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Biomedical subjects

L Juhlin

Publications and source records attributed to L Juhlin.

At least 37 records · Page 2Linked to original sources

Vitiligo.

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Anesthetics, Local↗

Comparison of fluticasone propionate cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, in the treatment of eczema.

This is a randomized, double-blind, parallel-group, multicenter study involving 120 patients comparing the safety and tolerability of two midpotency topical preparations, fluticasone propionate cream, 0.05%, and hydrocortisone-17-butyrate cream, 0.1%, in the treatment of moderate-to-severe eczema. Safety of the study medications was determined over a twelve-week period using laboratory tests for selected fasting blood chemical levels, hematologic analysis, urinalysis, and morning plasma cortisol levels, and by analyzing both the nature and frequency of reported adverse events. Efficacy was evaluated during the first four weeks of the study. None of the fluticasone-treated patients experienced any severe drug-related adverse events, but one hydrocortisone-17-butyrate-treated patient's eczema was severely exacerbated by drug therapy. Plasma cortisol monitoring revealed minimal hypothalamic-pituitary-adrenal axis suppression. Overall, the nature of drug-related adverse events in patients as young as 12 years old treated with fluticasone propionate cream, 0.05%, indicates this topical application was safe and well tolerated throughout the twelve-week study. Fluticasone cream was also found to be similar in efficacy to hydrocortisone-17-butyrate cream.

Administration, Topical↗

The PML growth-suppressor has an altered expression in human oncogenesis.

Altered sub-nuclear localisation of the nuclear body-associated PML protein in acute promyelocytic leukaemia, has been proposed to contribute to leukaemogenesis. We have recently shown that PML is a primary target gene of interferons. Here, it is shown that PML has growth suppressive properties and displays an altered expression pattern during human oncogenesis. PML is widely expressed in cell-lines and is cell-cycle regulated. Overexpression of the protein induces a sharp reduction in growth rates in vitro and in vivo. In contrast with cell-lines, in normal tissues (including those that rapidly proliferate) only a few cells have detectable PML levels. However, these can be upregulated by soluble factors (e.g. IFN, estrogens). Human epithelial tumors show a gradual increase of PML levels as the lesion progresses from benign dysplasia to carcinoma. A similar induction is found in the surrounding stroma and vessels, which likely results from paracrine interactions. Strikingly, when malignant cells turn invasive, they loose PML expression, while expression is conserved in the stromal compartment. These observations point to the existence of a consistent deregulation in the expression of the PML growth-suppressor during human oncogenesis.

Animals↗

Transplantation of melanocytes in vitiligo.

We report the results of a study on 100 patients (aged 12-68) with vitiligo, who were treated by transplantation of cultured autologous melanocytes to the depigmented areas, after removal of the epidermis at the recipient site by dermabrasion. The melanocytes were cultured from a 2 x 3 cm2 superficial shave biopsy taken from pigmented buttock skin. After 2-3 weeks in culture, 700-1000 cells per mm2 were applied on 60-500 cm2 dermabraded areas, and occluded for 1 week. The repigmented portion of the total treated area amounted to 95-100% in 40 patients, 65-94% in 32, 20-64% in 22, and 0-19% in six. It was more difficult to achieve complete pigmentation on the fingers, elbows and knees. In the first few months following the procedure, the treated areas were often hypo- or hyperpigmented, but after 6-8 months they had acquired the same colour as the surrounding skin. No scarring or other side-effects occurred. The donor site had repigmented after 3-6 months in all but two patients, who also showed poor pigmentation in the transplanted areas. At follow-up after 1 and 2 years in 50 and 10 patients, respectively, the repigmented areas remained unchanged. The method is time-consuming, but the results obtained indicate that the procedure can be valuable in motivated patients, when the extent of vitiligo does not exceed 30% of the total body area, and when the areas to be treated are not actively extending.

Adolescent↗

Synthesis of an N-methyldehydroalanine-containing fragment of microcystin by combination of solid phase peptide synthesis and beta-elimination in solution.

