Search PubMed⌕ Search

Biomedical subjects

B Ortel

Publications and source records attributed to B Ortel.

At least 37 records · Page 2Linked to original sources
PubMed1996

Bullous pemphigoid induced by PUVA therapy.

An 80-year-old psoriatic patient developed a blistering eruption during oral PUVA therapy. The diagnosis of bullous pemphigoid (BP) was established by routine histopathology, which demonstrated subepidermal blistering, and direct immunofluorescence, which revealed linear deposits of IgG, IgM and C3 along the basement membrane zone. Indirect immunofluorescence using normal human split skin revealed binding of IgG antibodies to the epidermal side, thus confirming a subepidermal blistering disorder. These proteins were identified by the immunoblotting technique as BP antigens I and II. Clinically, the lesions could be reproduced by phototesting using topical 8-methoxypsoralen. Again, the histopathological and immunopathological findings were consistent with the diagnosis of PUVA-induced BP. To the best of our knowledge, this is the first report demonstrating psoriasis-associated BP, in which the clinical diagnosis of BP is confirmed by immunoblotting analysis. The exact role of UV light in precipitating bullous lesions, particularly the question whether UV light may represent an unspecific epidermal injury leading to further attraction of autoantibodies to the basement membrane zone, as suggested recently by an experimental study in rodents, remains to be clarified in future studies.

Aged↗
PubMed1995

[Pyoderma gangrenosum as a precursor of myeloid leukemia].

A 34-year-old woman who was 20 weeks pregnant developed pyoderma gangrenosum while receiving treatment for infarct pneumonia. Because of her septic condition an abortion was performed. The patient received intravenous prednisolone as a pulse treatment for her pyoderma gangrenosum, which was followed by oral methylprednisolone and oral dapsone for 6 weeks. After dose reduction the patient had a severe relapse. The steroid dose was increased and dapsone was replaced by cyclosporin A. The smaller ulcers healed spontaneously, but skin grafting had to be performed for the large ulcer. The steroid therapy was tapered and discontinued. Cyclosporin A was continued for 10 weeks as monotherapy. Subsequently, the patient was free of symptoms for 7 months. Twelve months after the diagnosis of pyoderma gangrenosum the patient developed acute myeloid leukaemia accompanied by a recurrence of the skin disease.

Adult↗
PubMed1995

Photodynamic therapy of epithelial skin tumours using delta-aminolaevulinic acid and desferrioxamine.

Photodynamic therapy (PDT) uses photosensitizing drugs, such as porphyrins, and light for cancer treatment. In the present clinical study we employed topical application of the porphyrin precursor delta-aminolaevulinic acid (ALA) in combination with desferrioxamine (df) for the induction of endogenous porphyrin synthesis. Irradiation was performed with a light source consisting of a halogen lamp with a red filter and a fibreoptic device. Irradiances ranged from 50 to 300 mW/cm2. We treated 49 patients with this PDT regimen. In 32 patients we treated a total of 34 superficial basal cell carcinomas (BCCs) and 22 nodular BCCs, in nine patients 43 solar keratoses, and in eight patients 10 lesions of Bowen's disease. After a single treatment, 30 (88.2%) of the superficial and seven (31.8%) of the nodular BCCs, 35 of 43 (81.4%) solar keratoses, and three (30%) of the Bowen's disease lesions showed complete remission. The post-treatment observation period was up to 20 months. Repeat therapy was required in six nodular and four superficial BCCs. Biopsies were obtained before treatment, and at variable intervals after treatment. Topical PDT of skin tumours with ALA-df-induced porphyrins is effective in the management of epithelial skin tumours.

Aminolevulinic Acid↗
PubMed1994

Cytosolic and plastid forms of 5-enolpyruvylshikimate-3-phosphate synthase in Euglena gracilis are differentially expressed during light-induced chloroplast development.

