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Biomedical subjects

J D Bos

Publications and source records attributed to J D Bos.

At least 91 records · Page 5Linked to original sources
PubMed1997

A systematic review of five systemic treatments for severe psoriasis.

We systematically reviewed the evidence concerning the ability of five systemic treatments to induce remission in patients with severe psoriasis: ultraviolet B (UVB), photochemotherapy (PUVA), methotrexate (MTX), retinoids (RET) and cyclosporin A (CYA). An elaborate literature search was performed, the validity of studies was assessed, and data were analysed. In total, 89, 193, 101, 155 and 127 studies (n = 665) concerning UVB, PUVA, MTX, RET and CYA were found. The exclusion rate was high, mainly because of concomitant antipsoriatic therapy, outdated dosages or inadequate documentation. No study on MTX could be included. A total of 129 patient series was included in the analysis, reporting on 13,677 patients. Study size-weighted averages of the proportions of patients with clearance and good, moderate and poor response (defined, respectively, as 95-100%, 75-100%, 50-75% and < 50% reduction in the outcome measurements as compared with baseline) were calculated. PUVA therapy was associated with the highest average proportion of patients with clearance (70%), and the highest proportion of patients with good response (83%), followed by UVB (68%) and CYA (64%). Incidence of side-effects per week was highest in the RET group and lowest in the phototherapy groups. This review may provide a basis for the development of guidelines for the treatment of psoriasis. Trials comparing oral modalities applied according to currently accepted standards should also be carried out.

Chronic Disease↗
PubMed1996

Reduced IL-12 production by monocytes upon ultraviolet-B irradiation selectively limits activation of T helper-1 cells.

The capacity of APC to stimulate the proliferation of human peripheral blood T cells decreases upon ultraviolet-B (UVB) irradiation. The aim of this study was to investigate whether all T cell subsets are equally sensitive to this reduced APC function. Established human Th1, Th2, and Th0 clones were stimulated with monocytes in a soluble CD3 mAb-mediated assay that is dependent on the presence of APC. Monocytes were exposed to low nonlethal doses of UVB radiation before coculture with T cells. UVB irradiation inhibited the capacity of monocytes to stimulate the proliferation and IFN-gamma production of Th1 cells in a dose-related fashion. In contrast, UVB-treated monocytes induced normal proliferation and IL-4 production in Th2 cells. Stimulation of Th0 cell proliferation by UVB-irradiated monocytes was normal, but a preferential suppression of IFN-gamma production was observed, thus leading to a more Th2-like cytokine response. The loss of Th1 proliferation upon stimulation with UVB-irradiated monocytes could be overcome by rIL-2; however, IFN-gamma production remained suppressed. IFN-gamma production could be completely restored by rIL-12, whereas the addition of IL-1 beta, TNF-alpha, or indomethacin had no such effect, nor did the addition of mAb to CD28, added to compensate for the reduced B7 expression of UVB-irradiated monocytes. Monocytes exposed to UVB radiation exhibited reduced expression of mRNA for the IL-1 2 subunits p35 and p40 and suppressed production of the IL-12 p70 protein. Our results thus indicate that UVB irradiation of APC selectively impairs Th1-like responses, a phenomenon caused by the UVB-induced suppression of monocyte IL-12 production.

Cytokines↗
PubMed1996

Quantification of cutaneous sclerosis with a skin elasticity meter in patients with generalized scleroderma.

BACKGROUND: The skin score, a subjective assessment of skin elasticity, is widely used in patients with systemic sclerosis. Although this scoring method is regarded as a validated and accepted tool, the interobserver and intraobserver reproducibility is relatively poor. OBJECTIVE: Our purpose was to investigate whether the recently developed SEM 474 cutometer, which exerts a controlled vacuum force to the skin, can measure skin elasticity more objectively than the skin score. METHODS: Skin elasticity was measured in 74 different body areas in patients with systemic sclerosis and compared with the skin score obtained from the same areas. RESULTS: The cutometer produced quantitative and reproducible data. A large-diameter (8 mm) measuring probe was superior to a small probe. The interobserver intraclass correlation coefficient (ICC) was 0.92; the intraobserver ICC was 0.94. A linear correlation was found with the clinical skin score; the Spearman rank correlation test was 0.69. CONCLUSION: The correlation with the skin score was reasonable, despite the observation that regional differences in skin elasticity were detected by the cutometer but not by the human observer, who automatically compensates for these factors and integrates them into the skin score. The high interobserver and intraobserver ICC makes the cutometer more suitable for quantifying changes in skin thickness than the subjective skin score.

