tbuckley/cabot-search huggingface dataset:
Characterization of Circulating Endothelial Cells in Acute Myocardial Infarction
Authors: Samir Damani, Andrea Bacconi, Ondrej Libiger, Aparajita H. Chourasia, Rod Serry, Raghava Gollapudi, Ron Goldberg, Kevin Rapeport, Sharon Haaser, Sarah Topol, Sharen Knowlton, Kelly Bethel, Peter Kuhn, Malcolm Wood, Bridget Carragher, Nicholas J. Schork, John Jiang, Chandra Rao, Mark Connelly, Velia M. Fowler, Eric J. Topol
Journal: Science Translational Medicine (2012)

Acute myocardial infarction (MI), which involves the rupture of existing atheromatous plaque, remains highly unpredictable despite recent advances in the diagnosis and treatment of coronary artery disease. Accordingly, a clinical measurement that can predict an impending MI is desperately needed. Here, we characterize circulating endothelial cells (CECs) using an automated and clinically feasible CEC three-channel fluorescence microscopy assay in 50 consecutive patients with ST-segment elevation MI and 44 consecutive healthy controls. CEC counts were significantly elevated in MI cases versus controls, with median numbers of 19 and 4 cells/ml, respectively (P = 1.1 × 10(-10)). A receiver-operating characteristic (ROC) curve analysis demonstrated an area under the ROC curve of 0.95, suggesting near-dichotomization of MI cases versus controls. We observed no correlation between CECs and typical markers of myocardial necrosis (ρ = 0.02, creatine kinase-myocardial band; ρ = -0.03, troponin). Morphological analysis of the microscopy images of CECs revealed a 2.5-fold increase (P < 0.0001) in cellular area and a twofold increase (P < 0.0001) in nuclear area of MI CECs versus healthy controls, age-matched CECs, as well as CECs obtained from patients with preexisting peripheral vascular disease. The distribution of CEC images that contained from 2 to 10 nuclei demonstrates that MI patients were the only subject group to contain more than 3 nuclei per image, indicating that multicellular and multinuclear clusters are specific for acute MI. These data indicate that CEC counts may serve as a promising clinical measure for the prediction of atherosclerotic plaque rupture events.
Adipose-Derived Mesenchymal Stem Cells as Stable Source of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Delivery for Cancer Therapy
Authors: Giulia Grisendi, Rita Bussolari, Luigi Cafarelli, Istvan Petak, Valeria Rasini, Elena Veronesi, Giorgio De Santis, Carlotta Spano, Mara Tagliazzucchi, Helga Barti-Juhasz, Laura Scarabelli, Franco Bambi, Antonio Frassoldati, Giulio Rossi, Christian Casali, Uliano Morandi, Edwin M. Horwitz, Paolo Paolucci, PierFranco Conte, Massimo Dominici
Journal: Cancer Research (2010)

Adipose-derived mesenchymal stromal/stem cells (AD-MSC) may offer efficient tools for cell-based gene therapy approaches. In this study, we evaluated whether AD-MSC could deliver proapoptotic molecules for cancer treatment. Human AD-MSCs were isolated and transduced with a retroviral vector encoding full-length human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a proapoptotic ligand that induces apoptosis in a variety of human cancers but not normal tissues. Although several studies have documented the antitumor activity of recombinant human TRAIL, its use in vivo is limited by a short half-life in plasma due to a rapid clearance by the kidney. We found that these limitations can be overcome using stably transduced AD-MSC, which could serve as a constant source of TRAIL production. AD-MSC armed with TRAIL targeted a variety of tumor cell lines in vitro, including human cervical carcinoma, pancreatic cancer, colon cancer, and, in combination with bortezomib, TRAIL-resistant breast cancer cells. Killing activity was associated with activation of caspase-8 as expected. When injected i.v. or s.c. into mice, AD-MSC armed with TRAIL localized into tumors and mediated apoptosis without significant apparent toxicities to normal tissues. Collectively, our results provide preclinical support for a model of TRAIL-based cancer therapy relying on the use of adipose-derived mesenchymal progenitors as cellular vectors.
Current Perspectives on the Use of Gene Therapy for Hypertension
Authors: Craig H. Gelband, Michael J. Katovich, Mohan K. Raizada
Journal: Circulation Research (2000)

