloid-Derived Suppressor Cells and Their Relevance to Cancer Therapy
Authors: James E. Talmadge
Journal: Clinical Cancer Research (2007)

Abstract Cancer immunotherapy has focused on inducing and expanding CTLs and improving the immune recognition of weak antigenic determinants expressed by tumors. However, few positive clinical outcomes have been reported due, in part, to tumor-associated immunologic tolerance, supporting the need for an emphasis on overcoming immunosuppression. Systemic immunosuppression is associated with abnormal myelopoiesis secondary to tumor growth, myelosuppressive therapy, and growth factor administration and subsequent expansion/mobilization of bone marrow–derived immunosuppressive cells. These myeloid-derived suppressor cells (MDSC) reduce activated T-cell number and inhibit their function by multiple mechanisms, including depletion of l-arginine by arginase-1 (ARG1) production of nitric oxide, reactive oxygen species, and reactive nitrogen oxide species by inducible nitric oxide synthase. Increased numbers of MDSCs are associated with neoplastic, inflammatory, infectious, and graft-versus-host diseases where they restrain exuberant or novel T-cell responses. In this review, we discuss critical components of MDSC-mediated suppression of T-cell function, including cellular expansion and activation-induced secretion of immunosuppressive mediators. Both components of MDSC bioactivity are amenable to pharmacologic intervention as discussed herein. We also focus on the relationship between MDSCs, tumor growth, therapeutic responses, and the mechanisms of cellular expansion, activation, and immunosuppression.
Lymphocyte phenotypes in systemic sclerosis
Authors: EDIZ DALKILIÇ, KAMIL DILEK, MUSTAFA GÜLLÜLÜ, MAHMUT YAVUZ, YÜKSEL KARAKOÇ, MUSTAFA YURTKURAN, FERAH BUDAK, GÜHER GÖRAL
Journal: Annals of the Rheumatic Diseases (1999)

Although the pathophysiology of systemic sclerosis (SSc) is not fully clarified, there are considerable data implicating abnormalities of microvascular changes, fibroblast activation and immune system abnormalities. Immune system activation may play a part as a stimulus in both fibrotic and vascular damage.1 To investigate the immune system abnormalities in the pathogenesis of SSc we evaluated lymphocyte phenotypes in patients with SSc and healthy controls by flow cytometry (Epics Profile II) for total T (CD3), T helper (CD4), T supressor (CD8), B lymphocyte cell surface marker (CD19), activation marker (CD25) and natural killer (NK) cell surface marker NKH-1 (CD56).

We studied 29 patients (27 women, two men) 16 limited, 12 diffuse and one overlap who fulfilled preliminary criteria for classification of SSc.2 Anti-nuclear antibody was positive in 25 (86.2%) and anti-Scl70 antibodies was positive in seven (24.1 %) patients. The age range of the patients was 20–63 years (mean (SEM) 40 (5)) and the mean (SEM) disease duration was 5.6 (5.5) years. …
Neurotrophin-Induced Transport of a β-Actin mRNP Complex Increases β-Actin Levels and Stimulates Growth Cone Motility
Authors: H.L. Zhang, T. Eom, Y. Oleynikov, S.M. Shenoy, D.A. Liebelt, J.B. Dictenberg, R.H. Singer, G.J. Bassell
Journal: Neuron (2001)
Very Early Administration of Progesterone for Acute Traumatic Brain Injury
Authors: David W. Wright, Sharon D. Yeatts, Robert Silbergleit, Yuko Y. Palesch, Vicki S. Hertzberg, Michael Frankel, Felicia C. Goldstein, Angela F. Caveney, Harriet Howlett-Smith, Erin M. Bengelink, Geoffrey T. Manley, Lisa H. Merck, L. Scott Janis, William G. Barsan
Journal: New England Journal of Medicine (2014)

