Melanocyte transplantation in vitiligo.
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Biomedical subjects
Publications and source records attributed to L Juhlin.
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The monoclonal antibody F12, raised against epidermal cells from a psoriatic lesion, decorated antigens highly expressed in psoriatic epidermis and in cultured normal human keratinocytes. In normal human skin, F12 reacted only with follicular keratinocytes. Characterization of the immunoprecipitated antigens by two-dimensional gel electrophoresis revealed their identity with calgranulin A and B. A semiquantitative study with various established epithelial cell lines demonstrated that the expression of calgranulin A and B in hyperproliferative keratinocytes correlates with their potential to undergo terminal differentiation. In epidermis reconstructed in vitro, the antigen expression was stimulated by retinoids and suppressed under vitamin A starvation.
A murine monoclonal antibody, BC12, was obtained after immunization against suprabasal human keratinocytes. In the epidermis of normal human skin, the antigen recognized by BC12 (BC12 antigen) is located at the apex of keratinocytes in the upper stratum spinosum and stratum granulosum but is absent in other layers. The BC12 antigen is also present in hair follicles. Immunoblotting performed on keratinocyte subpopulations confirmed the presence of the BC12 antigen in differentiated keratinocytes only. Two-dimensional immunoblotting showed that the BC12 antigen corresponds to a set of polypeptides with an apparent molecular weight of approximately 33kD. In keratinocyte cultures, the antigen is present only in stratified areas. The distribution of the BC12 antigen, as studied by indirect immunofluorescence and immunoelectron microscopy, and its presence in certain subcellular fractions of epidermal cells suggest that it is a component of membrane coating granules (MCGs) or that it is associated with these structures. Strikingly, in psoriasis, eczema and many other diseases, the BC12 antibody does not label the epidermis, but vessels in dermal papillae. The BC12 antibody may thus be a useful tool in the study of keratinocyte differentiation and MCG physiology, and, also, in pathology.
The effects of one week's daily treatment with dexchlorpheniramine (3 + 3 mg x 2) and loratadine (10 mg x 2) on the cutaneous reactions to putative mediators of urticarial reactions were studied in healthy subjects and in patients with chronic urticaria. Biopsy specimens were taken from skin with delayed reactions and studied immunohistochemically for the presence of eosinophilic cationic protein (ECP). In healthy subjects both antihistamines significantly decreased the weal and flare induced by histamine and the histamine releaser compound 48/80. They also reduced the flare seen after injection of PAF (platelet activating factor) and kallikrein. In patients with chronic urticaria the delayed reactions to PAF and kallikrein were larger than in healthy subjects. The immediate flare seen after injection of histamine, 48/80 and PAF, and the delayed reaction to 48/80, were significantly decreased by treatment with loratadine. No correlation was found between the clinical response and test reactions. In the group of healthy subjects, eosinophils were increased in the skin of all subjects after intradermal injection of 100 micrograms of PAF and in 50% after 1 microgram of PAF, but no eosinophils were seen after injection of 1 ng of PAF. In patients with chronic urticaria the eosinophils were increased at all sites where 1 ng of PAF had been injected and also at a limited number of sites of injection of histamine, 48/80, kallikrein and saline. Treatment with the antihistamines had no effect on the influx of eosinophils in the skin.
The inhibition of erythema by drugs applied topically after irradiation with 0.2-0.8 J of 313 nm has been studied in healthy volunteers. Indomethacin and piroxicam markedly inhibited the erythema at 6 to 24 h after irradiation but erythema reappeared at 45 h. The results reported suggest that the UVB response is biphasic with an early phase responsive to nonsteroid anti-inflammatory drugs and a late phase which is not responsive. No effect on the intensity of the erythema was seen with betamethasone chloroquine and cetirizine. Oral intake of aspirin before and/or after irradiation did not influence the UV response.
Loricrin, the major component of the cornified envelope, is normally expressed in the granular layer of epidermis during the last steps of keratinocyte differentiation. Using an antiloricrin antiserum (A8-73), an increased expression of this envelope precursor was found in some disorders of hyperorthokeratosis (ichthyosiform erythroderma; lichen ruber), but not in others (keratodermia ichthyosis vulgaris). In disorders accompanied by parakeratosis, a sign of incomplete differentiation (psoriasis, prurigo nodularis) loricrin was not detected, whereas the tissue expressed filaggrin. Treatment of normal skin with retinoic acid, increasing epidermal thickness in some subjects, led to an increased expression of loricrin. Loricrin might be a useful indicator of the extent of terminal epidermal differentiation in skin disorders.
Biopsies of normal and diseased skin were immunohistochemically investigated for the presence of parathyroid hormone-related protein (PTH-rp). In normal skin and several skin disorders a monoclonal antibody against the 34-68 sequence of PTH-rp was found to be exclusively located in the granular layer. PTH-rp could not be detected in untreated psoriatic plaque lesions even when a granular layer was present. Psoriatic lesions improving after 1-2 weeks' treatment with betamethasone or vitamin D3 analogue revealed PTH-rp reactivity just above the granular layer. These findings substantiate a possible role for PTH-rp as a growth inhibitor. In the dermis the granular layer in the upper part of the hair follicles was stained for PTH-rp and the dermal infiltrates in 5 of 10 patients were stained with mycosis fungoides.
