Nevi related to thyroid diseases.
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Biomedical subjects
Publications and source records attributed to P Redondo.
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Normal human keratinocytes (HKC) are able to synthesize alpha-MSH. Because the production of alpha-MSH by HKC is induced significantly by ultraviolet B radiation, the involvement of keratinocyte-derived alpha-MSH in UV-induced immunosuppression has been suggested. The induction of the antiinflammatory cytokine IL-10 in monocytes is a major mechanism in the antiinflammatory actions of alpha-MSH. In the present study, HKC were investigated for their ability to produce IL-10 after alpha-MSH stimulation. HKC were obtained from the skin of human female breast sections and either left untreated or treated with 0.01 or 0.1 microg/ml alpha-MSH for different times. Using RT-PCR, HKC were shown to express IL-10 mRNA even under basal conditions, and treatment with alpha-MSH increased expression. Only minimal concentrations of IL-10 protein were detected in supernatants from the alpha-MSH-stimulated cultures. To the best of our knowledge this is the first report of IL-10 expression by cultured HKC after alpha-MSH stimulation. Further studies are needed to determine the biological and therapeutic relevance of these findings.
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CD24 or Nectadrin is a cell surface glycoprotein expressed in pre-B lymphocytes, T lymphocytes, neurons, muscle cells and carcinoma cells. Its function is not completely known, but it has been suggested that it is involved in cell adhesion and signalling. CD24 has recently been identified as the human molecule homologous to the murine heat-stable antigen (HSA). HSA is expressed by murine keratinocytes and delivers costimulatory signals in T-cell activation. Long-term cultures of normal human keratinocytes (HKC) were obtained from skin of human female breast sections and either left untreated or were treated with phorbol-12-myristate-13-acetate (PMA) at 10-100 ng/ml, calcium 0.5-2 mM or IFN-gamma 100-1000 U/ml, for 24-48 h. Using RT-PCR and flow cytometry we showed that HKC express low levels of CD24 even under basal conditions, and the treatment with calcium, PMA or IFN-gamma increased levels of CD24 mRNA and protein. To the best of our knowledge, this is the first report to measure CD24 expression and production by cultured HKC in basal conditions and after stimulation. Further studies are needed to determine biological and therapeutical relevance of these findings.
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Pentoxifylline (PTX) is a methylxanthine derivative used in a wide range of dermatoses. As well as its hemorrheologic activity, PTX has anti-inflammatory properties. Buflomedil chlorhydrate (BC) is another hemorrheological drug with peripheral vasodilatory action, whose clinical uses are similar to those of PTX. Both drugs increase intracellular levels of cAMP, either secondary to phosphodiesterase inhibition (PTX) or adenyl-cyclase stimulation (BC). Long-term cultures of normal human keratinocytes were prepared in a free-serum medium, and stimulated with 1 mg/ml of phorbol 12-myristate 13-acetate (TPA) and PTX or BC (100-1000 micrograms/ml). Levels of TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1 using ELISA and Northern blot or RT-PCR techniques were measured. TPA-induced TNF-alpha and IL-8 release from keratinocytes. TPA did not induce IL-1 alpha or IL-1 beta release of keratinocytes. TPA increased RNA expression of the TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1. BC diminished TPA-induced TNF-alpha and IL-8 release from keratinocytes; in the case of IL-8 it is possible that this inhibition occur to transcriptional level. Moreover PTX was unable to inhibit TNF-alpha and IL-8 synthesis and expression. PTX and BC reduced TPA-induced IL-1 alpha and beta expression. It is possible that BC action is specifically exerted on keratinocytes, because we did not find similar results with TNF-alpha and IL-8 synthesis in mononuclear peripheral blood cells.
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The efficacy of imipenem versus standard chemotherapy (both in addition to neurosurgery) in the treatment of brain abscess was compared in a retrospective study. Cure was obtained in 52 of 60 (86.7%) patients in the standard group, and in 15 of 15 (including 5 patients with multiple brain abscesses) in the imipenem group. Cure without neurosurgery was observed in 2 of 60 (3.3%) and 3 of 15 (20%) of the cases, respectively (p = 0.08). Levels of imipenem in blood, cerebrospinal fluid, and brain pus were above the minimum inhibitory concentrations of most of the abscess isolates. Side effects of imipenem were rare and tolerance was excellent. Imipenem monotherapy (3-4 g/day) for five weeks seems a reasonable therapeutic choice for treatment of bacterial brain abscesses.
