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Biomedical subjects

E M de Jong

Publications and source records attributed to E M de Jong.

At least 19 recordsLinked to original sources
PubMed2001

Localized and systemic scleroderma show different histological responses to methotrexate therapy.

Although morphoea (localized scleroderma) and systemic sclerosis are distinct disease entities, the skin lesions show identical histological characteristics and both diseases respond favourably to low-dose treatment with methotrexate (MTX). The aim of this study was to find out whether MTX treatment induces different histological response patterns in these two diseases. In seven patients with morphoea and eight with systemic sclerosis, skin biopsies were taken before and after 24 weeks of treatment with low-dose MTX. In the centre and active margin of morphoea lesions, a significant reduction in tenascin staining was seen after 24 weeks of treatment, in contrast to systemic sclerosis. The numbers of mast cells decreased in the active margin of morphoea lesions, whereas in systemic sclerosis no significant change was seen after MTX therapy. Epidermal proliferation and staining of heparan sulphate proteoglycans showed no changes. Although skin lesions from both diseases respond clinically to treatment with MTX, systemic sclerosis shows no change in the immunohistochemical parameters investigated, whereas morphoea does. This difference in dynamic pattern suggests that the apparently similar lesions in localized and systemic sclerosis are not identical.

Adult↗
PubMed1999

Systemic sclerosis: new insights in autoimmunity.

The strong female predilection of systemic sclerosis, especially in women after their childbearing years, and the clinical and histopathological similarities with chronic graft-versus-host disease make systemic sclerosis an interesting subject of debate. Recent studies concerning the pathogenesis of this disease demonstrated the persistence of fetal cells in the maternal circulation in a majority of female patients. How or whether microchimerism is involved in the pathogenesis of systemic sclerosis remains to be elucidated. The present paper reviews the recent findings on the subject.

Autoimmune Diseases↗
PubMed1999

Dystrophic psoriatic fingernails treated with 1% 5-fluorouracil in a nail penetration-enhancing vehicle: a double-blind study.

BACKGROUND: Topically applied nail therapeutics need to permeate the nail plate to reach the nail bed or nail matrix and exert their potential beneficial effect at these locations to obtain a therapeutic benefit. So far only topically applied 5-fluorouracil on affected nails of psoriatic patients has been shown to produce a notable clearance. Vehicle formulations enhancing nail permeation processes are thought to increase the concentration of the active agent and therefore therapeutic efficacy, possibly enabling the use of a low concentration of the active agent thereby lowering the incidence of adverse effects. OBJECTIVE: This study was designed to verify whether a recently developed nail penetration enhancer in a lotion formulation, Belanyx((R)) (urea, propylene glycol), improves the efficacy of a low concentration of 5-fluorouracil (1%) in psoriatic fingernail lesions. METHODS: In a randomised, double-blind, left-right study the efficacy of 1% 5-fluorouracil in the Belanyx vehicle was compared to the vehicle preparation Belanyx in dystrophic fingernails of 57 psoriatic patients. Both preparations were applied in a once daily regimen for 12 weeks. Responses and adverse effects of one selected target nail were recorded at screening, at baseline and at weeks 2, 4, 8 and 12 of treatment with a final assessment at week 16: 4 weeks after the end of treatment. As parameter of efficacy was chosen the total nail area severity (NAS) score, consisting of the separate parameters nail pitting area, number of nail pits, subungual keratosis, onycholysis, oil spots and the various scores of overall improvement. RESULTS: The efficacy of 1% 5-fluorouracil in lotion and that of the vehicle in suppressing the parameters of dystrophy were shown to be similar at the end of treatment (p = 0.063) or follow-up (p = 0.130). Both preparations produced statistically significant improvements (p </= 0.05) for almost all assessed parameters after 12 weeks of treatment and after the 4 weeks of follow-up. For Belanyx lotion this applied to the nail pitting area, the number of nail pits, subungual keratosis, onycholysis and oil spots. The investigators' and patients' opinion of overall improvement of severity as well as the total NAS score of one target nail likewise showed a statistically significant improvement at the end of treatment and at the end of the observation period (p </= 0.05). With the 1% 5-fluorouracil lotion the same statistically significant improvements were obtained in all of the assessed symptoms with the exception of the number of pits and onycholysis at week 12 and week 16. Possible treatment-related adverse effects were established in 6 patients showing inflammation and infection (3 patients) or discoloration (5 patients); 3 patients on 5-fluorouracil lotion showed onycholysis. CONCLUSION: Addition of 1% 5-fluorouracil to the nail permeation enhancer Belanyx does not increase the efficacy of the active agent in psoriatic nail dystrophy of this study population. The obtained results also suggest that Belanyx lotion can be used in this indication since it has shown a favourable efficacy-safety ratio.

