β2 Microglobulin expression in keratoacanthomas and squamous cell carcinoma

The cell surface expression of beta-2-microglobulin (beta 2 M) was investigated in 33 keratoacanthomas (KA) and 58 squamous cell carcinomas (SCC) to determine whether this antigen was expressed to a different extent in these two conditions and, thus, whether this constitutes a reliable and practical test for distinguishing them. Loss of beta 2 M expression was not a reliable feature for distinguishing between KA and SCC and seemed to be related more to the degree of cellular differentiation and maturation, than to malignancy as such.     

Decreased expression of α2β1 integrin in scleroderma fibroblasts

Abstract Systemic scleroderma (SSc) is a complex connective tissue disorder of unknown etiology. In early stages of the disease, libroblasts are activated to produce large amounts of collagen with subsequent fibrosis. Collagen metabolism of fibroblasts is modulated by their contact with the extracellular matrix (ECM), which involves distinct receptors on the cell surface, mainly belonging to the integrins. We investigated the expression of collagen receptor α₂β₁, in SSc and normal fibroblasts, since this receptor has been shown to be utilized by fibroblasts for adhesion to and reorganization of collagen I. 9 strains of scleroderma fibroblasts grown as monolayer cultures were first analyzed with respect to their collagen I expression. 6 of these strains were similar to controls (“low” producers) and 3 strains showed up to 2–3 × higher levels of collagen I mRNA expression (“high” producers). Northern hybridization using a cDNA probe specific for the α₂ integrin subunit revealed a decrease of the corresponding mRNA in SSc fibroblasts as compared to controls (75% versus 100%). “High” collagen producing cell strains displayed the lowest values for α₂ integrin mRNA. The decrease of α₂ integrin subunit expression at the mRNA level in selected fibroblasts was further substantiated by radioimmunoprecipitation using specific mAbs directed against α₂ integrin subunit. No significant changes in β₁ integrin expression could be observed-neither at mRNA nor at the protein level. Our data indicate a correlation between excessive synthesis of collagen and low levels of α₂ integrin subunit expression in SSc fibroblasts. Further experiments should clarify whether this observation is a phenomenon specific for scleroderma or whether it reflects an “activated” state of fibroblasts.     

Treatment of mycosis fungoides with etretinate and low-dose interferon α2a

Aims To evaluate the efficiency and tolerance of a treatment regime with etretinate and low-dose interferon-α_2a(IFN α_2a) in mycosis fungoides. Background Although there is no curative therapy for mycosis fungoides, remissions have been induced with etretinate and IFNα_2a, even in advanced stages, Recently, it has been shown that this combination is more effective in the induction and maintenance of the response than the separate administration of each drug. Methods Prospective study which includes nine patients with mycosis fungoides treated with 0.7 mg/kg/day of etretinate and 3 × 10⁶ IU/day of subcutaneous IFNα_2a during the first 3 months. Afterwards, the dosage of INFα_2a was modified in accordance with the response, without the daily dosis of INFα_2a surpassing 6 × 10⁶ [ U. Results: At the end of the study, a favourable response was obtained in four of six patients (66%), of whom one showed a complete and three partial remission. Two patients were non-evaluable and one discontinued therapy with partial remission of disease due to adverse effects attributable to etretinate. Side-effects were dose-dependent and reversible. Conclusions The combination of etretinate, 0.7 mg/kg/day, and IFNα_2a, 3 × 10⁶ subcutaneous IU/day, could be recommended to induce substained complete remission in later stages of cutaneous T-cell lymphoma.     

The influence of 8-methoxypsoralen plus UV-A (PUVA) on the excretion of the main urinary metabolite of prostaglandins F1α and F2α in patients with psoriasis

The 24-h urinary excretion of 52, 7α-dihydroxy-11-ketotetranorprosta-1,16-dioic acid (PGF-M) was measured in thirteen psoriatic patients for 2 days before and 2 days after a single dose of 8-MOP plus UV-A. Before treatment, the excretion of PGF-M was significantly higher in males than females (mean ± s.d.: 26.05 ±8-83 μg/24 h compared to 16.27±5.09 μg/24 h; .P < 0.005). The mean 24-h excretion of PGF-M was not altered significantly for up to 48 h after the single dose of 8-MOP plus UV-A. This is compatible with previous findings that prostaglandin synthesis in the skin is not increased by 8-MOP plus UV-A.     