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI.
A “Closed” Medical Intensive Care Unit (MICU) Improves Resource Utilization When Compared with an “Open” MICU
Authors: ALAN S. MULTZ, DONALD B. CHALFIN, ISRAEL M. SAMSON, DAVID R. DANTZKER, ALAN M. FEIN, HARRY N. STEINBERG, MICHAEL S. NIEDERMAN, STEVEN M. SCHARF
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We hypothesized that a "closed" intensive care unit (ICU) was more efficient that an "open" one. ICU admissions were retrospectively analyzed before and after ICU closure at one hospital; prospective analysis in that ICU with an open ICU nearby was done. Illness severity was gauged by the Mortality Prediction Model (MPM0). Outcomes included mortality, ICU length of stay (LOS), hospital LOS, and mechanical ventilation (MV). There were no differences in age, MPM0, and use of MV. ICU and hospital LOS were lower when "closed" (ICU LOS: prospective 6.1 versus 12.6 d, p < 0.0001; retrospective 6.1 versus 9.3 d, p < 0.05; hospital LOS: prospective 19.2 versus 33.2 d, p < 0.008; retrospective 22.2 versus 31.2 d, p < 0.02). Days on MV were lower when "closed" (prospective 2.3 versus 8.5 d, p < 0.0005; retrospective 3.3 versus 6.4 d, p < 0.05). Pooled data revealed the following: MV predicted ICU LOS; ICU organization and MPM0 predicted days on MV; MV and ICU organization predicted hospital LOS; mortality predictors were open ICU (odds ratio [OR] 1.5, p < 0.04), MPM0 (OR 1.16 for MPM0 increase 0.1, p < 0.002), and MV (OR 2.43, p < 0.0001). We conclude that patient care is more efficient with a closed ICU, and that mortality is not adversely affected.
Analysis of fluid phase mediators
Authors: V. Keatings, R. Leigh, C. Peterson, J. Shute, P. Venge, R. Djukanović
Journal: European Respiratory Journal (2002)

Sputum cellular indices are valid, reliable and responsive to change 1–7. Increasingly, numerous inflammatory mediators are being measured in the fluid phase of sputum; these include cytokines, chemokines, granulocyte proteins, markers of vascular leakage, eicosanoids, proteases and others. Many of these mediators are included in table 1⇓, which gives details of methods used by investigators to process sputum and measure mediator levels. The table also provides the median/mean levels measured in studied subject groups to give an indication of the expected levels of these mediators in sputum. However, the reproducibility, precision and validity of many of these measurements in sputum have not been investigated and, therefore, their utility as a research and clinical tool remains uncertain and requires confirmation.

The following issues are important in the analysis of mediators: 1) choice of methods for measuring fluid­phase mediators; 2) points to consider when planning an immunoassay; and 3) evaluation of the measurement of a soluble mediator in sputum, i.e. validation of the measurement method.

The three main types of method used for the measurement of sputum fluid­phase mediators are bioassays, enzyme assays and immunoassays.

### Bioassays

Bioassays rely on the retention of biological activity and the ability to exert a measurable effect, such as proliferation of cells, bone marrow colony formation or chemotaxis 3, 11, 58. Sputum processing with mucolytics such as dithiothreitol (DTT) or dithioerythritol, which are strong reducing agents, may decrease the biological activity of cytokines, many of which rely on disulphide bonds to provide a stable structure for bioactivity. Bioassays also have the disadvantage of being inconvenient, time­consuming and lacking in specificity 59. In addition, the presence of commonly occurring endogenous cytokine inhibitors, although allowing an estimate of net activity, may result in significant underestimation of total cytokine levels 58.

