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https://www.readbyqxmd.com/read/27933352/intracochlear-drug-delivery-in%C3%A2-combination-with-cochlear-implants-current-aspects
#1
S K Plontke, G Götze, T Rahne, A Liebau
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e...
December 8, 2016: HNO
https://www.readbyqxmd.com/read/27933089/a-rare-inherited-15q11-2-q13-1-interstitial-duplication-with-maternal-somatic-mosaicism-renal-carcinoma-and-autism
#2
Nora Urraca, Brian Potter, Rachel Hundley, Eniko K Pivnick, Kathryn McVicar, Ronald L Thibert, Christopher Ledbetter, Reed Chamberlain, Leticia Miravalle, Carissa L Sirois, Stormy Chamberlain, Lawrence T Reiter
Chromosome 15q11-q13.1 duplication is a common copy number variant associated with autism spectrum disorder (ASD). Most cases are de novo, maternal in origin and fully penetrant for ASD. Here, we describe a unique family with an interstitial 15q11.2-q13.1 maternal duplication and the presence of somatic mosaicism in the mother. She is typically functioning, but formal autism testing showed mild ASD. She had several congenital anomalies, and she is the first 15q Duplication case reported in the literature to develop unilateral renal carcinoma...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27932994/comparative-mrna-and-microrna-profiling-during-acute-myocardial-infarction-induced-by-coronary-occlusion-and-ablation-radio-frequency-currents
#3
Eduardo T Santana, Regiane Dos Santos Feliciano, Andrey J Serra, Eduardo Brigidio, Ednei L Antonio, Paulo J F Tucci, Lubov Nathanson, Mariana Morris, José A Silva
The ligation of the left anterior descending coronary artery is the most commonly used experimental model to induce myocardial infarction (MI) in rodents. A high mortality in the acute phase and the heterogeneity of the size of the MI obtained are drawbacks recognized in this model. In an attempt to solve the problem, our group recently developed a new MI experimental model which is based on application of myocardial ablation radio-frequency currents (AB-RF) that yielded MI with homogeneous sizes and significantly reduce acute mortality...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27932443/pd-l1-blockade-enhances-response-of-pancreatic-ductal-adenocarcinoma-to-radiotherapy
#4
Abul Azad, Su Yin Lim, Zenobia D'Costa, Keaton Jones, Angela Diana, Owen J Sansom, Philipp Kruger, Stanley Liu, W Gillies McKenna, Omer Dushek, Ruth J Muschel, Emmanouil Fokas
Pancreatic ductal adenocarcinoma (PDAC) is considered a non-immunogenic tumor, and immune checkpoint inhibitor monotherapy lacks efficacy in this disease. Radiotherapy (RT) can stimulate the immune system. Here, we show that treatment of KPC and Pan02 murine PDAC cells with RT and gemcitabine upregulated PD-L1 expression in a JAK/Stat1-dependent manner. In vitro, PD-L1 inhibition did not alter radio- and chemosensitivity. In vivo, addition of anti-PD-L1 to high (12, 5 × 3, 20 Gy) but not low (6, 5 × 2 Gy) RT doses significantly improved tumor response in KPC and Pan02 allografts...
December 8, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27932207/the-current-state-of-therapeutic-and-t-cell-based-vaccines-against-human-papillomaviruses
#5
REVIEW
Andrew Yang, Emily Farmer, John Lin, T-C Wu, Chien-Fu Hung
Human papillomavirus (HPV) is known to be a necessary factor for many gynecologic malignancies and is also associated with a subset of head and neck malignancies. This knowledge has created the opportunity to control these HPV-associated cancers through vaccination. However, despite the availability of prophylactic HPV vaccines, HPV infections remain extremely common worldwide. In addition, while prophylactic HPV vaccines have been effective in preventing infection, they are ineffective at clearing pre-existing HPV infections...
