Add-on Therapy for Symptomatic Asthma despite Long-Acting Beta-Agonists/Inhaled Corticosteroid

Dreher, Michael,Muller, Tobias The Korean Academy of Tuberculosis and Respiratory 2018 Tuberculosis and Respiratory Diseases Vol.81 No.1

Asthma, remains symptomatic despite ongoing treatment with high doses of inhaled corticosteroids (ICS) in conjunction with long-acting beta-agonists (LABA), is classified as "severe" asthma. In the course of caring for those patients diagnosed with severe asthma, stepping up from ICS/LABA to more aggressive therapeutic measures would be justified, though several aspects have to be checked in advance (including inhaler technique, adherence to therapy, and possible associated comorbidities). That accomplished, it would be advisable to step up care in accordance with the Global Initiative for Asthma (GINA) recommendations. Possible strategies include the addition of a leukotriene receptor antagonist or tiotropium (to the treatment regimen). The latter has been shown to be effective in the management of several subgroups of asthma. Oral corticosteroids have commonly been used for the treatment of patients with severe asthma in the past; however, the use of oral corticosteroids is commonly associated with corticosteroid-related adverse events and comorbidities. Therefore, according to GINA 2017 these patients should be referred to experts who specialize in the treatment of severe asthma to check further therapeutic options including biologics before starting treatment with oral corticosteroids.

유럽경쟁법의 현황과 향후의 전망

Meinrad Dreher,홍명수(역) ( Hong Myeong Su ) 한국경쟁법학회 2002 競爭法硏究 Vol.8 No.-

The Formation and Development of EU Competition Law

( Meinrad Dreher ) 한국경쟁법학회 2015 競爭法硏究 Vol.31 No.-

Der heutige Stand und die zukunftigen Entwicklungen im europaischen Wettbewerbsrecht

Meinrad Dreher 한국경쟁법학회 2002 競爭法硏究 Vol.8 No.-

Inclusion-Provocation for the 21st Century : Are We Afraid of Another 'Trojanian Horse'?

Walther Dreher 대구대학교 2002 Journal of Asia-Pacific Special Education Vol.2 No.2

What I have carried along for you mosaic stones for a fresco, for a picture of our world in the 21st century. Four mosaic stones represent four topics: 1. Inclusion - a provocation for special education. Or: Segregation - Integration - Inclision ......? 2. Inclusion - a provoction for Epistemology. Or: Are we digging our own grave? 3. Inclusion - a provocation for human culture. Or: Rethinking society? 4. Inclusion - an enterprise of the future Or: Are we afraid of a new 'trojanian horse'? The spirit of the 21st cenetury might be called: GENIUS 'Genius' is the created and created and creating power which emerges out of the future and which means emerging futures. 'Genius' is the power of each person and the bond of the power of mankind.

외국교수 초청강연 논문 : 독일카르텔법의 현재와 미래

Meinrad Dreher 延世大學校 法科大學 法學硏究所 2001 法學硏究 Vol.11 No.2

Add-on Therapy for Symptomatic Asthma despite Long-Acting Beta-Agonists/Inhaled Corticosteroid

( Michael Dreher ),( Tobias Muller ) 대한결핵 및 호흡기학회 2018 Tuberculosis and Respiratory Diseases Vol.81 No.1

Asthma, remains symptomatic despite ongoing treatment with high doses of inhaled corticosteroids (ICS) in conjunction with long-acting beta-agonists (LABA), is classified as “severe” asthma. In the course of caring for those patients diagnosed with severe asthma, stepping up from ICS/LABA to more aggressive therapeutic measures would be justified, though several aspects have to be checked in advance (including inhaler technique, adherence to therapy, and possible associated comorbidities). That accomplished, it would be advisable to step up care in accordance with the Global Initiative for Asthma (GINA) recommendations. Possible strategies include the addition of a leukotriene receptor antagonist or tiotropium (to the treatment regimen). The latter has been shown to be effective in the management of several subgroups of asthma. Oral corticosteroids have commonly been used for the treatment of patients with severe asthma in the past; however, the use of oral corticosteroids is commonly associated with corticosteroid-related adverse events and comorbidities. Therefore, according to GINA 2017 these patients should be referred to experts who specialize in the treatment of severe asthma to check further therapeutic options including biologics before starting treatment with oral corticosteroids.

