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Initial host-pathogen interactions explained by the Organism Prearranged Recognition Theory: fundamental role of saccharides
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作者 Luz P.Blanco 《Life Research》 2024年第3期9-23,共15页
Herein based on literature available a hypothesis is provided about molecular basis for initial events in establishment interactions.This hypothesis asserts that:"recognition and interaction that occur between or... Herein based on literature available a hypothesis is provided about molecular basis for initial events in establishment interactions.This hypothesis asserts that:"recognition and interaction that occur between organisms is prearranged.There are membrane receptors with or without soluble components derived from the respective organisms that bridge specific interactions".Organisms'prearranged recognition theory(OPRT)can be specifically applied to host-microbe interactions where most microbes are coated(opsonised)by soluble components(opsonins)from the host,but there are also some microbes that can bypass host opsonization expressing receptors for the host cells or secreting host’s opsonin-like molecules.The receptors involved in organism's interactions,their specificity and repertoire depend on saccharides from glycoproteins,glycolipids,and polysaccharides(glycans)which are abundant extracellular components.Based in OPRT is possible to explain species-specific interactions and several other phenomena,such as hyper-infectivity,tissue tropism,differential sensitivity to disease depending on type O-blood,and tumoral cell promiscuity.The lipid raft domain in cellular membrane is proposed as the main location where interactions will trigger cellular responses.Possible scientific and biotechnology applications and alternative routes to modify organism's interactions and consequences are discussed.It is a novel hypothesis regarding the degree to which an organism's interactions are prearranged and the role of saccharides epitopes. 展开更多
关键词 Species-specificity saccharides extracellular-matrix HOST-PATHOGEN ANTIBODIES
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Mitigating osteonecrosis of the jaw(ONJ) through preventive dental care and understanding of risk factors 被引量:3
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作者 Jason TWan Douglas MSheeley +1 位作者 Martha JSomerman Janice SLee 《Bone Research》 CAS CSCD 2020年第1期14-25,共12页
It is well established that alterations in phosphate metabolism have a profound effect on hard and soft tissues of the oral cavity. The present-day clinical form of osteonecrosis of the jaw(ONJ) was preceded by phosph... It is well established that alterations in phosphate metabolism have a profound effect on hard and soft tissues of the oral cavity. The present-day clinical form of osteonecrosis of the jaw(ONJ) was preceded by phosphorus necrosis of the jaw, ca. 1860. The subsequent removal of yellow phosphorus from matches in the early 20 th century saw a parallel decline in "phossy jaw" until the early 2000 s, when similar reports of unusual jaw bone necrosis began to appear in the literature describing jaw necrosis in patients undergoing chemotherapy and concomitant steroid and bisphosphonate treatment. Today, the potential side effect of ONJ associated with medications that block osteoclast activity(antiresorptive) is well known, though the mechanism remains unclear and the management and outcomes are often unsatisfactory. Much of the existing literature has focused on the continuing concerns of appropriate use of bisphosphonates and other antiresorptive medications, the incomplete or underdeveloped research on ONJ, and the use of drugs with anabolic potential for treatment of osteoporosis. While recognizing that ONJ is a rare occurrence and ONJ-associated medications play an important role in fracture risk reduction in osteoporotic patients, evidence to date suggests that health care providers can lower the risk further by dental evaluations and care prior to initiating antiresorptive therapies and by monitoring dental health during and after treatment. This review describes the current clinical management guidelines for ONJ, the critical role of dental-medical management in mitigating risks, and the current understanding of the effects of predominantly osteoclast-modulating drugs on bone homeostasis. 展开更多
关键词 DRUGS METABOLISM alterations
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Meeting report:a hard look at the state of enamel research 被引量:3
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作者 ophir d klein olivier duverger +11 位作者 wendy shaw rodrigo s lacruz derk joester janet moradian-oldak megan k pugach j timothy wright sarah e millar ashok b kulkarni john d bartlett thomas gh diekwisch pamela den besten james p simmer 《International Journal of Oral Science》 SCIE CAS CSCD 2017年第4期193-199,共7页
The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research (NI... The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field. 展开更多
关键词 ENAMEL mineralized tissue MINERALIZATION AMELOBLAST stem cell
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Laser capture microdissection enables cellular and molecular studies of tooth root development 被引量:1
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作者 Jian-Xun Sun Orapin V Horst +3 位作者 Roger Bumgarner Bryce Lakely Martha J Somerman Hai Zhang 《International Journal of Oral Science》 SCIE CAS CSCD 2012年第1期7-13,共7页
