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https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#1
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550160/corticotropin-releasing-hormone-receptor-2-exacerbates-chronic-cardiac-dysfunction
#2
Takuma Tsuda, Mikito Takefuji, Nina Wettschureck, Kazuhiko Kotani, Ryota Morimoto, Takahiro Okumura, Harmandeep Kaur, Shunsuke Eguchi, Teruhiro Sakaguchi, Sohta Ishihama, Ryosuke Kikuchi, Kazumasa Unno, Kunihiro Matsushita, Shizukiyo Ishikawa, Stefan Offermanns, Toyoaki Murohara
Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein-coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice...
May 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28549782/central-trkb-blockade-attenuates-icv-angiotensin-ii-hypertension-and-sympathetic-nerve-activity-in-male-sprague-dawley-rats
#3
Bryan K Becker, Hanjun Wang, Irving H Zucker
Increased sympathetic nerve activity and the activation of the central renin-angiotensin system are commonly associated with cardiovascular disease states such as hypertension and heart failure, yet the precise mechanisms contributing to the long-term maintenance of this sympatho-excitation are incompletely understood. Due to the established physiological role of neurotrophins contributing toward neuroplasticity and neuronal excitability along with recent evidence linking the renin-angiotensin system and brain-derived neurotrophic factor (BDNF) along with its receptor (TrkB), it is likely the two systems interact to promote sympatho-excitation during cardiovascular disease...
May 19, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28549771/calcineurin-and-mtor-inhibitor-free-post-transplantation-cyclophosphamide-and-bortezomib-combination-for-graft-versus-host-disease-prevention-after-peripheral-blood-allogeneic-hematopoietic-stem-cell-transplantation-a-phase-i-ii-study
#4
A Samer Al-Homsi, Kelli Cole, Marlee Muilenburg, Austin Goodyke, Muneer Abidi, Ulrich Duffner, Stephanie Williams, Jessica Parker, Aly Abdel-Mageed
Graft-versus-host disease (GvHD) hampers the utility of allogeneic hematopoietic stem cell transplantation (AHSCT). The purpose of this study was to determine the feasibility, safety, and efficacy of a novel combination of post-transplantation cyclophosphamide (PTC) and bortezomib for the prevention of GvHD. Patients undergoing peripheral blood AHSCT for hematological malignancies following reduced-intensity conditioning with grafts from human leukocyte antigen (HLA)-matched related or unrelated donors were enrolled in a phase I-II clinical trial...
May 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28549643/hypertonic-saline-for-raised-intracranial-pressure-following-aneurysmal-subarachnoid-hemorrhage-a-systematic-review
#5
REVIEW
Christopher R Pasarikovski, Naif M Alotaibi, Fawaz Al-Mufti, R Loch Macdonald
BACKGROUND: The use of hyperosmolar agents such as mannitol or hypertonic saline (HTS) to control high intracranial pressure (ICP) in traumatic brain injury patients has been well studied. However, the role of HTS in the management of aneurysmal subarachnoid hemorrhage (aSAH)-associated raised ICP is still unclear. METHODS: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome of this review is to quantify ICP reduction produced by HTS and its effect on clinical outcomes defined by any standardized functional score...
May 23, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28549524/-quadratus-lumborum-block-are-we-aware-of-its-side-effects-a-report-of-2-cases
#6
Miguel Sá, José Miguel Cardoso, Hugo Reis, Marta Esteves, José Sampaio, Isabel Gouveia, Pilar Carballada, Célia Pinheiro, Duarte Machado
BACKGROUND AND OBJECTIVES: The quadratus lumborum block was initially described in 2007 and aims at blocking the same nerves as the ones involved on the Transverse Abdominis Plane block, while accomplishing some visceral enervation as well due to closer proximity with the neuroaxis and sympathetic trunk. Given its versatility, we have successfully used it in a wide range of procedures. We report two cases where we believe the dispersion of local anesthetic is likely to have led to a previously undescribed complication...
May 23, 2017: Revista Brasileira de Anestesiologia
https://www.readbyqxmd.com/read/28549395/utility-and-clinical-profile-of-dexmedetomidine-in-pediatric-cardiac-catheterization-procedures-a-matched-controlled-analysis
#7
Ricardo Riveros, Natalya Makarova, Efrain Riveros-Perez, Praneeta Chodavarapu, Wael Saasouh, Hüseyin Oğuz Yılmaz, Evis Cuko, Rovnat Babazade, Stephen Kimatian, Alparslan Turan
BACKGROUND: Dexmedetomidine is increasingly used in children undergoing cardiac catheterization procedures. We compared the percentage of surgical time with hemodynamic instability and the incidence of postoperative agitation between pediatric cardiac catheterization patients who received dexmedetomidine infusion and those who did not and the incidence of postoperative agitation. MATERIALS AND METHODS: We matched 653 pediatric patients scheduled for cardiac catheterization...