α1-Antitrypsin deficiency in severe psoriasis

alpha 1-Antitrypsin phenotypes and trypsin-inhibitory capacities were measured in fifty-one patients with psoriasis. An increased number of variant phenotypes (MS, MZ, and SS) were found only in those patients with severe psoriasis (20% or more skin involvement) and not in those with lesser involvement. The psoriatic patients with variant phenotypes had an earlier disease onset than those psoriatic individuals (both mild and severe) without this association. Protease inhibitors may play a role in modifying disease activity in psoriasis.     

A double-blind study of topical 1α,25-dihydroxyvitamin D3 in psoriasis

Several open studies with active forms of vitamin D3 have been reported to be effective in the treatment of psoriasis. We report a double-blind study of 1 alpha,25-dihydroxycholecalciferol in psoriasis using 0.5 microgram of active substance applied topically twice daily. In contrast to previous studies, the present investigation does not provide evidence of clinical efficacy for the drug at that dosage and with the vehicle that was used.     

1α,25(OH)2 vitamin D3 increases intracellular calcium in human keratinocytes

Vitamin D3 metabolites have been found to improve psoriasis but their mechanism of action is not clear. Keratinocyte proliferation and differentiation are known to be dependent on calcium concentrations in vitro. The aim of this study was to examine whether 1 alpha,25(OH)2 vitamin D3 had any direct effect on intracellular free calcium concentrations in cultured keratinocytes. A response to 1 alpha,25(OH)2 vitamin D3 was seen in 88% of monolayers of normal human keratinocytes attached to glass coverslips. An increase in intracellular free calcium was seen in 80% of the reactive cultures, with over half the responses occurring within 30 s of exposure to 1 alpha,25(OH)2 vitamin D3 and the remainder occurring within minutes. Responses could be seen at physiological concentrations of 1 alpha,25(OH)2 vitamin D3 and were not blocked by the protein synthesis inhibitor cycloheximide. The response to 1 alpha,25(OH)2 vitamin D3 took the form of rapid transient increases in intracellular free calcium in 29 out of 59 coverslips. The basal intracellular free calcium was calculated to be 245 +/- 47 nM rising to a maximum of 834 +/- 267 nM (mean +/- SEM; n = 20) following exposure to 1 alpha,25(OH)2 vitamin D3. We conclude that 1 alpha,25(OH)2 vitamin D3 acts directly on keratinocytes to increase intracellular free calcium and that this may be relevant to its mechanism of action in psoriasis.     

α1-Antitrypsin Deficiency and Skin Abnormalities

A 19-year-old Moroccan male was found to have total absence of serum alpha₁-antitrypsin, a major inhibitor of elastase. This patient had chronic obstructive lung disease, hyperextensibility of the skin over the cheeks and wrists, and hyperlaxity of the hand joints. Microscopic sections of the skin revealed a thickened dermis with shortened and rarefied clastic fibers. Ultrastructural study showed collagen fibers with variable and irregular diameters. Elastic fibers were scarce and their relatively poor matrix was surrounded by numerous microfibrils. The outline of the fibers was irregular with deep recesses filled with microfibrils. The ergastoplasm of the fibroblasts was well developed. The differential diagnosis with other connective dystrophies showed the original characteristic of this case. Clinically and histopathologically, the skin abnormalities are probably related to the deficiency in elastase inhibitor.     

C-reactive protein and α2-macroglobulin plasma activity in medium–severe and severe psoriasis

BACKGROUND: An acute phase of psoriasis can be induced by cytokines involved in psoriatic pathogenic phenomena. Activation of the acute phase reaction by proinflammatory cytokines (including interleukins 1 and 6, tumour necrosis factor alpha) may account for systemic symptoms in severe psoriasis, especially in pustular and arthropathic forms of this disease. OBJECTIVE: To study the activity of selected acute phase proteins in psoriatics before and after effective treatment. METHOD: Plasma concentrations of C-reactive protein (CRP) and alpha2-macroglobulin (alpha2-MG) were examined in 175 males with medium-severe and severe psoriasis in the active stage, before treatment and in remission achieved with various treatments (local, acitretin, psoralen + ultraviolet A, retinoid + psoralen + UVA [Re-PUVA] methotrexate, cyclosporin A). Clinical activity of psoriasis was evaluated using the Psoriasis Area and Severity Index score, ranging from 18 to 70.8 (mean 29.2). Measurements were done using the immunoenzymatic method. The control group consisted of 30 healthy male volunteers. RESULTS: In the active stage of disease highly increased plasma levels of both CRP and alpha2-MG were found (P < 0.001). It appeared that efficacious treatment was correlated with a considerable decrease of the proteins examined towards the control values. Mean levels of alpha2-MG after treatment did not differ significantly from those of controls (P > 0.15). However, despite their strong decrease following all methods of treatment, mean plasma levels of CRP remained significantly elevated during remission compared with those of the healthy controls (P < 0.001). CONCLUSIONS: The results of this study indicate that in medium-severe and severe psoriasis the acute phase response can be initiated and is not completely extinguished in phases of clinical remission.     

