June 5, 2013

A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 475809, 8 pages
http://dx.doi.org/10.1155/2013/475809

Research Article

A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro

Guipeng Ding,¹ Ximin Chen,¹ Jin Zhu,² Nicholas S. Duesbery,³ Xunjia Cheng,⁴ and Brian Cao⁵

¹Department of Pathology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China
²Huadong Medical Institute of Biotechniques, 293 East Zhongshan Road, Nanjing 210002, China
³Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USA
⁴Department of Medical Microbiology and Parasitology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, China
⁵Laboratory of Antibody Technology, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USA

Received 10 March 2013; Revised 12 May 2013; Accepted 13 May 2013

Academic Editor: Roberto Burioni

Copyright © 2013 Guipeng Ding et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Human anthrax infection caused by exposure to Bacillus anthracis cannot always be treated by antibiotics. This is mostly because of the effect of the remaining anthrax toxin in the body. Lethal factor (LF) is a component of lethal toxin (LeTx), which is the major virulence of anthrax toxin. A murine IgG monoclonal antibody (mAb) against LF with blocking activity (coded LF8) was produced in a previous study. In this report, a human/murine chimeric Fab mAb (coded LF8-Fab) was developed from LF8 by inserting murine variable regions into human constant regions using antibody engineering to reduce the incompatibility of the murine antibody for human use. The LF8-Fab expressed in Escherichia coli could specifically identify LF with an affinity of L/mol and could neutralize LeTx with an EC₅₀ of 85 μg/mL. Even after LeTx challenge at various time points, the LF8-Fab demonstrated protection of J774A.1 cells in vitro. The results suggest that the LF8-Fab might be further characterized and potentially be used for clinical applications against anthrax infection.

Michigan Quality Improvement Consortium Guidelines on Asthma

The Michigan Quality Improvement Consortium will establish and implement a core set of clinical practice guidelines and performance measures with a focus on improvement for effecting positive health outcomes.

Asthma	Guideline Update Alert – Asthma Principles	2012	PDF
Asthma	General Principles for the Diagnosis and Management of Asthma Guideline	2012/07/31	PDF 29.2KB
Asthma	Management of Asthma in Children 0-4 Years Guideline	2012/07/31	PDF 35.6KB
Asthma	Management of Asthma in Children 5-11 Years Guideline	2012/07/31	PDF 30.2KB
Asthma	Management of Asthma in Youth 12 Years and Older and Adults Guideline	2012/07/31	PDF 36.7KB
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June 4, 2013

Atopic Dermatitis: A Practice Parameter Update 2012

Donald Leung, MD, PhD talks with Lynda Schneider, MD about Dr. Schneider's JACI article "Atopic Dermatitis: A Practice Parameter Update 2012", published in the February 2013 issue of the journal.
View the article here:
http://www.jacionline.org/article/S00...

Allergy Immunotherapy: Reduced Healthcare Costs in Adults and Children with Allergic Rhinitis

ACI editor Andrea Apter, MD talks with Linda Cox, MD & Cheryl Hankin, PhD about their article in the April 2013 issue of JACI, entitled "Allergy Immunotherapy: Reduced Healthcare Costs in Adults and Children with Allergic Rhinitis".

View the article here:
http://www.jacionline.org/article/S00...

Association of genes of protease-antiprotease balance pathway to lung function and emphysema subtypes

Research article

Association of genes of protease-antiprotease balance pathway to lung function and emphysema subtypes

Mari K Kukkonen, Emmi Tiili, Tapio Vehmas, Panu Oksa, Päivi Piirilä and Ari Hirvonen

For all author emails, please log on.

BMC Pulmonary Medicine 2013, 13:36 doi:10.1186/1471-2466-13-36

Published: 4 June 2013

Abstract (provisional)

Background

The imbalance between proteases and antiproteases has been proposed to participate to the pathogenesis of chronic obstructive pulmonary disease (COPD) and emphysema. Gene level variation in different metalloproteinases, metalloproteinase inhibitors, and cytokines affecting them may contribute to this imbalance and destruction of the lung parenchyma. We investigated whether polymorphisms in selected protease/antiprotease balance pathway genes predispose to different emphysema subtypes (centrilobular, paraseptal, panlobular, and bullae) and airflow limitation among Finnish construction workers.

Methods

Eleven single nucleotide polymorphisms (SNPs) from seven genes (GC: rs7041 and rs4588; MMP1: rs1799750; MMP9: rs3918242; MMP12: rs652438; TIMP2: rs2277698; TNF: rs1799724 and rs1800629; TGFB1: rs1800469, rs1800470 and rs2241718) were analyzed from 951 clinically and radiologically characterized construction workers. The genotype and haplotype data was compared to different emphysematous signs confirmed with high resolution computed tomography (HRCT), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and maximal expiratory flow at 50% of FVC (MEF50) by using linear and logistic regression analyses, adjusted for potential confounders.

Results

The TIMP2 rs2277698 SNP was associated with overall (p = 0.022) and paraseptal (p = 0.010) emphysema, as well as with FEV1/FVC ratio (p = 0.035) and MEF50 (p = 0.008). The TGFB1 rs2241718 and MMP9 rs3918242 SNPs were associated with centrilobular emphysema (p = 0.022 and p = 0.008), and the TNF rs1800629 SNP with paraseptal emphysema (p = 0.017). In stratified analysis, individuals with at least one TIMP2 rs2277698 or TNF rs1800629 variant allele were found to be at around two-fold risk for pathological paraseptal changes (OR 1.94, 95% CI 1.14-3.30; OR 2.10, 95% CI 1.24-3.56). On the contrary, the risk for pathological centrilobular changes was halved for individuals with at least one MMP9 rs3918242 (OR 0.51, 95% CI 0.30-0.86) or TGFB1 rs2241718 (OR 0.53, 95% CI 0.30-0.90) variant allele, or TGFB1 rs1800469-rs1800470 AT-haplotype (OR 0.55, 95% CI 0.33-0.93). MEF50, in turn, was significantly reduced among individuals with at least one TIMP2 rs2277698 variant allele (p = 0.011).

