tbuckley/cabot-search huggingface dataset:
Graft-versus-leukemia Effect of HLA-haploidentical Central-memory T-cells Expanded With Leukemic APCs and Modified With a Suicide Gene
Authors: Monica Casucci, Serena Kimi Perna, Laura Falcone, Barbara Camisa, Zulma Magnani, Massimo Bernardi, Alessandro Crotta, Cristina Tresoldi, Katharina Fleischhauer, Maurilio Ponzoni, Silvia Gregori, Federico Caligaris Cappio, Fabio Ciceri, Claudio Bordignon, Alessandro Cignetti, Attilio Bondanza, Chiara Bonini
Journal: Molecular Therapy (2013)

Allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-haploidentical family donor (haplo-HSCT) is a readily available and potentially curative option for high-risk leukemia. In haplo-HSCT, alloreactivity plays a major role in the graft-versus-leukemia (GVL) effect, which, however, is frequently followed by relapse due to emerging leukemic cell variants that have lost the unshared HLA haplotype as a mechanism of immune escape. We report that stimulation of HLA-haploidentical donor T lymphocytes with leukemic antigen-presenting cells (L-APCs) expands a population of leukemia-reactive T cells, which, besides alloreactivity to unshared HLAs, contain leukemia-associated specificities restricted by shared HLAs. According to a preferential central-memory (T(CM)) phenotype and to high interleukin (IL)-7Rα expression, these T cells persist in vivo and sustain a major GVL effect in a clinically relevant xenograft model. Moreover, we demonstrate that modifying L-APC-expanded T cells to express the herpes simplex virus thymidine kinase (HSV-tk) suicide gene enables their elimination with the prodrug ganciclovir (GCV), therefore providing a safety switch in case of graft-versus-host disease (GVHD). These results warrant the clinical investigation of L-APC-expanded T cells modified with a suicide gene in the setting of haplo-HSCT.
Angiogenic Therapy for Bronchopulmonary Dysplasia
Authors: Kurt R. Stenmark, Vivek Balasubramaniam
Journal: Circulation (2005)

ronchopulmonary dysplasia (BPD) is one of the most common and significant medical complications associated with preterm birth, affecting 5000 to 10 000 babies annually.It was originally defined as a disorder occurring in infants who were ventilated for neonatal respiratory distress with the primary lung features being mucosal metaplasia of the airways, emphysema, widespread interstitial fibrosis, and remodeling of the small pulmonary arteries. 1Improvements in neonatal care, including antenatal steroids, surfactant therapy, better ventilator strategies, and improved nutritional support, although not reducing the incidence of the disease (the overall numbers of patients with BPD has increased), have led to the development of what is now called "the new BPD."3][4] This impairment of alveolar and vascular development is believed to contribute increased morbidity including the development of late cardiopulmonary disease, exercise intolerance, increased risk of asthma, pulmonary hypertension, and the development of chronic obstructive pulmonary disease in these infants as they grow into adulthood. 4Thus, therapies aimed at promoting lung alveolar and vascular growth in these infants may be highly beneficial in the prevention of these sequelae of premature birth.
His-ventricular dissociation in a patient with reciprocating tachycardia and a nodoventricular bypass tract.
Authors: F Morady, M M Scheinman, R Gonzalez, D Hess
Journal: Circulation (1981)

A patient with recurrent bouts of atrial fibrillation and wide-complex regular tachycardia underwent electrophysiologic studies. Premature atrial stimulation or atrial pacing during sinus rhythm resulted in gradual lengthening of the PR and AH intervals, narrowing of the HV interval and progressive preexcitation with a left bundle branch block and left-axis contour. Induction of tachycardia was dependent on critical delay in the atrioventricular interval and was associated with attainment of a maximal preexcitation pattern. During tachycardia, the ventriculoatrial interval was constant, whereas the interval from His bundle deflection to the ventricular complex was variable. We postulate that the tachycardia circuit involved reciprocation within the atrioventricular node and that a nodoventricular bypass tract was present in close anatomic or functional association with the slow atrioventricular nodal pathway. Our data suggest that both the nodoventricular bypass tract and the His-Purkinje system may be passive "bystanders" rather than essential components of the tachycardia circuit. In addition, although HV dissociation usually implies ventricular tachycardia, this case demonstrates that HV dissociation during wide-complex regular tachyarrhythmia is not diagnostic of ventricular tachycardia.
Inspiratory muscle training and whole-body reconditioning in chronic obstructive pulmonary disease.
Authors: M J Berry, N E Adair, K S Sevensky, A Quinby, H M Lever
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