The intradermal effects of the H3 receptor agonist R α methylhistamine in human skin

We have investigated the possible existence of the H₃ histamine receptor in human skin with the highly selective ligands R α methylhistamine (RAMHA) (H₃ agonist) and thioperamide (H₃ antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H₁ antagonist terfenadine, and H₂ antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare responses that were approximately 10- and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine ( P  < 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histamine-induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H₃ receptors on cutaneous endothelial or mast cells.     

Expression of minichromosome maintenance proteins in Merkel cell carcinoma

Objective  Minichromosome maintenance (MCM) nuclear proteins have barely been employed in the diagnosis of skin malignancies. We aimed to assess whether MCM immunohistochemistry can be utilized to examine tumour proliferation in Merkel cell carcinoma (MCC).
Methods  In this pilot study, we studied skin specimens of eight patients with MCC. As a control, eight patients with cutaneous malignant melanoma (MM) were included. Immunohistochemistry was performed for MCM4, MCM6, MCM7, Ki-67, p53, and p21.
Results  Protein expression of MCM4 (66.0 ± 26.5% vs. 33.9 ± 22.4%; P  = 0.017), MCM6 (70.9 ± 11.9 vs. 31.7 ± 22.7; P  = 0.0031), and MCM7 (76.5 ± 16.4% vs. 34.9 ± 25.5%; P  = 0.0013) was significantly increased in tumour cells of MCC when compared to tumour cells of MM. Ki-67 immunoreactivity was also significantly higher in MCC than in MM (28.7 ± 7.9 vs. 11.0 ± 9.2; P  = 0.0012). Immunolabelling of p53 (68.6 ± 26.2 vs. 58.4 ± 28.8; P  = 0.46) and p21 (40.1 ± 38.8 vs. 25.8 ± 16.1; P  = 0.35) was relatively high but not significantly increased in MCC when compared to MM.
Conclusion  Our preliminary data indicate that MCM immunohistochemistry may be a useful tool for the determination of tumour cell proliferation in MCC.     

1α,25-(OH)2D3 Use on Psoriasis and Ichthyosis

The present work compared the clinical efficacy of topically applied 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) in 16 cases with psoriasis vulgaris, 5 with ichthyosis vulgaris and 8 with X-linked ichthyosis. Sixty-nine percent of the psoriatic cases responded to 1 alpha,25-(OH)2D3 therapy, whereas no ichthyotic patients responded. The present study confirms the previously suggested effectiveness of the active form of vitamin D3 for psoriasis and denies its possible efficiency against the ichthyoses. Direct suppression of hyperproliferative activity of the psoriatic epidermis is considered one of the most plausible mechanisms of 1 alpha,25-(OH)2D3 efficacy, through examination of the aforementioned evidence.     

1α-25-dihydroxyvitamin D3 increases intracellular free calcium in murine B16 melanoma

Vitamin D3 and its active metabolite I alpha-25-dihydroxyvitamin D3 (I alpha-25-(OH)2D3) have been reported to play a role in melanogenesis. Physiological concentrations of I alpha-25-(OH)2D3 were found to acutely elevate intracellular free calcium (using Fura 2) in B16 primary (Io) cells. Membrane phosphoinositide turnover was unaffected by I alpha-25-(OH)2D3. The rise in intracellular free calcium was entirely dependent on extracellular calcium and was not mimicked by vitamin D3. However, in neither B16-Io nor B16-F1 melanoma cells did vitamin D3 or I alpha-25-(OH)2D3 increase melanin production.     

Treatment of Angioblastoma with Recombinant Interferon-α2

Abstract: interferon-α₂ has been used successfully to treat anglomatous lesions such as Kaposi sarcoma and life-threatening hemangiomas, possibly by its antlangiogenetic activity. We report the successful use of this agent in a child with an angloblastoma of the right leg.