Adult↗
PubMed1998

Low-dose methotrexate in the treatment of widespread morphea.

BACKGROUND: Low-dose methotrexate (MTX) has been shown to be effective in the treatment of systemic sclerosis. OBJECTIVE: We evaluated the effect of low-dose MTX on widespread morphea in a 24-week trial. METHODS: Oral MTX, 15 mg/week, was administered to nine patients. Clinical records (modified skin score [MSS], durometer score, and the scores on a visual analogue scale (VAS) of feelings of tightness and itching), as well as laboratory data were examined. Serum aminoterminal propeptide of type III procollagen (PIIINP) was determined at weeks 0, 12, and 24. RESULTS: At the end of the 24-week treatment period, significant improvement was observed in MSS (P=.01) and the VAS score for tightness (P < .01), whereas the durometer score (P=.07) and the VAS for itching (P=.07) showed a tendency toward improvement. PIIINP level did not alter. No serious adverse events were noted. CONCLUSION: These results suggest a beneficial effect of MTX on widespread morphea. Because spontaneous improvements are not uncommon, prospective double-blind, placebo-controlled studies are necessary to determine the usefulness of MTX in this disease.

Adult↗
PubMed1998

The CD11b/CD18-integrin in the pathogenesis of psoriasis.

The aim of the present investigation was to study the distribution of CD11b, CD18, and ICAM-1 over the various cell populations present in the margin zone of the actively spreading psoriatic lesion and distant uninvolved psoriatic skin. This study was performed in order to obtain more insight in the relevance of these receptor molecules in the early phase of psoriatic plaque development. Skin biopsies were taken and inflammation markers were assessed using immunohistochemical techniques. All dermal changes in the margin zone preceded those in the epidermis. In the margin zone the most peripheral change was a decrease in dermal ICAM-1-expression, followed by an increase in dermal CD11b-expression. CD11b-positive cells showed a different tissue distribution from polymorphonuclear leukocytes and were more abundantly present, suggesting significant amounts of CD11b-bearing cell populations other than polymorphonuclear leukocytes in the early phase of psoriasis. Decreased numbers of CD18-positive cells in distant uninvolved skin suggest the existence of a selective modulating mechanism altering the trafficking of myeloid subpopulations. Polymorphonuclear leukocytes appeared to invade the skin well after the appearance of CD11b- and CD18-positive cells.

Adult↗
PubMed1998

The efficacy of a new topical treatment for psoriasis: Mirak.

BACKGROUND: A new natural product for the treatment of psoriasis has recently become available in many European countries: Mirak. The Mirak Home Care Packs consist of natural spring water, volcanic earth and vitamin E cream. Recently, the efficacy of Mirak has come into question. As this treatment is used by many psoriasis patients in Europe, it is important for dermatologists to be informed about the clinical effects of the therapy. AIM: To evaluate the efficacy and side effects of the Mirak Home Care Packs. METHODS: By means of a placebo-controlled left/right comparison, both clinical and histological parameters were evaluated during 6 weeks of treatment. RESULTS: The reduction in induration was significantly greater in the Mirak-treated lesions than in the lesions treated with a placebo. A reduction in desquamation was found in both treatments; the difference between the treatments was not statistically significant. A decrease in number of proliferative cells in the Mirak-treated lesions was seen, but the difference with placebo-treated lesions was not significant. The other investigated parameters did not change during treatment. No side effects were seen. CONCLUSIONS: The Mirak Home Care Pack induces a modest therapeutic effect compared to placebo treatment, without significant side effects. Treatment with the Mirak Home Care Packs alone will probably not be able to compete with the already existing treatments for psoriasis.