To examine the efficacy of targeted inspiratory muscle training (IMT), 25 patients with moderate COPD were randomly assigned to one of three groups. Eight patients received IMT along with general exercise reconditioning, GER+IMT; nine patients received general exercise reconditioning, GER; eight patients received sham breathing exercises, CONTROL. All groups used a spring-loaded inspiratory muscle trainer; however, the GER and CONTROL groups breathed through these devices at only 15% of their maximal inspiratory pressure. The GER+IMT group increased the load on these devices until at 6 wk the load was equal to 80% of their maximal inspiratory pressure. All patients exercised three times per week for a 12-wk period in supervised sessions. Analysis of covariance revealed no significant differences in spirometric measurements, maximal inspiratory pressure, or maximal oxygen consumption among any of the three groups after the intervention (p > 0.05). Twelve-minute walk distance was significantly greater in the GER+IMT and GER groups than in the CONTROL group (p = 0.03). After the intervention, there was a trend (p = 0.08) for treadmill time to be greater for the GER+IMT and GER groups than for the CONTROL group. Dyspnea ratings at different exercise intensities were not found to be significantly different among the three groups after the intervention. These results demonstrate that GER+IMT and GER alone are equally effective in improving exercise performance in patients with COPD. Additionally, the combination of GER and IMT does not appear to provide any clinically significant improvements in exercise performance or perceptions of dyspnea during exercise when compared with GER alone.
Downregulation of tumor necrosis factor receptors on macrophages and endothelial cells by microtubule depolymerizing agents.
Authors: A H Ding, F Porteu, E Sanchez, C F Nathan
Journal: The Journal of Experimental Medicine (1990)

Exposure of murine and human macrophages and human umbilical vein endothelial cells to micromolar concentrations of five microtubule (MT)-depolymerizing agents (colchicine, nocodazole, podophyllotoxin, vincristine, and vinblastine) resulted in a loss of binding sites for iodinated TNF-alpha. The reduction amounted to 40-60% by 1 h and approximately 75% by 2-4 h. In 1 h, specific binding was reduced 50% by 0.1-5 microM of these drugs at 37 degrees C, but not at 4 degrees C. Inactive isomers of colchicine were ineffective, as were microfilament-destabilizing cytochalasins. The active agents did not compete with TNF-alpha R for binding. Antiserum against TNF-alpha did not neutralize the effect of colchicine and nocodazole. PGE1 and dibutyryl-cAMP could not mimic, and cyclooxygenase inhibitors could not prevent the drug effects. All the binding sites were regenerated within 3 h after removal of nocodazole, which binds tubulin reversibly, whereas little recovery was found even 18 h after the removal of colchicine, which binds tubulin irreversibly. These findings suggested that MT disassembly was responsible for the observed downregulation of TNF-alpha R. The protein synthesis inhibitor cycloheximide inhibited binding of TNF-alpha to a similar extent and with a similar time course as colchicine in the absence of added ligand. Neither drug affected binding of IFN-gamma to macrophages, nor binding of TNF-alpha to human polymorphonuclear leukocytes. Thus, an intact MT network appears to be important in maintenance of the steady state of TNF-alpha R on those cells in which TNF-alpha R turns over rapidly in the absence of ligand. The antiinflammatory actions of MT-depolymerizing agents may result in part from their interference with the ability of such cells to respond to TNF-alpha.
A CASE OF LIGHT SENSITIZATION
Authors: DAVID ERSKINE
Journal: British Journal of Dermatology (1944)

Journal Article A CASE OF LIGHT SENSITIZATION Get access DAVID ERSKINE, M.D., D.P.H. DAVID ERSKINE, M.D., D.P.H. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 56, Issue 9-10, 1 September 1944, Pages 195–198, https://doi.org/10.1111/j.1365-2133.1944.tb10864.x Published: 01 September 1944
Neuronal Nitric Oxide Synthase Regulates Basal Microvascular Tone in Humans In Vivo
Authors: Michael D. Seddon, Philip J. Chowienczyk, Sally E. Brett, Barbara Casadei, Ajay M. Shah
Journal: Circulation (2008)

