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T cell proliferation

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https://www.readbyqxmd.com/read/28329703/successful-and-maladaptive-t-cell-aging
#1
REVIEW
Jörg J Goronzy, Cornelia M Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329691/myocardial-infarction-primes-autoreactive-t-cells-through-activation-of-dendritic-cells
#2
Katrien Van der Borght, Charlotte L Scott, Veronika Nindl, Ann Bouché, Liesbet Martens, Dorine Sichien, Justine Van Moorleghem, Manon Vanheerswynghels, Sofie De Prijck, Yvan Saeys, Burkhard Ludewig, Thierry Gillebert, Martin Guilliams, Peter Carmeliet, Bart N Lambrecht
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329565/dermatological-clues-to-the-diagnosis-of-atypical-complete-digeorge-syndrome
#3
Lucia Seminario-Vidal, Lauren Kole, Charles Knapp, Prem Fort, Suthida Kankirawatana, T Prescott Atkinson, Kristopher M McKay, Amy Theos
Atypical complete DiGeorge syndrome (DGS) is an extremely rare congenital disease characterized by an eczematous dermatitis, lymphadenopathy, and an oligoclonal T-cell proliferation. Because its initial presentation may be confused with other types of eczematous dermatitis, diagnosis and treatment are usually delayed. We describe herein a case of an infant with atypical complete DGS to draw attention to the clinical and histopathological findings that lead us to the diagnosis.
November 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329187/bumped-kinase-inhibitors-for-therapy-of-cryptosporidiosis
#4
Matthew A Hulverson, Sumiti Vinayak, Ryan Choi, Deborah A Schaefer, Alejandro Castellanos-Gonzalez, Rama S R Vidadala, Carrie F Brooks, Gillian T Herbert, Dana P Betzer, Grant R Whitman, Hayley N Sparks, Samuel L M Arnold, Kasey L Rivas, Lynn K Barrett, A Clinton White, Maly Dustin J, Michael W Riggs, Boris Striepen, Wesley C Van Voorhis, Kayode K Ojo
Bumped kinase inhibitors (BKIs) of Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) are leading candidates for treatment of cryptosporidiosis diarrhea. Potential cardiotoxicity related to anti-human ether-à-go-go potassium channel (hERG) activity of the first generation anti-Cryptosporidium BKIs triggered further testing for efficacy. A luminescence assay adapted for high-throughput screening was used to measure inhibitory activities of BKIs on in vitro C. parvum. Furthermore, neonatal and interferon-γ knockout mouse models of C...
March 3, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28328614/a-newborn-with-familial-hemophagocytic-lymphohistiocytosis-complicated-with-transfusion-associated-graft-versus-host-disease
#5
Ahmet Ozdemir, Tamer Gunes, Samuel C C Chiang, Ekrem Unal
Hemophagocytic lymphohistiocytosis (HLH) is characterized by activation of cytotoxic T and natural killer (NK) cells, and macrophages related to a spectrum of hyperinflammatory disorders. The clinical findings mainly include high fever, cytopenia, splenomegaly, phagocytosis, and proliferation of histiocytes in lymphoreticular tissue. To the best of our knowledge, transfusion-associated graft versus host disease (TA-GVHD) in a 13-day old male newborn with HLH is being reported first time in the literature. The aim of this report was to emphasize the importance of blood products irradiation in the prevention of the development of graft versus host disease especially among high-risk subjects such as newborns with HLH...
March 21, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28327194/upregulation-of-the-long-noncoding-rna-uca1-affects-the-proliferation-invasion-and-survival-of-hypopharyngeal-carcinoma
#6
Ye Qian, Dayu Liu, Shengda Cao, Ye Tao, Dongmin Wei, Wenming Li, Guojun Li, Xinliang Pan, Dapeng Lei
BACKGROUND: Several long noncoding RNAs (lncRNAs) are involved in oncogenesis. METHODS AND RESULTS: Our microarray analysis showed that numerous lncRNAs are dysregulated in hypopharyngeal squamous cell carcinoma (HSCC) tumor tissues as compared with normal tissues. Among those lncRNAs, urothelial carcinoma-associated 1 (UCA1) has been found to have an oncogenic role in HSCC. We confirmed the upregulation of UCA1 in HSCC by assessing its expression levels in a cohort of 53 patient tumors and paired non-tumor samples...
March 21, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28327189/microrna-27a-contributes-to-the-malignant-behavior-of-gastric-cancer-cells-by-directly-targeting-ph-domain-and-leucine-rich-repeat-protein-phosphatase-2
#7
Lei Ding, Shanyong Zhang, Mu Xu, Renwen Zhang, Pengcheng Sui, Qing Yang
BACKGROUND: Accumulating evidence indicates that microRNA-27a (miR-27a) is involved in carcinogenesis and tumor progression. However, the exact function and molecular mechanism of miR-27a in gastric cancer remain unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-27a and its target gene. The function of miR-27a in gastric cancer was investigated through in vitro and in vivo assays (MTT assay, colony formation assay, flow cytometry assay, wound healing assay, migration and invasion assay, immunohistochemistry (IHC), immunofluorescence (IF) and Western blot)...