Administration, Topical↗
PubMed1997

The regulation of CD11b integrin levels on human blood leukocytes and leukotriene B4-stimulated skin by a specific leukotriene B4 receptor antagonist (LY293111).

CD11b is part of the beta2-integrin Mac-1 and plays an important role in neutrophil adhesion. Leukotriene B4 (LTB4) is an active upregulator of neutrophil CD11b-expression, acts as a potent chemoattractant to neutrophils and is also known to upmodulate epidermal proliferation. We performed a placebo-controlled study on LY293111, an oral LTB4 receptor antagonist. Twenty healthy male volunteers were randomised over three treatment groups that received placebo, 48 mg, or 200 mg drug twice daily for 10 days. Before and after treatment, flow cytometrical CD11b assessment was performed on in vitro LTB4-stimulated peripheral blood neutrophils. Additionally, skin biopsies were taken at 24 and 72 h after epicutaneous LTB4 application, before and after treatment. The effects on skin were assessed immunohistochemically using various markers. All observed effects were dose related. CD11b upregulation on blood neutrophils was significantly suppressed in both treatment groups compared to placebo. In skin, a significant suppression of inflammation and hyperproliferation occurred. Pronounced inhibition was observed on neutrophil migration into the epidermis and the inflammatory infiltrate was decreased. A similar but weaker response was seen in the dermis. The number of cycling cells as well as suprabasal keratin-16 expression were decreased in both treatment groups. LY293111 proved to be a potent inhibitor of LTB4-induced cutaneous inflammation and hyperproliferation. The potent antiinflammatory effect in vivo and the fact that in the present study the compound showed no clinically significant side effects make it an interesting drug in the future treatment of inflammatory conditions predominated by neutrophils.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Epicutaneous application of leukotriene B4 induces patterns of tenascin and a heparan sulfate proteoglycan epitope that are typical for psoriatic lesions.

Application of leukotriene B4 (LTB4) to normal human skin induces changes similar to those found in psoriatic skin, and it has proved to be a useful model for studying the pathogenesis and treatment of psoriasis. We studied the expression patterns of molecules that have recently been shown to be altered in lesional psoriatic skin, including the extracellular matrix protein tenascin (TN) and the basement membrane and cell surface-associated heparan sulfate proteoglycans (HSPGs). During 72-h the expression of these markers was studied immunohistochemically and the expression of TN was correlated with epidermal proliferation and influx of inflammatory cells. Following the peak influx of polymorphonuclear leukocytes, a marked increase in TN expression was noted in the papillary dermis 72 h after LTB4 application. The expression patterns of basal membrane-associated epitopes of HSPG remained unaltered, whereas the expression of cell surface-associated HSPG disappeared 72 h after LTB4 application. A significant correlation was found between dermal TN expression and epidermal hyperproliferation, and between TN expression and the presence of dermal T cells. These findings indicate that the model of LTB4-induced acute cutaneous inflammation displays many characteristics of early psoriatic lesions and could serve as a model to study some of the cell biological changes in this disease.

Administration, Cutaneous↗
PubMed1997

Recruitment of cycling epidermal cells and expression of filaggrin, involucrin and tenascin in the margin of the active psoriatic plaque, in the uninvolved skin of psoriatic patients and in the normal healthy skin.