Nitric oxide (NO) has a pivotal role in the regulation of vascular tone and blood flow, with dysfunctional release contributing to disease pathophysiology. These effects have been attributed to NO production by the endothelial NO synthase (eNOS); however, recent evidence suggests that a neuronal NO synthase (nNOS) may also be expressed in arterial vessels.We undertook a first-in-humans investigation of the role of nNOS in the local regulation of vascular blood flow in healthy subjects. Brachial artery infusion of the nNOS-specific inhibitor S-methyl-L-thiocitrulline (SMTC, 0.025 micromol/min to 0.2 micromol/min) caused a dose-dependent reduction in basal flow, with a 30.1+/-3.8% decrease at the highest dose (n=10; mean+/-SE; P<0.01). The effect of SMTC was abolished by coinfusion of the NO synthase substrate L-arginine but was unaffected by D-arginine. A similar reduction in basal flow with the nonselective NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 37.4+/-3.1%, n=10) required a 20-fold higher dose of 4 micromol/min. At doses that produced comparable reductions in basal flow, only L-NMMA (4 micromol/min) and not SMTC (0.2 micromol/min) inhibited acetylcholine-induced vasodilation; however, both SMTC and L-NMMA inhibited the forearm vasodilator response to mental stress.Basal forearm blood flow in humans is regulated by nNOS-derived NO, in contrast to the acetylcholine-stimulated increase in blood flow, which, as shown previously, is mediated primarily by eNOS. These data indicate that vascular nNOS has a distinct local role in the physiological regulation of human microvascular tone in vivo.
Assessment of the Medicare Quality Improvement Organization Program
Authors: William Rollow, Terry R. Lied, Paul McGann, James Poyer, Lawrence LaVoie, Robert T. Kambic, Dale W. Bratzler, Allen Ma, Edwin D. Huff, Lawrence D. Ramunno
Journal: Annals of Internal Medicine (2006)

Background: Studies have shown improvement in quality of health care in the United States. However, the factors responsible for this improvement are largely unknown. Objective: To evaluate the effect of the Medicare Quality Improvement Organization (QIO) Program in 4 clinical settings by using performance data for 41 quality measures during the 7th Scope of Work. Design: Observational study in which differences in quality measures were compared between baseline and remeasurement periods for providers that received different levels of QIO interventions. Setting: Nursing homes, home health agencies, hospitals, and physician offices in the 50 U.S. states, the District of Columbia, and 2 U.S. territories. Participants: Providers receiving focused QIO assistance related to quality measures and providers receiving general informational assistance from QIOs. Measurements: 5 nursing home quality measures, 11 home health measures, 21 hospital measures, and 4 physician office measures. Results: For nursing home, home health, and physician office measures, providers recruited specifically by QIOs for receipt of assistance showed greater improvement in performance on 18 of 20 measures than did providers who were not recruited; similar improvement was seen on the other 2 measures. Nursing homes and home health agencies improved more in all measures on which they chose to work with the QIO than in other measures. Nineteen of 21 hospital measures showed improvement; in this setting, QIOs were contracted for improvement initiatives solely at the statewide level. Overall, improvement was seen in 34 of 41 measures from baseline to remeasurement in the 7th Scope of Work. Limitations: As in any observational study, selection bias, regression to the mean, and secular trends may have influenced the results. Conclusions: These findings are consistent with an impact of the QIO Program and QIO technical assistance on the observed improvement. Future evaluations of the QIO Program will attempt to better address the limitations of the design of this study.
Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor
Authors: Mauro Perretti, Nan Chiang, Mylinh La, Iolanda M. Fierro, Stefano Marullo, Stephen J Getting, Egle Solito, Charles N. Serhan
Journal: Nature Medicine (2002)
Abstract 514: A novel dual color mouse model for studying the tumor microenvironment of pancreatic adenocarcinoma
Authors: Cynthia S. Snyder, Sharmeela Kaushal, Chanae R. Hardamon, Hop S. Tran Cao, Rhiana S. Menen, Cristina A. Metildi, Andrew M. Lowy, Robert M. Hoffman, Michael Bouvet
Journal: Cancer Research (2011)