March 21, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28326648/changes-in-expression-of-the-cd200-tolerance-signaling-molecule-and-its-receptor-cd200r-by-villus-trophoblasts-during-first-trimester-missed-abortion-and-in-chronic-histiocytic-intervillositis
#8
David A Clark, Jennifer M Dmetrichuk, Elizabeth McCready, Sukhbinder Dhesy-Thind, Jorge L Arredondo
PROBLEM: Expression of CD200 at the feto-maternal interface is associated with successful murine and human pregnancy. CD200 binding to CD200 receptors on lymphomyeloid cells suppresses inflammation and induces Tregs. CD200 receptors are also expressed on mouse and human placental trophoblast cells. What is the expression of CD200 and CD200R in human missed abortions which have preserved Treg levels and in chronic histiocytic intervillositis (CHI) where maternal inflammatory cells cause IUGR? METHODS: Immunohistiochemistry for CD200, CD200R, and Ki67 using human placental sections from missed abortions, term placenta, and CHI...
March 22, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28326569/the-dynamics-of-the-oesophageal-squamous-epithelium-normalisation-process-in-patients-with-gastro-oesophageal-reflux-disease-treated-with-long-term-acid-suppression-or-anti-reflux-surgery
#9
L Mastracci, R Fiocca, C Engström, S Attwood, C Ell, J P Galmiche, J G Hatlebakk, G Långström, S Eklund, T Lind, L Lundell
BACKGROUND: Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). AIM: To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. METHODS: In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180)...
March 21, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28326562/liposome-encapsulated-hemoglobin-accelerates-skin-wound-healing-in-diabetic-db-db-mice
#10
Tsuyoshi Fukui, Akira T Kawaguchi, Susumu Takekoshi, Muneo Miyasaka, Hideaki Sumiyoshi, Rica Tanaka
Since liposome-encapsulated hemoglobin with high O2 affinity (h-LEH, P50 O2  = 10 mm Hg) has been reported to accelerate skin wound healing in normal mice, it was tested in dB/dB mice with retarded wound healing, as seen in human diabetics. Two full-thickness dorsal wounds 6 mm in diameter encompassed by silicone stents were created in dB/dB mice. Two days later (day 2), the animals were randomly assigned to receive intravenous h-LEH (2 mL/kg, n = 7) or saline (2 mL/kg, n = 7). The same treatment was repeated 4 days after wounding (day 4), and the size of the skin lesions was analyzed by photography, surface perfusion was detected by Laser-Doppler imager, and plasma cytokines and chemokines were determined on days 0, 2, 4, and 7, when all animals were euthanized for morphological studies...
March 21, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28326125/determination-of-the-wound-healing-potentials-of-medicinal-plants-historically-used-in-ghana
#11
Sara H Freiesleben, Jens Soelberg, Nils T Nyberg, Anna K Jäger
The present study was carried out to investigate the wound healing potentials of 17 medicinal plants historically used in Ghana for wound healing. Warm and cold water extracts were prepared from the 17 dried plant species and tested in vitro in the scratch assay with NIH 3T3 fibroblasts from mice. The wound healing scratch assay was used to evaluate the effect of the plants on cell proliferation and/or migration in vitro, as a test for potential wound healing properties. After 21 hours of incubation increased proliferation and/or migration of fibroblasts in the scratch assay was obtained for 5 out of the 17 plant species...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28325750/molecular-pathways-evaluating-the-potential-for-b7-h4-as-an-immunoregulatory-target
#12
Heather L MacGregor, Pamela S Ohashi
With the clinical success of CTLA-4 and PD-1 blockade in treating malignancies, there is tremendous interest in finding new ways to augment anti-tumor responses by targeting other inhibitory molecules. In this review, we describe one such molecule. B7-H4, a member of the B7 family of immunoregulatory proteins, inhibits T cell proliferation and cytokine production through ligation of an unknown receptor expressed by activated T cells. Notably, B7-H4 protein expression is observed in a high proportion of patients' tumors across a wide variety of malignancies...
March 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28324192/the-presence-of-human-papillomavirus-hpv-in-placenta-and-or-cord-blood-might-result-in-th2-polarization
#13
H-M Koskimaa, A Paaso, M J P Welters, S Grénman, K Syrjänen, S H van der Burg, S Syrjänen
The purpose of this study was to evaluate if an early exposure to human papillomavirus (HPV) during the prenatal period or infancy could result in HPV16-specific T helper (Th) responses resembling those of adults with HPV-induced lesions. We tested HPV16-specific cell-mediated immunity (CMI) in children born with HPV-positive umbilical cord blood and/or placenta or having persistent oral HPV infection and in constantly oral HPV-negative controls. Peripheral blood mononuclear cells from 33 children from the Finnish HPV Family Study cohort (mean age 14...