The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (EC 2.5.1.19), the target of the herbicide glyphosate [N-(phosphonomethyl)glycine], exists in two molecular forms in Euglena gracilis. One form has previously been characterized as a monofunctional 59 kDa protein. The other form constitutes a single domain of the multifunctional 165 kDa arom protein. The two enzyme forms are inversely regulated at the protein and mRNA levels during light-induced chloroplast development, as demonstrated by the determination of their enzyme activities after non-denaturing polyacrylamide gel electrophoresis and Northern hybridization analysis with a Saccharomyces cerevisiae ARO1 gene probe. The arom protein and its mRNA predominate in dark-grown cells, and the levels of both decline upon illumination. In contrast, the monofunctional EPSP synthase and its mRNA are induced by light, the increase in mRNA abundance preceding accumulation of the protein. The two enzymes are localized in different subcellular compartments, as demonstrated by comparing total protein patterns with those of isolated organelles. Glyphosate-adapted wild-type cells and glyphosate-tolerant cells of a plastid-free mutant of E. gracilis, W10BSmL, were used for organelle isolation and protein extraction, as these cell lines overproduce EPSP synthase and the arom protein, respectively. Evidence was obtained for the cytosolic localization of the arom protein and the plastid compartmentalization of the monofunctional EPSP synthase. These conclusions are further supported by the observation that EPSP synthase precursor, produced by in vitro translation of the hybrid-selected mRNA, was efficiently taken up and processed to mature size by isolated chloroplasts from photoautotrophic wild-type E. gracilis cells, while the in vitro-synthesized arom protein was not sequestered by isolated Euglena plastids.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1994

A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin.

5-Aminolaevulinic acid (ALA)-induced porphyrin biosynthesis and phototoxicity in vitro was investigated in five malignant and two normal cell lines. Intracellular protoporphyrin IX (PpIX) content was quantified by extraction and fluorescence spectroscopy. Cellular PpIX content did not always correlate with cell proliferation rate as measured by the doubling times of cell lines. Cellular efflux of PpIX was also investigated. In a bladder carcinoma cell line, the observed rapid efflux was not blocked by verapamil, an inhibitor of the P-glycoprotein efflux pump. These data support the view that cellular PpIX accumulation is a dynamic process that is determined by both the efflux of PpIX from the cells and enzyme activities in the haem biosynthesis pathway. Desferrioxamine (desferal), a modulator of PpIX biosynthesis, enhanced ALA-induced cellular PpIX content significantly in all carcinoma cell lines but not in non-malignant cell lines. The enhanced PpIX cellular accumulation is attributed to inhibition of ferrochelatase activity, the enzyme responsible for the conversion of PpIX to haem. PpIX-mediated cellular photodestruction following irradiation with an argon ion laser at 514.5 nm was determined by the 'MTT assay'. There appeared to be a 'threshold' effect of cellular PpIX content; cells that synthesised less than 140 ng/mg-1 protein exhibited very little phototoxic damage, while cell lines having greater than 140 ng PpIX/mg-1 protein [corrected] exhibited a consistent phototoxic response. Among the cell lines which did undergo phototoxic damage, there was not a strict correlation between PpIX cellular content and ALA-induced phototoxicity. Desferal enhanced the PpIX content and phototoxic effect in the responsive cells. Fluorescence microscopy of the ALA-treated cells revealed marked accumulation of PpIX in mitochondria (rhodamine 123 co-staining). That the primary site of phototoxic damage is also the mitochondria was confirmed by electron micrographs of cells photosensitised with ALA-induced PpIX, which showed swelling of mitochondria within minutes after irradiation while other suborganelles appeared to be unaffected. The repair or further destruction of the mitochondria was fluence and cell-type dependent. The data from this study suggest that the basis of increased ALA-induced PpIX accumulation in tumours is a combination of various aspects of the metabolic process and pharmacokinetics and that the efficacy of photodestruction of malignancy will be determined not only by the rate of PpIX synthesis but also by specific cellular and tissue characteristics.