Abstract —Systemic hypertension is a pathophysiological state that is manifested as high blood pressure and is a major risk factor for stroke, ischemic heart disease, peripheral vascular disease, and progressive renal damage. Pulmonary hypertension occurs in 3 distinct forms: primary pulmonary hypertension, pulmonary hypertension of the newborn, or secondary pulmonary hypertension attributable to a variety of lung and cardiovascular diseases. This review discusses the use of gene therapy in the control of systemic and pulmonary hypertension. Overexpression of vasodilator genes as well as antisense knockdown of vasoconstrictor genes has been successfully used in animal models of both forms of hypertension. Furthermore, the use of viral vectors to deliver these constructs has achieved long-term control of hypertension. The successful establishment of gene therapy techniques in the animal models of hypertension coupled with the anticipated advances in the genetic aspects of this disease would make it highly feasible to attempt gene delivery in the control of human hypertension.
Action of Lobeline and Capsaicine on Afferent Endings in the Pulmonary Artery of the Cat
Authors: John A. Bevan
Journal: Circulation Research (1962)

A comparison has been made of the anatomical localization and some of the characteristics of the visceral afferent endings stimulated by capsaicine, lobeline, and phenyldiguanide. The reflex hypotensive responses to these drugs have been measured following injection into the right atrium and different positions of the pulmonary artery tree in cats anesthetized with α-chloralose. In comparison with the magnitude of the hypotensive responses to capsaicine, lobeline, and phenyldiguanide from the right atrium, the response to capsaicine and lobeline was small or absent on injection into the right or left branch of the pulmonary artery at the level of the hilum. The response to phenyldiguanide was the same on injection at these two positions. The latent period between the injection and the reflex responses to capsaicine and lobeline, and the sensitivity of these responses to blocking doses of sodium pentobarbital and procaine hydrochloride were the same. Tetraethylammonium chloride will block the reflex action of lobeline in doses that have little effect on the reflex action of capsaicine. It is concluded that, in the cat, the capsaicine-and lobeline-sensitive receptors have a similar distribution and are probably situated in the pulmonary artery and the extrapulmonary part of its main branches and that these are anatomically separate from those stimulated by phenyldiguanide.
Benfotiamine Protects against Peritoneal and Kidney Damage in Peritoneal Dialysis
Authors: Lars P. Kihm, Sandra Müller-Krebs, Julia Klein, Gregory Ehrlich, Laura Mertes, Marie-Luise Gross, Antonysunil Adaikalakoteswari, Paul J. Thornalley, Hans-Peter Hammes, Peter P. Nawroth, Martin Zeier, Vedat Schwenger
Journal: Journal of the American Society of Nephrology (2011)

Residual renal function and the integrity of the peritoneal membrane contribute to morbidity and mortality among patients treated with peritoneal dialysis. Glucose and its degradation products likely contribute to the deterioration of the remnant kidney and damage to the peritoneum. Benfotiamine decreases glucose-induced tissue damage, suggesting the potential for benefit in peritoneal dialysis. Here, in a model of peritoneal dialysis in uremic rats, treatment with benfotiamine decreased peritoneal fibrosis, markers of inflammation, and neovascularization, resulting in improved characteristics of peritoneal transport. Furthermore, rats treated with benfotiamine exhibited lower expression of advanced glycation endproducts and their receptor in the peritoneum and the kidney, reduced glomerular and tubulointerstitial damage, and less albuminuria. Increased activity of transketolase in tissue and blood contributed to the protective effects of benfotiamine. In primary human peritoneal mesothelial cells, the addition of benfotiamine led to enhanced transketolase activity and decreased expression of advanced glycation endproducts and their receptor. Taken together, these data suggest that benfotiamine protects the peritoneal membrane and remnant kidney in a rat model of peritoneal dialysis and uremia.
Energy substrate metabolism in fresh and stored human platelets
Authors: Phin Cohen, Benjamin Wittels
Journal: Journal of Clinical Investigation (1970)

The latent capacity of human platelets for oxidizing several important energy-yielding substrates has been revealed by hypoosmolaric incubation conditions. The data show that the human platelet has a considerable capacity to oxidize both glucose and long-chain fatty acids. Long-chain fatty acids appear to rank favorably with glucose as a potential energy substrate. In a number of mammalian tissues, (-)-carnitine serves to regulate the rate at which long-chain fatty acids are oxidized. Evidence was obtained which suggests that (-)-carnitine functions in a similar role in the platelet. After storage of human platelets at 4 degrees C for 24 hr, the oxidative capacity for glucose was reduced by approximately 25% and for long-chain fatty acids by almost 50%. Investigation of the component parts of the metabolic pathways indicated that a marked decrease in the capacity of the Krebs cycle could be responsible for the decrement in energy substrate oxidation.
Smooth Muscle Cells Healing Atherosclerotic Plaque Disruptions Are of Local, Not Blood, Origin in Apolipoprotein E Knockout Mice
Authors: Jacob F. Bentzon, Claus S. Sondergaard, Moustapha Kassem, Erling Falk
Journal: Circulation (2007)

