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https://www.readbyqxmd.com/read/28927259/generation-diversity-determination-and-application-to-antibody-selection-of-a-human-na%C3%A3-ve-fab-library
#1
Sangkyu Kim, Insoo Park, Seung Gu Park, Seulki Cho, Jin Hong Kim, Nagesh S Ipper, Sun Shim Choi, Eung Suk Lee, Hyo Jeong Hong
We constructed a large naïve human Fab library (3 x 1010 colonies) from the lymphocytes of 809 human donors, assessed available diversities of the heavy-chain variable (VH) and κ light-chain variable (VK) domain repertoires, and validated the library by selecting Fabs against 10 therapeutically relevant antigens by phage display. We obtained a database of unique 7,373 VH and 41,804 VK sequences by 454 pyrosequencing, and analyzed the repertoires. The distribution of VH and VK subfamilies and germline genes in our antibody repertoires slightly differed from those in earlier published natural antibody libraries...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28927257/differential-and-correlated-expression-of-p16-p21-p27-p38-in-mammary-gland-tumors-of-aged-dogs
#2
Hyun-Woo Kim, Jong-Il Shin, Byung-Joon Seung, Jung-Hyung Ju, Jung-Hyang Sur
The inhibitory effect of neutering on mammary gland tumor development in dogs is well known. However, we found that the effect of neutering on tumor malignancy may be altered by aging. Therefore, we aimed to characterize mammary tumors in aged dogs by analyzing the expression of cellular senescence markers, from the viewpoint of senescence. The expression of p16, p38, p21, and p27 antibodies, which are senescence-associated markers, was detected in canine mammary tumors of aged dogs via immunohistochemistry...
September 20, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28927202/role-of-molecular-biomarkers-in-the-diagnosis-of-invasive-fungal-diseases-in-children
#3
Anna R Huppler, Brian T Fisher, Thomas Lehrnbecher, Thomas J Walsh, William J Steinbach
Invasive fungal diseases are important clinical problems that are often complicated by severe illness and therefore the inability to use invasive measures to definitively diagnose the disease. Tests for a range of fungal biomarkers that do not require an invasive sample-collection procedure have been incorporated into adult clinical practice, but pediatric data and pediatric-specific recommendations for some of these diagnostic tools are lacking. In this review, we summarize the published literature and contemporary strategies for using the biomarkers galactomannan, (1→3)-β-d-glucan, Candida mannan antigen and anti-mannan antibody, and fungal polymerase chain reaction for diagnosing invasive fungal disease in children...
September 1, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28927164/hyalinizing-clear-cell-carcinoma-of-the-lung-case-report-and-review-of-the-literature
#4
Susanne K Jeffus, Jerad M Gardner, Matthew A Steliga, Akeesha A Shah, Edward B Stelow, Konstantinos Arnaoutakis
Objectives: Hyalinizing clear cell carcinoma (HCCC) is common in head and neck sites but extremely rare in the lung. This case report describes an HCCC in the lung of a 54-year-old female patient. Methods: We summarize the histomorphologic, immunophenotypic, and molecular features for our and three previously reported HCCCs of the lung with emphasis on potential diagnostic pitfalls. Results: Sections of a well-circumscribed 3.5-cm lung mass were characterized by a bronchocentric tumor growing in sheets, nests, and cords in a background of hyalinized stroma...
July 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28927079/new-use-of-microsatellite-instability-analysis-in-endometrial-cancer
#5
Haruko Kunitomi, Kouji Banno, Megumi Yanokura, Takashi Takeda, Moito Iijima, Kanako Nakamura, Miho Iida, Masataka Adachi, Keiko Watanabe, Yusuke Matoba, Yusuke Kobayashi, Eiichiro Tominaga, Daisuke Aoki
The increasing incidence of obesity and diabetes due to changes in diet, earlier menarche, delayed menopause, late marriage, and declining birth rate have resulted in an increase in the number of endometrial cancer cases over the last few decades. Although surgical therapy is sufficient for early endometrial cancer, there is no effective therapy for patients with advanced and recurrent endometrial cancer. The oncogenic mechanism of endometrial cancer involves microsatellite instability (MSI) caused by dysfunction of DNA mismatch repair genes in 30% of patients...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926977/mouse-monoclonal-antibodies-generated-from-full-length-human-cereblon-detection-of-cereblon-protein-in-patients-with-multiple-myeloma
#6
Xiubao Chang, Qinqin Xu, Yuexian Hou, Cynthia Li, Ye Xu, A Keith Stewart
Immunomodulatory drugs (IMiDs) are profoundly active compounds in the treatment of patients with multiple myeloma (MM). However, despite the fact that treatment with IMiDs has dramatically improved survival for patients with MM, the majority of MM patients develop IMiDs resistance over time. We have found that expression of functional cereblon is required for IMiDs' action. In addition, it has been reported that cells expressing high levels of cereblon are resistant to proteasome inhibitor, implying that patients with high levels of cereblon should be resistant to proteasome inhibitor...
