Khusru Asadullah - Academia.edu (original) (raw)

Papers by Khusru Asadullah

Interleukin Protocols, 2001

ABSTRACT Cytokines are considered to be of major importance for the pathogenesis of several cutan... more ABSTRACT Cytokines are considered to be of major importance for the pathogenesis of several cutaneous disorders. Their considerable impact may result from autocrine, paracrine, or endocrine effects. Consequently, numerous investigations aim to measure cytokines, including interleukins. Since reliable determination of cutaneous interleukin expression at the protein level is problematic (see Notes 1–7), determination of mRNA expression came to the forefront of scientific interest. Such approaches, however, are associated with difficulties in the quantification of gene transcripts.

Nature reviews. Drug discovery, 2015

Expert opinion on drug discovery, 2006

Inflammatory skin diseases have a high prevalence in Western countries and pharmaceutical compani... more Inflammatory skin diseases have a high prevalence in Western countries and pharmaceutical companies spend increasing amounts of money to develop drugs for these disorders. However, their complex pathophysiology is only partially reflected in classical rodent models, limiting their predictivity, and new compounds frequently fail in clinical trials. Therefore, there is an urgent need for more predictive and reliable animal models. Humanised mouse models seem to combine the convenience of small animal models with good correlation to the situation in patients and, thus, promise to be a valuable technique for translational medicine. Here, the authors summarise how mice can be humanised and which humanised models for inflammatory skin diseases exist. Application of these models in drug discovery and their advantages and limitations are discussed.

Ernst Schering Research Foundation workshop, 2005

Page 1. 15 Acute and Chronic Models of Allergic Contact Dermatitis: Advantages and Limitations TM... more Page 1. 15 Acute and Chronic Models of Allergic Contact Dermatitis: Advantages and Limitations TM Zollner, FH Igney, K. Asadullah 15.1 Introduction . . . . . 255 15.2 Ideal or Ideology: Features of Ideal Animal Models of ACD . ...

Journal of Investigative Dermatology, 2014

2 Abbreviations: BD, -defensin,; CALML5, calmodulin-like 5; DNFB, 2,4-dinitro-1-fluorobenzene; DS... more 2 Abbreviations: BD, -defensin,; CALML5, calmodulin-like 5; DNFB, 2,4-dinitro-1-fluorobenzene; DSC1, desmocollin 1; HPRT, hypoxanthine phosphoribosyl-transferase 1; KLK7, kallikrein 7; K10, keratin 10; LCN2, lipocalin-2; MMP1, matrix metalloproteinease 1/collagenase 1.

Overcoming Steroid Insensitivity in Respiratory Disease, 2008

... Symptoms disappear with termination of medication and recur when the inhalation of GCs is rei... more ... Symptoms disappear with termination of medication and recur when the inhalation of GCs is reinitiated at higher doses (Hederos, 2004). Short-term systemic treat-ment for acute asthma exacerbation may lead to acute behavioural effects (Kayani and Shannon, 2002). ...

Trends in Pharmacological Sciences, 2004

Differences between humans and mice often hamper the transfer of promising results from the bench... more Differences between humans and mice often hamper the transfer of promising results from the bench to the clinic. For ethical reasons, research that involves patients is limited, and so there is an urgent need for models that mimic the human situation as closely as possible. In recent years, there has been considerable progress in generating humanized mouse models, and their application to drug discovery has proved fruitful. So, how can mice be humanized, and how can humanized mice be employed in immunology research and drug discovery? In this article, we answer these questions, focusing on T-cell-mediated skin diseases as an example.

Trends in Molecular Medicine, 2005

Fumaric acid esters (FAEs) have been used for the oral treatment of psoriasis since 1959 and have... more Fumaric acid esters (FAEs) have been used for the oral treatment of psoriasis since 1959 and have been registered for this indication in Germany since 1994. Dimethylfumarate (DMF) and its metabolite methylhydrogenfumarate (MHF) are the pharmacologically active compounds, with DMF being the main component of the marketed FAE-mixture. However, the mechanism of action of FAE is yet to be fully understood. It has been shown that DMF inhibits NFkappaB translocation, which leads to (i) the inhibition of pro-inflammatory cytokine production and adhesion molecule expression, (ii) the inhibition of dendritic cell differentiation and, at higher concentrations, (iii) the induction of apoptosis. Recent evidence also shows that these effects are mediated through the interference of the intracellular redox system by DMF. Here, the mode of action of FAE and its clinical use for psoriasis will be discussed.

Trends in Immunology, 2001

Trends in Immunology, 2003

ABSTRACT Recent papers on the role of fucosyltransferase VII (FucTVII) in leukocyte trafficking u... more ABSTRACT Recent papers on the role of fucosyltransferase VII (FucTVII) in leukocyte trafficking underscore the importance of this glycosyltransferase for selectin ligand synthesis, inflammation and skin homing. Furthermore, other data have shown how another transferase, FucTIV, might compensate for FucTVII functions and contribute to the generation of functional binding epitopes involved in tethering and rolling functions.

Pharmacology & Therapeutics, 2002

Nature Medicine, 1997

Neutralization of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) or i... more Neutralization of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1), decreases mortality in several animal models of sepsis. However, recent clinical trials did not show an unequivocal improvement in survival. In contrast to animals, which succumb to shock during the first 72 hours, we found that many patients die much later with signs of opportunistic infections accompanied by downregulation of their monocytic HLA-DR expression and reduced ability to produce lipopolysaccharide (LPS)-induced TNF-alpha in vitro. This phenomenon of monocyte deactivation in septic patients with fatal outcome shows similarities to experimental monocytic refractoriness induced by LPS desensitization or by pretreatment with its endogenous mediators IL-10 and transforming growth factor-beta (TGF-beta). In order to strengthen their antimicrobial defense, here we tested whether interferon-gamma (IFN-gamma) can improve monocytic functions in these patients and in experimental monocytic deactivation. The considerably lowered in vitro levels of LPS-induced TNF-alpha in these situations were significantly enhanced by IFN-gamma, but did not reach the extremely high levels of IFN-gamma primed naive cells from healthy donors. Moreover, IFN-gamma applied to septic patients with low monocytic HLA-DR expression restored the deficient HLA-DR expression and in vitro LPS-induced TNF-alpha secretion. Recovery of monocyte function resulted in clearance of sepsis in eight of nine patients. These data suggest that IFN-gamma treatment in carefully selected septic patients is a novel therapeutic strategy worth pursuing.

Molecular and Cellular Endocrinology, 2007

Please cite this article as: Schäcke, H., Berger, M., Rehwinkel, H., Asadullah, K., Selective Glu... more Please cite this article as: Schäcke, H., Berger, M., Rehwinkel, H., Asadullah, K., Selective Glucocorticoid Receptor Agonists (SEGRAs): Novel ligands with an improved therapeutic index, Molecular and Cellular Endocrinology (2007),