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Biomedical subjects

S Reitamo

Publications and source records attributed to S Reitamo.

At least 19 recordsLinked to original sources

Leukoregulin, a T cell-derived cytokine, induces IL-8 gene expression and secretion in human skin fibroblasts. Demonstration and secretion in human skin fibroblasts. Demonstration of enhanced NF-kappa B binding and NF-kappa B-driven promoter activity.

It was shown previously that leukoregulin (LR), a T cell-derived cytokine with unique antitumor properties, modulates fibroblast functions in vitro, including prostaglandin production, matrix synthesis, and protease gene expression. Here, we have focused on the ability of LR to modulate IL-8 gene expression in human dermal fibroblasts. Using a specific ELISA, we demonstrated a dose-dependent enhancement of IL-8 production by LR, accompanied by a parallel elevation of the corresponding mRNA levels, as measured by Northern hybridizations. Maximum accumulation of IL-8 mRNA was observed after 6 h of incubation with LR, and the elevation persisted over 24 h. Inhibition of protein synthesis by cycloheximide resulted in superinduction of IL-8 mRNAs by LR. Dexamethasone, all-trans-retinoic acid, and TGF-beta 1 failed to counteract the effect of LR on IL-8 gene expression. Transient cell transfections with an IL-8 promoter/CAT reporter gene construct showed a dose-dependent enhancement of the promoter activity by LR, suggesting transcriptional regulation. Gel shift assays with oligonucleotides containing the consensus NF-kappa B binding sequences of the IL-8 and Ig kappa light chain genes showed enhanced binding activity in nuclear extracts from cells incubated with LR. Transient transfection experiments using a NF-kappa B/SV2 promoter-CAT reporter gene construct showed enhanced CAT activity by LR. Taken together, these data suggest that LR may up-regulate IL-8 gene expression by activation of the binding of NF-kappa B to the corresponding cis-acting element in the IL-8 promoter. Our results demonstrate that LR, together with IL-1 and TNF-alpha, could participate in the recruitment of neutrophils to the sites of inflammation by induction of IL-8 production in fibroblasts.

Antineoplastic Agents

Cyclosporin for palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by persistent erythematous, scaly plaques incorporating sterile pustules on palms and soles, which is resistant to most treatments. Recently, two published uncontrolled studies suggested that cyclosporin (CsA) could be an effective treatment for PPP. Similarly, an unpublished, randomized, placebo-controlled study showed that CsA is effective in preventing new pustule formation in PPP. In the present paper we review the treatment of PPP with special emphasis on CsA treatment.

Cyclosporine

Interleukin-8 immunoreactivity in the skin of healthy subjects and patients with palmoplantar pustulosis and psoriasis.

Previous studies have shown that neutrophil-activating peptide 1/interleukin-8 (IL-8) is present in psoriatic scales and to a lesser extent in normal human epidermis. A panel of monoclonal antibodies and polyclonal antisera raised against IL-8 was used to localize IL-8 with immunoperoxidase techniques in non-lesional and lesional skin of patients with psoriasis and palmo-plantar pustulosis (PPP), and in corresponding sites from healthy subjects. Intracellular IL-8 immunoreactivity was found in all epidermal cell layers in biopsies of healthy subjects and in non-lesional and lesional skin in both PPP and psoriasis. The most intense immunolabeling was regularly found in the basal cell layer. Intercellular epidermal IL-8 immunolabeling was regularly detected in lesional biopsies in PPP and psoriasis, but not in healthy subjects or non-lesional skin in PPP and psoriasis. No intercellular immunolabeling was detected after successful treatment of lesional skin. The majority of cells along the eccrine sweat glands, dermal mononuclear cell infiltrates, and endothelial cells were IL-8 immunoreactive in all biopsies studied. The present study suggests that IL-8, its precursor form, or, alternatively, a degradation product is present in normal human epidermis.

Humans

Interleukin 1 immunoreactivity in sebaceous glands.

Interleukin 1 (IL-1) immunoreactivity in sebaceous glands was studied in paraffin sections of normal human skin. A panel of antibodies against IL-1 alpha and beta was tested using an immunoperoxidase labelling method. All the antibodies showed a similar specific labelling pattern: both glandular and ductal cells were immunoreactive for both IL-1 alpha and beta, provided optimal tissue fixation was used.