Signs of preceding episodes of plaque rupture and smooth muscle cell (SMC)-mediated healing are common in atherosclerotic plaques, but the source of the healing SMCs is unknown. Recent studies suggest that activated platelets adhering to sites of injury recruit neointimal SMCs from circulating bone marrow-derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE-/-) mice.To determine the origin of SMCs after spontaneous plaque disruption, irradiated 18-month-old apoE-/- mice were reconstituted with bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic apoE-/- mice and examined when they died up to 9 months later. Plaque hemorrhage, indicating previous plaque disruption, was widely present, but no bone marrow-derived eGFP+ SMCs were detected. To examine the origin of healing SMCs in a model that recapitulates more features of human plaque rupture and healing, we developed a mechanical technique that produced consistent plaque disruption, superimposed thrombosis, and SMC-mediated plaque healing in apoE-/- mice. Mechanical plaque disruption was produced in irradiated apoE-/- mice reconstituted with eGFP+ apoE-/- bone marrow cells and in carotid bifurcations cross-grafted between apoE-/- and eGFP+ apoE-/- mice. Apart from few non-graft-derived SMCs near the anastomosis site in 1 transplanted carotid bifurcation, no SMCs originating from outside the local arterial segment were detected in healed plaques.Healing SMCs after atherosclerotic plaque disruption are derived entirely from the local arterial wall and not circulating progenitor cells in apoE-/- mice.
Peroxisome proliferator-activated receptor-γ haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis
Authors: Keigo Setoguchi, Yoshikata Misaki, Yasuo Terauchi, Toshimasa Yamauchi, Kimito Kawahata, Takashi Kadowaki, Kazuhiko Yamamoto
Journal: Journal of Clinical Investigation (2001)

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) controls adipogenesis and glucose metabolism. It was reported recently that PPAR gamma activation by its agonistic ligands modifies lymphocyte function. Since synthetic ligands are known to exert their effect via PPAR gamma-dependent and -independent pathways, we examined the physiological role of PPAR gamma in lymphocytes by using heterozygote mutant mice in which one allele of PPAR gamma is deleted (PPAR gamma(+/-)). In contrast to T cells, which did not exhibit a significant difference, B cells from PPAR gamma(+/-) showed an enhanced proliferative response to stimulation by either lipopolysaccharide or cross-linking of antigen receptors. Dysregulation of the NF-kappa B pathway in B cells from PPAR gamma(+/-) was indicated by spontaneous NF-kappa B activation, as well as increased I kappa B alpha phosphorylation and gel-shift activity following LPS stimulation. Mice primed with either ovalbumin or methylated BSA also showed enhanced antigen-specific immune response of both T and B cells, an immunological abnormality that exacerbated antigen-induced arthritis. These findings indicate that PPAR gamma plays a critical role in the control of B cell response and imply a role in diseases in which B cell hyperreactivity is involved, such as arthritis and autoimmunity.
Further studies on platelet serotonin transporter binding in depression
Authors: C B Nemeroff, D L Knight, J Franks, W E Craighead, K R Krishnan
Journal: American Journal of Psychiatry (1994)

There is an impressive literature implicating abnormalities in serotonergic neural systems in depression. Many investigators, but not all, have reported low numbers of platelet and brain serotonin (5-HT) transporter sites in drug-free depressed patients. In the present study the authors sought to determine whether the low platelet 5-HT transporter binding in depressed patients is due to previous antidepressant drug exposure. In addition, the binding of both [3H]imipramine and the more specific ligand [3H]paroxetine to the platelet 5-HT transporter was compared in drug-free depressed patients and age- and sex-matched normal comparison subjects.In the first experiment blood samples were obtained from 12 depressed patients who had never received antidepressant drugs and 12 normal comparison subjects, and platelet 5-HT transporter binding was measured by using [3H]imipramine. In the second experiment blood samples were obtained from 28 drug-free depressed patients and 28 age- and sex-matched comparison subjects, and platelet 5-HT transporter binding was assessed by using both [3H]imipramine and [3H]paroxetine.In the first experiment the never-medicated depressed patients exhibited fewer platelet [3H]imipramine binding sites than did the comparison subjects. In the second experiment the drug-free depressed patients had fewer platelet binding sites for both [3H]imipramine and [3H]paroxetine than did the comparison subjects.The low number of platelet [3H]imipramine binding sites does not appear to be due to prior antidepressant drug exposure. The Bmax of platelet binding sites for both [3H]imipramine and [3H]paroxetine, ligands used to measure 5-HT transporter binding, is abnormally low in depressed patients.
Electrocardiographic Left Ventricular Hypertrophy in Renal Transplant Recipients
Authors: Claudio Rigatto, Robert Foley, John Jeffery, Carol Negrijn, Carrie Tribula, Patrick Parfrey
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Left ventricular hypertrophy (LVH) is an independent risk factor for death and cardiovascular disease in the general population and dialysis patients. However, the causes and consequences of LVH have not been well described in renal transplant recipients (RTR). A retrolective cohort study was conducted in 473 RTR who were alive and free of cardiac disease at 1 yr. LVH was defined using the Cornell electrocardiographic (EKG) criteria. A total of 416 patients had an interpretable first-year EKG (88%), and 284 had an interpretable fifth-year EKG (78% of 5-yr survivors). Baseline characteristics were similar in patients with and without EKG. Of 416 patients, 57 had LVH in the first year, whereas 38 of 284 patients had LVH in the fifth year, of which 18 cases were de novo. Baseline LVH was a risk factor for death (RR 1.9 [1.22, 3.22]) and congestive heart failure (CHF) (RR 2.27 [1.08, 4.81]) and was independent of other major prognostic variables. Persistent or de novo LVH in the fifth year predicted subsequent death (RR 2.15 [1.14,4.01]) and CHF (2.71 [1.17, 6.30]). Anemia and diastolic BP were independent risk factors for increasing Cornell voltage (a marker of LV mass) between first and fifth years. Systolic BP was the only predictor of de novo LVH at 5 yr. It seems that EKG LVH is a significant risk factor for death and CHF in RTR and that anemia and hypertension are risk factors for LV growth. Whether aggressive treatment of hypertension and anemia can improve outcomes merits further study. E-mail: [email protected]
Organ Preservation for Advanced Larynx Cancer: Issues and Outcomes
Authors: Arlene A. Forastiere, Randal S. Weber, Andy Trotti
Journal: Journal of Clinical Oncology (2015)