Adult↗
PubMed1996

Expression of the T-cell activation antigens CD27 and CD28 in normal and psoriatic skin.

Activated T lymphocytes are thought to be involved in the pathogenesis of psoriasis. From studies with peripheral blood T lymphocytes it is known that T cells show a decrease in membrane expression of CD27 molecules during continuous antigenic stimulation. The T-cell activation molecule CD28 is thought to be involved in the transduction of an antigen-non-specific costimulatory signal. Therefore, in order to elucidate further the pathogenesis of psoriasis we studied the expression of CD27 and CD28, together with CD4, CD8 and CD45RA in this benign inflammatory dermatological disease. We used immunohistochemical techniques to determine absolute numbers of T lymphocytes and expression of these T-cell activation and T-subset-specific molecules in normal (n = 7), uninvolved perilesional (n = 7) and lesional psoriatic (n = 7) skin. We found that not only lesional but also clinically uninvolved perilesional skin showed an increased number of T cells. Further, immunohistochemical studies showed that CD27 is expressed by a minority of normal skin T cells, while in lesional psoriatic skin, expression was even lower, and almost absent in perilesional skin sections. In contrast to normal skin, both perilesional and lesional psoriatic skin contained no CD28 positive T cells. In lesional psoriatic skin, however, T cells showed predominantly the CD4 phenotype, while in perilesional skin CD8 positive T cells were dominant. Two conclusions were reached: first, the absolute number of T cells, their CD27, CD28 and CD45RA expression, and the influx of CD8 positive T cells, indicate that perilesional psoriatic skin is different from normal and lesional psoriatic skin; and secondly, the data on CD27 and CD28 suggest that not only lesional but also perilesional psoriatic skin is subject to continuous antigenic stimulation, thus leading to decreased CD27 and CD28 expression on skin T cells.

CD28 Antigens↗
PubMed1996

The long-term safety and efficacy of cyclosporin in severe refractory atopic dermatitis: a comparison of two dosage regimens.

An open, randomized trial was performed to determine the optimal dosage schedule with regard to the efficacy and safety of cyclosporin in severe atopic dermatitis. The study also provided clinical experience with regard to the efficacy and safety of long-term cyclosporin treatment. During a 2-month dose-finding period, 78 patients with severe, long-standing atopic dermatitis received cyclosporin at a dose of either 5 mg/kg per day, decreasing to 3 mg/kg per day (Group A), or 3 mg/kg per day, increasing to 5 mg/kg per day (Group B), Patients were maintained on their optimal dose for a further 10 months. Patients in Group A showed a significantly greater improvement in efficacy parameters over the first 2 weeks than with patients in Group B, but as the dose was decreased in Group A and increased in Group B, these differences were minimized. After 1 year, cyclosporin showed an efficacy of 59.8% in Group A and 51.7% in Group B, assessed by a severity score. Assessed in terms of an area score, these figures were 48.7% and 40%, respectively. Cyclosporin demonstrated a good safety profile during long-term treatment and was generally well tolerated. The lower starting dosage was not associated with higher dropout rates. This study showed no differences in efficacy or adverse events between the two dosage schedules in long-term treatment.

Adolescent↗
PubMed1996

Solar-simulated ultraviolet irradiation induces selective influx of CD4+ T lymphocytes in normal human skin.

The proportion and composition of the human cutaneous CD3+ T lymphocyte population was determined in situ following a single exposure to physiological, erythema-inducing doses of simulated solar radiation, mainly consisting of UV radiation. Biopsies were taken 1, 2 and 7 days after local irradiation of normal volunteers with 1, 2 and 4 MED by a xenonarc lamp and immunohistochemistry was performed on cryostat sections. Ultraviolet radiation caused an initial decrease of intraepidermal CD3+ T-cell numbers or even could lead to T-cell depletion 24 and 48 h postirradiation, and this was followed by an infiltration of T cells in the epidermis as determined 1 week after UV exposure. The number of dermal CD3+ T cells was increased 24 h after irradiation, reached a maximum at 48 h and subsequently declined at day 7, though remained significantly higher than the unirradiated control. Double staining demonstrated that the CD3+ T cells, which immigrated into the (epi)dermis upon UV exposure, coexpressed CD4 but not CD8. Therefore the CD4/CD8 ratio in skin was markedly increased during the first week upon UV exposure. Our time course study shows that UV radiation affects the T-cell population within human skin by depleting the majority of epidermal T cells and initiating a selective influx of CD4+ T cells.

