Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by presence of noncaseating granulomas in the involved organs. The pulmonary interstitium is most commonly affected but extrapulmonary involvement can occur in almost any other organ system. Such an involvement can occur with or without the presence of pulmonary involvement, but isolated extrapulmonary involvement has been noted only in around 10% of cases. Isolated splenomegaly is very rare and an uncommon presentation of sarcoidosis. It is clinically challenging because of the extensive differential diagnosis. Among the many considerations are hematologic malignancies, primary splenic or metastatic tumors, infiltrative disorders, inflammatory disorders, and infections. We hereby discuss an interesting case of a 40-year-old female with isolated splenic sarcoidosis.
https://ift.tt/2ySN7Qt
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 4 Νοεμβρίου 2018
Sarcoidosis and Its Splenic Wonder: A Rare Case of Isolated Splenic Sarcoidosis
Lambda interferons come to light: dual function cytokines mediating antiviral immunity and damage control
Evangelos Andreakos | Ivan Zanoni | Ioanna E Galani
https://ift.tt/2JCAqgQ
IgE blockade during food allergen ingestion enhances the induction of inhibitory IgG antibodies
IgE-mediated food allergy is a growing problem with no curative therapy1. Oral immunotherapy (OIT) has shown promise, but its utility is limited by reactions during treatment and a lack of sustained protection following therapy. IgE antibodies trigger hypersensitivity reactions to foods. Their effects, mediated by FcεRI on mast cells and basophils, can be countered by IgG antibodies of shared specificity signaling via the inhibitory Fc receptor, FcγRIIb2. OIT induces only modest reductions in specific IgE antibodies but stimulates dramatic increases in inhibitory IgG3, 4.
https://ift.tt/2PDFsPF
Reset Osmostat: A Challenging Case of Hyponatremia
Hyponatremia is the most common electrolyte abnormality seen in hospitalised patients with up to 15–20% of patients having a sodium level of less than 135 mmol/L (Reddy and Mooradian, 2009). Cases of hyponatremia were first described in the 1950s (George et al., 1955). As the differential diagnosis for hyponatremia is broad, a systematic and logical approach is needed to identify the cause. We describe a case of a 30-year-old gentleman who was found to have chronic hyponatremia. After a thorough workup, he was diagnosed to have reset osmostat. Reset osmostat is an uncommon and under recognised cause of hyponatremia which does not require any treatment. This diagnosis needs to be considered when the hyponatremia workup suggests SIADH, but the hyponatremia is not amenable to fluid restriction, salt or urea supplementation, and diuretic treatment.
https://ift.tt/2DmnNq6
Extracellular vimentin modulates human dendritic cell activation
Publication date: December 2018
Source: Molecular Immunology, Volume 104
Author(s): Mary Beth Yu, Joshua Guerra, Anthony Firek, William H.R. Langridge
Abstract
Vimentin is an intermediate filament protein traditionally considered to be an intracellular protein with a structural role. However, recent evidence suggests that vimentin can also be found outside the cell in disease conditions such as cancer, traumatic tissue injury, and inflammation. Extracellular vimentin was previously found to stimulate innate immunity by increasing monocyte and macrophage ability to kill bacteria. However, vimentin has also been previously found to decrease neutrophil infiltration into inflamed tissue. How extracellular vimentin affects the initiation of adaptive immune responses is unknown. Initiation of adaptive immunity involves priming of naïve T cells by antigen-presenting cells, the most effective of which are dendritic cells (DCs). In this study, we demonstrate how extracellular vimentin modulates lipopolysaccharide (LPS) – induced activation of human DCs. Using cytometric bead arrays, we show that extracellular vimentin decreases LPS-activated DC secretion of pro-inflammatory cytokines IL-6 and IL-12 while increasing secretion of the anti-inflammatory cytokine IL-10. Using flow cytometry, we show that extracellular vimentin does not significantly affect LPS-induced DC surface expression of MHC I (HLA-ABC) or MHC II (HLA-DR) presentation molecules, costimulatory factors (CD80, CD86), or the DC maturation marker (CD83). Further, LPS-stimulated DCs co-cultured with allogeneic naïve CD4 + T cells (Th0) induced less secretion of the pro-inflammatory Th1 effector cytokine IFN-γ in the presence of vimentin than in the presence of LPS alone. This result suggests that vimentin reduces Th1 differentiation. Taken together, our data suggest that extracellular vimentin may inhibit pro-inflammatory adaptive immune responses, by blocking DC secretion of pro-inflammatory cytokines. Thus, extracellular vimentin may play an important role in cancer or trauma-complications by inducing suppression of the adaptive immune response. In a positive sense, the presence of extracellular vimentin may prevent tissue-damage from contributing to the development of autoimmunity. Consequently, extracellular vimentin may become a novel drug target for treatment of a variety of pro- and anti-inflammatory disease conditions.
