SummaryPhotodynamic therapy (PDT) is currently under investigation in phase II and III clinical studies for the treatment of tumours in superficial localisations. Thus far, the underlying mechanisms of PDT regarding cellular responses and gene regulation are poorly understood. Photochemically generated singlet oxygen (102) is mainly responsible for cytotoxicity induced by PDT. If targeted cells are not disintegrated, photo-oxidative stress leads to transcription and translation of various stress response and cytokine genes. Tumour necrosis factor (TNF) a, interleukin (IL) 1 and IL-6 are strongly induced by photodynamic treatment, supporting inflammatory action and immunological anti-tumour responses. To investigate the first steps of gene activation, this study focused on the proto-oncogenes c-jun and c-fos, both coding for the transcription factor activator protein 1 (AP-1), which was found to mediate IL-6 gene expression. We here determine the effects of photodynamic treatment on transcriptional regulation and DNA binding of transcription factor AP-1 in order to understand the modulation of subsequent regulatory steps. Photodynamic treatment of epithelial HeLa cells was performed by incubation with Photofrin and illumination with 630 nm laser light in vitro. Expression of the c-jun and c-fos genes was determined by way of Northern blot analysis, and DNA-binding activity of the transcription factor AP-1 was evaluated by electrophoretic mobility shift assay (EMSA). Photofrin-mediated photosensitisation of HeLa cells resulted in a rapid and dose-dependent induction of both genes but preferential expression of c-jun. Compared with the transient expression of c-jun and c-fos by phorbol ester stimulation, photodynamic treatment led to a prolonged activation pattern of both immediate early genes. Furthermore, mRNA stability studies revealed an increased half-life of c-jun and c-fos transcripts resulting from photosensitisation. Although mRNA accumulation after PDT was stronger and more prolonged compared with phorbol ester stimulation, with regard to AP-1 DNA-binding activity, phorbol ester was more efficient. Surprisingly, in addition to the activation of AP-1 DNA-binding via PDT, photodynamic treatment can decrease AP-1 DNA-binding of other strong inducers, such as the protein kinase C-mediated pathway of phorbol esters and the antioxidant pyrrolidine dithiocarbamate (PDTC). This study demonstrates a strong induction of c-jun and c-fos expression by PDT, with prolonged kinetics and mRNA stabilisation as compared with activation by phorbol esters. Interestingly, this observation is not coincident with an overinduction of AP-1 DNA-binding, hence suggesting that post-translational modifications are dominant regulatory mechanisms after PDT that tightly control AP-1 activity in the nucleus thus limiting the risk of deregulated oncogene expression.
The leucocyte specific transcript - 1 (LST1) represents the human homolog of the mouse B144 transcript, encoded within the tumor necrosis factor (TNF) region of the human major histocompatibility complex class III interval. The gene is localized about 4 kilobases upstream of the lymphotoxin beta gene. It spans a polymorphic genomic region encompassing the microsatellites TNFd and TNFe in intron 3 and a polymorphic Pvu II restriction site 260 base pairs downstream of the polyadenylation signal. Isolation of a full-length cDNA clone revealed that LST1 codes for IFN-gamma-inducible 800 nt transcripts, which are present in lymphoid tissues, T cells, macrophages, and histiocyte cell lines. The cDNA contains three long open reading frames (ORF) with the most likely ORF encoding a transmembrane protein. Its close linkage to the TNF genes and pattern of expression point toward a possible role for LST1 in the immune response.
Ectopic late cutaneous schistosomiasis is usually preceded or accompanied by visceral schistosomiasis infection. Our patient presented the very rare case of late cutaneous schistosomiasis as an isolated skin manifestation. Perigenital lesions occurred 1 year after contact with infested water. Identification of the few eggs remaining in the late lesion among the dense cellular infiltrate was difficult. Electron-microscopic studies clearly demonstrated the characteristic eggshell ultrastructure.
Sir, paromomycin at a dose of about 25 mg/kg bodyweight (three times 500 mg daily). After a short exacerbation Despite more than 80 years of controversial debate since its rst description by AlexieV in 1911 (1), most issues of the complaints on the second day of treatment, palmoplantar pruritus began to decrease on the third regarding Blastocystis hominis-taxonomy, epidemiology, pathogenicity, mode of transmission, clinical sig-day, before completely subsiding and has not recurred now for 6 months. Three further stool analyses per-ni cance and therapy-have still to be resolved satisfactorily (2). While some authors consider B. hom-formed 1 month after treatment were negative for B. hominis. inis as a commensal protozoan without pathogenic signicance (3-5), others suggest that it could cause This course suggests that infection by B. hominis was the cause of unbearable palmoplantar pruritus in this gastrointestina l symptoms, such as diarrhoea, abdominal pain or discomfort, cramps, atulence and nausea patient. The initial aggravation of the condition could indicate an underlying immunological mechanism (6-8). In addition, an association of urticaria and B. hominis infection has been reported in 10 patients, and quickly enhanced by antigen released from degraded B. hominis at the beginning of therapy. treatment with paromomycin cured the urticaria in these cases (9). Cutaneous rashes and itching might be further clinical variants of B. hominis infection (10).
Although chronic widespread dermatophyte infection is reported widely in the literature, neither a uniform nomenclature, nor even a clear definition of this syndrome have been established so far. Thus, we suggest Trichophyton rubrum syndrome (TRS) for denomination and define the following obligatory clinical and mycological criteria for TRS. (A) Skin lesions at the following four sites: (1) feet, often involving soles; (2) hands, often involving palms; (3) nails; and (4) at least one lesion in another location than (1) (2) or (3), except for groins. (B) Positive microscopic analyses of potassium hydroxide preparations of skin scrapings in all four locations. (C) Identification of Trichophyton rubrum by cell culture at three of the four locations at least. For diagnosis of TRS the criteria (A) and (B) and (C) have to be fulfilled. This standardization is a prerequisite for further investigations of underlying mechanisms of this disease. The typical clinical pattern of TRS is illustrated by the presentation of two paradigmatic cases.
The case of a 42-year-old father is presented with 6 weeks' history of a painful kerion-like sycosis barbae. His two children had suffered from tinea manus 3 months previously, also caused by the zoophilic fungus Trichophyton mentagrophytes probably acquired from guinea-pigs. Seemingly ignoring the pathogenetic link, oral antibacterial treatment had been the first therapeutic attempt initiated by the family physician. Finally, successful treatment was performed by means of oral application of fluconazole 50 mg daily for a period of 6 weeks.
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