Aminolevulinic Acid↗
PubMed1994

Safety and effectiveness of an aggressive and individualized bath-PUVA regimen in the treatment of psoriasis.

BACKGROUND: The optimal therapeutic regimen of bath-PUVA therapy of psoriasis is still under debate. OBJECTIVE: We investigated the safety and efficacy of an aggressive and individualized bath-PUVA regimen. METHODS: Two closely matched groups of 22 psoriatic patients were treated either with 30-min baths in 0.0003% 8-methoxypsoralen (8-MOP) aqueous solution or oral administration of the drug. According to the standard European regimen, treatments were delivered 4 times a week starting with the minimal phototoxic dose. RESULTS: Complete clearing or marked improvement was observed in all the patients. However, with bath-PUVA, the same therapeutic effect required smaller cumulative UVA doses (39.3 +/- 15.8 vs. 123.8 +/- 39.9 J/cm2) and lower numbers of exposures (15.2 +/- 4.4 vs. 20.6 +/- 4.2). Both differences were significant at the 0.01 level (Student's t test). Gastro-intestinal side-effects were of course restricted to oral 8-MOP. The incidences of burns and pruritus were similar. CONCLUSION: Using an aggressive and individualized schedule, bath-PUVA therapy showed a greater efficacy than oral PUVA therapy while being just as safe.

Administration, Oral↗
PubMed1994

[Therapy of cutaneous T-cell lymphomas].

Cutaneous T-cell lymphomas (CTCL) show a wide clinical spectrum of cutaneous diseases caused by a clonal proliferation of malignant T-helper cells. In the early stages of CTCL diagnosis is challenging and may require a combination of clinical, pathological, immunomorphologic and molecular findings. The identification of early disease is crucial for the rapid implementation of adequate treatment, which may even be curative as has been reported with psoralen photochemotherapy (PUVA), total skin electron beam (TSEB) irradiation and topical chemotherapy. The combination of these treatment modalities with each other and, in addition, with management by synthetic retinoids and interferons has increased the therapeutic potential. Systemic (poly)-chemotherapy has been used so far exclusively for advanced stages of CTCL and may result in partial remission. Extracorporeal photochemotherapy (photopheresis) has been shown to be the most efficient mode of treatment for the Sézary syndrome.

Combined Modality Therapy↗
PubMed1993

Overproduction by gene amplification of the multifunctional arom protein confers glyphosate tolerance to a plastid-free mutant of Euglena gracilis.

Cells of the plastid-free mutant line of Euglena gracilis var. bacillaris, W10BSmL, can be adapted to glyphosate [N-(phosphonomethyl)glycine] by gradually increasing the concentration of the herbicide in the culture medium. The molecular basis of glyphosate tolerance is the selective ca. ten-fold overproduction of the multifunctional arom protein catalyzing steps 2-6 in the pre-chorismate pathway. Determination of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (E.C.2.5.1.19), shikimate:NADP+ oxidoreductase (E.C.1.1.1.25) and shikimate kinase (E.C.2.7.1.71) activities after non-denaturing gel electrophoresis, in combination with two-dimensional separations, revealed an increase in all three enzyme activities associated with overproduction of a 165 kDa protein in cells adapted to 6 mM glyphosate. Further evidence for an involvement of the multifunctional arom protein in aromatic amino acid synthesis in the plastid-free W10BSmL cells was obtained by Northern hybridization with ARO1-, aroA-, aroL- and aroE-specific Saccharomyces cerevisiae gene probes encoding the entire arom protein or parts of the EPSP synthase, shikimate:NADP+ oxidoreductase and shikimate kinase domains, respectively. Overproduction in adapted relative to control cells of a 5.3 kb transcript that cross-hybridized with all of the different probes could be demonstrated. The elevated content of the arom transcript correlated with a selective amplification of two out of five genomic sequences that hybridized with the S. cerevisiae ARO1 gene probe in Southern blots. One of the amplified genomic fragments is assumed to encode the previously identified monofunctional 59 kDa EPSP synthase, which is thought to be an organellar protein, that accumulates to a certain extent in its enzymatically active precursor form of 64.5 kDa in the plastid-free W10BSmL cells.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1993

Comparison of narrow-band (311 nm) UVB and broad-band UVA after oral or bath-water 8-methoxypsoralen in the treatment of psoriasis.