March 21, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28324020/paracrine-pathways-in-uterine-leiomyoma-stem-cells-involve-insulin-like-growth-factor-2-and-insulin-receptor-a
#14
Molly B Moravek, Ping Yin, John S Coon V, Masanori Ono, Stacy A Druschitz, Saurabh S Malpani, Matthew T Dyson, Alfred W Rademaker, Jared C Robins, Jian-Jun Wei, J Julie Kim, Serdar E Bulun
Context: Uterine leiomyoma (fibroids) are the most common benign tumor in women. Recently, three populations of leiomyoma cells were discovered based on CD34 and CD49b expression, but the molecular differences between these populations remain unknown. Objective: Define differential gene expression and signaling pathways in leiomyoma cell populations. Design: Cells from human leiomyoma were sorted by flow cytometry into three populations: CD34+/CD49b+, CD34+/CD49b-, and CD34-/CD49b-...
January 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323876/pim1-minicircle-as-a-therapeutic-treatment-for-myocardial-infarction
#15
Nan Liu, Bingyan J Wang, Kathleen M Broughton, Roberto Alvarez, Sailay Siddiqi, Rebeca Loaiza, Nicky Nguyen, Pearl Quijada, Natalie Gude, Mark A Sussman
PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28323513/transmembrane-tnf-dependent-uptake-of-anti-tnf-antibodies
#16
Arun Deora, Subramanya Hegde, Jacqueline Lee, Chee-Ho Choi, Qing Chang, Cheryl Lee, Lucia Eaton, Hua Tang, Dongdong Wang, David Lee, Mark Michalak, Medha Tomlinson, Qingfeng Tao, Nidhi Gaur, Bohdan Harvey, Shaun McLoughlin, Boris Labkovsky, Tariq Ghayur
TNF-alpha (TNF), a pro-inflammatory cytokine is synthesized as a 26 kDa protein, anchors in the plasma membrane as transmembrane TNF (TmTNF), and is subjected to proteolysis by the TNF-alpha converting enzyme (TACE) to release the 15 kDa form of soluble TNF (sTNF). TmTNF and sTNF interact with two distinct receptors, TNF-R1 (p55) and TNF-R2 (p75), to mediate the multiple biological effects of TNF described to date. Several anti-TNF biologics that bind to both forms of TNF and block their interactions with the TNF receptors are now approved for the treatment of a variety of immune-mediated diseases...
March 21, 2017: MAbs
https://www.readbyqxmd.com/read/28322559/identification-of-novel-inhibitors-of-leishmania-donovani-%C3%AE-glutamylcysteine-synthetase-using-structure-based-virtual-screening-docking-molecular-dynamics-simulation-and-in-vitro-studies
#17
Pragati Agnihotri, Arjun Kumar Mishra, Shikha Mishra, Vijay Kumar Sirohi, Amogh A Sahasrabuddhe, J Venkatesh Pratap
Trypansomatids maintain their redox balance by the trypanothione based redox system, enzymes of which exhibit differences from mammalian homologues. γ-glutamylcysteine synthetase (Gcs) is an essential enzyme of this pathway performing the first and rate limiting step. L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of Gcs induces toxicity in hosts infected with T. brucei underlining for novel Gcs inhibitors. The present study reports identification of Ld Gcs inhibitors using computational approaches and their experimental validation...
March 21, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28322331/targeted-disruption-of-tc-ptp-in-the-proliferative-compartment-augments-stat3-and-akt-signaling-and-skin-tumor-development
#18
Hyunseung Lee, Mihwa Kim, Minwoo Baek, Liza D Morales, Ik-Soon Jang, Thomas J Slaga, John DiGiovanni, Dae Joon Kim
Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2(fl/fl)) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322201/association-of-cardiac-galectin-3-expression-myocarditis-and-fibrosis-in-chronic-chagas-disease-cardiomyopathy
#19
Bruno Solano de Freitas Souza, Daniela Nascimento Silva, Rejane Hughes Carvalho, Gabriela Louise de Almeida Sampaio, Bruno Diaz Paredes, Luciana Aragão França, Carine Machado Azevedo, Juliana Fraga Vasconcelos, Cassio Santana Meira, Paulo Chenaud Neto, Simone Garcia Macambira, Kátia Nunes da Silva, Kyan James Allahdadi, Fabio Tavora, João David de Souza Neto, Ricardo Ribeiro Dos Santos, Milena Botelho Pereira Soares
Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts...
March 16, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28321811/interleukin-2-old-and-new-approaches-to-enhance-immune-therapeutic-efficacy
#20
Pooja Dhupkar, Nancy Gordon
Interleukin-2 (IL-2) is a very well-known cytokine that has been studied for the past 35 years. It plays a major role in the growth and proliferation of many immune cells such NK and T cells. It is an important immunotherapy cytokine for the treatment of various diseases including cancer. Systemic delivery of IL-2 has shown clinical benefit in renal cell carcinoma and melanoma patients. However, its use has been limited by the numerous toxicities encountered with the systemic delivery. Intravenous IL-2 causes the well-known "capillary leak syndrome," or the leakage of fluid from the circulatory system to the interstitial space resulting in hypotension (low blood pressure), edema, and dyspnea that can lead to circulatory shock and eventually cardiopulmonary collapse and multiple organ failure...
2017: Advances in Experimental Medicine and Biology
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