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https://www.readbyqxmd.com/read/29229829/psma-targeted-polyinosine-polycytosine-vector-induces-prostate-tumor-regression-and-invokes-an-antitumor-immune-response-in-mice
#1
Yael Langut, Alaa Talhami, Samarasimhareddy Mamidi, Alexei Shir, Maya Zigler, Salim Joubran, Anna Sagalov, Efrat Flashner-Abramson, Nufar Edinger, Shoshana Klein, Alexander Levitzki
There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine-polyethyleneglycol (PEI-PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29224663/obstruction-of-the-biliary-and-urinary-system
#2
William O'Connell, Jay Shah, Jason Mitchell, J David Prologo, Louis Martin, Michael J Miller, Jonathan G Martin
Biliary and urinary obstructions can be managed endoscopically or cystoscopically, surgically or by percutansous intervention or drainage. If the obtructed system is infected, emergent decompression is needed. Early recognition and treatment is paramount in both conditions. Acute cholangitis can present many different ways, from mild symptoms to fulminant sepsis. It is usually a result of ascending bacterial colonization and biliary obstruction resulting in bacterial overgrowth. Therefore, those patients with recent biliary instrumentation or previous biliary modification are at higher risk...
December 2017: Techniques in Vascular and Interventional Radiology
https://www.readbyqxmd.com/read/29221962/drug-delivery-and-tissue-engineering-to-promote-wound-healing-in-the-immunocompromised-host-current-challenges-and-future-directions
#3
Alexander M Tatara, Dimitrios P Kontoyiannis, Antonios G Mikos
As regenerative medicine matures as a field, more promising technologies are being translated from the benchtop to the clinic. However, many of these strategies are designed with otherwise healthy hosts in mind and validated in animal models without other co-morbidities. In reality, many of the patient populations benefiting from drug delivery and tissue engineering-based devices to enhance wound healing also have significant underlying immunodeficiency. Specifically, patients suffering from diabetes, malignancy, human immunodeficiency virus, post organ transplantation, and other compromised states have significant pleotropic immune defects that affect wound healing...
December 5, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29208633/in-vivo-visualization-of-beta-cells-by-targeting-of-gpr44
#4
Olof Eriksson, Peter Johnström, Zsolt Cselenyi, Mahabuba Jahan, Ram K Selvaraju, Marianne Jensen-Waern, Akihiro Takano, Maria Sörhede Winzell, Christer Halldin, Stanko Skrtic, Olle Korsgren
GPR44 expression has recently been described as highly beta cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes.A radiolabeled small molecule GPR44 antagonist, [11C]AZ12204657, was evaluated for visualization of beta cells in pigs and non-human primates by Positron Emission Tomography (PET) as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from non-diabetic and diabetic subjects, in combination with insulin staining, was performed to assess beta cell selectivity of the radiotracer...
December 5, 2017: Diabetes
https://www.readbyqxmd.com/read/29207803/radiological-manifestations-of-pulmonary-tuberculosis-a-comparative-study-between-immunocompromised-and-immunocompetent-patients
#5
Manoj Mathur, Rajesh K Badhan, Sudesh Kumari, Navkiran Kaur, Saryu Gupta
Introduction: Pulmonary tuberculosis has atypical radiological manifestations in patients with underlying immunocompromised disease like diabetes and human immunodeficient virus infection. Computed tomography has important role in such patients for early diagnosis of disease and management to minimize complication. Aim: To evaluate and compare the computed tomography chest features of pulmonary tuberculosis in between immunocompromised patients and immunocompetent patients...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29184888/targeting-dna-replication-and-repair-for-the-development-of-novel-therapeutics-against-tuberculosis
#6
REVIEW
Michael A Reiche, Digby F Warner, Valerie Mizrahi
Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), an infectious disease which results in approximately 10 million incident cases and 1.4 million deaths globally each year, making it the leading cause of mortality from infection. An effective frontline combination chemotherapy exists for TB; however, this regimen requires the administration of four drugs in a 2 month long intensive phase followed by a continuation phase of a further 4 months with two of the original drugs, and is only effective for the treatment of drug-sensitive TB...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29184449/diabetes-metabolic-syndrome-and-dyslipidemia-in-people-living-with-hiv-in-africa-re-emerging-challenges-not-to-be-forgotten
#7
REVIEW
Nazik Elmalaika Husain, Sufian K Noor, Wadie M Elmadhoun, Ahmed O Almobarak, Heitham Awadalla, Clare L Woodward, Dushyant Mital, Mohamed H Ahmed
Background: The current challenge in managing people living with human immunodeficiency virus (PLWHIV) includes the identification and monitoring for comorbid health risks associated with HIV and its treatment and longer survival. Dyslipidemia, diabetes mellitus and metabolic syndrome are increasingly seen in PLWHIV. Objective: In this narrative review, we aimed to summarize the current knowledge about diabetes, dyslipidemia and metabolic syndrome in PLWHIV in Africa and also to discuss the challenges that patients as well as health authorities in Africa may face...