May 1, 2017: Seminars in Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28549082/pharmacokinetics-and-pharmacodynamics-of-propofol-changes-in-patients-with-frontal-brain-tumours
#8
M M Sahinovic, D J Eleveld, T Miyabe-Nishiwaki, M M R F Struys, A R Absalom
Background: Models of propofol pharmacokinetics and pharmacodynamics developed in patients without brain pathology are widely used for target-controlled infusion (TCI) during brain tumour excision operations. The goal of this study was to determine if the presence of a frontal brain tumour influences propofol pharmacokinetics and pharmacodynamics and existing PK-PD model performance. Methods: Twenty patients with a frontal brain tumour and 20 control patients received a propofol infusion to achieve an induction-emergence-induction anaesthetic sequence...
May 26, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28548279/significant-decreases-in-blood-propofol-concentrations-during-adrenalectomy-for-phaeochromocytoma
#9
Tatsunori Watanabe, Haruhiko Hiraoka, Takuya Araki, Daisuke Nagano, Tohru Aomori, Tomonori Nakamura, Koujirou Yamamoto, Hiroshi Baba
AIM: The kinetics of propofol are influenced by cardiac output. The aim of this study was to examine changes in blood propofol concentrations during phaeochromocytoma surgery using target-controlled infusion (TCI) anaesthesia with propofol. METHODS: This is a prospective observational study. Ten patients with phaeochromocytoma who underwent unilateral adrenalectomy were included. Cardiac output was measured using an arterial pressure-based cardiac output analysis method...
May 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28547342/trichosporon-asteroides-isolated-from-cutaneous-lesions-of-a-suspected-case-of-paracoccidioidomycosis-ceti-in-a-bottlenose-dolphin-tursiops-truncatus
#10
Keiichi Ueda, Ichiro Nakamura, Eiko Nakagawa Itano, Kazunori Takemura, Yasutomo Nakazato, Ayako Sano
"Paracoccidioidomycosis ceti" is a rare zoonotic fungal infection affecting dolphins and is endemic worldwide. The causative agents are Paracoccidioides species; however, it is impossible to isolate the fungal species. We isolated Trichosporon asteroides from multifocal, irregularly raised skin lesions on a female bottlenose dolphin (Tursiops truncatus) captured off coast of Japan, which was suspected to have "paracoccidioidomycosis ceti." An abundance of round, yeast-like cells was detected in a potassium hydroxide direct-mount specimen of the skin samples; however, nested PCR targeting the partial sequence of 43-kDa glycoprotein-coding gene correspondent to Paracoccidioides sp...
May 25, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28546489/genome-sequence-of-a-marine-spirillum-oceanospirillum-multiglobuliferum-atcc-33336-t-isolated-from-japan
#11
Joshua G Carney, Ariel M Trachtenberg, Bruce A Rheaume, Joshua D Linnane, Natalie L Pitts, Donald L Mykles, Kyle S MacLea
Oceanospirillum multiglobuliferum ATCC 33336(T) is a motile gammaproteobacterium with bipolar tufted flagella, noted for its low salt tolerance compared to other marine spirilla. This strain was originally isolated from the putrid infusions of Crassostrea gigas near Hiroshima, Japan. This paper presents a draft genome sequence for O. multiglobuliferum ATCC 33336(T).
May 25, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28546312/prefrontal-dopamine-d1-and-d2-receptors-regulate-dissociable-aspects-of-decision-making-via-distinct-ventral-striatal-and-amygdalar-circuits
#12
Nicole L Jenni, Joshua D Larkin, Stan B Floresco
Mesocortical dopamine (DA) regulates a variety of cognitive functions via actions on D1 and/or D2 receptors. For example, risk/reward decision making is differentially modulated by these two receptors within the prefrontal cortex (PFC), with D2 receptors enabling flexible decision making and D1 receptors promoting persistence in choice biases. Yet, it is unclear how DA mediates opposing patterns of behavior by acting on different receptors within the same terminal region. We explored the possibility that DA may act on separate networks of PFC neurons that are modulated by D1 or D2 receptors and in turn interface with divergent downstream structures, such as the basolateral amygdala (BLA) or nucleus accumbens (NAc)...
May 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28546310/heterozygous-gnal-mice-are-a-novel-animal-model-to-study-dystonia-pathophysiology
#13
Assunta Pelosi, Fabien Menardy, Daniela Popa, Jean-Antoine Girault, Denis Hervé
Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions. Its pathophysiological mechanisms are still poorly understood. Dominant mutations of the GNAL gene are a cause of isolated dystonia (DYT25) in patients. Some mutations result in a complete loss of function of the encoded protein, Gαolf, an adenylyl-cyclase-stimulatory G protein highly enriched in striatal projection neurons, in which it mediates the actions of dopamine and adenosine. We used male and female heterozygous Gnal knockout mice (Gnal+/-) to study how GNAL haplodeficiency is implicated in dystonia...