December 5, 2016: Virus Research
https://www.readbyqxmd.com/read/27932160/successful-short-term-intravenous-treatment-of-disseminated-nocardia-farcinica-infection-with-severe-hyponatremia-after-kidney-transplantation-a-case-report
#6
A L Herzog, C Wanner, K Lopau
BACKGROUND: Nocardia is a genus of gram-positive Actinomycetes that are ubiquitous in decaying organic material, soil, and water. Some Nocardia species can infect humans, mainly by airborne transmission. Several reports describe disseminated infections, which are rare and mostly affect strongly immunocompromised patients because intact T-cell-mediated immunity is the major protective mechanism. CASE REPORT: We report a case of disseminated pulmonary, cerebral, and cutaneous infection with Nocardia farcinica in a 66-year-old kidney transplant recipient treated with low-dose triple immunosuppression...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932138/potential-immunomodulatory-role-of-specific-anticytomegalovirus-intravenous-immunoglobulin-in-heart-recipients
#7
J Carbone, A Gallego, J Fernandez Yañez, I Sousa, E Sarmiento
BACKGROUND: Specific anticytomegalovirus (anti-CMV) intravenous immunoglobulin (IVIG) has the potential to influence the immune response, but its complex mode of action has not been well evaluated. METHODS: An immunologic study of 6 CMV-seronegative heart transplant patients receiving anti-CMV prophylaxis with the use of ganciclovir and CMV-IVIG (150 mg/kg within 24 hours after transplantation and 100 mg/kg on days 2, 7, 14, 22, 35, 56, and 77 after transplantation) was performed in a single center...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931835/management-of-patients-with-recurrent-advanced-cervical-cancer-beyond-first-line-platinum-regimens-where-do-we-stand-a-literature-review
#8
REVIEW
Stergios Boussios, Esmeralda Seraj, George Zarkavelis, Dimitrios Petrakis, Aristomenes Kollas, Aikaterini Kafantari, Abraam Assi, Konstantina Tatsi, Nicholas Pavlidis, George Pentheroudakis
BACKGROUND: Cervical cancer is the fourth most common cancer affecting women worldwide. Despite advances in screening and human papillomavirus (HPV) vaccination, a significant number of women present with or develop advanced disease. Palliative platinum-based chemotherapy (CT) is the standard first-line treatment for metastatic/recurrent cervical cancer. The prognosis remains poor and effective second line options are urgently needed. METHODS: We searched the English-language medical literature as well as relevant guideline databases, published from January 1981 to December 2015 and identified publications related to cervical cancer and its therapies...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27931684/inhibition-of-apoptosis-by-rv2456c-through-nuclear-factor-%C3%AE%C2%BAb-extends-the-survival-of-mycobacterium-tuberculosis
#9
Kristen L Jurcic Smith, Sunhee Lee
Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8(+) T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID)...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27931306/idiopathic-cd4-lymphocytopenia
#10
Joel P Brooks, Gisoo Ghaffari
BACKGROUND: Idiopathic CD4 lymphocytopenia (ICL) is a rare disorder of unknown etiology. Diagnostic criteria include a persistent CD4 T-cell lymphopenia with no underlying primary or secondary immune deficiencies and a CD4 T-cell count of 300 cells/mL or 20% total lymphocyte on multiple occasions. OBJECTIVE: To increase awareness of ICL and to provide a review of the clinical characteristics, diagnosis, and management of this disease process. Presently, many of these patients receive prophylactic treatment similar to other T-cell deficient conditions, most notably patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome; however, the same indications may not necessarily apply to this patient population because the T cells are not affected by a virus as in HIV...
November 2016: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/27931084/association-of-higher-cd4-cd25-high-cd127-low-foxp3-and-il-2-t-cell-frequencies-early-after-lung-transplantation-with-less-chronic-lung-allograft-dysfunction-at-two-years
#11
J Salman, F Ius, A-K Knoefel, W Sommer, Th Siemeni, C Kuehn, I Tudorache, M Avsar, T Nakagiri, G Preissler, R Hatz, M Greer, T Welte, A Haverich, G Warnecke
Regulatory T cells (Treg) can regulate alloantigens and may counteract chronic lung allograft dysfunction (CLAD) in lung transplantation. We analyzed Treg in peripheral blood prospectively and correlated percentages of subpopulations with the incidence of CLAD at two years. Among lung-transplanted patients between 01/2009 and 07/2011, only patients with sufficient Treg measurements were included into the study. Tregs were measured immediately before lung transplantation, at 3 weeks and 3, 6, 12 and 24 months after transplantation and were defined as CD4(+) CD25(high) T cells and further analyzed for CTLA4, CD127, FoxP3 and IL-2 expressions...
December 8, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27931022/hydrogen-sulfide-and-t-type-ca2-channels-in-pain-processing-neuronal-differentiation-and-neuroendocrine-secretion
#12
Kazuki Fukami, Fumiko Sekiguchi, Atsufumi Kawabata
BACKGROUND: Hydrogen sulfide (H2S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H2S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Cav3.2 T-type Ca2+ channels mediate some of the biological activity of H2S, we focus on the role of the H2S/Cav3...
December 9, 2016: Pharmacology
https://www.readbyqxmd.com/read/27930631/cd19-targeted-car-t-cells-as-novel-cancer-immunotherapy-for-relapsed-or-refractory-b-cell-acute-lymphoblastic-leukemia
#13
Marco L Davila, Renier J Brentjens
Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable...
October 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27930550/role-of-immune-cells-in-pancreatic-cancer-from-bench-to-clinical-application-an-updated-review
#14
Jae Hyuck Chang, Yongjian Jiang, Venu G Pillarisetty
BACKGROUND: Pancreatic cancer (PC) remains difficult to treat, despite the recent advances in various anticancer therapies. Immuno-inflammatory response is considered to be a major risk factor for the development of PC in addition to a combination of genetic background and environmental factors. Although patients with PC exhibit evidence of systemic immune dysfunction, the PC microenvironment is replete with immune cells. METHODS: We searched PubMed for all relevant English language articles published up to March 2016...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27930389/therapy-related-myeloid-neoplasms
#15
Arnold Ganser, Michael Heuser
PURPOSE OF REVIEW: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis...