Graphical abstract
https://ift.tt/2D1bC0Y
Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production
Publication date: December 2018
Source: Molecular Immunology, Volume 104
Author(s): Zizhen Gong, Shengnan Zhao, Jiefei Zhou, Junkai Yan, Lingyu Wang, Xixi Du, Hui Li, Yingwei Chen, Wei Cai, Jin Wu
Abstract
Background
NLRP3 inflammasome mediates IL-1β maturation, therefore plays a vital role in the development of IBD. Curcumin is known for possessing strong anti-inflammatory property.
Objective
The present study was to investigate the protective effects of curcumin on dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome activation and IL-1β production.
Methods
LPS-primed macrophages were treated with curcumin prior to DSS triggering NLRP3 inflammasome activation, IL-1β secretion and ASC oligomerization were observed. The mechanisms of curcumin in the inhibition of DSS-induced inflammasome activation were explored. Curcumin or caspase-1/NLRP3 inhibitor was administrated respectively in DSS-induced colitis mouse model. The changes of body weight, disease activity index, colon length were measured. Additionally, mature IL-1β and other inflammatory cytokines, MPO activity and histopathological damage were analyzed for the evaluation of colitis severity.
Results
NLRP3 inflammasome activation was dramatically inhibited by curcumin in DSS-stimulated macrophages, as evidenced by decreased IL-1β secretion, less caspase-1 activation and ASC specks. Mechanistically, curcumin prevented DSS-induced K+ efflux, intracellular ROS formation and cathepsin B release, three major cellular events mediating NLRP3 inflammasome activation. In DSS-induced colitis, curcumin administration significantly ameliorated colitis symptoms by reducing weight loss, DAI and colon length shortening. Meanwhile, curcumin significantly decreased the expression of multiple inflammatory cytokines (including mature IL-1β, IL-6, MCP-1), MPO activity, caspase-1 activity as well as histopathological damage. Furthermore, blockage of NLRP3 inflammasome activation in vivo with specific NLRP3 inhibitor abrogated the further inhibitory effect of curcumin on DSS-induced colitis.
Conclusion
Curcumin could strongly suppress DSS-induced NLRP3 inflammsome activation and alleviate DSS-induced colitis in mice, thus it may be a promising candidate drug in clinical application for IBD therapy.
https://ift.tt/2P7nLJ5
The intricacies of self-lipid antigen presentation by CD1b
Publication date: December 2018
Source: Molecular Immunology, Volume 104
Author(s): Adam Shahine
Abstract
The CD1 family of glycoproteins are MHC class I-like molecules that present a wide array of self and foreign lipid antigens to T-cell receptors (TCRs) on T-cells. Humans express three classes of CD1 molecules, denoted as Group 1 (CD1a, CD1b, and CD1c), Group 2 (CD1d), and Group 3 (CD1e). Of the CD1 family of molecules, CD1b exhibits the largest and most complex antigen binding groove; allowing it the capabilities to present a broad spectrum of lipid antigens. While its role in foreign-lipid presentation in the context of mycobacterial infection are well characterized, understanding the roles of CD1b in autoreactivity are recently being elucidated. While the mechanisms governing proliferation of CD1b-restricted autoreactive T cells, regulation of CD1 gene expression, and the processes controlling CD1+ antigen presenting cell maturation are widely undercharacterized, the exploration of self-lipid antigens in the context of disease have recently come into focus. Furthermore, the recently expanded pool of CD1b crystal structures allow the opportunity to further analyze the molecular mechanisms of T-cell recognition and self-lipid presentation; where the intricacies of the two-compartment system, that accommodate both the presented self-lipid antigen and scaffold lipids, are scrutinized. This review delves into the immunological and molecular mechanisms governing presentation and T-cell recognition of the broad self-lipid repertoire of CD1b; with evidence mounting pointing towards a role in diseases such as microbial infection, autoimmune diseases, and cancer.