Conclusion

Our findings strengthen the hypothesis of the importance of protease-antiprotease balance in pathogenesis of emphysema and shed light on the aetiology of different emphysema subtypes by associating MMP9 and TGFB1 to centrilobular emphysema, and TIMP2 and TNF to paraseptal emphysema and/or airflow obstruction.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

The Fine Scratches of the Spectacle Frames and the Allergic Contact Dermatitis

Annals of Dermatology 2013 May; 25(2): 152~155

The Fine Scratches of the Spectacle Frames and the Allergic Contact Dermatitis

In Su Kim, Kwang Ho Yoo, Myeung Nam Kim, Hyuck Ki Hong¹, Yeon Shik Choi¹, Young Chang Jo¹, Beom Joon Kim, Ju Suk Lee²

Department of Dermatology, College of Medicine, Chung-Ang University, ¹Medical IT Convergence Research Center Korea Electronics Technology Institute, Seoul, ²Department of Pediatrics, Samsung Changwon Hospital, School of Medicine, Sungkyunkwan University, Changwon, Korea

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Spectacle contact allergy is not infrequent. The fine scratches on the spectacle frames which may play a role in the sensitization to the potential allergenic components have not been studied. Objective: We sought the relationship between the scratches on the spectacle frames and the allergic contact dermatitis (ACD) in the Republic of Korea. Methods: A total of 42 Korean patients with ACD at the spectacle contact sites were enrolled. Their spectacle frames were examined with the dimethylglyoxime (DMG) test and analyzed by the scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). Patch tests (thin-layer rapid use epicutaneous test [TRUE tests]) were performed to identify the skin allergens. Results: The DMG-positive spectacle frames were identified in 78.5% of the frames. The SEM results showed that there were more scratches on the skin-contacting parts of the spectacle frames than the non-skin-contacting parts of the same frames. In the EDS findings, the mean nickel content (weight, %) of the spectacle frames was 15.7±5.5, and the mean chromium content was 20.3±3.4 at the skin-contacting parts. In the TRUE tests, nickel sulphate was the most common allergen (31 cases, 73.8%), and potassium dichromate was the second (9 cases, 21.4%). Three patients presented simultaneous positive reactions with nickel sulphate and potassium dichromate. Conclusion: Minor visible and non-visible fine scratches on the spectacle frames may present the provocation factors of the ACD. Nickel sulphate was the most common allergen suspected of provoking the spectacle frame-induced ACD, followed by potassium dichromate. (Ann Dermatol 25(2) 152∼155, 2013)

Annals of Dermatology 2013 May; 25(2): 152~155

Keyword : Allergic contact dermatitis, Fine scratch, Spectacle frame

Food Hypersensitivity in Patients with Childhood Atopic Dermatitis in Korea

Annals of Dermatology 2013 May; 25(2): 196~202

Food Hypersensitivity in Patients with Childhood Atopic Dermatitis in Korea

Hye One Kim, Soo Ick Cho, Jin Hye Kim, Bo Young Chung, Hee Jin Cho, Chun Wook Park, Cheol Heon Lee

Department of Dermatology, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea

Background: It is well known that atopic dermatitis (AD) is related to food hypersensitivity, although its prevalence varies among several studies according to age group, severity, country, survey time, and test method. Objective: To examine the prevalence and status of food hypersensitivity among childhood AD patients in Korea. Methods: A total of 95 patients were enrolled in the study. The history of food hypersensitivity was collected by interviews. The severity of AD was evaluated by eczema area and severity index (EASI). We took blood samples to measure serum total and food-specific immunoglobulin E (IgE) levels. Based on the histories and serum IgE levels, open oral food challenge (OFC) testing was performed to confirm food hypersensitivity. Results: Forty- two (44.2%) of the 95 AD patients had histories of food hypersensitivity. They reported that the most common suspicious foods were egg (n=13, 13.7%), pork (n=9, 9.5%) and cow milk (n=8, 8.4%). The mean EASI score was 16.05±9.76. Thirty-nine (41.1%) of the 95 patients showed elevated serum food-specific IgE levels. The specific IgE levels were elevated for egg (n=17, 17.9%), milk (n=12, 12.6%), peanut (n=10, 10.5%) and wheat (n=8, 8.4%). Fifty-one (53.8%) of 95 patients underwent open OFC, and only 7 (13.7%) of these patients showed positive reactions. Conclusion: The overall prevalence of food hypersensitivity in patients with childhood AD in Korea was 8.3% (7/84). The most common foods causing food hypersensitivity were egg and milk. Among the foods causing hypersensitivity, AD patients in Korea often underestimated peanut, while they overestimated pork. (Ann Dermatol 25(2) 196∼202, 2013)

Annals of Dermatology 2013 May; 25(2): 196~202

Keyword : Atopic dermatitis, Food allergy, Food hypersensitivity, Korean, Oral food challenge

Allergy, Asthma and Immunology

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June 5, 2013

A Human/Murine Chimeric Fab Antibody Neutralizes Anthrax Lethal Toxin In Vitro