December 7, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27930309/sox2-progenitors-in-sharks-link-taste-development-with-the-evolution-of-regenerative-teeth-from-denticles
#16
Kyle J Martin, Liam J Rasch, Rory L Cooper, Brian D Metscher, Zerina Johanson, Gareth J Fraser
Teeth and denticles belong to a specialized class of mineralizing epithelial appendages called odontodes. Although homology of oral teeth in jawed vertebrates is well supported, the evolutionary origin of teeth and their relationship with other odontode types is less clear. We compared the cellular and molecular mechanisms directing development of teeth and skin denticles in sharks, where both odontode types are retained. We show that teeth and denticles are deeply homologous developmental modules with equivalent underlying odontode gene regulatory networks (GRNs)...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27930306/mir-17%C3%A2-92-family-clusters-control-inkt-cell-ontogenesis-via-modulation-of-tgf-%C3%AE-signaling
#17
Maya Fedeli, Michela Riba, Jose Manuel Garcia Manteiga, Lei Tian, Valentina Viganò, Grazisa Rossetti, Massimiliano Pagani, Changchun Xiao, Adrian Liston, Elia Stupka, Davide Cittaro, Sergio Abrignani, Paolo Provero, Paolo Dellabona, Giulia Casorati
Invariant natural killer T cells (iNKT) cells are T lymphocytes displaying innate effector functions, acquired through a distinct thymic developmental program regulated by microRNAs (miRNAs). Deleting miRNAs by Dicer ablation (Dicer KO) in thymocytes selectively impairs iNKT cell survival and functional differentiation. To unravel this miRNA-dependent program, we systemically identified transcripts that were differentially expressed between WT and Dicer KO iNKT cells at different differentiation stages and predicted to be targeted by the iNKT cell-specific miRNAs...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929752/efficient-production-of-bispecific-igg-of-different-isotypes-and-species-of-origin-in-single-mammalian-cells
#18
Michael Dillon, Yiyuan Yin, Jianhui Zhou, Luke McCarty, Diego Ellerman, Dionysos Slaga, Teemu T Junttila, Guanghui Han, Wendy Sandoval, Meric A Ovacik, Kedan Lin, Zhilan Hu, Amy Shen, Jacob E Corn, Christoph Spiess, Paul J Carter
Bispecific IgG production in single host cells has been a much sought-after goal to support the clinical development of these complex molecules. Current routes to single cell production of bispecific IgG include engineering heavy chains for heterodimerization and redesign of Fab arms for selective pairing of cognate heavy and light chains. Here, we describe novel designs to facilitate selective Fab arm assembly in conjunction with previously described knobs-into-holes mutations for preferential heavy chain heterodimerization...
December 8, 2016: MAbs
https://www.readbyqxmd.com/read/27929746/exogenous-expression-of-samhd1-inhibits-proliferation-and-induces-apoptosis-in-cutaneous-t-cell-lymphoma-derived-hut78-cells
#19
Karthik M Kodigepalli, Minghua Li, Shan-Lu Liu, Li Wu
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a mammalian dNTP hydrolase (dNTPase) that regulates intracellular dNTP balance. We have previously reported that SAMHD1 mRNA and protein levels are significantly downregulated in CD4(+) T-cells of patients with cutaneous T-cell lymphoma (CTCL), a disease characterized by infiltration of neoplastic CD4(+) T-lymphocytes into the skin. However, functional significance of SAMHD1 in CTCL development and progression remains unknown. Here we investigate the mechanism by which SAMHD1 induces apoptosis in CTCL-derived CD4(+) T-cells...
December 8, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27929521/efficient-footprint-free-human-ipsc-genome-editing-by-consolidation-of-cas9-crispr-and-piggybac-technologies
#20
Gang Wang, Luhan Yang, Dennis Grishin, Xavier Rios, Lillian Y Ye, Yong Hu, Kai Li, Donghui Zhang, George M Church, William T Pu
Genome editing of human induced pluripotent stem cells (hiPSCs) offers unprecedented opportunities for in vitro disease modeling and personalized cell replacement therapy. The introduction of Cas9-directed genome editing has expanded adoption of this approach. However, marker-free genome editing using standard protocols remains inefficient, yielding desired targeted alleles at a rate of ∼1-5%. We developed a protocol based on a doxycycline-inducible Cas9 transgene carried on a piggyBac transposon to enable robust and highly efficient Cas9-directed genome editing, so that a parental line can be expeditiously engineered to harbor many separate mutations...
January 2017: Nature Protocols
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