A new method for the synthesis of dehydroalanine (delta Ala)-containing peptides has been developed by combining solid phase peptide synthesis (tert-butyloxycarbonyl/HF-chemistry) with solution synthesis. A sequence from cyanobacterial hepatotoxin microcystin, Ac-D-gamma-Glu-[N-Me-delta Ala]-D-Ala-Leu amide was chosen as a model peptide. The precursor for the synthesis of the dehydroalanine-containing peptide, Ac-D-gamma-Glu-[N,S-diMeCys]-D-Ala-Leu, was synthesized on a solid phase followed by sulfonium salt formation on the resin. The resulting S,S-dimethylated peptide was cleaved from the resin with liquid HF. The HPLC-purified S,S-dimethylated cysteine-containing precursor peptide was subjected to beta-elimination in solution catalysed by DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in methanol. The final product, Ac-D-gamma-Glu-[N-Me-delta Ala]-D-Ala-Leu amide, was purified by HPLC, and analysed by mass spectrometry and 1H NMR spectroscopy. The stability of the model peptide under acidic, neutral and basic conditions has been studied.

Alanine↗

Histochemical studies of hyaluronan and the hyaluronan receptor ICAM-1 in psoriasis.

Histochemical stainings of frozen sections of human normal and psoriatic skin were used to study the localization of hyaluronan (HA) and intercellular adhesion molecule 1 (ICAM-1). HA staining was found in all areas of the skin, with the exception of the stratum corneum, in both normal and psoriatic cases without any apparent quantitative differences between the conditions. The staining for ICAM-1 was detected in vessels in normal skin and at lower levels in normal areas of the skin in patients with psoriasis. However, in these patients the staining increased to about the same level as in normal skin after hyaluronidase treatment of the sections prior to staining. In psoriatic lesions, distinct staining for ICAM-1 was localized mainly to vessels and infiltrating leukocytes. Treatment of the sections with hyaluronidase increased the staining of vessels only slightly, but more strongly around leukocytes. These findings show that ICAM-1 is predominantly free from bound HA on vessel endothelium in psoriasis lesions but not on vessels in normal areas of the skin, and suggests that systematically administered HA, previously shown to reduce chronic inflammation in animal models, might have a beneficial effect in psoriasis via blocking of endothelial ICAM-1 and thereby causing a reduced invasion of leukocytes into the skin.

Histocytochemistry↗

Vitiligo: repigmentation with cultured melanocytes after cryostorage.

We have developed a technique through which we can multiply melanocytes in culture from a small specimen of normally pigmented buttock skin and reimplant them into depigmented sites of vitiligo. To date, 90 patients have benefited in our hands from such autologous transplantation of pigment cells. Often we have an excess of cells which we would like to store for later use in the event a patient requires further treatment. We report here on 4 cases in which we have cryostored cultured melanocytes for 6-12 months, reimplanted them into vitiliginous sites of the donor after one week of reculture, and obtained optimal repigmentation. We now routinely freeze melanocytes left over after treatment.

Adult↗

CT-diagnosis of deep-seated lipomas with alarming symptoms.

Deep-seated lipomas can present with symptoms very different from those of the common subcutaneous variety. Rapid growth and nerve encroachment may cause suspicion of malignancy. The case histories as well as the clinical and radiographic findings of 2 patients with alarming symptoms from deep-seated lipomas of hand and forearm, respectively, are described. By means of CT an accurate preoperative diagnosis could be made, and surgery planned accordingly.

Adult↗

Intensity and area increase of UVB-induced erythema: two variables used for studies of the influence of topically applied drugs.

The area of UV erythema produced by a small beam head was found to increase with increasing doses. The aim was to investigate whether measurement of the area could be a more useful indicator of UV-induced damage than classic visual grading. Topical pretreatment with all-trans retinoic acid (tretinoin) and betamethasone valerate was used to test the applicability of the method in pharmacological studies. We used a round outlet head (5 mm2) connected by optical fibre to a monochromatic irradiator, and doses ranging from 0.05 to 0.2 Joule of 300 mm UV light were applied to the skin of 6 healthy subjects. Erythemal area was calculated by the measurement of two diameters, and intensity was graded visually (0-6 scale). The area of the erythema correlated with the increase in intensity up to score 6. Area measurement was less subject to intra-investigators' variability than the intensity score. By multiplying intensity by area, a good indicator of UV-induced reactivity was obtained. Pretreatment with betamethasone valerate decreased the area of erythema, as did tretinoin 12 h after irradiation. Thus, area measurement of erythema is a useful adjunct to visual grading of UV-induced skin reactions.

Administration, Cutaneous↗

Differential expression of calgranulin A and B in various epithelial cell lines and reconstructed epidermis.

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.

Antibodies, Monoclonal↗

A new marker of epidermal differentiation associated with the membrane coating granules: characterization and applications to pathology.

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.

Antibodies, Monoclonal↗