Τρίτη 24 Νοεμβρίου 2020

Cat-NPC2, a Newly Identified Allergen, With High Cross-Reactivity to Can f 7.

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Icon for The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease Related Articles

Cat-NPC2, a Newly Identified Allergen, With High Cross-Reactivity to Can f 7.

Allergy Asthma Immunol Res. 2021 Jan;13(1):122-140

Authors: Zhu DX, Li L, Xu ZQ, Zhang C, Zhang JS, Sun JL, Wei JF

Abstract
PURPOSE: Pet-derived allergens are the common indoor inhalant allergens. Among them, cat and dog allergens constitute more than 80% of animal allergic patients, which greatly affect the quality-of-life of patients and increase the burden of social health care. The aim of this study was to identify Cat-Niemann pick type C2 (NPC2) protein, a homologue of Can f 7, as a new allergen.
METHODS: Cat-NPC2 complementary DNA (cDNA) was cloned and optimized for amplification and expression in Escherichia coli. Then, recombinant Cat-NPC2 (rCat-NPC2) was purified by Ni2+ affinity chromatography. The allergenicity was assessed by enzyme-linked immunosorbent assay (ELISA), western blot and basophil activation test (BAT). Based on the sequence similarity, the cross-reactivity between Cat-NPC2 and Can f 7 was investigated by inhibition ELISA. Circular dichroism spectroscopy and homology modeling were used to characterize the structure of Cat-NPC2.
RESULTS: The cDNA sequence of Cat-NPC2 was cloned with a 450-bp open reading frame coding for 149 amino acids (GenBank MN_737596). The condon-optimized NPC2 gene was subcloned and expressed in E. coli with a molecular weight of 18.9 kDa. The native Cat-NPC2 was detected in cat dander extracts. The allergenicity determined by ELISA, western blot and BAT suggested at least 14.5% cat-allergic patients displayed high specific immunoglobulin E (IgE) recognition of Cat-NPC2. The predicted structure of Cat-NPC2 was found to consist of 7 β-strands arranged in 2 β-sheets. An ELISA based assay showed that rCat-NPC2 bound to cholesterol in a dose dependent manner. Based on the structure and sequence similarities, IgE cross-reactivity was demonstrated between Cat-NPC2 and Can f 7/Der f 2.
CONCLUSIONS: In the study, a novel cat allergen, belonging to the NPC2 protein family, was identified and characterized at both molecular and immunological levels. The study will offer a deeper understanding of cat allergens and improve a component-resolved diagnosis in pet allergy.

PMID: 33191681 [PubMed]

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Agreement Between Predictive, Allergen-Specific IgE Values Assessed by ImmunoCAP and IMMULITE 2000 3gAllergy™ Assay Systems for Milk and Wheat Allergies.

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Icon for The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease Related Articles

Agreement Between Predictive, Allergen-Specific IgE Values Assessed by ImmunoCAP and IMMULITE 2000 3gAllergy™ Assay Systems for Milk and Wheat Allergies.

Allergy Asthma Immunol Res. 2021 Jan;13(1):141-153

Authors: Al Hawi Y, Nagao M, Furuya K, Sato Y, Ito S, Hori H, Hirayama M, Fujisawa T, IPAD3g investigators

Abstract
PURPOSE: ImmunoCAP® (ImmunoCAP) and IMMULITE® 2000 3gAllergy™ (3gAllergy) systems are major quantitative allergen-specific immunoglobulin E (sIgE) assay methods. Due to the heterogeneous nature of allergenic extracts and differences in the assay format, quantitation of allergen-sIgEs is not expected to correlate well between different methods. However, we have recently reported good agreement between the methods in the diagnosis of egg allergy. This study aimed to determine and correlate the predictive values of sIgE by the two systems in the diagnosis of milk and wheat allergies.
METHODS: Children who had undergone oral food challenge (OFC) for the diagnosis of milk and wheat allergies were enrolled. The OFCs were performed to diagnose either true allergy in the 1-year-old group (A) or tolerance in the 2- to 6-year-old group (B). Milk, casein and β-lactoglobulin, and wheat and ω-5 gliadin sIgE values were measured using the 2 systems. The predictive accuracy of each sIgE for the OFC outcome was assessed using receiver operating characteristic (ROC) curves. The probability of a positive OFC outcome was estimated by logistic regression analysis.
RESULTS: A total of 395 patients were recruited from 7 primary care clinics and 19 hospitals in Japan. Milk and wheat OFCs were performed for 87 and 102 group A patients, and 124 and 82 group B patients, respectively. ROC analysis yielded similar areas under the curve for the 2 assays (0.7-0.9). The log-transformed sIgE data showed a strong linear correlation with the estimated probabilities (R > 0.9).
CONCLUSIONS: The 2 systems may be interchangeable for diagnosis of milk and wheat allergies in young children.