Adolescent↗
PubMed1996

Production and modulation of T-cell cytokines in atopic allergy.

Atopic allergy is associated with allergen-specific CD4+ T cells showing a bias to production of the type-2 cytokines interleukin (IL)-4 and IL-5. There are indications that this bias is also evident in atopic T-helper (Th) cells with other antigen specificities. The balance between the production of type-1 and type-2 cytokines is influenced by various factors present in the microenvironment of the Th cells during their activation. Factors of special interest are antigen-presenting cell-derived IL-12 and prostaglandin E2, skewing to type-1 and type-2 cytokine production, respectively. The production of IL-12 and prostaglandin E2 is induced by the interaction between CD40 and CD40 ligand expressed by Th cells, and by biologically active agents such as micro-organisms or their products. The IL-12/prostaglandin E2 production ratio depends on the antigen-presenting cell type, the type of stimulus and the presence of certain cytokines. Other Th-cytokine-skewing factors are autocrine or paracrine IFN-gamma and IL-4. In fact, the type-1/type-2 cytokine production balance in Th cells is under the control of various soluble products that act in a complex network of type-1 (e.g. IL-12, IFN-gamma) or type-2 (e.g. IL-4, IL-10 and prostaglandin E2) factors and are produced by Th cells and their accessory antigen-presenting or bystander cells. The levels of these factors may further be determined by gene polymorphisms or aberrant hormone levels. Despite the growing knowledge of the regulation of Th-cell cytokine production, the etiology of biased cytokine production in atopic allergic individuals is still enigmatic.

Animals↗
PubMed1996

Soluble interleukin-2 receptor (sIL-2R) is a marker of disease activity in psoriasis: a comparison of sIL-2R, sCD27, sCD4, sCD8 and sICAM-1.

Psoriasis is a T-cell-mediated inflammatory skin disease which can be treated successfully with immunosuppressive drugs. Our purpose was to evaluate disease activity of psoriasis and the effect of immunosuppressive treatment by monitoring the soluble T-cell products sIL-2R, sCD27, sCD4, sCD8 and sICAM-1. Twenty-two patients were treated orally with escalating dosages of cyclosporin A (n = 17)(3-5 mg/kg/day) or FK506 (n = 5)(0.05-0.15 mg/kg/day). The Psoriasis Area and Severity Index (PASI) was used to monitor clinical activity of psoriasis. Serum samples were analyzed by ELISA. sIL-2R levels showed the highest correlation with psoriasis disease activity (rs = 0.89; p < 0.05). The longitudinal part of this study showed that levels of sIL-2R and sCD27 decreased during immunosuppressive treatment but remained above normal even in patients successfully treated. Our data indicate that sIL-2R levels are well correlated with disease activity in patients with psoriasis. sIL-2R levels closely follow the decrease of disease activity during immunosuppressive treatment.

Adolescent↗
PubMed1996

Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis.

BACKGROUND: In dermatology and rheumatology, methotrexate is frequently prescribed in low dosages per week; in oncology, high dosages per week are prescribed. Methotrexate osteopathy was first reported in children with leukemia treated with high doses of methotrexate. In animal studies, low doses of methotrexate proved to have an adverse effect on bone metabolism, especially on osteoblast activity. OBSERVATIONS: Methotrexate osteopathy is a relatively unknown complication of low-dose methotrexate treatment. We describe three patients treated with low-dose oral methotrexate in whom signs and symptoms were present that were similar to those found in children treated with high doses of methotrexate. All three patients had a triad of severe pain localized in the distal tibiae, osteoporosis, and compression fractures of the distal tibia, which could be identified with radiographs, technetium Tc 99m scanning, and magnetic resonance imaging. CONCLUSIONS: Methotrexate osteopathy can occur in patients treated with low doses of methotrexate, even over a short period of time. As pain is localized in the distal tibia, it is easily misdiagnosed as psoriatic arthritis of the ankle, but the diagnosis can be correctly made by careful investigation and use of imaging techniques. The only therapy is withdrawal of methotrexate. It is important that more physicians become aware of this side effect of methotrexate therapy, which can occur along with arthritic symptoms.

