tbuckley/cabot-search huggingface dataset:
Identification of a molecular signature for leukemic promyelocytes and their normal counterparts: focus on DNA repair genes
Authors: I Casorelli, E Tenedini, E Tagliafico, M F Blasi, A Giuliani, M Crescenzi, E Pelosi, U Testa, C Peschle, L Mele, D Diverio, M Breccia, F Lo-Coco, S Ferrari, M Bignami
Journal: Leukemia (2006)
Telepsychiatry and e-Mental Health
Authors: K. Fister
Journal: BMJ (2003)

The earliest reports of telepsychiatry (defined in this book as “the delivery of health care and the exchange of information for purposes of providing psychiatric services across distances”) date from the late 1950s, when an interactive television link was used in Nebraska, United States, to connect a teaching hospital department of psychiatry with a state institution. Today, e-mental health (“mental health services provided through any form of electronic medium, most commonly via the …
Dermatology: The Eccrine Sweat Glands
Authors: W C Lobitz, R L Dobson
Journal: Annual Review of Medicine (1961)

Although much is known about the human eccrine sweat glands as a re­ sult of extensive studies carried out during the past half century, surprisingly little can be stated concerning the function of these organs without fear of contradiction. This situation has arisen for three major reasons: (a) It is now known that during active function the cellular structure of the eccrine sweat gland is undergoing significant alterations. (b) The function of the sweat gland is, in great part, dependent on the state of both the external and internal environment. (Careful control of both of these variables is essential to an experimental situation from which interpretable information is to be derived.) (c) Interpret�tion of the function of the sweat gland is considerably influenced by the method of sweat collection, the area from which the sweat is collected and the method employed to produce sweating. This review will not deal with specific diseases of the eccrine sweat gland. Nor will it be concerned with the alterations in structure and function of the sweat apparatus that occur when the skin itself is altered by disease. We will not emphasize environmental physiology and the problems of acclimatiza­ tion . The reader is referred to a most excellent and comprehensive review by . Weiner & Hellmann (53) on the total eccrine and apocrine sweat gland story. The interested reader, too, should refer to the recent book edited by Yoshi� mura, Ogata & Itoh on climatic physiology (54). In this review it is our hope to integrate, as much as possible, the many aspects now known of eccrine sweat gland structure and function in health and associated with non-cutaneous medical disease. In this way perhaps the interpretations of isolated findings on this subject will be made easier. In addition, we will take opportunities, too. to emphasize the many areas in which further investigative studies may be especially fruitful. On the basis of location, two types of eccrine glands can be differentiated: those on the palms and soles which respond primarily to mental work and emotional stimuli, and those in the remainder of the skin which act mainly in a thermoregulatory role. All eccrine sweat glands are innervated by sym­ pathetic fibers, but the secretion is induced by cholinergic agents. The nerve
Regulation of mitochondrial proliferation in the heart: power-plant failure contributes to cardiac failure in hypertrophy
Authors: S GOFFART, J VONKLEISTRETZOW, R WIESNER
Journal: Cardiovascular Research (2004)

During hypertrophy, proliferation of mitochondria does not keep pace with the increasing energy demand of the heart. This probably contributes importantly to cardiac failure, together with other phenotypic changes occurring during the growth process. The problem may be even aggravated if defects of mitochondrial function itself and not external factors cause the hypertrophic process. Here we review the basic mechanisms controlling mitochondrial biogenesis, especially the pathways coordinating expression of nuclear encoded mitochondrial genes and the small mitochondrial genome, and how these mechanisms may be connected to the cardiomyocyte differentiation program during development as well as under physiological and pathological circumstances.
Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation
Authors: Ana-Maria Lennon-Duménil, Arnold H. Bakker, René Maehr, Edda Fiebiger, Herman S. Overkleeft, Mario Rosemblatt, Hidde L. Ploegh, Cécile Lagaudrière-Gesbert
Journal: The Journal of Experimental Medicine (2002)