2017: HIV/AIDS: Research and Palliative Care
https://www.readbyqxmd.com/read/29181100/kinesin-family-member-11-contributes-to-the-progression-and-prognosis-of-human-breast-cancer
#8
Yuan-Yuan Pei, Gao-Chi Li, Jian Ran, Feng-Xiang Wei
The present study aimed to clarify the association between kinesin family member 11 (KIF11) and human breast cancer, and the effect of KIF11 on breast cancer cell progression. Western blot analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, retroviral infection, immunohistochemistry staining, MTT assay, anchorage-independent growth ability assay and tumorigenicity assay were all used in the present study. Western blot and RT-qPCR analysis revealed that the expression of KIF11 was markedly increased in malignant cells compared with that in non-tumorous cells at the mRNA and protein level...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29161418/no-improvement-in-hemoglobin-a1c-following-hepatitis-c-viral-clearance-in-patients-with-and-without-hiv
#9
Chloe S Chaudhury, Julia Sheehan, Cheryl Chairez, Elizabeth Akoth, Chloe Gross, Rachel Silk, Sarah Kattakuzhy, Elana Rosenthal, Shyam Kottilil, Henry Masur, Colleen Hadigan
Hepatitis C clearance with directly acting antivirals (DAAs) may be associated with acute decreases in hemoglobin A1c (HbA1c). We prospectively evaluated 251 chronic hepatitis C virus (HCV)-infected subjects (31% human immunodeficiency virus [HIV] positive) pre- and post-DAA therapy (median follow-up 28 months). Changes in HbA1c and glucose were minimal and did not differ by sustained virologic response (SVR), HIV, diabetes, or fibrosis. Following SVR, mean change in HbA1c was -0.022 ± 0.53%; however, total and low-density lipoprotein cholesterol increased significantly...
November 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29159964/blocking-antibodies-induced-by-allergen-specific-immunotherapy-ameliorate-allergic-airway-disease-in-a-human-mouse-chimeric-model
#10
Caterina Vizzardelli, Miriam Gindl, Simone Roos, Christian Möbs, Birgit Nagl, Felix Zimmann, Veronika Sexl, Lukas Kenner, Alina Neunkirchner, Gerhard J Zlabinger, Winfried F Pickl, Wolfgang Pfützner, Barbara Bohle
BACKGROUND: Allergen-specific immunotherapy (AIT) induces specific blocking antibodies (Ab) which are claimed to prevent IgE-mediated reactions to allergens. Additionally, AIT modulates cellular responses to allergens, e.g. by desensitizing effector cells, inducing regulatory T and B lymphocytes and immune deviation. It is still enigmatic which of these mechanisms mediate(s) clinical tolerance. We sought to address the role of AIT-induced blocking Ab separately from cellular responses in a chimeric human/mouse model of respiratory allergy...
November 21, 2017: Allergy
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#11
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29114388/epistatic-interactions-between-mutations-of-taci-tnfrsf13b-and-tcf3-result-in-a-severe-primary-immunodeficiency-disorder-and-systemic-lupus-erythematosus
#12
Rohan Ameratunga, Wikke Koopmans, See-Tarn Woon, Euphemia Leung, Klaus Lehnert, Charlotte A Slade, Jessica C Tempany, Anselm Enders, Richard Steele, Peter Browett, Philip D Hodgkin, Vanessa L Bryant
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29113445/the-noncommunicable-disease-outcomes-of-primary-healthcare-screening-in-two-rural-subdistricts-of-the-eastern-cape-province-south-africa
#13
Paul Rheeder, Angela A Morris-Paxton, Rose-Marie G Ewing, Dillon Woods
BACKGROUND: Middle and lower income countries are challenged with a double burden of disease: while still coping with the onslaught of Human Immunodeficiency Virus (HIV) and increasing levels of tuberculosis (TB), there is a considerable increase in the level of noncommunicable diseases (NCDs). The poor are especially disadvantaged and are at an increased risk for NCDs. Adequate healthcare resources for this environment can only be allocated once the extent and exact nature of the problem is determined...
October 31, 2017: African Journal of Primary Health Care & Family Medicine
https://www.readbyqxmd.com/read/29113169/lentivirus-mediated-rna-interference-inhibits-the-tumorigenicity-of-cluster-of-differentiation-44-tumor-cells-in-hypopharyngeal-cancer
#14
Chenling Shen, Bin Ye, Haixia Hu, Chen Nie, Yan Ma, Jingrong Lv, Hao Wu, Mingliang Xiang
The present study aimed to investigate whether the inhibition of cluster of differentiation (CD)44 expression reduces the tumorigenicity of CD44(+) cancer stem cells in hypopharyngeal cancer. To assess this, effective recombinant CD44 short hairpin RNA-expressing lentiviruses were produced. Lentivirus-mediated RNA interference (RNAi) was then used to knockdown CD44 gene expression in the hypopharyngeal cancer FaDu cell line. The viability of FaDu cells in the two control groups and the RNAi group (RNAi-CD44 lentiviral vector) was detected using an MTT assay in vitro...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29110756/apol1-nephropathy-a-population-genetics-and-evolutionary-medicine-detective-story
#15
REVIEW
Etty Kruzel-Davila, Walter G Wasser, Karl Skorecki
Common DNA sequence variants rarely have a high-risk association with a common disease. When such associations do occur, evolutionary forces must be sought, such as in the association of apolipoprotein L1 (APOL1) gene risk variants with nondiabetic kidney diseases in populations of African ancestry. The variants originated in West Africa and provided pathogenic resistance in the heterozygous state that led to high allele frequencies owing to an adaptive evolutionary selective sweep. However, the homozygous state is disadvantageous and is associated with a markedly increased risk of a spectrum of kidney diseases encompassing hypertension-attributed kidney disease, focal segmental glomerulosclerosis, human immunodeficiency virus nephropathy, sickle cell nephropathy, and progressive lupus nephritis...