Abstract We have developed a novel, dual color, immunocompetent mouse model for studying the pancreatic tumor microenvironment using fluorescence imaging. To develop this model, we used mice engineered to constitutively express a conditional tdTomato fluorescent transgene that converts to the expression of EGFP following Cre recombinase-mediated intramolecular rearrangement of the transgene. The reporter transgene is driven by a strong, ubiquitous promoter from a well-characterized genomic locus. Both tdTomato and EGFP fluorescent proteins are membrane-targeted, allowing distinction of single cells and cell processes within the microenvironmental setting. For our studies of the pancreatic microenvironment, we used PdxCre (Pdx-1-Cre) transgenic mice. PdxCre mice express Cre recombinase within the developing pancreas during embryogenesis. To generate mice in which the pancreatic parenchyma, expressing membrane-targeted green fluorescence (mG), is highlighted against the red fluorescent (mT) backlight of stromal and non-pancreatic tissues, we crossed PdxCre transgenic mice with conditional fluorescent (mTmG) indicator mice. Both lines are on a mixed C57Bl/6 × Sv129 background, backcrossed several generations onto C57Bl/6. We used PDA4964 pancreatic adenocarcinoma cells, derived from genetically engineered triple transgenic (LSL-KrasG12D/+;LSL-Trp53R172H/+; PdxCre) mutant mice, to generate orthotopic tumors in the pancreata of PdxCre+, mTmG+ dual transgenic, dual color mice. Using a dosage of 1 × 106 tumor cells per mouse, half of the mice developed tumors within 4-6 weeks. Ex vivo imaging of orthotopic tumor-bearing mice at necropsy revealed large pancreatic tumors comprised of non-fluorescent tumor cells supported and nourished by red fluorescent host stromal and vascular cells. The expanding tumor masses distorted and displaced the adjacent green fluorescent host pancreatic parenchyma. Upon microscopic examination of the tumor-host interface, cell borders of individual host pancreatic parenchymal and stromal cells were clearly outlined. Our preliminary findings indicate that this novel, dual color, immunocompetent mouse model will be valuable for studying the pancreatic tumor microenvironment using fluorescence imaging. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 514. doi:10.1158/1538-7445.AM2011-514
Lineage-specific regulation of allergic airway inflammation by the lipid phosphatase Src homology 2 domain–containing inositol 5-phosphatase (SHIP-1)
Authors: Matthew J. Gold, Michael R. Hughes, Frann Antignano, Jeremy A. Hirota, Colby Zaph, Kelly M. McNagny
Journal: Journal of Allergy and Clinical Immunology (2015)
Surgery of the Ambulatory Child
Authors: Thomas S. Morse
Journal: JAMA (1962)

This is a simple, straightforward book dealing with the diagnosis and management of surgical problems in childhood as they are managed in the office or in the emergency room. The material is well organized. The illustrations are large and clear, and the references are pertinent and up to date. Particularly useful is the section on the care of children with operatively created stomata, such as tracheostomy and ileostomy. The care of these artificial appertures is frequently neglected. While the book is written with a great deal of common sense, the distinction between those problems which can be managed in an ambulatory fashion and those in which the patient requires hospital admission is somewhat unclear. The book could have been considerably shorter had photographs and paragraphs devoted to major surgical problems been omitted. Those physicians, who having mastered a standard textbook on minor surgery require further information concerning this field as
Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: Implications for inhibition of the internal pool of GPIIb/IIIa receptors
Authors: Neal S. Kleiman, Albert E. Raizner, Robert Jordan, Ann L. Wang, Daniel Norton, Kenneth F. Mace, Alaknanda Joshi, Barry S. Coller, Harlan F. Weisman
Journal: Journal of the American College of Cardiology (1995)
Coexisting Hyperparathyroidism and Oncogenic Osteomalacia: Sestamibi and Somatostatin Receptor Scintigraphy
Authors: Ba D. Nguyen
Journal: Clinical Nuclear Medicine (2006)

Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia, hyperphosphaturia, elevated alkaline phosphatase, normal calcemia, and decreased 1,25 dihydroxy vitamin D. Even with blatant metabolic imbalance and debilitating musculoskeletal symptomatology, the causative neoplasm is difficult to detect. Thus, oncogenic osteomalacia remains chronic until a definitive cure from tumor localization and resection. Long-term supply of phosphate and vitamin D may induce tertiary hyperparathyroidism to oncogenic osteomalacia making the whole clinical picture more confusing. The author presents such a case with parathyroid hyperplasia and phosphaturic mesenchymal tumor demonstrated by technetium-99m sestamibi and indium-111 octreotide.
Interferon (IFN)-gamma is a main mediator of keratinocyte (HaCaT) apoptosis and contributes to autocrine IFN-gamma and tumour necrosis factor-alpha production.
Authors: A. Konur, U. Schulz, G. Eissner, R. Andreesen, E. Holler
Journal: British Journal of Dermatology (2005)