Here, we describe a new approach designed to monitor the proteolytic activity of maturing phagosomes in live antigen-presenting cells. We find that an ingested particle sequentially encounters distinct protease activities during phagosomal maturation. Incorporation of active proteases into the phagosome of the macrophage cell line J774 indicates that phagosome maturation involves progressive fusion with early and late endocytic compartments. In contrast, phagosome biogenesis in bone marrow–derived dendritic cells (DCs) and macrophages preferentially involves endocytic compartments enriched in cathepsin S. Kinetics of phagosomal maturation is faster in macrophages than in DCs. Furthermore, the delivery of active proteases to the phagosome is significantly reduced after the activation of DCs with lipopolysaccharide. This observation is in agreement with the notion that DCs prevent the premature destruction of antigenic determinants to optimize T cell activation. Phagosomal maturation is therefore a tightly regulated process that varies according to the type and differentiation stage of the phagocyte.
Clinical and Immunohistochemical Features Associated with a Response to Bortezomib in Patients with Multiple Myeloma
Authors: Mark A. Dawson, Stephen S. Opat, Yamna Taouk, Mark Donovan, Michele Zammit, Katherine Monaghan, Noemi Horvath, Andrew W. Roberts, H. Miles Prince, Mark Hertzberg, Catriona A. McLean, Andrew Spencer
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Multiple myeloma is an incurable disease with heterogeneous clinical behavior. Bortezomib has offered some patients with relapsed and refractory disease an opportunity for prolonged survival. However, there remains a paucity of data in patients treated with bortezomib that accurately delineates and identifies such patients. This information is crucial to guide management. Experimental Design: In this study, we aimed to identify the patients most likely to respond to bortezomib salvage therapy. We analyzed the baseline clinical variables and profiled the baseline expression of a broad range of immunohistochemical markers of cell cycle activity, apoptosis, and angiogenesis in a large cohort of multiply relapsed myeloma patients recruited to one of two prospective multicentre trials assessing the efficacy of bortezomib salvage therapy. Results: Using the European Group for Bone Marrow Transplantation criteria, response (complete or partial) to bortezomib salvage therapy was associated with a previous history of complete response to alternative antimyeloma treatment. Patients who expressed cyclin D1 were more likely to achieve a response. In contrast, patients who expressed p16INK4A, cytoplasmic p53, and the highest intensity of Bcl-2 staining had a poor response. Patients who achieved a response to bortezomib and those patients who expressed cyclin D1 at baseline showed a significant survival advantage. Patients who expressed FGFR3, a poor prognostic marker, responded equally well and had similar outcomes with bortezomib compared with FGFR3-negative patients. Conclusions: Baseline clinical variables and selective immunohistochemical markers expressed by patients may be used effectively to identify patients that are most likely to achieve a meaningful clinical response to bortezomib salvage therapy.
Measurement of myocardial infarct size from plasma fatty acid-binding protein or myoglobin, using individually estimated clearance rates
Authors: M de Groot
Journal: Cardiovascular Research (1999)

Objective: In patients with acute myocardial infarction (AMI), estimation of infarct size from the early markers, fatty acid-binding protein (FABP) and myoglobin (MYO), usually assumes average (fixed) rate constants (FCR) for protein clearance from plasma. However, individual variation in FCR is large. Renal dysfunction causes slower clearance of FABP and MYO from plasma and, hence, overestimation of infarct size in 20–25% of patients. We investigated whether or not more accurate values of infarct size could be obtained with individually estimated clearance rates. Methods: Concentrations of FABP and MYO and, for comparison, activities of the established cardiac markers, creatine kinase (CK) and α-hydroxybutyrate dehydrogenase (HBDH), were assayed in serial plasma samples from 138 patients with AMI. Individual FCR values of FABP and MYO were estimated from plasma creatinine concentrations, sex and age. Results: Individual FCR values varied from 0.4 to 2.4 h−1. Use of these individual FCR values significantly improved the correlation between infarct size, as estimated from FABP or MYO on the one hand, and from CK and HBDH on the other. Approximately equal estimates of infarct size were obtained for all four marker proteins. Conclusions: Using individually estimated clearance rates, renal insufficiency no longer hampers calculation of infarct size from FABP and MYO, and reliable estimates of total myocardial damage can be obtained within 24 h after first symptoms.
Copeptin Helps in the Early Detection of Patients With Acute Myocardial Infarction
Authors: Alan Maisel, Christian Mueller, Sean-Xavier Neath, Robert H. Christenson, Nils G. Morgenthaler, James McCord, Richard M. Nowak, Gary Vilke, Lori B. Daniels, Judd E. Hollander, Fred S. Apple, Chad Cannon, John T. Nagurney, Donald Schreiber, Christopher deFilippi, Christopher Hogan, Deborah B. Diercks, John C. Stein, Gary Headden, Alexander T. Limkakeng, Inder Anand, Alan H.B. Wu, Jana Papassotiriou, Oliver Hartmann, Stefan Ebmeyer, Paul Clopton, Allan S. Jaffe, W. Frank Peacock
Journal: Journal of the American College of Cardiology (2013)
Severe Hypoglycemia and Mortality After Cardiovascular Events for Type 1 Diabetic Patients in Sweden
Authors: Tom W.C. Lung, Dennis Petrie, William H. Herman, Andrew J. Palmer, Ann-Marie Svensson, Bjorn Eliasson, Philip M. Clarke
Journal: Diabetes Care (2014)