BACKGROUND: There is a disparity between the absorption spectrum of 8-methoxypsoralen and the action spectrum for psoralen-sensitized erythema. In an action spectrum corrected for unsensitized reaction 313 and 365 nm have similar efficacies. OBJECTIVE: We evaluated the relative erythemogenic and antipsoriatic efficacy of narrow-band (311 nm) UVB with and without prior psoralen exposure. We also compared the effects of narrow-band UVB and broad-band UVA after oral and bath-water psoralen exposure. METHODS: Patients with psoriasis underwent half-side comparison studies. In one group the therapeutic efficacy of 311 nm UVB with and without oral psoralen was assessed. The second group received UVA and 311 nm UVB after oral psoralen. The third group was exposed to both radiation sources after bath-water exposure. RESULTS: The erythemogenic, pigmentogenic, and therapeutic efficacy of 311 nm was increased by oral psoralen. With systemic 8-methoxypsoralen, UVA was comparable to 311 nm UVB. After bath-water exposure, 311 nm was clearly superior to broad-band UVA. CONCLUSION: The efficacy of narrow-band 311 nm UVB can be enhanced by psoralen. Narrow-band 311 nm UVB is also effective after psoralen bath-water delivery.

Administration, Cutaneous↗
PubMed1993

Lethal photosensitization by endogenous porphyrins of PAM cells--modification by desferrioxamine.

The effects of exogenous delta-aminolevulinic acid (ALA) on cultured PAM 212 cells were investigated. PAM cells exposed to ALA produce an excess of products of the heme biosynthesis pathway within hours. The endogenous porphyrins render the cells photosensitive in a time-, ALA dose- and irradiation-dependent manner. Independently of the ALA-induced photosensitized processes, ALA itself reduces the proliferation rate of PAM cells during the exponential growth phase. Iron deprivation by addition of the chelating agent desferrioxamine (df) accelerates the photosensitizing process, and thus makes it more efficient at lower ALA concentrations. The effects of df were compared with the effects of manganese-df and iron-df. The results indicate that iron trapping is the most important factor for the potentiation of ALA-stimulated photodynamic sensitization as well as for the dark toxicity. Iron complexing agents may thus be used to optimize ALA effects in the photodynamic treatment of cutaneous neoplasms with endogenous porphyrins.

Aminolevulinic Acid↗
PubMed1993

UVA does not photoreactivate pyrimidine dimers in cultured human fibroblasts.

Pyrimidine dimers were induced in duplicates of cultured human skin fibroblasts by irradiation with various doses of UVB radiation. Subsequently, one set of cells was further exposed to either 5 or 10 J/cm2 of UVA radiation to assess the photoreactivating activity of this spectral range in a human cell system. Following irradiation, pyrimidine dimers were quantified in all cells by determining the number of endonuclease-sensitive sites (ESS). No difference in the yield of ESS was observed between cells which had been irradiated with UVB only as compared to cells which subsequently had been exposed to 5 or 10 J/cm2 UVA. In contrast, subsequent exposure of UVB-irradiated cells of Monodelphis domestica to 10 J/cm2 UVA resulted in an almost 50% reduction of UVB-induced pyrimidine dimers. These data indicate that UVA does not induce photoenzymatic repair in human fibroblasts.

Adult↗
PubMed1992

Severe sun sensitivity and the presence of antinuclear antibodies in patients with polymorphous light eruption-like lesions. A form fruste of photosensitive lupus erythematosus?