Epithelial-mesenchymal interactions(EMIs) are critical for tooth development.Molecular mechanisms mediating these interactions in root formation is not well understood.Laser capture microdissection(LCM) and subseq... Epithelial-mesenchymal interactions(EMIs) are critical for tooth development.Molecular mechanisms mediating these interactions in root formation is not well understood.Laser capture microdissection(LCM) and subsequent microarray analyses enable large scale in situ molecular and cellular studies of root formation but to date have been hindered by technical challenges of gaining intact histological sections of non-decalcified mineralized teeth or jaws with well-preserved RNA.Here,we describe a new method to overcome this obstacle that permits LCM of dental epithelia,adjacent mesenchyme,odontoblasts and cementoblasts from mouse incisors and molars during root development.Using this method,we obtained RNA samples of high quality and successfully performed microarray analyses.Robust differences in gene expression,as well as genes not previously associated with root formation,were identified.Comparison of gene expression data from microarray with real-time reverse transcriptase polymerase chain reaction(RT-PCR) supported our findings.These genes include known markers of dental epithelia,mesenchyme,cementoblasts and odontoblasts,as well as novel genes such as those in the fibulin family.In conclusion,our new approach in tissue preparation enables LCM collection of intact cells with well-preserved RNA allowing subsequent gene expression analyses using microarray and RT-PCR to define key regulators of tooth root development. 展开更多
关键词 gene laser capture microdissection microarray PCR root
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Utility of positron emission tomography-magnetic resonance imaging in musculoskeletal imaging
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作者 Ammar A Chaudhry Maryam Gul +3 位作者 Elaine Gould Mathew Teng Kevin Baker Robert Matthews 《World Journal of Radiology》 CAS 2016年第3期268-274,共7页
Differentiation between neoplastic and nonneoplastic conditions magnetic resonance imaging(MRI) has established itself as one of the key clinical tools in evaluation of musculoskeletal pathology. However, MRI still ha... Differentiation between neoplastic and nonneoplastic conditions magnetic resonance imaging(MRI) has established itself as one of the key clinical tools in evaluation of musculoskeletal pathology. However, MRI still has several key limitations which require supplemental information from additional modalities to complete evaluation of various disorders. This has led to the development hybrid positron emission tomography(PET)-MRI which is rapidly evolving to address key clinical questions by using the morphological strengths of MRI and functional information of PET imaging. In this article, we aim to review physical principles and techniques of PET-MRI and discuss clinical utility of functional information obtained from PET imaging and structural information obtained from MRI imaging for the evaluation of musculoskeletal pathology. More specifically, this review highlights the role of PET-MRI in musculoskeletal oncology including initial diagnosis and staging, treatment planning and posttreatment follow-up. Also we will review utility of PET-MRI in evaluating musculoskeletal infections(especially in the immunocompromised and diabetics) and inflammatory condition. Additionally, common pitfalls of PET-MRI will be addressed. 展开更多
关键词 MAGNETIC RESONANCE IMAGING Osteosarcoma POSITRON EMISSION tomography-magnetic RESONANCE IMAGING Osteomyelitis POSITRON EMISSION tomographycomputed TOMOGRAPHY POSITRON EMISSION TOMOGRAPHY Multiple myeloma Lymphoma
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Competition between TRAF2 and TRAF6 Regulates NF-κB Activation in Human B Lymphocytes 被引量:6
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作者 Wen Zhang Xuan Zhang +4 位作者 Xiao-li Wu Liu-sheng He Xiao-feng Zeng Amrie C. Grammer Peter E. Lipsky 《Chinese Medical Sciences Journal》 CAS CSCD 2010年第1期1-12,共12页
Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell li... Objective To investigate the role of TNF receptor-associated factor 2 (TRAF-2) and TRAF6 in CD40-induced nuclear factor-κB (NF-κB) signaling pathway and whether CD40 signaling requires TRAF2. Methods Human B cell lines were transfected with plasmids expressing wild type TRAF2 or dominant negative TRAF2,TRAF2-shRNA,or TRAF6-shRNA. The activation of NF-κB was detected by Western blot,kinase assay,transfactor enzyme-linked immunosorbent assay (ELISA),and fluorescence resonance energy transfer (FRET). Analysis of the role of TRAF-2 and TRAF-6 in CD40-mediated NF-κB activity was examined following stimulation with recombinant CD154. Results TRAF2 induced activity of IκB-kinases (IKKα,IKKi/ε),phosphorylation of IκBα,as well as nuclear translocation and phosphorylation of p65/RelA. In contrast,TRAF6 strongly induced NF-κB activation and nuclear translocation of p65 as well as p50 and c-Rel. Engagement of CD154-induced nuclear translocation of p65 was inhibited by a TRAF6-shRNA,but conversely was enhanced by a TRAF2-shRNA. Examination of direct interactions between CD40 and TRAFs by FRET documented that both TRAF2 and TRAF6 directly interacted with CD40. However,the two TRAFs competed for CD40 binding. Conclusions These results indicate that TRAF2 can signal in human B cells,but it is not essential for CD40-mediated NF-κB activation. Moreover,TRAF2 can compete with TRAF6 for CD40 binding,and thereby limit the capacity of CD40 engagement to induce NF-κB activation. 展开更多