OBJECTIVE To examine whether previous severe hypoglycemic events were associated with the risk of all-cause mortality after major cardiovascular events (myocardial infarction [MI] or stroke) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS This study is based on data from the Swedish National Diabetes Register linked to patient-level hospital records, prescription data, and death records. We selected patients with type 1 diabetes who visited a clinic during 2002–2010 and experienced a major cardiovascular complication after their clinic visit. We estimated a two-part model for all-cause mortality after a major cardiovascular event: logistic regression for death within the first month and a Cox proportional hazards model conditional on 1-month survival. At age 60 years, 5-year cumulative mortality risk was estimated from the models for patients with and without prior diabetes complications. RESULTS A total of 1,839 patients experienced major cardiovascular events, of whom 403 had previously experienced severe hypoglycemic events and 703 died within our study period. A prior hypoglycemic event was associated with a significant increase in mortality after a cardiovascular event, with hazard ratios estimated at 1.79 (95% CI 1.37–2.35) within the first month and 1.25 (95% CI 1.02–1.53) after 1 month. Patients with prior hypoglycemia had an estimated 5-year cumulative mortality risk of 52.4% (95% CI 45.3–59.5) and 39.8% (95% CI 33.4–46.3) for MI and stroke, respectively. CONCLUSIONS We have found evidence that patients with type 1 diabetes in Sweden with prior severe hypoglycemic events have increased risk of mortality after a cardiovascular event.
Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score
Authors: A.P. Oranje, E.J. Glazenburg, A. Wolkerstorfer, F.B. de Waard-van der Spek
Journal: British Journal of Dermatology (2007)

It is important to determine the severity of atopic dermatitis (AD) for evaluation of disease improvement after and during therapy. Scoring of the severity of AD is demanded in clinical trials. The European Task Force on Atopic Dermatitis (ETFAD) has developed the SCORAD (SCORing AD) index to create a consensus on assessment methods for AD, so that study results of different trials can be compared. However, modification of the SCORAD index has led on several occasions to wrong and incorrect use of the system. To measure the extent of AD, the rule of nines is applied on a front/back drawing of the patient's inflammatory lesions. The extent can be graded 0-100. The intensity part of the SCORAD index consists of six items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness. Each item can be graded on a scale 0-3. The subjective items include daily pruritus and sleeplessness. Both subjective items can be graded on a 10-cm visual analogue scale. The maximum subjective score is 20. All items should be filled out in the SCORAD evaluation form. The SCORAD index formula is: A/5 + 7B/2 + C. In this formula A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The maximum SCORAD score is 103. Based on training sessions by the ETFAD, the SCORAD index was modified by excluding the subjective symptoms (objective SCORAD). The objective SCORAD consists of just the extent and intensity items, the formula being A/5 + 7B/2. The maximum objective SCORAD score is 83 (plus an additional 10 bonus points). Bonus points are given for severe disfiguring eczema (on face and hands). The three-item severity (TIS) score involves the scoring of erythema (redness), oedema and excoriations (scratches) in one representative lesion, marked as R-O-S. The TIS score corresponds well with the more detailed objective SCORAD and can be used as a prescreening system or as a quick system in studies and is excellent for epidemiological studies.
PD-1 Blockade Enhances T-cell Migration to Tumors by Elevating IFN-γ Inducible Chemokines
Authors: Weiyi Peng, Chengwen Liu, Chunyu Xu, Yanyan Lou, Jieqing Chen, Yan Yang, Hideo Yagita, Willem W. Overwijk, Gregory Lizée, Laszlo Radvanyi, Patrick Hwu
Journal: Cancer Research (2012)