Adult

Signal transduction pathways leading to the production of IL-8 by human monocytes are differentially regulated by dexamethasone.

Previous studies have shown that IL-8 gene expression is enhanced by various stimuli, which induce different signal transduction pathways. A lipopolysaccharide (LPS)-induced pathway has been reported to be inhibited by glucocorticoids in monocytes. We have now examined the effect of dexamethasone on the LPS-induced and other signal transduction pathways leading to the production of IL-8 by human monocytes. Dexamethasone inhibited the production of IL-8 stimulated with a cyclic adenosine monophosphate analog or LPS. In contrast, dexamethasone had no significant effect on a phorbol ester (PMA)-stimulated IL-8 production. These results suggest that the signal transduction pathways leading to the production of IL-8 by human monocytes are differentially regulated by dexamethasone.

Bucladesine

Contact allergy to tioconazole.

In 15 months, we detected allergic patch test reactions to tioconazole in 14 patients. 9 of the 14 patients were allergic to additional imidazole derivatives used as antifungal agents. The positive patch test reactions to tioconazole may have been caused either by simultaneous sensitization or more probably by cross-reactivity between the various commercially used imidazole derivatives with a similar chemical structure. The abundant use of tioconazole in concentrated (up to 28%) topical formulations in Finland could be the major cause of the apparent increase in allergic reactions.

Administration, Cutaneous

Suction blister fluid histamine in fixed drug eruption.

The histamine concentration was measured from suction blister fluid obtained from normal and lesional skin of 8 patients with fixed drug eruption (FDE) caused by phenazone salicylate and from that of 2 healthy control subjects. In blister fluid samples obtained before peroral challenge with phenazone salicylate, the histamine concentrations were below 5 nmol/l both in uninvolved skin and in sites of previous FDE lesion (sample 0). After challenge, samples were taken from the incipient reaction that was visible after an average of 155 min. Histamine levels were significantly elevated in the blister fluid of 2 out of 8 FDE lesions (200 and 640 nmol/l) but in none of the uninvolved skin (sample 1). Two hours later (sample 2) the histamine levels were elevated in both uninvolved (mean 51.4 nmol/l) and lesional skin (mean 168 nmol/l). After 24 h (sample 3) the corresponding mean value was 25.4 nmol/l for uninvolved skin and 108 nmol/l for lesional skin. The histamine values in the blister fluid from FDE lesions in samples 2 and 3 were significantly higher (p less than 0.05) than those in the control blisters of uninvolved skin. An elevation of histamine levels comparable to that in the uninvolved skin of FDE patients was seen in the 2 healthy control subjects studied. The present study provides direct evidence of early release of histamine from mast cells or basophils in FDE and suggests that histamine is one of the mediators of clinical symptoms of FDE.

Adolescent

Familial benign chronic pemphigus (Hailey-Hailey disease). Treatment with carbon dioxide laser vaporization.

BACKGROUND: Familial benign chronic pemphigus (Hailey-Hailey disease) is characterized by recurrent blistering lesions, mainly in the neck and intertriginous areas. No controlled studies on laser treatment of this condition have been published. OBSERVATIONS: We used carbon dioxide laser vaporization to treat skin lesions in eight patients. In the six patients with symmetrical skin lesions, one lesion was chosen for CO2 laser vaporization and a corresponding lesion of similar location, size, and severity on the other side of the body was left untreated. Laser vaporization was performed in defocus in four to five layers. In five of six patients with symmetrical control lesions, laser-treated lesions showed substantial improvement in comparison with the untreated lesions. A similar improvement was seen in the treated lesions of the two patients without control lesions. During the mean follow-up of 20 months (range, 10 to 27 months), skin lesions recurred in the laser-treated areas in three patients, but not in the other five. Histopathologic studies performed on two patients indicated that the effect of the CO2 treatment might be due to fibrosis of the upper dermal tissues. The adnexal glands were unaffected. CONCLUSIONS: Carbon dioxide laser vaporization is an effective treatment for familial benign chronic pemphigus.

Adult

Systemic hydrocortisone/cortisol induces allergic skin reactions in presensitized subjects.