Patterns of Metabolite Changes Identified from Large-Scale Gene Perturbations in Arabidopsis Using a Genome-Scale Metabolic Network

Kim, Taehyong,Dreher, Kate,Nilo-Poyanco, Ricardo,Lee, Insuk,Fiehn, Oliver,Lange, Bernd Markus,Nikolau, Basil J.,Sumner, Lloyd,Welti, Ruth,Wurtele, Eve S.,Rhee, Seung Y. American Society of Plant Biologists 2015 Plant Physiology Vol.167 No.4

<P><I>Global patterns of metabolic responses upon single gene perturbations are specific to gene functions, but they are coordinated with characteristics of the perturbed genes.</I></P><P>Metabolomics enables quantitative evaluation of metabolic changes caused by genetic or environmental perturbations. However, little is known about how perturbing a single gene changes the metabolic system as a whole and which network and functional properties are involved in this response. To answer this question, we investigated the metabolite profiles from 136 mutants with single gene perturbations of functionally diverse Arabidopsis (<I>Arabidopsis thaliana</I>) genes. Fewer than 10 metabolites were changed significantly relative to the wild type in most of the mutants, indicating that the metabolic network was robust to perturbations of single metabolic genes. These changed metabolites were closer to each other in a genome-scale metabolic network than expected by chance, supporting the notion that the genetic perturbations changed the network more locally than globally. Surprisingly, the changed metabolites were close to the perturbed reactions in only 30% of the mutants of the well-characterized genes. To determine the factors that contributed to the distance between the observed metabolic changes and the perturbation site in the network, we examined nine network and functional properties of the perturbed genes. Only the isozyme number affected the distance between the perturbed reactions and changed metabolites. This study revealed patterns of metabolic changes from large-scale gene perturbations and relationships between characteristics of the perturbed genes and metabolic changes.</P>

Encapsidation of genomic but not subgenomic Turnip yellow mosaic virus RNA by coat protein provided in trans

Cho, Tae-Ju,Dreher, Theo W. Elsevier 2006 Virology Vol.356 No.1

<P><B>Abstract</B></P><P>We have studied the encapsidation requirements of <I>Turnip yellow mosaic virus</I> (TYMV) genomic and subgenomic RNA using an “agroinfiltration” procedure involving transient expression of RNAs and coat protein (CP) in <I>Nicotiana benthamiana</I> leaves. Although <I>N. benthamiana</I> is a nonhost, expression of TYMV RNA in its leaves by agroinfiltration resulted in efficient local infection and production of the expected virions containing genomic and subgenomic RNAs together with empty capsids. A nonreplicating genomic RNA with a mutation in the polymerase domain was efficiently encapsidated by CP provided in trans, even though RNA levels were a thousand-fold lower than in normal infections. In contrast, encapsidation of CP mRNA was not observed under these conditions, even when the CP mRNA had authentic 5′- and 3′-termini. Deletion of the 3′-tRNA-like structure from the genomic RNA did not alter the encapsidation behavior, suggesting that this feature does not play a role in the encapsidation of TYMV RNA. Our results indicate differences in the encapsidation process between genomic and subgenomic RNAs, and suggest an interaction between RNA replication and the packaging of subgenomic RNA.</P>

Empty Turnip yellow mosaic virus capsids as delivery vehicles to mammalian cells

Kim, Doyeong,Lee, Younghee,Dreher, Theo W.,Cho, Tae-Ju ELSEVIER 2018 VIRUS RESEARCH Vol.252 No.-

<P><B>Abstract</B></P> <P>Turnip yellow mosaic virus (TYMV) was able to enter animal cells when the spherical plant virus was conjugated with Tat, a cell penetrating peptide (CPP). Tat was chemically attached to the surface lysine residues of TYMV using hydrazone chemistry. Baby hamster kidney (BHK) cells were incubated with either unmodified or Tat-conjugated TYMV and examined by flow cytometry and confocal microscopic analyses. Tat conjugation was shown to be more efficient than Lipofectamine in allowing TYMV to enter the mammalian cells. Tat-assisted-transfection was also associated with less loss of cell viability than lipofection. Among the CPPs tested (Tat, R8, Pep-1 and Pen), it was observed that R8 and Pen were also effective while Pep-1 was not. We also examined if the internal space of TYMV can be used to load fluorescein dye as a model cargo. When TYMV is treated by freezing and thawing, the virus is known to convert into a structure with a 6–8 nm hole and release viral RNA. When the resultant pot-like particles were reacted with fluorescein-5-maleimide using interior sulfhydryl groups as conjugation sites, about 145 fluorescein molecules were added per particle. The fluorescein-loaded TYMV particles were conjugated with Tat and introduced into BHK cells, again with higher transfection efficiency compared to lipofection. Our studies demonstrate the potential of modified TYMV as an efficient system for therapeutic cargo delivery to mammalian cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Turnip yellow mosaic virus (TYMV) conjugated with Tat enters cells efficiently. </LI> <LI> Tat-assisted transfection was more efficient and less harmful than lipofection. </LI> <LI> TYMV particles can be made empty through a freezing and thawing process. </LI> <LI> Empty TYMV can be internally loaded with fluorescein using interior Cys residues. </LI> <LI> Fluorescein-loaded TYMV efficiently enters BHK cells when conjugated with Tat. </LI> </UL> </P>