The peripheral changes in the uninvolved skin adjacent to the extending psoriatic lesions may represent early events. The sequence of these events remains controversial. In the present study we evaluated epidermal and dermal aspects of the margin of the progressive psoriatic plaque, the distant uninvolved skin and normal healthy skin, using immunohistochemistry with markers for keratinization, proliferation and connective tissue: filaggrin, involucrin, Ki-67 and tenascin. The results showed that: (i) processes in distant uninvolved skin were comparable with the observations in normal skin; (ii) in the margin zone of the spreading psoriatic lesion, following the increased appearance of tenascin, the transition into parakeratosis, abnormal expression of filaggrin, involucrin and recruitment of cycling epidermal cells, happened simultaneously. The simultaneous normalization of these epidermal processes might be a consequence of a signal which is simultaneously transduced to the basal and suprabasal cell layers of the epidermis. Based on the present results and earlier findings, we would like to propose a triple stage model for the development of the psoriatic lesion: Stage 1, involvement of the stroma; stage II, inflammatory infiltrate formation and penetration into the upper layers of the epidermis, with suprabasal expression of keratin 16; stage III, recruitment of cycling epidermal cells and abnormal terminal differentiation. Further studies are required on the regulation of tenascin expression, focusing on factors derived from the stroma affecting both recruitment of cycling epidermal cells, involucrin and filaggrin expression. An intermediate step in the dermo-epithelial interrelation is the inflammatory infiltrate, penetrating into the most superficial zone of the epidermis, and the suprabasal expression of keratin 16.

Adult↗
PubMed1997

Altered distribution of heparan sulfate proteoglycans in psoriasis.

Heparan sulfate proteoglycans (HSPGs) are components of the basement membrane (BM) of various tissues. They consist of a core protein and negatively charged glycosaminoglycan side chains: the heparan sulfate (HS) moieties. In psoriasis, uninvolved skin of psoriasis patients and in normal skin, the distribution of HSPGs was studied immunohistochemically by means of three different monoclonal antibodies: JM-72, directed against the HSPG-core protein, JM-13 against the sulfated domains of HS and JM-403 against the unmodified/low sulfated parts of HS. In psoriasis JM-13 staining was consistently absent in the tips of the dermal papillae, whereas JM-13 showed a continuous staining in the BM of uninvolved and normal skin. JM-403 staining was present in BM of all specimens. In addition, a honeycomb-like staining was found in epidermis of normal skin and to a lesser extent in uninvolved skin, due to binding with plasma membrane-associated HS. In psoriasis this JM-403 staining of the epidermis was invariably absent. JM-72 showed a continuous staining of BM in all biopsies. In conclusion, normal human skin and involved psoriatic skin show clear differences in expression of HS. These data may provide insight into the role of HSPGs in psoriasis, which remains further to be elucidated.

Adult↗
PubMed1997

Differences in extracellular matrix proteins, epidermal growth and differentiation in discoid lupus erythematosus, lichen planus and the overlap syndrome.

Lichen planus (LP) and discoid lupus erythematosus (DLE) are separate disease entities. Nevertheless, patients with a so-called "overlap syndrome" have been described occasionally. The aim of the present study was to establish whether the LE/LP overlap syndrome, based on clinical and routine histological features, could be delineated from DLE or LP using immunohistochemical techniques. Formalin-fixated, paraffin-embedded skin biopsies of patients with DLE, LP and the overlap syndrome were compared regarding immunohistochemical markers for epidermal growth and differentiation and extracellular matrix components. With the markers for extracellular matrix proteins, it was possible to delineate the overlap syndrome from LP. This was not possible for the overlap syndrome and DLE. These findings might indicate that the LE/LP overlap syndrome could be considered as LP-like DLE rather than as a distinct disease entity.

Adult↗
PubMed1997

Extremely low levels of epidermal skin-derived antileucoproteinase/elafin in a patient with impetigo herpetiformis.