Given the variability of patient problems, it is difficult to construct a single drug therapy regimen for treatment of chronic urticaria. However, the following regimen should prove to be a useful outline to follow for most cases. The first line of therapy will usually be antihistamines. In general, antihistamines should be always used on a regular basis and not only after hives occur. If drowsiness or anticholinergic adverse symptoms limit the use of one drug in effective doses, other H1-blockers should be tried. For day-time use, the newer, less sedating antihistamines are preferred. If antihistamines fail to control symptoms when used at full doses, addition of glucocorticosteroids can be tried for short periods. Most patients respond to doses equivalent to 40 mg of prednisone daily. The end point of use of corticosteroids is to reach quickly an effective low, alternate-day dose followed by their discontinuation.
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The objective of this study was to compare the clinical efficacy and acceptability of two dithranol creams (Micanol and Amitase) in patients with plaque type psoriasis treating themselves daily at home. Thirty-five patients started with Amitase (0.1%) and 37 with Micanol (0.1%) applied at night in this 6-week single-blind parallel groups comparison study. Patients who responded more slowly than a theoretically estimated "standard" rate of improvement had their concentration increased to 0.25% at the visit after 2 or 4 weeks. By the end of the study slightly more than half of the number of patients remained on 0.1%. There was no difference between the treatment groups. In comparison with the level at start the composite sign severity score for patients in the Amitase group was reduced by 24% after 1 week, 36% after 2 weeks, 49% after 4 weeks and 62% after 6 weeks. The reduction in the Micanol group was similar. Patients in the Micanol group showed after 1 week of treatment more irritative reactions than patients in the Amitase group. At all follow-up visits, staining of perilesional skin was more prevalent in the Micanol group. Staining of clothing was, however, far more prevalent and severe for patients given the Amitase cream. It may be concluded that Micanol is an important alternative for home treatment of psoriasis.
Dermatographism and cold-induced urticaria are two common physical urticarias. Traditional treatment with antihistamines has been somewhat effective in alleviating symptoms; however, the sedative side effects of the agents pose problems. Results of treatment with the new low-sedating H1 antihistamines have been encouraging.
In atopic subjects, intradermal injection of platelet-activating factor (PAF), 40 and 400 ng, resulted in an immediate edema reaction markedly blocked by cetirizine, 10 mg twice a day. PAF challenge also induced a significant eosinophil accumulation evidenced by a skin window technique at 2, 4, 8 and 24 h. This inflammatory phenomenon was significantly inhibited by cetirizine. In patients with chronic urticaria, PAF, 100 micrograms intradermally, induced immediate and late cutaneous reactions (LCR) also blocked by cetirizine, 10 mg twice a day. These LCR were accompanied by an infiltration of the deep dermis by degranulated eosinophils. The pathophysiological mechanism of the PAF-induced skin reactions is discussed as well as the mechanism of action of cetirizine.
Eosinophil cationic protein (ECP) is exclusively secreted only by the eosinophilic leukocyte. In this study the ECP concentration in the serum was measured in patients (n = 155) with various skin disorders and compared with the number of circulating eosinophils. The presence of activated eosinophils in the skin was also studied immunohistochemically using the monoclonal antibody EG-2, which recognizes both the eosinophil protein X (EPX/EDN) and ECP. EG-2 distinctly revealed these proteins in the eosinophils and their granules. Non-activated eosinophils were studied with the monoclonal antibody EG-1. In most cases this did not disclose any more eosinophils and often it was located more diffusely and not seldom on collagen fibers. Elevated serum ECP but normal numbers of circulating eosinophils were found in half of the patients with progressive plaque psoriasis and long-standing daily chronic urticaria. In patients with prurigo nodularis, papular erythematous eruptions, vasculitis, purpura and toxic drug reactions, Wells' syndrome, porphyria cutanea tarda and persistent light reaction the serum ECP was increased, although in some cases the number of circulating eosinophils was normal. In these disorders an increased number of activated eosinophils was found in the skin. Both serum ECP and the number of activated eosinophils normalized when the patients' condition improved. In atopic dermatitis the serum ECP and the number of activated eosinophils in the skin were increased only during exacerbation of the disease. High serum levels of ECP and activated eosinophils in the skin are frequent findings in many skin disorders in spite of often normal blood eosinophil counts.(ABSTRACT TRUNCATED AT 250 WORDS)
Osteoid osteoma is infrequently localized to the hand. Initially the lesion causes unspecific symptoms, and the radiographic changes are discrete. Three cases were seen during a period of 5 years. Bone scintigraphy was a useful diagnostic tool, and CT facilitated the identification of the nidus. One of the lesions was a double nidus osteoid osteoma of the scaphoid bone. Only 12 instances of multifocal osteoid osteomas have been reported, none of which was localized to the carpal bones.
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The effects of oral administration of the antihistamine cetirizine on the weal and flare caused by intradermal injection of platelet activating factor (PAF-acether), kallikrein, histamine and the patient's own serum were investigated in 10 patients with chronic urticaria. Cetirizine markedly reduced the weal and flare induced by all these agents as measured 12 min after the injections. The delayed reactions observed after injection of PAF, kallikrein and serum were also inhibited by cetirizine at 6 hours. In addition, reactions which were present 20 h after injection of the agent before administration of cetirizine were found to be inhibited at the same point in time after cetirizine treatment. These effects might explain the good inhibitory clinical effect of cetirizine on the patients' urticaria. No side-effects were noted during the treatment.
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