BACKGROUND: Initial lesions seen in some cases of lupus erythematosus may simulate the clinical features of polymorphous light eruption. OBJECTIVE: To evaluate the significance of antinuclear antibody screening in patients with polymorphous light eruption or to find better methods to define patients at risk to have lupus erythematosus, we analyzed the data of 198 patients with polymorphous light eruption. METHODS: History, type, and persistence of skin lesions were reviewed, and serologic variables, the minimal erythema dose, and the ultraviolet action spectrum for inducing skin lesions were determined. RESULTS: The morphologic features of skin lesions and results of phototesting were consistent with previously published characteristics of patients with polymorphous light eruption. Twenty-eight (14%) had high titers of antinuclear antibody (greater than or equal to 1:80). We found a highly significant correlation between severe sun sensitivity and the presence of high antinuclear antibody titers. Of these patients with severe sun sensitivity and high titers of antinuclear antibody, in three the diagnosis of systemic lupus erythematosus could be established according to American Rheumatism Association criteria. CONCLUSION: These results suggest that a combination of severe sun sensitivity and high titers of antinuclear antibody may characterize a subset of sun-sensitive patients with some features of lupus erythematosus.

Adult↗
PubMed1992

A reappraisal of the use of 5-methoxypsoralen in the therapy of psoriasis.

5-methoxypsoralen (5-MOP) is considered an alternative to 8-methoxypsoralen (8-MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy and tolerability of 5-MOP (1.2 mg/kg)-UVA versus 8-MOP (0.6 mg/kg)-UVA therapy in 25 patients of skin type III and IV, affected by relapsing plaque-type psoriasis of similar body involvement; indeed, the same patients were given 8-MOP during 1 year and 5-MOP during the subsequent year after relapsing. Both treatments cleared psoriatic lesions with a comparable number of exposures, but 5-MOP required significantly higher cumulative UVA doses. The difference was due to the lower phototoxicity of 5-MOP, as assessed by the determination of the minimal phototoxic dose, and to its higher tanning activity, as assessed by the weekly grading of pigmentation. Nevertheless, therapy by 5-MOP-UVA seemed particularly interesting in that it showed a higher tolerability since only 1 patient experienced nausea, whereas during therapy with 8-MOP-UVA nausea and/or vomiting occurred in 7 patients, sunburn in 6 and itching in 3. Since we have treated the same patients with the two drugs, our results were not influenced by interindividual variations of phototoxic responses, tanning ability and susceptibility to develop psoralen-induced short-term side-effects. It was concluded that, although long-term side-effects of the 5-MOP-UVA treatment have still to be determined, such treatment of psoriasis should be reappraised due to its higher tolerability in comparison to 8-MOP-UVA treatment.

5-Methoxypsoralen↗
PubMed1992

8-MOP vs 5-MOP.

Explore the source record for details and available documents.

5-Methoxypsoralen↗
PubMed1992

Middermal elastolysis in an elderly man with evidence of elastic fiber phagocytosis.

BACKGROUND: Middermal elastolysis is a clinically and histologically distinct entity. This idiopathic loss of dermal elastic fibers has mostly been reported in younger adults. To our knowledge, the present case, which has been followed up for 4 years, is the first to occur in an elderly man. OBSERVATIONS: Two years after the onset of progressive wrinkling of the upper aspect of the thorax, the patient underwent a biopsy. Histologic examination of the specimens confirmed previous findings of middermal elastolysis. Examination of extracutaneous elastic tissue showed normal findings. Electron microscopy demonstrated elastic fibers embraced by macrophages, which is suggestive of elastic fiber phagocytosis. For the following 4 years, the patient has remained in stable clinical condition. CONCLUSIONS: Middermal elastolysis is probably more common than has been assumed so far. It does not affect nondermal elastic tissue. After progressive loss of dermal elasticity in a circumscribed area, a benign course follows, with a stable condition over several years. Electron microscopic findings indicate that elastic fiber phagocytosis is operative in the disappearance of the middermal elastic tissue.

Aged↗