September 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926962/anti-nkg2d-mab-a-new-treatment-for-crohn-s-disease
#7
REVIEW
Kasper Vadstrup, Flemming Bendtsen
Crohn's disease (CD) and ulcerative colitis (UC) are immunologically-mediated, debilitating conditions resulting from destructive inflammation of the gastrointestinal tract. The pathogenesis of IBD is incompletely understood, but is considered to be the result of an abnormal immune response with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56⁺ T, and CD8⁺ T cells...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926956/carbonic-anhydrase-inhibition-and-the-management-of-hypoxic-tumors
#8
REVIEW
Claudiu T Supuran
Hypoxia and acidosis are salient features of many tumors, leading to a completely different metabolism compared to normal cells. Two of the simplest metabolic products, protons and bicarbonate, are generated by the catalytic activity of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), with at least two of its isoforms, CA IX and XII, mainly present in hypoxic tumors. Inhibition of tumor-associated CAs leads to an impaired growth of the primary tumors, metastases and reduces the population of cancer stem cells, leading thus to a complex and beneficial anticancer action for this class of enzyme inhibitors...
September 16, 2017: Metabolites
https://www.readbyqxmd.com/read/28926954/evidence-for-complex-formation-of-the-bacillus-cereus-haemolysin-bl-components-in-solution
#9
Franziska Tausch, Richard Dietrich, Kristina Schauer, Robert Janowski, Dierk Niessing, Erwin Märtlbauer, Nadja Jessberger
Haemolysin BL is an important virulence factor regarding the diarrheal type of food poisoning caused by Bacillus cereus. However, the pathogenic importance of this three-component enterotoxin is difficult to access, as nearly all natural B. cereus culture supernatants additionally contain the highly cytotoxic Nhe, the second three-component toxin involved in the aetiology of B. cereus-induced food-borne diseases. To better address the toxic properties of the Hbl complex, a system for overexpression and purification of functional, cytotoxic, recombinant (r)Hbl components L₂, L₁ and B from E...
September 16, 2017: Toxins
https://www.readbyqxmd.com/read/28926943/monoclonal-antibodies-in-preclinical-eae-models-of-multiple-sclerosis-a-systematic-review
#10
REVIEW
Katja Schmitz, Gerd Geisslinger, Irmgard Tegeder
Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926673/combinatorial-genome-and-protein-engineering-yields-monoclonal-antibodies-with-hypergalactosylation-from-cho-cells
#11
Cheng-Yu Chung, Qiong Wang, Shuang Yang, Sean A Ponce, Brian J Kirsch, Hui Zhang, Michael J Betenbaugh
One of the key quality attributes of monoclonal antibodies is the glycan pattern and distribution. Two terminal galactose residues typically represent a small fraction of the total glycans from antibodies. However, antibodies with defined glycosylation properties including enhanced galactosylation have been shown to exhibit altered properties for these important biomedical modalities. In this study, the disruption of two α-2,3 sialyltransferases (ST3GAL4 and ST3GAL6) from Chinese Hamster Ovary (CHO) cells was combined with protein engineering of the Fc region to generate an IgG containing 80% bigalactosylated and fucosylated (G2F) glycoforms...
July 7, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28926602/autoimmune-disease-mouse-model-exhibits-pulmonary-arterial-hypertension
#12
Koichi Sugimoto, Kazuhiko Nakazato, Akihiko Sato, Satoshi Suzuki, Akiomi Yoshihisa, Takeshi Machida, Shu-Ichi Saitoh, Hideharu Sekine, Yasuchika Takeishi
BACKGROUND: Pulmonary arterial hypertension is often associated with connective tissue disease. Although there are some animal models of pulmonary hypertension, an autoimmune disease-based model has not yet been reported. MRL/lpr mice, which have hypergammaglobulinemia, produce various autoimmune antibodies, and develop vasculitis and nephritis spontaneously. However, little is known about pulmonary circulation in these mice. In the present study, we examined the pulmonary arterial pressure in MRL/lpr mice...
2017: PloS One
https://www.readbyqxmd.com/read/28926601/utility-of-abdominal-skin-plus-subcutaneous-fat-and-rectal-mucosal-biopsy-in-the-diagnosis-of-al-amyloidosis-with-renal-involvement
#13
Ting Li, Xianghua Huang, Shuiqin Cheng, Liang Zhao, Guisheng Ren, Wencui Chen, Qingwen Wang, Caihong Zeng, Zhihong Liu
OBJECTIVES: Skin fat biopsy of the abdominal wall is a simple and safe method for detecting amyloidosis, and rectal mucosal biopsy is also frequently used for screening for the disease; however, the sensitivity of these approaches has not been fully studied. The aim of this study was to evaluate the efficacy of skin fat biopsy combined with rectal mucosal biopsy as a screening procedure for the diagnosis of systemic immunoglobulin light-chain (AL) amyloidosis. METHODS: We retrospectively analyzed 224 AL amyloidosis patients confirmed by renal biopsy, including a test group of 165 patients and validation group of 59 patients...