https://ift.tt/2D1buyw
Identification of a linear B-cell epitope in the catalytic domain of bothropasin, a metalloproteinase from Bothrops jararaca snake venom
Publication date: December 2018
Source: Molecular Immunology, Volume 104
Author(s): Denis A. Molina Molina, Clara Guerra-Duarte, Dayane L. Naves de Souza, Fernanda Costal-Oliveira, Giovana Reis de Ávila, Vanete T. Soccol, Ricardo A. Machado-de-Ávila, Carlos Chávez-Olórtegui
Abstract
Bothropasin is a hemorrhagic snake venom metalloproteinase (SVMP) from Bothrops jararaca venom, the snake responsible for most bites in Southeastern Brazil. SVMPs, such as bothropasin, are involved in the main bothropic envenoming symptoms, which include hemorrhage, inflammation, necrosis and blood coagulation deficiency. B-cell epitope mapping of SVMPs can lead to the identification of peptides capable of inducing neutralizing antibodies without causing toxic effects, therefore improving anti-venom production. Here, using the SPOT synthesis technique, we have identified an epitope located in the catalytic domain of bothropasin (202KARMYELANIVNEILRYLYMH222) which was synthesized and named BotEp1. The peptide was used to immunize Swiss mice and Anti-BotEp1 serum cross-reacted with bothropasin and crude venoms from B. jararaca and B. atrox venoms. Furthermore, Anti-BotEp1 antibodies were able to completely neutralize the hemorrhagic activity of a chromatographic fraction from B. jararaca venom, which contains hemorrhagic SVMPs. In addition, the coagulation activity of the hemorrhagic fraction showed to be diminished when tested in serum from rabbit immunized with BotEp1 (compared to serum from non-immunized animal). Our results show the identification of neutralizing epitopes in bothropasin and provide basis for the use of synthetic peptides to improve the production of immunotherapeutics.
https://ift.tt/2P4yALI
A case of pediatric cervicofacial actinomyces masquerading as malignancy: Case report and review of the literature
Publication date: Available online 3 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Emily Savoca, Saral Mehra, Erik H. Waldman
Abstract
Cervicofacial actinomyces is an uncommon infection, especially in children. Notoriously low culture sensitivity and malignant appearance make diagnosis challenging. Treatment requires a prolonged antibiotic course often in conjunction with surgical debridement or drainage. We report an amorphous anterior neck mass in a 10-year-old girl due to actinomyces. Diagnosis required open biopsy after non-diagnostic fine needle aspirate and core needle biopsies. The patient responded well to six-week course of parenteral penicillin followed by six months of convalescent therapy with oral penicillin. In addition to a case discussion, we review cervicofacial actinomyces in the literature with a focus on pediatrics.
https://ift.tt/2OofrPS
Language outcome in children with congenital hearing impairment: the influence of etiology
Publication date: Available online 3 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Eveline Dieleman, Lone Percy-Smith, Per Caye-Thomasen
Abstract
Objectives
To investigate the possible association between the etiology of hearing impairment (HI) and language outcome in children with congenital HI after an early medical-technical intervention and three years of AVT.
Methods
A retrospective, two-center study was conducted of 53 patients who were divided in four categories of etiology (degeneratio labyrinthi acustici (DLA) congenita hereditaria, DLA congenita non specificata, DLA congenita postinfectiosa and auditory neuropathy). Language outcome was assessed by examining receptive vocabulary (Peabody Picture Vocabulary Test, PPVT-4), receptive language (Reynell test) and productive language (the Danish 'Viborgmaterialet'). All tests were conducted 1, 2 and 3 years after the children received their hearing device. Test scores were calculated from the child's chronological age. Analysis of possible associations was performed using Fisher's exact test and McNemar's test was conducted to examine possible differences between each year of testing for every speech-language test. Subsequently, univariate analyses were performed to search for other possible covariates associated with language outcome.
Results
No significant associations were found between the etiology of the HI and the language outcome of children with HI after 1 year of AVT (PPVT, p=0,234; Reynell, p=0,845; Viborgmaterialet, p=0,667), neither after 2 years of AVT (PPVT, p=0,228; Reynell, p=0,172; Viborgmaterialet, p=0,659) nor after 3 years of AVT (PPVT, p=0,102; Reynell, p=0,512 Viborgmaterialet, p=0,580). Some significant associations were found between language outcome and the type of hearing device and between language outcome and additional disabilities, however no strong evidence was found.
Conclusion
Most children with congenital HI developed a comparable level of speech and language regardless of the etiology of their HI. This study highlights the interest of further research using objective assessments techniques in a larger and more homogeneous population. If the findings from this study will be confirmed in future studies, this will have a clinical and societal impact regarding the diagnostics of HI.
https://ift.tt/2yPR9t7
Clinical characteristics of obstructive sleep apnea versus infectious adenotonsillar hyperplasia in children
Publication date: Available online 3 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): James Johnston, Holly McLaren, Murali Mahadevan, Richard G. Douglas
Abstract
Introduction
Children who undergo adenotonsillectomy have a range of symptoms. Some present with infective symptoms, others with obstructive symptoms, and many with a combination of both. The most common surgical indication has changed over the past several decades from infective symptoms to obstructive symptoms. However, there are few data available to differentiate these groups of children in terms of their clinical characteristics. This study aimed to determine the clinical characteristics of children with obstructive sleep apnea versus infectious adenotonsillar hyperplasia.
Methods
Data were obtained from the medical records of two district health boards in Auckland, New Zealand. Extraction of clinical information was performed following the identification of all patients under the age of 16 years undergoing adenotonsillectomy between December 2015 and December 2017.