May 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28545857/different-valsalva-manoeuvre-procedures-for-the-diagnosis-of-right-to-left-shunt-by-contrast-transcranial-doppler
#14
Chao Liu, Teng Lu, Ni-Na Zhai, Ning Bu, Hu-Qing Wang, Meng-Yi Chen, Hai-Qin Wu
The main purpose of this study was to compare two contrast agent injection times during the Valsalva manoeuvre (VM) for the diagnosis of right-to-left shunt using contrast-transcranial Doppler (c-TCD). In total, 992 consecutive patients underwent testing. All patients underwent step 1, and then a coin toss was used to determine the order of steps 2 and 3. The following testing steps were repeated twice: (1) a contrast agent (CA) was infused at rest (CA at rest testing); (2) the VM was initiated immediately after CA injection and released 10 s after CA injection (CA pre-VM testing); and (3) a CA was injected 5 s after initiating the VM, which was released 5 s after CA injection (CA mid-VM testing)...
May 22, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28545564/dexmedetomidine-in-combination-with-sufentanil-for-postoperative-analgesia-after-partial-laryngectomy
#15
Minju Qin, Kaizheng Chen, Tingjie Liu, Xia Shen
BACKGROUND: Dexmedetomidine as an adjunct with opioids has been confirmed to spare opioids usage and improve analgesia for postoperative pain treatment. Furthermore, dexmedetomidine can attenuate the airway reflex. The aim of this study is to assess the safety and efficacy of dexmedetomidine combined with sufentanil for postoperative analgesia after partial laryngectomy. METHODS: A total of 60 adult male patients were recruited and randomly allocated to receive sufentanil 1...
May 25, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28545191/%C3%A2-mate%C3%A2-intake-hormone-based-risk-factors-and-breast-cancer-a-case-control-study
#16
Alvaro L Ronco, Edison Espinosa, Juan M Calderon, Eduardo Lasalvia- Galante, Alejandro De Rosa, Gustavo Sanchez
Previous reports on the inverse association between ‘mate’ intake (infusion of Ilex Paraguariensis herb) and breast cancer (BC) risk led us to consider two main roles for the infusion: as a substantial antioxidant contributor and as a hormone regulator, particularly through anti-aromatase capacities. Since menstrual-reproductive risk factors for BC reflect women’s estrogenic exposure during the reproductive lifespan, and considering that ‘mate’ intake exerts putative stronger protection among high antioxidant contributors, we attempted to analyze interactions among the infusion, hormon-linked reproductive factors and BC risk, which have hitherto remained unexplored...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28544885/overcoming-interference-with-the-detection-of-a-stable-isotopically-labeled-microtracer-in-the-evaluation-of-beclabuvir-absolute-bioavailability-using-a-concomitant-microtracer-approach
#17
Hao Jiang, Craig Titsch, Jianing Zeng, Barry Jones, Philip Joyce, Yash Gandhi, Wesley Turley, Richard Burrell, Anne F Aubry, Mark E Arnold
The oral absolute bioavailability of beclabuvir in healthy subjects was determined using a microdose (100μg) of the stable isotopically labeled tracer via intravenous (IV) infusion started after oral dosing of beclabuvir (150mg). To simultaneously analyze the concentrations of the IV microtracer ([(13)C6]beclabuvir) and beclabuvir in plasma samples, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method was initially developed. Surprisingly beclabuvir significantly interfered with the IV microtracer detection when using the selected reaction monitoring (SRM) in the assay...
May 17, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28544780/spinal-metastatic-disease-a-review-of-the-role-of-the-multidisciplinary-team
#18
REVIEW
Mark Curtin, Robert P Piggott, Evelyn P Murphy, Sudarshan Munigangaiah, Joseph F Baker, John P McCabe, Aiden Devitt
Historically, a simple approach centered on palliation was applicable to the majority of patients with metastatic spinal disease. With advances in diagnosis and treatment, a more complicated algorithm has devolved requiring a multidisciplinary approach with institutional commitment and support. We performed a database review including pertinent articles exploring the multidisciplinary management of spinal metastatic disease. The wide variation in clinical presentation and tumor response to treatment necessitates a multidisciplinary approach that integrates the diagnosis and treatment of the cancer, symptom management, and rehabilitation for optimal care of patients with spinal metastases...
May 24, 2017: Orthopaedic Surgery
https://www.readbyqxmd.com/read/28544684/insulin-glulisine-for-continuous-subcutaneous-insulin-infusion-in-pediatric-type-1-diabetes
#19
Tatsuhiko Urakami, Yusuke Mine, Masako Aoki, Misako Okuno, Junichi Suzuki
We evaluated the efficacy and safety of insulin glulisine (GLU) used for continuous s.c. insulin infusion (CSII) in 20 children with type 1 diabetes after 1 year of GLU treatment. There were no significant differences in mean plasma glucose before breakfast and before dinner between before and after using GLU, but the levels after breakfast and after dinner significantly improved, from 192.5 ± 31.7 to 162.0 ± 27.3 mg/dL for breakfast, and from 191.1 ± 33.3 to 161.1 ± 24.5 mg/dL for dinner (P < 0...
May 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28544595/severe-cytokine-release-syndrome-in-a-patient-receiving-pd-1-directed-therapy
#20
Seth J Rotz, Daniel Leino, Sara Szabo, Jennifer L Mangino, Brian K Turpin, Joseph G Pressey
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids...
May 24, 2017: Pediatric Blood & Cancer
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