Biomedical subjects

A Vahlquist

Publications and source records attributed to A Vahlquist.

130 records · Page 8Linked to original sources

PubMedDate not supplied

Impaired release of vitamin A from liver in primary biliary cirrhosis.

In 44 patients with primary biliary cirrhosis serum levels of vitamin A, retinol-binding protein and transthyretin (prealbumin) were found to be significantly lower than in 25 sex- and age-matched controls. Liver biopsies were available for chemical analyses in 28 of the patients. Their mean liver vitamin A concentration (2.8 +/- 2.0 mumoles per gm wet weight) did not differ significantly from that in 22 cases of sudden death which served as controls (2.0 +/- 1.5 mumoles per gm wet weight). Immunohistochemical investigation showed a normal distribution of serum retinol-binding protein in the patients' livers, whereas the staining pattern of cellular retinol-binding protein, believed to be involved in the intrahepatic transport of vitamin A, was abnormal. Thus, the number size and cellular retinol-binding protein staining intensity of fat-storing (Ito) cells were clearly higher in the patients as compared with controls. The results suggest that the low serum vitamin A levels in primary biliary cirrhosis are not a consequence of vitamin A deficiency but instead reflect a defective mobilization of vitamin A from the liver.

Female↗

PubMedDate not supplied

Uptake of vitamin A and retinol-binding protein by human placenta in vitro.

The mechanisms involved in the transplacental passage of vitamin A bound to serum retinol-binding protein (RBP) were investigated. Samples of full-term human placenta were incubated for up to 3 h with 125I-RBP or [3H]retinol-RBP. The tissue 125I activity was monitored in washed, whole samples, while [3H]retinol was extracted from homogenized samples and separated by high-pressure liquid chromatography before counting. An accumulation of [3H]retinol and, to a much lesser degree, of 125I-RBP was noted. The placental uptake of both compounds was dependent on temperature and could be inhibited by adding unlabelled retinol-RBP. About 40 per cent of the tritium activity consisted of retinyl esters formed after the uptake of [3H]retinol. When washed placental specimens were postincubated for a few hours in a tracer-free medium, about 25 per cent of the 125I activity and 80 per cent of the tritium activity were released into the medium, provided that it was supplemented with fetal serum. The results illustrate two possible mechanisms by which vitamin A can pass the placental membranes: a direct transfer of retinol-RBP involving cellular uptake and release of the protein-ligand complex; cellular uptake of retinol by a cell-surface receptor specific for RBP, transient esterification of retinol, and release of the vitamin into fetal serum.

Biological Transport↗

PubMedDate not supplied

Decreased mRNA levels of retinoic acid receptor alpha, retinoid X receptor alpha and thyroid hormone receptor alpha in lesional psoriatic skin.

Retinoic acid, vitamin D3 and triiodothyronine regulate keratinocyte proliferation and differentiation--processes that are disturbed in psoriatic skin--via binding to nuclear receptors for retinoic acid (RAR-alpha,-gamma), vitamin D3 (VDR), thyroid hormone (TR-alpha,-beta) plus the common heterodimer partners, the 9-cis-retinoic acid receptors (RXR-alpha,-beta). By using a new quantitative real-time polymerase chain reaction assay, the expression of these receptors and three housekeeping genes (cyclophilin, GAPDH and beta-actin) was studied in psoriatic skin. The expression of housekeeping genes was consistently 2.7-4.3 times higher in lesional than in non-lesional skin. When the beta-actin expression was used to normalize the receptor mRNA values, the RARalpha, RXRalpha and TRalpha transcripts were found to be 58-75% lower in lesional vs. non-lesional skin and the RXRalpha:RARgamma ratio was reduced from 3.2 to 1.5. Topical treatment for 4 days with 0.025% all-trans-retinoic acid or calcipotriol under occlusion did not normalize the altered mRNA expression of RARs, RXR and VDR in lesional skin. The results suggest that retinoid and thyroid hormone signalling is abnormal in lesional psoriatic skin, but how this relates to the pathogenesis of the disease is still unclear.

Calcitriol↗

PubMedDate not supplied

Phenotypic/genotypic correlations in patients with epidermolytic hyperkeratosis and the effects of retinoid therapy on keratin expression.

Dominant-negative mutations in the KRT1 and KRT10 genes cause epidermolytic hyperkeratosis, a rare form of ichthyosis sometimes associated with palmoplantar keratoderma. Although there is no permanent cure, some patients improve on retinoid therapy. More knowledge is needed, however, about the mechanism of action of retinoids and the genotypic/phenotypic correlations in this disease. Thirteen patients from 10 families with generalized disease and 2 sporadic patients with nevoid lesions were studied, probably representing most of the patients in Sweden and Norway. All patients, except one nevoid case, were known to have KRT1 or KRT10 mutations. Those with mutated keratin 1 (K1) invariably had associated keratoderma (n=6). In contrast, only 1 of 7 patients with K10 mutations had this problem (p = 0.0047). Five out of 6 patients with KRT10 mutations benefited from treatment with oral acitretin (5-25mg/day) or topical tretinoin/tazarotene, but none of the patients with KRT1 mutations derived any benefit. Quantitative analysis of K1 and K10 mRNA in skin biopsies obtained before and after retinoid therapy (n=8) showed no consistent down-regulation of mutated keratin that would explain the therapeutic outcome. Instead, the mRNA expression of K2e (a normal constituent of the upper epidermis) diminished especially in nonresponders. In contrast, K4 mRNA and protein (marker of retinoid bioactivity in normal epidermis) increased in almost all retinoid-treated patients. In conclusion, our study confirms a strong association between KRT1 mutations and palmoplantar keratoderma. Retinoid therapy is particularly effective in patients with KRT10 mutations possibly because they are less vulnerable to a down-regulation of K2e, potentially functioning as a substitute for the mutated protein in patients with KRT1 mutations.

Adolescent↗