PMID: 33191682 [PubMed]

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Expression in Escherichia coli and Purification of Folded rDer p 20, the Arginine Kinase From Dermatophagoides pteronyssinus: A Possible Biomarker for Allergic Asthma.

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Icon for The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease Related Articles

Expression in Escherichia coli and Purification of Folded rDer p 20, the Arginine Kinase From Dermatophagoides pteronyssinus: A Possible Biomarker for Allergic Asthma.

Allergy Asthma Immunol Res. 2021 Jan;13(1):154-163

Authors: Sarzsinszky E, Lupinek C, Vrtala S, Huang HJ, Hofer G, Keller W, Chen KW, Panaitescu CB, Resch-Marat Y, Zieglmayer P, Zieglmayer R, Lemell P, Horak F, Duchêne M, Valenta R

Abstract
Arginine kinase (AK) was first identified as an allergen in the Indian-meal moth and subsequently shown to occur as allergen in various invertebrates and shellfish. The cDNA coding for AK from the house dust mite (HDM) species Dermatophagoides pteronyssinus, Der p 20, has been isolated, but no recombinant Der p 20 (rDer p 20) allergen has been produced and characterized so far. We report the expression of Der p 20 as recombinant protein in Escherichia coli. rDer p 20 was purified and shown to be a monomeric, folded protein by size exclusion chromatography and circular dichroism spectroscopy, respectively. Using AK-specific antibodies, Der p 20 was found to occur mainly in HDM bodies, but not in fecal particles. Thirty percent of clinically well-characterized HDM allergic patients (n = 98) whose immunoglobulin E (IgE) reactivity profiles had been determined with an extensive panel of purified HDM allergens (Der f 1, 2; Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 18, 21, 23 and 37) sh owed IgE reactivity to Der p 20. IgE reactivity to Der p 20 was more frequently associated with lung symptoms. AKs were detected in several invertebrates with specific antibodies and Der p 20 showed IgE cross-reactivity with AK from shrimp (Litopenaeus vannamei). Thus, Der p 20 is a cross-reactive HDM allergen and may serve as a diagnostic marker for HDM-induced lung symptoms such as asthma.

PMID: 33191683 [PubMed]

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Infectious Mononucleosis Resulting in Acute Necrotizing Mediastinitis: A Case Report and Literature Review.

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Infectious Mononucleosis Resulting in Acute Necrotizing Mediastinitis: A Case Report and Literature Review.

Eur J Case Rep Intern Med. 2020;7(11):001829

Authors: Van Noten H, Markowicz S, Cappeliez S, Cherifi S

Abstract
The serological prevalence of Epstein-Barr virus (EBV) among young adults exceeds 90% worldwide. Even though EBV primary infection is usually benign, severe complications can occur in adolescents and young adults and so the disease must be promptly diagnosed. The development of an oropharyngeal abscess leading to a descending necrotizing mediastinitis (DNM) is exceptional and potentially lethal, so early diagnosis with a CT scan, appropriate antibiotics and surgery are essential. The authors present a case where DNM was associated with reactive hemophagocytic syndrome as a result of infectious mononucleosis, as well as a review of similar cases in the English literature.
LEARNING POINTS: The incidence of serious complications in Epstein-Barr virus (EBV) primary infection increases with age.Respiratory symptoms (e.g., pleuritic pain, dyspnoea) and unusually prolonged fever (>10 days) in patients with infectious mononucleosis could be 'red flags' for life-threatening complications such as empyema and descending necrotizing mediastinitis.The threshold for performing cervical and chest computed tomography in septic patients with infectious mononucleosis should be low.

PMID: 33194856 [PubMed]

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Management of Patients after Failed Peroral Endoscopic Myotomy: a Multicenter Study.

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Management of Patients after Failed Peroral Endoscopic Myotomy: a Multicenter Study.

Endoscopy. 2020 Nov 16;:

Authors: Ichkhanian Y, Assis D, Familiari P, Ujiki MB, Su B, Khan SR, Pioche M, Draganov PV, Young Cho J, Eleftheriadis N, Barret M, Haji A, Velanovich V, Tantau M, Marks J, Bapaye A, Sedarat A, Albéniz E, Bechara R, Kumta NA, Costamagna G, Perbtani Y, Patel M, Sippey M, Korrapati SK, Jain R, Estremera Arevalo F, El Zein MH, Brewer Gutierrez OI, Khashab MA