Results
A total of 1538 children were included in this study. There were 112 (7.3%) with recurrent tonsillitis (RT) symptoms only, 624 (40.6%) with RT and sleep-disordered breathing symptoms (SDB), and 802 (52.1%) with symptoms suggestive of obstructive sleep apnea (OSA). Children with OSA were more likely to be male (p < 0.001), younger (p < 0.001), and have lower body mass indexes at time of surgery (p < 0.001). There was no difference between groups in the number of antibiotic courses prescribed in the year before surgery (p=0.7). There was no significant difference in tonsil or adenoid grade between groups (p=0.2). Children with OSA were more likely to have a diagnosis of asthma (p < 0.001) and allergic rhinitis (p < 0.001), but less likely than those with RT to have a diagnosis of eczema (p < 0.001). Children with OSA were more likely to have otitis media with effusion requiring ventilation tube insertion (p < 0.001) and a documented history of speech delay (p < 0.001). Thirty-day readmission rates were higher in the OSA (8.5%) and SDB/RT (9.3%) groups when compared to those with RT (1.8%) (p=0.03).
Conclusion
Children with OSA have different perioperative characteristics than those with recurrent tonsillitis, including increased risk of postoperative bleeding and need for post op readmission. Therefore, management strategy may vary according to the indications for tonsillectomy and adenoidectomy.
https://ift.tt/2OpAtNU
A rare pure embryonal rhabdomyosarcoma of the urinary bladder in an adult successfully managed with neoadjuvant chemotherapy and surgery: a case report
Rhabdomyosarcoma of the urinary bladder in adults is an extremely rare malignant neoplasm that develops from the bladder wall.
https://ift.tt/2qsuC0X
Target volume selection and delineation (T and N) for primary radiation treatment of oral cavity, oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma
Publication date: December 2018
Source: Oral Oncology, Volume 87
Author(s): Vincent Grégoire, Cai Grau, Michel Lapeyre, Philippe Maingon
Abstract
Target volume selection and delineation for both the primary tumor and the lymph nodes are critical steps in the treatment of head and neck tumors with Intensity Modulated Radiation therapy (IMRT). These steps should be based on a probabilistic approach, which is that selection and delineation will be considered as optimal when reaching the best compromise between a too tight volume that could be associated to an unacceptable rate of local recurrence, and a too large volume, which could be associated to an unacceptable rate of treatment morbidity. Failure to do so have been reported to be associated to a higher risk of loco-regional recurrences and/or morbidity after treatment. In this framework, groups of experts proposed sets of guidelines for the radiation oncology community, aiming at standardizing radiotherapy practices of head and neck cancer patients. Although in constant improvement, such guidelines have been shown to translate into more consistent treatment approaches.
This review article summarizes the knowledge accumulated over the years on target volume selection and delineation and tries to reconcile the various schools of thoughts on the topic.
https://ift.tt/2Djqxof
First-reported pediatric cases of American ginseng anaphylaxis and allergy
Ginseng is a perennial herb used in traditional Chinese medicine, which has become increasingly popular world-wide due to its proposed medicinal effects. There are two major species of ginseng, Panax ginseng (Kor...
https://ift.tt/2qqVgar
High levels of Butyrate and Propionate in early life are associated with protection against atopy
Allergy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2SJwG1l
BLT1 signaling in epithelial cells mediates allergic sensitization via promotion of IL‐33 production
Allergy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2zuwytB
Mast Cell Disorders: from Infancy to Maturity
Allergy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2SHqTcx
In Vitro Study of Deuterium Effect on Biological Properties of Human Cultured Adipose-Derived Stem Cells
In current in vitro study we have shown the impact of deuterium content in growth medium on proliferation rate of human cultured adipose-derived stem cells (ADSC). ADSCs have also demonstrated morphological changes when cultured in deuterated growth medium: the cell cultures did not reach confluence but acquired polygonal morphology with pronounced stress fibers. At high deuterium concentrations the ADSCs population doubling time increased which indicated the cell cycle retardation and decrease of cell proliferation rate. The deuterated and deuterium-depleted growth media demonstrated acute and chronic cytotoxicity, respectively. The minimal migration ability was observed in deuterated medium whereas the highest migration activity was observed in the medium with the deuterium content close to natural. The cells in deuterated growth medium demonstrated decrease in metabolic activity after three days in culture. In contrast, in deuterium-depleted medium there was an increase in ADSC metabolic activity.
https://ift.tt/2Dl8xcP
Activography reveals aberrant proteolysis in desquamating diseases of differing backgrounds
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2RBDXix
Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Pz11kD
Detection of fluid secretion of three‐dimensional reconstructed eccrine sweat glands by magnetic resonance imaging
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2RC16RT