### Enzyme assays

Many …
Advanced Technologies for Gastrointestinal Endoscopy
Authors: Pietro Valdastri, Massimiliano Simi, Robert J. Webster
Journal: Annual Review of Biomedical Engineering (2012)

The gastrointestinal tract is home to some of the most deadly human diseases. Exacerbating the problem is the difficulty of accessing it for diagnosis or intervention and the concomitant patient discomfort. Flexible endoscopy has established itself as the method of choice and its diagnostic accuracy is high, but there remain technical limitations in modern scopes, and the procedure is poorly tolerated by patients, leading to low rates of compliance with screening guidelines. Although advancement in clinical endoscope design has been slow in recent years, a critical mass of enabling technologies is now paving the way for the next generation of gastrointestinal endoscopes. This review describes current endoscopes and provides an overview of innovative flexible scopes and wireless capsules that can enable painless endoscopy and/or enhanced diagnostic and therapeutic capabilities. We provide a perspective on the potential of these new technologies to address the limitations of current endoscopes in mass cancer screening and other contexts and thus to save many lives.
Interactions Between Ankyrin-G, Plakophilin-2, and Connexin43 at the Cardiac Intercalated Disc
Authors: Priscila Y. Sato, Wanda Coombs, Xianming Lin, Oxana Nekrasova, Kathleen J. Green, Lori L. Isom, Steven M. Taffet, Mario Delmar
Journal: Circulation Research (2011)

The early description of the intercalated disc defined 3 structures, all of them involved in cell-cell communication: desmosomes, gap junctions, and adherens junctions. Current evidence demonstrates that molecules not involved in providing a physical continuum between cells also populate the intercalated disc. Key among them is the voltage-gated sodium channel complex. An important component of this complex is the cytoskeletal adaptor protein Ankyrin-G (AnkG).To test the hypothesis that AnkG partners with desmosome and gap junction molecules and exerts a functional effect on intercellular communication in the heart.We used a combination of microscopy, immunochemistry, patch-clamp, and optical mapping to assess the interactions between AnkG, Plakophilin-2, and Connexin43. Coimmunoprecipitation studies from rat heart lysate demonstrated associations between the 3 molecules. With the use of siRNA technology, we demonstrated that loss of AnkG expression caused significant changes in subcellular distribution and/or abundance of PKP2 and Connexin43 as well as a decrease in intercellular adhesion strength and electric coupling. Regulation of AnkG and of Na(v)1.5 by Plakophilin-2 was also demonstrated. Finally, optical mapping experiments in AnkG-silenced cells demonstrated a shift in the minimal frequency at which rate-dependence activation block was observed.These experiments support the hypothesis that AnkG is a key functional component of the intercalated disc at the intersection of 3 complexes often considered independent: the voltage-gated sodium channel, gap junctions, and the cardiac desmosome. Possible implications to the pathophysiology of inherited arrhythmias (such as arrhythmogenic right ventricular cardiomyopathy) are discussed.
Inhaled Hypertonic Saline in Infants and Young Children With Cystic Fibrosis
Authors: Elliott C. Dasenbrook, Michael W. Konstan
Journal: JAMA (2012)

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
Effects of Myosin Heavy Chain Isoform Switching on Ca <sup>2+</sup> -Activated Tension Development in Single Adult Cardiac Myocytes
Authors: Joseph M. Metzger, Philip A. Wahr, Daniel E. Michele, Faris Albayya, Margaret V. Westfall
Journal: Circulation Research (1999)

Abstract —Cardiac myosin heavy chain (MHC) isoforms are known to play a key role in defining the dynamic contractile behavior of the heart during development. It remains unclear, however, whether cardiac MHC isoforms influence other important features of cardiac contractility, including the Ca 2+ sensitivity of isometric tension development. To address this question, adult rats were treated chemically to induce the hypothyroid state and cause a transition in the ventricular cardiac MHC isoform expression pattern from predominantly the α-MHC isoform to exclusively the β-MHC isoform. We found a significant desensitization in the Ca 2+ sensitivity of tension development in β-MHC–expressing ventricular myocytes (pCa 50 =5.51±0.03, where pCa is –log[Ca 2+ ], and pCa 50 is pCa at which tension is one-half maximal) compared with that in predominantly α-MHC–expressing myocytes (pCa 50 =5.68±0.05). No differences between the 2 groups were observed in the steepness of the tension-pCa relationship or in the maximum isometric force generated. Instantaneous stiffness measurements were made that provide a relative measure of changes in the numbers of myosin crossbridges attached to actin during Ca 2+ activation. Results showed that the relative stiffness-pCa relationship was shifted to the right in β-MHC–expressing myocytes compared with the α-MHC–expressing cardiac myocytes (pCa 50 =5.47±0.05 versus 5.76±0.05, respectively). We conclude that MHC isoform switching in adult cardiac myocytes alters the Ca 2+ sensitivity of stiffness and tension development. These results suggest that the activation properties of the thin filament are in part MHC isoform dependent in cardiac muscle, indicating an additional role for MHC isoforms in defining cardiac contractile function.
Clinical and radiological (CR) features of tuberculosis formed as a result of immunosuppressive therapy (IT)
Authors: Pavel Gavrilov, Liudmila Archacova, Viacheslav Zhuravlev
Journal: European Respiratory Journal (2012)