Adoptive cell transfer (ACT) is considered a promising modality for cancer treatment, but despite ongoing improvements, many patients do not experience clinical benefits. The tumor microenvironment is an important limiting factor in immunotherapy that has not been addressed fully in ACT treatments. In this study, we report that upregualtion of the immunosuppressive receptor programmed cell death-1 (PD-1) expressed on transferred T cells at the tumor site, in a murine model of ACT, compared with its expression on transferred T cells present in the peripheral blood and spleen. As PD-1 can attenuate T-cell-mediated antitumor responses, we tested whether its blockade with an anti-PD-1 antibody could enhance the antitumor activity of ACT in this model. Cotreatment with both agents increased the number of transferred T cells at the tumor site and also enhanced tumor regressions, compared with treatments with either agent alone. While anti-PD-1 did not reduce the number of immunosuppressive regulatory T cells and myeloid-derived suppressor cells present in tumor-bearing mice, we found that it increased expression of IFN-γ and CXCL10 at the tumor site. Bone marrow-transplant experiments using IFN-γR-/- mice implicated IFN-γ as a crucial nexus for controlling PD-1-mediated tumor infiltration by T cells. Taken together, our results imply that blocking the PD-1 pathway can increase IFN-γ at the tumor site, thereby increasing chemokine-dependent trafficking of immune cells into malignant disease sites.
Antielastin B-cell and T-cell immunity in patients with chronic obstructive pulmonary disease
Authors: Manuela Rinaldi, An Lehouck, Nele Heulens, Renaud Lavend'Homme, Vincent Carlier, Jean-Marie Saint-Remy, Marc Decramer, Ghislaine Gayan-Ramirez, Wim Janssens
Journal: Thorax (2012)

<h3>Rationale</h3> Antielastin autoimmunity has been hypothesised to drive disease progression in chronic obstructive pulmonary disease (COPD). The proposed mechanism is currently disputed by conflicting data. The authors aimed to explore antibody responses against elastin in a large and extensively characterised COPD population and to assess elastin-specific peripheral T-cell reactivity in a representative subgroup. <h3>Methods</h3> Antielastin antibodies were analysed with indirect ELISA on the plasma of 320 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease 1–4) and 143 smoking controls. In a second group of 40 patients with COPD and smoking controls, T-cell responses against extracellular matrix (elastin, collagen I and collagen V) were determined with enzyme-linked immunosorbent spot (EliSpot) (interferon γ (IFNγ) and interleukin-2) on peripheral blood mononuclear cells and compared with the responses of 11 never-smoking controls. <h3>Results</h3> Antielastin antibody titres were not elevated in patients with COPD compared with smoking controls and even decreased significantly with increasing severity of COPD (p&lt;0.001). Lower antielastin antibody titres were also found in a subgroup of patients with CT-proven emphysema. Elastin-specific INFγ-mediated T helper 1 responses could not be revealed in smoking subjects with and without COPD. Collagen I-mediated T-cell responses were also absent, which contrasted with a significant increased anticollagen V response in the smoking controls and patients with COPD compared with the never smokers (p=0.008). Collagen V-mediated T-cell responses could not discriminate between patients with COPD and smoking controls. <h3>Conclusion</h3> A systemic immune response against elastin could not be identified in patients with COPD. By contrast, collagen V-mediated autoimmunity was increased in the subgroup of smokers and may potentially contribute to the pathogenesis of COPD.
Recovery of Herpes-Simplex Virus from Human Trigeminal Ganglions
Authors: J. Richard Baringer, Peggy Swoveland
Journal: New England Journal of Medicine (1973)