2017: PloS One
https://www.readbyqxmd.com/read/28926521/blockade-of-hla-antibody-triggered-classical-complement-activation-in-sera-from-subjects-dosed-with-the-anti-c1s-monoclonal-antibody-tnt009-results-from-a-randomized-first-in-human-phase-1-trial
#14
Jakob Mühlbacher, Bernd Jilma, Markus Wahrmann, Johann Bartko, Farsad Eskandary, Christian Schörgenhofer, Michael Schwameis, Graham C Parry, James C Gilbert, Sandip Panicker, Georg A Böhmig
BACKGROUND: Complement may play a key role in antibody-mediated rejection. A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1. METHODS: In this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody. Sixty-four adult healthy volunteers received either single (n = 48; 7 consecutive cohorts, 0...
October 2017: Transplantation
https://www.readbyqxmd.com/read/28926420/seronegative-paraneoplastic-limbic-encephalitis-associated-with-thymoma
#15
Jaime Toro, David Cuellar-Giraldo, Alejandra Duque, Karla Minota, Jorge Patiño, Manuel García
Paraneoplastic limbic encephalitis is an autoimmune syndrome characterized by the acute or subacute onset of encephalopathy, memory loss, confusion, temporal lobe seizures, and behavioral and mood changes. Although most patients with paraneoplastic limbic encephalitis have antineuronal antibodies, advances in the field now permit the diagnosis without autoantibody test results. In this case illustrating the new diagnostic criteria, we report a 70-year-old woman who was brought to the emergency room after the acute onset of cognitive impairment, altered mental status, and choreoathetoid movements...
September 2017: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
https://www.readbyqxmd.com/read/28926419/peduncular-hallucinosis-and-autonomic-dysfunction-in-anti-aquaporin-4-antibody-syndrome
#16
Renee Berry, Peter K Panegyres
Neuromyelitis optica is a rare, severe inflammatory demyelinating disease of the central nervous system, previously described as affecting only the optic nerve and spinal cord. Since the discovery of a highly specific autoantibody, anti-aquaporin-4, lesions are now recognized outside these regions. We report a man with severe, debilitating symptoms resulting from a symptomatic lesion within the diencephalon, manifesting with abnormal circadian rhythms, autonomic dysfunction, behavioral disturbance, and complex visual hallucinations...
September 2017: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
https://www.readbyqxmd.com/read/28926408/serum-glycan-binding-igg-antibodies-in-hiv-1-infection-and-during-the-development-of-broadly-neutralizing-responses
#17
Cathrine Scheepers, Sudipa Chowdhury, W Shea Wright, Christopher T Campbell, Nigel J Garrett, Quarraisha Abdool Karim, Salim S Abdool Karim, Penny L Moore, Jeffrey C Gildersleeve, Lynn Morris
BACKGROUND: The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses. However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV infected individuals. We aimed to determine whether anti-glycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs. METHODS: IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids and Tn-peptides...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926399/natural-killer-cells-in-hiv-1-infection-and-therapy
#18
Joanna Mikulak, Ferdinando Oriolo, Elisa Zaghi, Clara Di Vito, Domenico Mavilio
: Natural killer (NK) cells are important effectors of innate immunity playing a key role in the eradication and clearance of viral infections. Over the recent years, several studies have shown that HIV-1 pathologically changes NK cell homeostasis and hampers their antiviral effector functions. Moreover, high levels of chronic HIV-1 viremia markedly impair those NK cell regulatory features that normally regulate the cross-talks between innate and adaptive immune responses. These pathogenic events take place early in the infection and are associated with a pathologic redistribution of NK cell subsets that includes the expansion of anergic CD56 NK cells with an aberrant repertoire of activating and inhibitory receptors...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926356/development-of-bell-s-palsy-after-treatment-with-ipilimumab-and-nivolumab-for-metastatic-melanoma-a-case-report
#19
Julia M Zecchini, Sara Kim, Kendra Yum, Philip Friedlander
Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-related adverse events (irAEs) of gastrointestinal, dermatologic, and endocrine origin are commonly seen, ranging between 18% and 44%, with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Rare irAEs include neurological, renal, and hematologic toxicities. Bell's palsy is a form of neurological toxicity that presents as an idiopathic paralysis of the muscles on one side of the face...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28926326/prevalence-of-hepatitis-a-virus-antibody-in-portuguese-travelers-a-new-paradigm
#20
Sónia Rocha, Sandra Tejo, Eugénia Ferreira, Luís Trindade, Eduardo Rabadão, Nuno Marques, José Saraiva da Cunha
INTRODUCTION: In Portugal, the prevalence of hepatitis A virus infection has decreased in the past decades, especially in young adults. The aim of this study was to detect the prevalence of antibody to hepatitis A virus in a population observed in our Travel Clinic. MATERIAL AND METHODS: Antibodies against hepatitis A, hepatitis B, hepatitis C and human immunodeficiency virus were tested using standard enzyme immunoassay in patients older than 18. The exclusion criteria were: prior vaccination for hepatitis A virus, previous diagnosis of infection with hepatitis B virus, hepatitis C virus and/or human immunodeficiency virus, foreign travelers and long-term expatriates...
August 31, 2017: Acta Médica Portuguesa
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