Aged↗
PubMed1996

Novel predictive assay for contact allergens using human skin explant cultures.

Contact allergens sensitize the immune system by the binding to and subsequent activation of Langerhans cells (LCs), the antigen-presenting cells of the skin. At present, new chemicals are usually tested for their contact allergenicity in animal models. To develop an animal-replacing predictive in vivo assay for the identification of potential contact allergens, we compared the effects of epicutaneous application of six known contact allergens, five known irritants and two dermatologically inactive chemicals on LCs in skin biopsy cultures from seven healthy donors. Immunohistochemical analysis of cryostat sections of all the biopsies treated with contact allergens showed 1) a large reduction in the number of LCs in epidermis, as evaluated by a decrease in human leukocyte antigens (HLA)-DR-expressing cells, and CD1a-expressing cells and 2) accumulation of the remaining LCs at the epidermal-dermal junction. In contrast, the irritants, inactive chemicals, and solvents did not induce these changes. Morphometrical analysis indicated that the contact allergen-induced reduction in the number of HLA-DR+ and CD1a+ LCs per millimeter of epidermis was significant and was dependent on the concentration of the contact allergens. Flow cytometric analysis of isolated epidermal cells confirmed the immunohistochemical findings. In combination, these results suggest that the culture of ex vivo human skin explants provides a promising model to predict potential allergenicity of newly produced chemical compounds and can therefore replace current animal models.

Allergens↗
PubMed1996

Effects of contact allergens on human Langerhans cells in skin organ culture: migration, modulation of cell surface molecules, and early expression of interleukin-1 beta protein.

Epidermal Langerhans cells (LC) and cytokines play a critical role in the initiation phase of contact hypersensitivity reactions in the skin. Most of the studies of these aspects have been performed in animal models and relatively little is known about the human system. Short-term human skin organ cultures, in which LC preserved their characteristics and distribution within the epidermis, were used to examine the time course effects of contact allergens on human LC in situ and whether these effects are mediated by cytokines. Epicutaneous application of nontoxic concentrations of contact allergens 2,4-dinitrofluorobenzene, 2,4-dinitrochlorobenzene, and nickel sulphate, but not the irritants sodium dodecylsuphaye and croton oil or the tolerogen 2,4-dichloronitrobenzene, significantly reduced the total number of LC in the epidermis: remaining LC were localized along the epidermal-dermal junction, suggesting a migration of LC within and out of the epidermis. LC that are migrated to the epidermal-dermal junction showed a decreased expression of CD1a+ and MHC-II and an upregulation of ICAM-I. While these effects were observed after 24 hours, the expression of IL-1 beta protein was induced exclusively by LC as early as 4 hours after skin challenge with contact allergens alone. After 24 hours, contact allergens not only increased the expression of IL-1 beta but also induced the expression of IL-1 alpha, TNF-alpha, GM-CSF, and IL-6 proteins mainly by suprabasal keratinocytes. In an attempt to study the possible relation between allergen-induced epidermal cytokines and the migration and phenotypic changes of LC, skin explants were incubated with corresponding human recombinant (hr) cytokines. After 12 hours, hr IL-1 beta, but not other hr cytokines (IL-1 alpha, TNF-alpha, GM-CSF, and IL-6), induced the migration within and out of the epidermis and decreased the expression of CD1a+ and MHC-II on remaining epidermal LC similar to that caused by contact allergens. Pre-incubation of skin explants with neutralizing IL-1 beta antibodies, but not antibodies to IL-1 alpha, TNF-alpha, or GM-CSF, significantly prevented the allergen-induced migration of LC. This study showed that contact allergens preferentially induced the migration of LC within and out of the epidermis and modulated the expression of cell surface molecules on migrated LC as well as induced the early expression of LC-derived IL-1 beta. We also provide evidence that IL-1 beta is critically involved in contact allergen-induced changes on human epidermal LC and suggest that IL-1 beta plays a role in the initiation of contact hypersensitivity in human skin in vivo.

Allergens↗
PubMed1996

Incomplete functional deficiencies of the fourth (C4) and second (C2) components of complement in a patient with linear frontoparietal scleroderma and his family. Deficiencies determined by a gene not linked to human leukocyte antigen system.