To provide a review of the clinical data, controversies, and limitations that underpin current recommendations for approaches to larynx preservation for locally advanced larynx cancer requiring total laryngectomy.The key findings from pivotal randomized controlled trials are discussed, including quality of life, late effects, and function assessments. Trials investigating taxane inclusion in induction chemotherapy and trials of epidermal growth factor receptor inhibition for radiosensitization are put into perspective for larynx cancer. Controversies in the management of T4 primaries and the opportunities for conservation laryngeal surgery are reviewed.There are data from clinical trials to support induction chemotherapy, followed by radiotherapy (preferred approach in Europe) and concomitant cisplatin plus radiotherapy (preferred in North America) for nonsurgical preservation of the larynx. Treatment intensification by a sequential approach of induction, followed by concomitant treatment, is investigational. Transoral laryngeal microsurgery and transoral robotic partial laryngectomy have application in selected patients.The management of locally advanced larynx cancer is challenging and requires an experienced multidisciplinary team for initial evaluation, response assessment, and support during and after treatment to achieve optimal function, quality of life, and overall survival. Patient expectations, in addition to tumor extent, pretreatment laryngeal function, and coexisting chronic disease, are critical factors in selecting surgical or nonsurgical primary treatment.
Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose
Authors: Cesare Guglielmi, William Arcese, Francesco Dazzi, Ronald Brand, Donald Bunjes, Leo F. Verdonck, Anton Schattenberg, Hans-Jochem Kolb, Per Ljungman, Agnes Devergie, Andrea Bacigalupo, Marta Gomez, Mauricette Michallet, Ahmet Elmaagacli, Alois Gratwohl, Jane Apperley, Dietger Niederwieser
Journal: Blood (2002)
Cold Urticaria
Authors: Stephen I. Wasserman, Nicholas A. Soter, David M. Center, K. Frank Austen
Journal: Journal of Clinical Investigation (1977)

Sera were obtained from the venous effluents of cold-challenged arms of patients with idiopathic cold urticaria without plasma or serum cryoproteins; these sera exhibited increased neutrophil chemotactic activity without alterations of the complement system. A two- to fourfold augmentation of the base-line neutrophil chemotactic activity of serum from the immersed extremity began within 1 min, peaked at 2 min, and returned to base-line levels within 15 min, whereas there was no change in the serum chemotactic activity in the control arm. The augmented chemotactic activity in the serum specimens from the challenged arm of each patient appeared in a high molecular-weight region, as assessed by the difference in activity recovered after Sephadex G-200 gel filtration of the paired lesional and control specimens. Sequential purification of this high molecular-weight activity by anion- and cation-exchange chromatography revealed a single peak of activity at both steps. The partially purified material continued to exhibit a high molecular weight, being excluded on Sepharose 4B, and had a neutral isoelectric point. The partially purified material showed a preferential chemotactic activity for neutrophilic polymorphonuclear leukocytes, required a gradient for expression of this function, and exhibited a capacity to deactivate this cell type. This active principle, termed high molecular-weight neutrophil chemotactic factor, exhibited a time-course of release that could be superimposed upon that of histamine and the low molecular-weight eosinophil chemotactic factor and may represent another mast cell-derived mediator.
Placebo Effects in Infants, Toddlers, and Parents
Authors: Luana Colloca
Journal: JAMA Pediatrics (2015)

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