关键词 human B lymphocytes TNF receptor-associated factor 2 TNF receptor-associated factor 6 IκB kinase IΚBΑ P65
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Cementomimetics——constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides 被引量:6
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作者 Mustafa Gungormus Ersin E Oren +7 位作者 Jeremy A Horst Hanson Fong Marketa Hnilova Martha J Somerman Malcolm L Snead Ram Samudrala Candan Tamerler Mehmet Sarikaya 《International Journal of Oral Science》 SCIE CAS CSCD 2012年第2期69-77,共9页
Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavio... Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides (HABPs) previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 (ADP5) was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbiditv associated with tooth loss. 展开更多
关键词 AMELOGENIN amelogenin-derived peptides bioinformatics biomineralization cementomimetics CEMENTUM demineral-ization REMINERALIZATION
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Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis 被引量:5
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作者 Laura E Zweifler Mudita K Patel +4 位作者 Francisco H Nociti Jr Helen F Wimer Jose L Milln Martha J Somerman Brian L Foster 《International Journal of Oral Science》 SCIE CAS CSCD 2015年第1期27-41,共15页
Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cement... Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate (Pi) to mineral inhibitor pyrophosphate (PPi), where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enppl null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enppl gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected. 展开更多
关键词 CEMENTUM bone ectonucleotide pyrophosphatase phosphodiesterase 1 periodontal ligament progressive ankylosis protein tissue-nonspecific aJkalJne phosphatase
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Multicentric Reticulohistiocytosis (MRH): First Case Report with Tenosynovial Fluid Analysis and Tenosynovial Histology Demonstrating the Classic Histologic Findings
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作者 Megha Sawhney Peter Levitin 《Open Journal of Rheumatology and Autoimmune Diseases》 2016年第2期23-25,共3页
Multicent ricreticulohistiocytosis (MRH) is a rare systemic disease of unclear etiology characterized by destructive, deforming arthritis, nodules in the skin, mucous membrane and internal organs and can be associated... Multicent ricreticulohistiocytosis (MRH) is a rare systemic disease of unclear etiology characterized by destructive, deforming arthritis, nodules in the skin, mucous membrane and internal organs and can be associated with malignancy. The tenosynovial fluid and tenosynovium histologic findings have not been reported in any case reports of MRH in the literature. To our knowledge, this is the first case report of tenosynovial fluid and tenosynovium demonstrating the classic histologic findings of histiocytes with a foamy eosinophilic cytoplasm. This case also demonstrates a non-deforming arthritis. 展开更多
关键词 TENOSYNOVITIS Tenosynovial Fluid Analysis
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Fever of unknown origin:a retrospective review of pediatric patients from an urban,tertiary care center in Washington,DC 被引量:2
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作者 Ann Marie Szymanski Hugo Clifford Tova Ronis 《World Journal of Pediatrics》 SCIE CAS CSCD 2020年第2期177-184,共8页
Background Fever of unknown origin(FUO)continues to challenge clinicians to determine an etiology and the need for treatment.This study explored the most common etiologies,characteristics,and average cost of hospitali... Background Fever of unknown origin(FUO)continues to challenge clinicians to determine an etiology and the need for treatment.This study explored the most common etiologies,characteristics,and average cost of hospitalization for FUO in a pediatric population at an urban,tertiary care hospital in Washington,DC.Methods Records from patients admitted to Children's National Health System between September 2008 and April 2014 with an admission ICD-9 code for fever(780.6)were reviewed.The charts of patients 2-18 years of age with no underlying diagnosis and a temperature greater than 38.3℃for 7 days or more at time of hospitalization were included.Final diagnoses,features of admission,and total hospital charges were abstracted.Results 110 patients qualified for this study.The majority of patients(n=42,38.2%)were discharged without a diagnosis.This was followed closely by infection,accounting for 37.2%(n=41)of patients.Rheumatologic disease was next(n=16,14.5%),followed by miscellaneous(n=6,5.4%)and oncologic diagnoses(n=5,4.5%).The average cost of hospitalization was 40,295 US dollars.Conclusions This study aligns with some of the most recent publications which report undiagnosed cases as the most common outcome in patients hospitalized with FUO.Understanding that,often no diagnosis is found may reassure patients,families,and clinicians.The cost associated with hospitalization for FUO may cause clinicians to reconsider inpatient admission for diagnostic work-up of fever,particularly given the evidence demonstrating that many patients are discharged without a diagnosis. 展开更多
关键词 FEVER Fever of unknown origin INFECTION Healthcare costs
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