Toxic epidermal necrolysis (TEN) is a life-threatening disease, the pathogenesis of which remains largely unknown. We describe a 23-year-old woman under treatment with clobazam who developed lesions of TEN in light-exposed areas. Patch and photopatch tests with clobazam were negative. The cellular phenotype and cytokines were studied in blister fluid. The cellular infiltrate was composed mainly of T lymphocytes with a predominant cytotoxic phenotype. There was an increase in the level of tumour necrosis factor (TNF)-alpha in blister fluid compared with the control (a patient with bullous pemphigoid).
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The urocanic acid cis isomer (cis-UCA) is a possible cutaneous photoreceptor for the immunomodulatory phenomena that follow ultraviolet B irradiation. Several experiments in animals show an inhibitory action of cis-UCA on cellular immunity. However, the action of cis-UCA on the synthesis of cytokines in keratinocytes remains unknown. Long-term cultures of normal human keratiocytes were prepared in a serum-free medium, and stimulated with 1 microgram/ml of phorbol 12-myristate 13-acetate (TPA) and UCA or UVB-UCA (10-100 micrograms/ml). Synthesis of the following cytokines was measured using ELISA and Northern blot techniques: TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TGF-beta 1. TPA increased TNF-alpha protein levels in culture supernatants. No changes in Il-1 alpha and IL-1 beta protein levels were detected in basal culture supernatant after TPA stimulus. TPA augmented RNA expression for TNF-alpha, IL-1 alpha, IL-1 beta and TGF-beta 1. UCA isomers did not induce cytokine changes in protein synthesis. Expression of IL-1 alpha and IL-1 beta genes was increased after exposure to 100 micrograms/ml UVB-UCA (70 micrograms/ml cis-UCA). A slight increase in TNF-alpha RNA expression was detected when the dose of UVB-UCA reached 100 micrograms/ml. No effects on cytokine synthesis were found after UCA stimulus. These results suggest that low doses of cis-UCA do not effect cytokine synthesis by keratinocytes.
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BACKGROUND: The frequency of skin cancer in organ transplant recipients is high, up to 15%. OBJECTIVE: Our purpose was to determine the incidence of skin cancer in patients who underwent immunosuppression after heart transplantation and to determine the factors important in the appearance of skin cancer. METHODS: We studied the frequency of skin cancer in 92 of 111 patients after they underwent heart transplantation between January 1984 and December 1993. RESULTS: At least one cutaneous neoplasm (squamous cell carcinoma and/or basal cell carcinoma) developed in 14 patients (15.2%). The basal cell carcinoma to squamous cell carcinoma ratio was 1:1.5. The skin cancer appeared an average of 31.5 months after transplantation; the average was 36 months for squamous cell carcinoma and 25.3 months for basal cell carcinoma. Cumulative risk rose from 4.3% at 1 year up to 43.8% at 7 years after transplantation. The overall incidence of both types of skin cancer was 45.3 per 1000 posttransplant person-years, with an incidence of 25.8 for basal cell carcinoma and 29.1 for squamous cell carcinoma. Most skin cancers developed between 2 and 3 years after transplantation. All patients were exposed to a significant amount of ultraviolet radiation and had skin type II or III. We did not find a significant association between skin cancer and haplotype HLA-A3, HLA-A11, HLA-DR, and the number of mismatches for HLA-B. CONCLUSION: We found an increased progressive cumulative incidence of skin cancer in heart transplant recipients for two reasons: (1) immunosuppression and increased exposure to ultraviolet radiation in some patients, and (2) the skin type of certain patients. We emphasize the need for photoprotection in this group of patients and regular skin cancer screening examinations.
We report a heart transplant recipient who developed graft-versus-host disease (GVHD) following blood transfusion. We consider that heart transplant recipients should be included in the category of immunosuppressed patients who may develop this disease after being treated with blood products. We also consider that, at the present time, irradiation of blood products is the only useful method of avoiding development of GVHD in these patients.