BACKGROUND: In a previous study, a patient suffering from linear frontoparietal scleroderma and some of his family members were found to have an incomplete functional deficiency of the second component (C2) of complement (C). In this study, the proband and the rest of his family members were investigated for functional deficiencies of C2 and the fourth component of C (C4). A search for null alleles of C2 (C2*Q0) and C4 (C4*Q0) was made to find out whether their occurrence is responsible for incomplete functional deficiencies. HLA analysis was performed to find out whether deficiencies are linked to HLA alleles known to be associated with C4*Q0 and C2*Q0. Possible large deletions at C4 and 21-hydroxylase (21-OH) gene loci were also investigated in some family members. OBSERVATIONS: The proband had a combined functional deficiency of C4 and C2. Some of his family members had a partial functional deficiency of C4, some of C2 and some of C4 and C2; none had null alleles of C2 (C2*Q0), factor B (B*Q0) or C4B (C4B*Q0). C4*Q0 or functional C4 deficiency in this family was not associated with HLA-A1;B8;DR3 alleles. C2 deficiency was also not associated with HLA antigens known to be associated with type I and II C2 deficiencies. No gene deletion or unusual polymorphism at C4A and 21-OHA loci could be seen by restriction fragment length polymorphism (RFLP) studies. CONCLUSIONS: Combined and isolated partial functional deficiencies of C4 and C2 observed in the proband and many of his family members were not caused by C activation or null alleles. They were not linked to HLA system and were reminiscent of those observed previously in a family in which C4 deficiency was determined by a gene not linked to the HLA system.

Alleles↗
PubMed1995

Functional maturation of human naive T helper cells in the absence of accessory cells. Generation of IL-4-producing T helper cells does not require exogenous IL-4.

In the human model, requirements for the primary onset of IFN-gamma and IL-4 production in maturing T helper lymphocytes were compared. Stimulation of freshly isolated CD4+CD45RA+ naive Th cells with immobilized CD3 mAb in the presence of exogenous IL-2 resulted in the proliferative response of this subset, which was equal to or higher than CD4+CD45R0+ memory Th cells. Throughout the first 6 days after this mode of stimulation, naive Th cells did not secrete IL-4 and produced only small amounts of IFN-gamma, whereas high amounts of both lymphokines were secreted by stimulated autologous memory Th cells. Under these conditions, naive Th cells acquired the CD45RA-CD45R0+ memory phenotype. After restimulation, such in vitro-generated CD45R0+ cells produced high amounts of IFN-gamma but, despite the full phenotype conversion, they produced only trace amounts of IL-4. In contrast, when the primary stimulation and the expansion of cells proceeded in the presence of IL-1 beta or CD28 mAb, both IFN-gamma and IL-4 were produced after restimulation, in similar amounts compared with those produced by memory Th cells. The effect of IL-1 beta and CD28 signaling could not be obtained by the administration of exogenous IL-4 nor could the onset of IL-4 production be prevented by the presence of a neutralizing anti-IL-4 Ab in primary cultures. These data show that the development of human IL-4-producing Th cells can proceed in the absence of any pre-existing source of IL-4 and can be driven solely by the APC-related signals.

Antigen-Presenting Cells↗
PubMed1995

Corticosteroids class-dependently inhibit in vitro Th1- and Th2-type cytokine production.

Corticosteroids (CS) are very potent immunosuppressive agents and are widely used to treat inflammatory diseases. On the basis of their clinical efficacy and potency CS have been divided into different classes. In the present study we investigated whether the class-associated effects of CS are correlated with a differential in vitro effect on cytokine production by T lymphocytes. Therefore, we determined the in vitro effects of CS on the production of Th1- and Th2-type cytokines. The addition of CS, in the range of 10(-9) to 10(-4) M, resulted in a class- and dose-dependent inhibition of the production of both IFN-gamma and IL-4. Notably, at the lowest doses tested, hydrocortisone and hydrocortisone 17-butyrate had a stimulatory effect on IL-4 production. CS class-dependently inhibited the IL-2 production by T cells but did not affect IL-2R expression of the T cells. Addition of rIL-2 could not completely restore the inhibitory effect of the CS on proliferation and on IFN-gamma and IL-4 production, indicating that CS act only partially via inhibition of IL-2 production. The demonstrated positive correlation between the clinical efficacy and the in vitro effects of the different classes of CS strongly suggests that the effect of CS on T-cell-mediated inflammation follows from inhibition of proliferation and cytokine production by T lymphocytes. The in vitro method used will be valuable for investigating and classifying new types of CS and other substances for applications in T-cell-mediated diseases.

Adrenal Cortex Hormones↗