Dermato-Venereology in the Nordic Countries
Looking Back on 45 Years of Research Activity
ANDERS VAHLQUIST
Department of Dermatology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
E-mail: anders.vahlquist@medsci.uu.se
It all started in 1969, when I interrupted medical school at
Uppsala University for 3 years, starting as a PhD student at
the Department of Medical and Physiological Chemistry (Fig.
1). My tutor had recently puri?ed a vitamin A transporting
low-molecular weight protein from human urine that turned
out to be identical to the retinol-binding protein (RBP) concurrently discovered at Columbia University. My task was to ?nd a
more ef?cient way to purify RBP and to characterise its turnover in humans by injecting small amounts of radiolabelled
protein into the blood stream. Turnover studies in healthy
volunteers (including myself) showed a very short half-life
of RBP, whereas in haemodialysis patients the half-life was
markedly prolonged. This is consistent with a physiological
model whereby the free fraction of plasma RBP – unbound to
its complex partner thyroxine-binding prealbumin – is easily
?ltrated through the glomeruli and subsequently reabsorbed
in the tubuli. This model explains why chronic renal failure
leads to an accumulation of RBP (and vitamin A) in blood,
whereas tubular necrosis yields proteinuria containing high
amounts of RBP.
My thesis in 1972 encouraged future studies on the transport
and function of vitamin A, an exciting research ?eld not
least in the mid 70s when cellular binding proteins for both
retinol and retinoic acid were discovered and new retinoid
analogues were being synthesised as promising remedies for
both cancer, acne and certain disorders of keratinisation.
No wonder I got interested in dermatology when choosing
specialist training in 1976, especially as Professors Lennart
Juhlin and Gerd Michaëlsson at the skin clinic in Uppsala
were already pursuing research on vitamin A and zinc, and
previous Swedish researchers had shown spectacular results of
high-dose vitamin A therapy in a rare genodermatosis (Fig. 2).
My aim was to establish a technique for measuring vitamin
A levels in the skin and to screen patients with keratinising
disorders, looking for abnormalities in the cutaneous vitamin
A composition that might be related to the pathogenesis of
the diseases and explain the frequent therapeutic success with
high-doses of vitamin A or synthetic retinoids.
A new method called high-pressure liquid chromatography
(HPLC) turned out to be a breakthrough in analysing minute
amounts of retinoids in tissue extracts. Thus, in a super?cial
shave biopsy it became possible to detect as little as 1 ng of
142
retinol in epidermis. Other retinoids were also separated
on the HPLC column and could subsequently be collected
from the out?ow. This approach enabled me to identify a
totally unanticipated form of vitamin A in human skin, viz.
3,4-didehydroretinol or vitamin A2. High amounts of this
compound, previously known to occur in certain amphibians,
were found in biopsies from psoriatic and Darier disease skin,
possibly indicating abnormal vitamin A signalling in diseased
keratinocytes.
In the beginning of the 1980s, together with 3 PhD students,
Ola Rollman, Berit Berne and Hans Törmä, our studies were focused on the tissue distribution of both natural and synthetic
retinoids in normal and diseased skin, on the interaction between UV irradiation and retinoids, and on the metabolism of
retinol in cultured cells involving its delivery via RBP receptors
to keratinocytes and subsequent transformation into 3,4-didehydroretinol, retinyl esters and retinoic acid. Although
much was learnt from these studies, and our achievements
were grati?ed with several reseach awards (Fig. 3), our main
hypothesis that inborn errors of vitamin A metabolism might
explain certain disorders of keratinisation was never veri?ed.
Fig. 1. Experimenting as PhD-student in 1969 at the Department of
Medical and Physiological Chemistry, Uppsala University.
Forum for Nord Derm Ven 2013, Vol. 18, No. 4