Abstract In six of seven patients, herpes-simplex virus was recovered from trigeminal ganglions obtained at autopsy from unselected cadavers less than 12 hours after death and maintained in culture for 10 to 45 days. The virus was not obtained from similarly handled cultures of trigeminal nerve or root from the same patients. The identity of the virus was confirmed by fluorescent-antibody and neutralization tests and by electron microscopy. The results indicate that herpes-simplex virus is present in a high proportion of human trigeminal ganglions and suggest this as a possible site of latent virus causing recurrent oral infection.
Sorafenib Inhibits Hypoxia-Inducible Factor-1α Synthesis: Implications for Antiangiogenic Activity in Hepatocellular Carcinoma
Authors: Li-ping Liu, Rocky L. K. Ho, George G. Chen, Paul B. S. Lai
Journal: Clinical Cancer Research (2012)

The overexpression of hypoxia-inducible factor 1α (HIF-1α) is a common finding in hepatocellular carcinoma (HCC), and it leads to angiogenesis and poor prognosis. Sorafenib, a multikinase inhibitor, has shown significant improvement in survival in patients with advanced HCC in clinical trials. However, the mechanisms that account for the antiangiogenic efficiency of sorafenib have not been fully elucidated. The present study aims to explore the effect of sorafenib on HIF-1α expression and activation in HCC cells and xenografts.HCC cells and xenografts were treated with sorafenib or vehicles. Western blotting and quantitative PCR array were used to determine protein and mRNA expression, respectively. HIF-1α activity, de novo protein synthesis, and VEGF secretions were determined using assay kits.Sorafenib dose dependently decreased the hypoxia-induced accumulation and activation of HIF-1α protein. Further analysis revealed that such reduction of HIF-1α was associated with the inhibition of HIF-1α protein synthesis rather than the promotion of HIF-1α protein degradation or the reduction of HIF-1α mRNA. Moreover, the phosphorylation levels of mTOR, extracellular signal-regulated kinase (ERK), p70S6K, RP-S6, 4E-BP1, and eIF4E were significantly suppressed by sorafenib. In vivo studies further confirmed the inhibitory effect of sorafenib on the expression of HIF-1α and VEGF proteins, leading to a decrease in tumor vascularization and growth of the xenografts.Sorafenib-mediated inhibition of HIF-1α synthesis is associated with previously undefined pathways in which mTOR/p70S6K/4E-BP1 and ERK phosphorylation are downregulated. Our preclinical data expand our understanding of sorafenib's antiangiogenic mechanism of action by inhibiting HIF-1α and VEGF protein expression.
Coronary atherosclerosis is associated with left ventricular dysfunction and dilatation in aortic stenosis.
Authors: V I Vekshtein, R W Alexander, A C Yeung, T Plappert, M G Sutton, P Ganz, A P Selwyn, J A Bittl
Journal: Circulation (1990)

Patients with aortic stenosis develop widely variable patterns of left ventricular hypertrophy and dysfunction. We postulated that coronary atherosclerosis (CAD) may be associated with impaired left ventricular function and chamber dilatation in patients with aortic stenosis. Left ventricular mass and volumes were quantified from two-dimensional echocardiography and correlated with coronary angiography in 78 patients with severe aortic stenosis and no previous myocardial infarction or regional wall motion abnormalities. Eighteen patients (group 1) had smooth coronary arteries, 25 patients had irregular coronary arteries with 50% or less stenosis (group 2), and 35 patients had obstructive CAD (group 3). Even though the calculated valve area was similar in all three study groups, group 1 patients had higher values for ejection fraction (65 +/- 9%, 51 +/- 17%, and 48 +/- 13%; p = 0.0002), systolic mass-to-volume ratio (9.2 +/- 3.9, 5.6 +/- 2.8, and 5.2 +/- 2.2; p = 0.0001), and cardiac index (2.9 +/- 0.7, 2.5 +/- 0.7, and 2.3 +/- 0.6 l/min.min2; p = 0.015) than patients in groups 2 and 3, respectively (mean +/- SD). Mean circumferential wall stress was inversely related to severity of CAD. Multivariate analysis showed that CAD is an independent predictor of ejection fraction and mass-to-volume ratio in this group of patients. Thus, in an elderly population with severe aortic stenosis, patients with both obstructive and nonobstructive CAD have an increased incidence of left ventricular enlargement and systolic dysfunction.