Yearbook 01


Vega Seidler
Home Institution Freie Universität Berlin Host Institution Johns Hopkins University School of Medicine, Baltimore, Asthma and Allergy Center, Division of Clinical Immunology Mentor: Robert P. Schleimer, PhD Clinical Rotation Franklin D. Adkinson Jr., MD, Outpatient Center E-Mail vegaseidler@yahoo.de
Research Topic see Abstract
Personal Reactions to the U.S. Experience The best thing about my stay in the U.S. was the chance to be at Johns Hopkins University and to experience both basic and clinical research there. I went to the immunology class for first year medical students and was impressed by the level of the lectures. Also the research and clinical conferences in the Division and interdisciplinary talks at the main hospital were of inestimable value. Research opportunities were impressive. I had the chance to pursue my own project and was continuously and effectively encouraged by my supervisor. Advice from clinical and research fellows in the Division was always available. There were a lot of helpful comments and criticism that motivated me during my work. Besides the research work, I spent most Thursdays in the clinic with the allergist, Dr. Adkinson, which was a very good experience and complemented my research work with a clinical perspective. Besides my work, I took every opportunity to explore other cities in the USA, as Baltimore is certainly not representative of the rest of the country. I enjoyed visiting New York, San Francisco, and also Washington D.C. a lot, and didn't miss a chance to go away for the weekends. We also went hiking in Virginia, New York State and even went to Canada and Niagara Falls.
Greatest Difficulties Encountered Following the events of September 11th, the start here was somewhat complicated and not the most favorable. There was a feeling of unease and vulnerability throughout the whole country. The acclimatization was even more difficult as the reaction to the terrorist attacks among many Americans included a surge of nationalism. Debating these issues with fellows and students was not always easy, as our political views were considerably different. After a certain time period, I realized that I was starting to avoid political discussions. Having said that, there were also many foreign students and some Americans who experienced similar reactions to the events that I had, which made me feel less isolated. In addition, as far as the city of Baltimore itself is concerned, well… I have to admit that I wasn't really thrilled. A lot of positive thinking is required to like it.
Most humorous incident The fact that people start to scream when they see somebody on a bike. One of the fellows used to wear a helmet when riding a bike, not only because of the cars, but because people used to throw things at him.
Helpful Hints for Future Students For the students who decide to go to Johns Hopkins, make sure you can afford the obligatory health insurance (even if you have a German one) and the special Johns Hopkins registration fee (or ask your supervisor if he/she would agree to pay it). I would suggest having German health insurance as well, as you still have to pay 20% of both doctor's visits and prescriptions, which can be quite a lot (especially here). Make sure you find a nice and safe place to stay, because the main hospital campus is not in the nicest area. Think seriously about buying a car, as it can be quite adventurous to survive without one - although I did (so far). Enjoy your stay at Hopkins!
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Abstract on Research Topic:
Leukocyte migration in a human skin equivalent: Testskin(TM)

Authors:
Vega Seidler; Carol Bickel, MA.; Lisa A. Beck, MD; Bruce S. Bochner, MD; Robert P. Schleime,r PhD

Institution at which research was done:
Asthma and Allergy Center, Division of Clinical Immunology, Johns Hopkins University School of Medicine

Introduction:
Our laboratories focus on the molecular and cellular mechanisms of inflammatory cell recruitment characteristically found in asthma and other allergic diseases. Molecular characterization of expressed eosinophil products, adhesion molecules on leukocytes and endothelium, and specific chemoattractant molecules is ongoing. The regulation of the transcription of genes important in these processes is also being analyzed. The mechanism of action of anti-inflammatory steroids in the treatment of allergic disorders is being actively studied.

Purpose:
Skin diseases such as atopic dermatitis and psoriasis are characterized by invasion of leukocytes into lesional skin. We have attempted to establish a model for leukocyte trafficking in human skin using the tissue engineered product Testskin(TM) (supplied by Organogenesis Inc.), which consists of human keratinocytes grown on a bed of fibroblasts and which recapitulates remarkably well the structural organization of human skin. Our goal is to stimulate keratinocytes as well as fibroblasts with pro-inflammatory stimuli known to induce the production of chemokines that recruit leukocytes. By providing leukocytes to the system we intend to study the magnitude, kinetics and specificity of the resultant leukocyte migration.

Materials and Methods:
We use TestskinTM as a human skin equivalent. The skin is pre- or co-stimulated for different time periods with IL-4, IFNg, fMLP, TNFa, IL-13, IL-8, LPS, corticosteroids or Fas-antibody. Leukocytes are co-incubated with the skin. Leukocytes are derived either from normal donors and then primed with growth factors such as GMCSF or IL-5 or isolated from donors with active atopic dermatitis or psoriasis. Chemokine production is verified with ELISA. Skin samples are fixed, sectioned, and stained to evaluate leukocyte migration.

Preliminary Results:
Stimuli such as TNFa cause dose- and time-dependent effects on keratinocytes, fibroblasts and leukocytes. We observed what appear to be apoptotic responses in keratinocytes as well as fibroblasts with TNFa and anti-Fas antibody treatment. Glucocorticoids modified these effects on keratinocytes depending on the stimulus. Adhesion of leukocytes to the base of the dermis and modest invasion of neutrophils into the dermis was seen after treatment of the skin with IL-8.

Conclusion:
Testskin(TM) may provide a useful model for studies of the pathogenesis of inflammatory skin diseases. We need to further optimize this system, so that we can study the process of invasion of leukocytes into the skin. Ideally, the process of transmigration of leukocytes through vessels into the dermis could be mimicked by including endothelial cell cultures in the protocol.

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