To determine whether systemic hydrocortisone can elicit allergic skin reactions in patients with contact hypersensitivity to hydrocortisone, we studied four patients with contact hypersensitivity to hydrocortisone and hydrocortisone-17-butyrate and two patients with contact hypersensitivity to hydrocortisone-17-butyrate but not to hydrocortisone. Open oral provocation with 100 or 250 mg hydrocortisone in patients with hydrocortisone contact hypersensitivity elicited cutaneous reactions at sites of previous allergic dermatitis caused by hydrocortisone in two patients and at sites of earlier allergic patch test reactions caused by hydrocortisone in the other two patients. Provocations in two patients with contact hypersensitivity to hydrocortisone-17-butyrate but not to hydrocortisone remained negative. To determine whether the adrenal cortical hormone cortisol, which is identical to hydrocortisone, could induce similar skin reactions, one patient with hydrocortisone contact hypersensitivity underwent adrenocorticotropic hormone stimulation tests; as a control, one hydrocortisone-sensitive patient underwent analogous provocations with placebo. After an 8-hour infusion with the adrenocorticotropic hormone analog tetracosactide, a similar skin reaction to that seen with oral hydrocortisone was observed, whereas provocations with placebo remained negative. We conclude that both oral hydrocortisone and intrinsic cortisol are able to induce allergic skin reactions in presensitized subjects.

Administration, Oral

Membrane and cytosolic interleukin-1 alpha and beta in normal human epidermal cells: variability of epitope exposure in immunohistochemistry.

Previous studies have shown that interleukin-1 (IL-1) is present in normal human epidermis. However, with immunohistochemical techniques, epidermal IL-1 immunoreactivity has been found in only a limited number of epidermal cells. In the present study, we show that both IL-1 alpha and beta immunoreactivities can be detected in all epidermal cell layers, provided optimal processing of tissue samples is used. The use of isolated epidermal cells showed that keratinocytes at various stages of maturation display both membrane-associated and cytosolic IL-1 alpha and beta immunoreactivities. After protease treatment of tissue sections, the IL-1 beta immunoreactivity of the granular cell layer was enhanced by some antibodies used, whereas in the other cell layers it was clearly lower. We a) suggest a different cellular localization, processing, and/or binding to subcellular structures of IL-1 during the differentiation process of human keratinocytes and b) outline the technical difficulties in any immunohistologic approach to IL-1 status in diseased skin.

Cell Membrane

Effect of fixation on the antigenicity of human lactoferrin in paraffin-embedded tissues and cytocentrifuged cell smears.

Immunoperoxidase techniques were used to study the preservation of the antigenicity of human lactoferrin (LF) of polymorphonuclear neutrophils (PMN) and various exocrine glandular cells in paraffin-embedded tissue blocks and cytocentrifuged cell smears. Tissues fixed in Carnoy's fluid in contrast to other fixatives used, showed good preservation of LF antigenicity irrespective of the fixation time. Cell smears fixed in Carnoy's fluid showed diffuse nuclear and cytoplasmic staining for LF, although morphologic integrity was poorly preserved. Granular cytoplasmic staining for LF with no staining of nuclei was seen in cell smears fixed in buffered formol acetone for 2--10 min. The nature of nuclear LF staining and future applications of the present methods are discussed.

Antigens

Immunohistochemical identification of renal lysozyme during allograft rejection in man.

An immunoperoxidase staining method was used to identify lysozyme in biopsy or transplantectomy specimens of human renal allografts during reversible and irreversible rejection of the grafts. Proximal tubules in apparently functioning nephrons showed lysozyme staining. In irreversibly rejected grafts, infiltrating mononuclear phagocytes in and near peritubular and glomerular capillaries also stained intensely for lysozyme. In acute necrotizing arteritis, lysozyme-positive cells (mononuclear phagocytes) infiltrated the blood vessel wall. The presence of infiltrating lysozyme-positive cells in the transplant was consistent with poor graft survival. The variation in lysozyme staining of proximal tubular cells apparently was a reflection of the differences in the reabsorption capacity of the tubular cells, attributable to the tubular dysfunction of renal allografts. The infiltrating lysozyme-positive cells probably contribute to the increased urinary excretion of lysozyme during acute rejection.

Adolescent