Research objective was an analysis of features of pulmonary tuberculosis (PT) formed as a result of IT.

Material and methods. CR features of PT were retrospectively studied in 31 patients who have undergone long-term courses (from 4,5 up to 26 months) of IT: prednisolone, cytostatics for – 23 patients with bronchial asthma, histiocytosis X, kidney allotransplantation, vasculitis, rheumatoid arthritis (1 group). 8 patients (2 group) - monoclonal antibodies for rheumatoid process.

Results. CR picture of PT has often been interpreted as progression of basic disease – in 67,7% of patients - in 4-9 months. Marked clinical symptoms were registered in 89,5% and 58,3% of patients, polysegmentary, bilateral changes were noted in 84,2% (1 group) and 100,0% (2 group) with prevalence of changes in lower parts of the lungs in 57,9% and 75,0% accordingly. Long-term absence of bacterioexcretion of MBT is typical for the patients of both groups. The patients, who were taking monoclonal antibodies had twice as high incidence of destructive changes (50,0% against 21,1%). 100,0% of patients of II group had visible bilateral enlargement of intrathoracic lymph nodes and tubercular affection of bronchial tree in 58,3% of cases. Generalized forms were registered in 25% of II group patients vs. 2,0% of I group patients. Characteristic property of PT in 2 group was wavelike course of the process with slow progression.

 Conclusion:  Disseminated processes are typical for PT formed as a result of IT. A feature of tuberculosis process in patients taking monoclonal antibodies, is marked bilateral affection of intrathoracic lymph nodes, predisposition to generalization of the infection and wavelike course.
Multiple, heart-cross-reactive epitopes of streptococcal M proteins.
Authors: J B Dale, E H Beachey
Journal: The Journal of Experimental Medicine (1985)

We present evidence that a highly purified pepsin extract of type 5 streptococcal M protein (pep M5) contains at least three epitopes that are cross-reactive with sarcolemmal membrane proteins of human myocardium. The tissue-cross-reactive determinants of pep M5 are also partially shared with pep M6 and pep M19. Three rabbits immunized with a single 300 micrograms dose of pep M5 developed significant levels of heart-cross-reactive antibodies, as determined by indirect immunofluorescence tests. All three sera also contained antibodies that cross-reacted with pep M6 and pep M19. The heart tissue--specific antibodies that were eluted from sarcolemmal membranes opsonized types 5, 6, and 19 streptococci, indicating that they were directed against protective M protein epitopes on the surface of virulent organisms. Immunofluorescence inhibition tests, using purified M proteins as soluble inhibitors of heart-cross-reactive antibodies, revealed the number and M protein serotype distribution of the tissue-cross-reactive epitopes. Immunoblot analyses demonstrated the sarcolemmal membrane proteins containing the various cross-reactive antigenic determinants.
Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery
Authors: Dustin Boothe, Robert Young, Yoshiya Yamada, Alisa Prager, Timothy Chan, Kathryn Beal
Journal: Neuro-Oncology (2013)