November 2017: Seminars in Nephrology
https://www.readbyqxmd.com/read/29105400/effects-of-klf4-and-c-myc-knockdown-on-pluripotency-maintenance-in-porcine-induced-pluripotent-stem-cell
#16
Yu-Jing Liao, Yi-Shiou Chen, Ja-Xin Lee, Lih-Ren Chen, Jenn-Rong Yang
OBJECTIVES: The importance of Oct4 and Sox2 in maintaining pluripotency and self-renewal is well-understood, but the functions of Klf4 and c-Myc has not been fully investigated. In the present study, we attempted to determine the roles of Klf4 and c-Myc on pluripotency maintenance of porcine induced pluripotent stem (piPS) cells. MATERIALS AND METHODS: In this experimental study, we performed short hairpin RNA (shRNA) to knock down the Klf4 and c-Myc functions of piPS cells and examined pluripotency markers and teratoma formation to evaluate piPS cell pluripotency...
January 2018: Cell Journal
https://www.readbyqxmd.com/read/29102562/prostaglandin-e2-increases-lentiviral-vector-transduction-efficiency-of-adult-human-hematopoietic-stem-and-progenitor-cells
#17
Garrett C Heffner, Melissa Bonner, Lauryn Christiansen, Francis J Pierciey, Dakota Campbell, Yegor Smurnyy, Wenliang Zhang, Amanda Hamel, Seema Shaw, Gretchen Lewis, Kendrick A Goss, Olivia Garijo, Bruce E Torbett, Holly Horton, Mitchell H Finer, Philip D Gregory, Gabor Veres
Gene therapy currently in development for hemoglobinopathies utilizes ex vivo lentiviral transduction of CD34(+) hematopoietic stem and progenitor cells (HSPCs). A small-molecule screen identified prostaglandin E2 (PGE2) as a positive mediator of lentiviral transduction of CD34(+) cells. Supplementation with PGE2 increased lentiviral vector (LVV) transduction of CD34(+) cells approximately 2-fold compared to control transduction methods with no effect on cell viability. Transduction efficiency was consistently increased in primary CD34(+) cells from multiple normal human donors and from patients with β-thalassemia or sickle cell disease...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29078283/humanized-mouse-model-supports-development-function-and-tissue-residency-of-human-natural-killer-cells
#18
Dietmar Herndler-Brandstetter, Liang Shan, Yi Yao, Carmen Stecher, Valerie Plajer, Melanie Lietzenmayer, Till Strowig, Marcel R de Zoete, Noah W Palm, Jie Chen, Catherine A Blish, Davor Frleta, Cagan Gurer, Lynn E Macdonald, Andrew J Murphy, George D Yancopoulos, Ruth R Montgomery, Richard A Flavell
Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 (IL15) and human signal regulatory protein alpha (SIRPA) knock-in mouse on a Rag2-/- Il2rg-/- background (SRG-15)...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29076676/adrenal-insufficiency-in-pakistani-hiv-infected-patients
#19
Bahjat Afreen, Khurshid Ahmed Khan, Amna Riaz
BACKGROUND: Adrenal insufficiency (AI) is the most common endocrine complication among patients with AIDS/HIV infection and there are number of causes of AI in HIV patients. Human immunodeficiency virus directly as well as indirectly destroys adrenal glands. The estimates of its prevalence and severity vary. AI is the most life threatening but readily correctable endocrine complication that occurs in persons with HIV infection. This study was carried out to determine the frequency of Adrenal Insufficiency in HIV patients and their clinical features as proper diagnosis and timely treatment have been shown to improve quality of life and long-term mortality in AIDS patients...
July 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/29068151/cytomegalovirus-retinitis-in-hiv-negative-patients-associated-conditions-clinical-presentation-diagnostic-methods-and-treatment-strategy
#20
REVIEW
Yinon Shapira, Michael Mimouni, Vicktoria Vishnevskia-Dai
In recent years, numerous reports have tied cytomegalovirus retinitis (CMVR) with multiple systemic conditions in the absence of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). These range from reports in apparently healthy individuals, through conditions rendering limited immune dysfunction such as advanced age and diabetes mellitus, and finally severe immune dysfunction such as in haematological and rheumatological conditions. Reports are also emerging, suggesting that induced local ocular immunosuppression is a risk factor for CMVR...
October 25, 2017: Acta Ophthalmologica
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