Impetigo herpetiformis (IH) is a rare pustular dermatosis with unknown aetiology, typically occurring during pregnancy. Based upon a similar clinical and histological presentation, i.e. spongiform accumulation of polymorphonuclear leucocytes in the stratum corneum, several authors consider IH as a variant of generalized pustular psoriasis (GPP), while others state that IH is a separate entity. Skin-derived antileucoproteinase (SKALP) is a strong and specific inhibitor of human leucocyte elastase (HLE) and proteinase 3, two neutral proteinases that have been implicated in leucocyte migration and tissue destruction. Previously, we reported decreased SKALP activity in pustular forms of psoriasis compared with plaque psoriasis. In this study we present a case study of a patient with IH, where SKALP activity was measured using biochemical and immunochemical techniques. Epidermal scales and sera were collected during the course of the disease. Comparison was made with three patients with GPP and six patients with plaque psoriasis. Initially, anti-HLE activity in epidermal scales of the patient with IH was comparable with values in patients with GPP, i.e. decreased compared with plaque psoriasis. During the course of the disease, anti-elastase activity dropped to undetectable levels, concomitant with the appearance of free elastase activity. This finding suggests a total saturation of epidermal anti-HLE activity. Low levels of SKALP, presumably complexed with HLE, could be measured immunochemically in scale extracts. Serum levels of total SKALP correlated with the disease activity. We suggest that a reduced amount of epidermal SKALP contributes to an imbalance between elastase and its inhibitor, resulting in the formation of epidermal pustules. This mechanism of pustule formation could apply both to GPP and IH, suggesting a final common pathway in the pathogenic mechanisms of IH and GPP.

Adult↗
PubMed1996

[Tinea capitis].

Explore the source record for details and available documents.

Animals↗
PubMed1996

The immunohistochemical effects of a single challenge with an intermediate dose of ultraviolet B on normal human skin.

Ultraviolet B (UVB) irradiation has extensively been advocated for use in the investigation of cutaneous inflammation in vivo. Mostly doses above the threshold of skin damage have been used. Therefore it is not clear whether the changes observed are specific effects of UVB or to a certain extent represent wound healing. In this study the dose-dependent effects of UVB on normal human skin were assessed using histology and immunohistochemistry. The dose of 1 MED was chosen as a dose unducing tissue changes with adequate morphology: no toxicity but evident immunohistochemical changes. The sequential effects of this 1 MED of UVB were studied for up to 14 days after irradiation, using immunohistochemistry with a panel of monoclonal antibodies. Substantial effects were observed, mainly on proliferation and differentiation; the markers for inflammation did not reveal major changes. This model might be a promising approach to evaluate the effect of drugs on epidermal proliferation and differentiation in vivo.

Adult↗
PubMed1996

Epidermal differentiation characteristics of the psoriatic plaque during treatment with calcipotriol.

Treatment of psoriasis with vitamin D3 analogues is well established in present dermatological practice. One of the clinical signs of the psoriatic plaque that reduces early and markedly during treatment with the vitamin D3 analogue calcipotriol is scaling. Since scaling is the clinical manifestation of disordered epidermal differentiation, early changes in immunohistochemical markers for differentiation (transglutaminase, involucrin and filaggrin) were studied in patients who had been treated with calcipotriol for 4 weeks. Markers for proliferation (Ki-67 antigen) and inflammation (polymorphonuclear leucocytes and T lymphocytes) were also studied and correlated with the differentiation characteristics. Clinically, a major improvement was seen in all patients. A significant decrease in the percentage of transglutaminase-positive cell layers was observed during the first week of treatment. In contrast, an increase in transglutaminase activity in epidermal cell cultures following incubation with calcipotriol has been reported. Involucrin expression was only slightly modulated in vivo. However, a major restoration of the filaggrin-positive cell layer and significant reduction in the recruitment of cycling epidermal cells characterized the epidermal response to calcipotriol treatment. Markers for inflammation (T11-positive cells and elastase-positive cells) were also reduced substantially during the first week of treatment with calcipotriol. From this study it may be concluded that inhibition of epidermal growth and recovery of the filaggrin-positive cell layer are among the in vivo effects of calcipotriol.

Adult↗