Cerebral radiation necrosis (RN) is a difficult to treat complication of stereotactic radiosurgery (SRS) that can result in progressive neurologic decline. Currently, steroids are the standard of care treatment for brain RN despite their adverse effect profile and limited efficacy. The purpose of this study was to evaluate the treatment efficacy of cerebral RN to bevacizumab in patients with brain metastases previously treated with SRS.We retrospectively reviewed 14 lesions in 11 patients treated with bevacizumab for brain RN secondary to SRS for their brain metastases. Steroid dosing, RN-associated symptoms, and magnetic resonance imaging (MRI) scans were examined before, during, and after bevacizumab administration.Of the 11 patients included, 6 had metastatic non-small cell lung cancer, and 5 had metastatic breast cancer. The mean percentage decrease in RN volume seen on T1 post-Gadolinium and fluid-attenuated inversion recovery (FLAIR) MRI at first follow-up, at a mean of 26 days (range, 15-43 days), was 64.4% and 64.3%, respectively. MRI changes were sustained on follow-up MRI scans, obtained at a mean of 33 days (range, 7-58 days) after bevacizumab discontinuation. After bevacizumab treatment, all patients initially receiving steroids had a reduction in steroid requirement, and all but one had an improvement in or stability of RN-associated symptoms. No patients experienced intratumoral bleeds or other adverse effects related to their bevacizumab treatment.Bevacizumab is effective and safe for the treatment of RN after SRS for brain metastasis. In this context, bevacizumab offers symptomatic relief, a reduction in steroid requirement, and a dramatic radiographic response.
Direct evidence of secondary necrosis of neutrophils during intense lung inflammation
Authors: K. Rydell-Törmänen, L. Uller, J. S. Erjefält
Journal: European Respiratory Journal (2006)

Several pulmonary inflammatory conditions are characterised by infiltration of neutrophils. Normally, neutrophils are silently removed by apoptosis, followed by phagocytosis. However, if phagocytosis fails, apoptotic cells undergo secondary necrosis. Recent findings of increased levels of the pan-necrosis marker lactate dehydrogenase in bronchoalveolar lavage from lipopolysaccharide-exposed mice implies potential involvement of secondary necrosis. Using a similar model, this study aimed to identify the source of lactate dehydrogenase and to search for direct histological evidence of secondary necrosis. Lipopolysaccharide (LPS) was administered to the lungs of BALB/c mice, and bronchoalveolar lavage and tissue samples were collected 4, 12, 24, 36, 48, 60 and 72 h after administration. LPS induced a patchy neutrophil-rich lung inflammation, where the numbers of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling-positive neutrophils were increased at 12 h and onwards. Lavage levels of neutrophils and lactate dehydrogenase increased significantly at 4 and 24 h, respectively. Detailed electron microscopic assessment of neutrophil activation and death modes revealed that up to 14% of the neutrophils were undergoing secondary necrosis, whereas apoptotic or primary necrotic structural cells were rarely found. In summary, this study provides direct evidence that secondary necrosis of neutrophils is a common process during intense lung inflammation. This implies that neutrophil apoptosis may cause rather than resolve airway inflammation.
Angiosarcoma of the Liver Following Vinyl Chloride Exposure
Authors: J. Bradford Block
Journal: JAMA (1974)

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
THE RESPONSES OF THE SKIN TO TETRAHYDROFURFURYL NICOTINATE (TRAFURIL) STUDIED BY CONTINUOUS SKIN PERFUSION
Authors: J. SONDERGAARD, M. W. GREAVES
Journal: British Journal of Dermatology (1970)

Journal Article THE RESPONSES OF THE SKIN TO TETRAHYDROFURFURYL NICOTINATE (TRAFURIL) STUDIED BY CONTINUOUS SKIN PERFUSION Get access J. SØNDERGAARD, J. SØNDERGAARD University Department of Dermatology, Newcastle upon Tyne 1, England Search for other works by this author on: Oxford Academic Google Scholar M. W. GREAVES M. W. GREAVES University Department of Dermatology, Newcastle upon Tyne 1, England Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue 1, 1 January 1970, Pages 14–18, https://doi.org/10.1111/j.1365-2133.1970.tb02186.x Published: 01 January 1970 Article history Accepted: 09 July 1969 Published: 01 January 1970