Background Apoptosis of keratinocytes or intestinal epithelial cells is an important pathophysiological mechanism of organ damage during acute graft‐versus‐host disease. Objectives To analyse in detail the mediators and their mutual interaction leading to keratinocyte apoptosis. Methods Experiments were performed using a keratinocyte cell line (HaCaT) and human skin explant cultures. Results Supernatants (SN) of major histocompatibility complex nonmatched mixed lymphocyte cultures (MLCs) induced apoptosis in HaCaT cells and also in keratinocytes from skin biopsies. Although both interferon (IFN)‐γ and Fas ligand (FasL) were detected in MLC‐SN by enzyme‐linked immunosorbent assay, the apoptosis‐inducing capacity could be fully abrogated by neutralization of IFN‐γ, but not by neutralization of FasL. Recombinant (r) IFN‐γ induced HaCaT keratinocyte apoptosis in a dose‐ and time‐dependent manner. Induction of HaCaT apoptosis by rFasL alone was induced only at higher doses than present in MLC‐SN, but apoptosis was dramatically enhanced in the presence of rIFN‐γ. Further synergistic effects with IFN‐γ in the induction of apoptosis were also observed with agonistic antitumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) receptor 2 antibody, soluble TRAIL and TNF‐α. However, in contrast to FasL and TRAIL, TNF‐α alone did not induce HaCaT apoptosis. Interleukin‐1β and lipopolysaccharide did not enhance the apoptosis‐inducing effect of IFN‐γ. Beside its apoptosis‐inducing capacity in HaCaT cells, rIFN‐γ also induced autocrine IFN‐γ production, and combined treatment with IFN‐γ and TNF‐α induced autocrine TNF‐α production. Neutralization of autocrine IFN‐γ protected HaCaT cells from apoptosis. Conclusions Taken together, our data suggest a central role for IFN‐γ in HaCaT keratinocyte apoptosis but also show the importance of co‐acting mediators such as TNF‐α, TRAIL and FasL, which potentiate the effect of paracrine and autocrine IFN‐γ and TNF‐α release.
Metabolic Response to Oral Challenge of Hydrogenated Starch Hydrolysate Versus Glucose In Diabetes
Authors: Madelyn L Wheeler, S Edwin Fineberg, Reid Gibson, Naomi Fineberg
Journal: Diabetes Care (1990)

Our objective was to determine whether 1) hydrogenated starch hydrolysates (HSHs), bulking/sweetening agents used in hard candies, produce a diminished postmeal glycemic response relative to glucose in individuals with and without diabetes and 2) any diminished glycemia is secondary to altered carbohydrate absorption. This study followed a randomized double-blind crossover design and was performed in 12 individuals with diabetes (6 non-insulin dependent, 6 insulin dependent) and 6 nondiabetic individuals. Each group consisted of 3 men and 3 women, none with known neuropathy. After an overnight fast, each subject was challenged with 50 g of glucose, HSH 5875 (7% sorbitol/60% maltitol), and HSH 6075 (14% sorbitol/78% hydrogenated maltooligosaccharides)/1.73 m2 of body surface area in random order on 3 successive days. Individuals with diabetes were maintained on continuous subcutaneous insulin infusion throughout the study to achieve prechallenge glucose levels between 4.5 and 6.7 mM. For all groups, the order of plasma glucose responses over 5 h postchallenge was glucose&amp;gt;HSH 6075&amp;gt;HSH 5875, P &amp;lt; 0.001 (glucose vs. HSH). Pooled data for all groups for areas under the curve confirmed that HSH 6075 resulted in greater glycemia than HSH 5875 (P &amp;lt; 0.05). This was reflected in the order of C-peptide responses seen in the nondiabetic and non-insulindependent groups (glucose&amp;gt;HSH 6075&amp;gt;HSH 5875, P &amp;lt; 0.001). Breath H2 after glucose was low, whereas HSH 5875 &amp;gt; HSH 6075 (P = 0.003). Gastric distress was noticed with all products. HSH ingestion as a single carbohydrate ingredient results in decreased glycemia relative to glucose in individuals with and without diabetes. Decreased glycemia results from altered small intestinal carbohydrate absorption. HSH as a single ingredient appears to be a suitable product for consumption by individuals with diabetes mellitus.