Abstract
BACKGROUND AND AIMS: Although Peroral Endoscopic Myotomy (POEM) is highly effective for the management of achalasia, clinical failures may occur. The optimal management of patients who fail POEM is not well known. This study aims to compare the outcomes of different management strategies in patients who had failed POEM.
PATIENTS AND METHODS: This is an international, multicenter, retrospective study at 16 tertiary centers between 1/2012 and 11/2019. All patients who underwent POEM and experienced persistent or recurrent symptoms (Eckardt score (ES) > 3) were included. The primary outcome was to compare the rate of clinical success (ES ≤ 3) between different management strategies.
RESULTS: A total of 99 patients (50 (50.5%) males, mean age 51.4 (16.2) yrs.) experienced clinical failure during the study period with a mean ES of 5.5 (0.2). A total of 29 (32.2%) patients were managed conservatively and 70 (71%) underwent re-treatment [repeat POEM 33 (33%), pneumatic dilation (PD) 30 (30%), and laparoscopic Heller myotomy (LHM) 7 (7.1%)]. During a median follow-up of 10 (IQR: 3-20) months, clinical success was highest in patients who underwent repeat POEM (25/33 (76%), mean ES 2.1 (2.1)), followed by PD (18/30 (60%), mean ES 2.8 (2.3)), and LHM (2/7 (29%), 4 (1.8)) (p=0.12). A total of 11 (37.9%, mean ES 4 (1.8)) patients in the conservative achieved clinical success.
CONCLUSION: This study comprehensively assessed an international cohort of patients who underwent management of failed POEM. Repeat POEM and PD achieved acceptable clinical success with excellent safety profile.

PMID: 33197943 [PubMed - as supplied by publisher]

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Effects of different pulp-capping materials on cell death signaling pathways of lipoteichoic acid-stimulated human dental pulp stem cells

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Μέσω Odontology

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Abstract

Purpose

This study aimed to evaluate the response of dental pulp stem cells (DPSCs) cultured with and without lipoteichoic acid (LTA) to different pulp-capping materials. Methods: The cells were cultured and seeded in 6-well plates and exposed to 1% LTA solution. Dycal, ProRoot MTA and Biodentine materials were applied on cells and all groups were evaluated by cell proliferation, viability, cell cycle and cell death signaling pathways for 24 and 72 h.

Results

LTA + Dycal treatment significantly inhibited the proliferation of DPSCs and increased the apoptosis rate of cells more than the other groups at 72 h. Compared to other groups, LTA + Dycal treatment significantly increased the levels of Caspase-3 and AKT and decreased the levels of p-AKT.

Conclusions

The results of this study revealed that all tested materials caused apoptosis in DPSCs via an extrinsic apoptotic pathway. The DPSCs showed an early apoptosis response to the Dycal and a late apoptosis response to the ProRoot MTA and Biodentine treatments. LTA led autophagy and inhibited the proliferation of DPSCs. ProRoot MTA and Biodentin eliminated the LTA's bioactivity with higher efficiency than Dycal.

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NLRP3 inflammasome activation in human vestibular schwannoma: Implications for tumor-induced hearing loss.

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NLRP3 inflammasome activation in human vestibular schwannoma: Implications for tumor-induced hearing loss.

Hear Res. 2019 09 15;381:107770

Authors: Sagers JE, Sahin MI, Moon I, Ahmed SG, Stemmer-Rachamimov A, Brenner GJ, Stankovic KM

Abstract
Vestibular schwannoma (VS) is the fourth most common intracranial tumor, arising from neoplastic Schwann cells of the vestibular nerve and often causing debilitating sensorineural hearing loss (SNHL) and tinnitus. Previous research suggests that the abnormal upregulation of inflammatory pathways plays a highly significant, though infrequently described role in VS pathobiology, and that VS-associated SNHL is due not only to mechanical compression of the auditory nerve but also to differences in the intrinsic biology of these tumors. We hypothesize that patients who present with poor hearing associated with VS experience a more robust inflammatory response to this tumor than VS patients who present with good hearing. To investigate this hypothesis, we conducted a comprehensive pathway analysis using gene expression data from the largest meta-analysis of vestibular schwannoma microarray data, comprising 80 tumors and 16 healthy peripheral nerves. We identified the NLRP3 inflamma some as a novel target worthy of further exploration in VS research and validated this finding at the gene and protein expression level in human VS tissue using qRT-PCR and immunohistochemistry. To date, NLRP3 inflammasome activation has not been reported in VS, and this finding may represent a new and potentially significant therapeutic avenue. Notably, after analysis of 30 VSs, we observe that overexpression of key components of the NLRP3 inflammasome is preferentially associated with tumors that produce increased hearing loss in VS patients. Therefore, therapeutic development for VS should include considerations for minimizing NLRP3-associated inflammation to best preserve hearing.

PMID: 31430634 [PubMed - indexed for MEDLINE]

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