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Biomedical subjects

Jan D Bos

Publications and source records attributed to Jan D Bos.

At least 19 recordsLinked to original sources
PubMed2006

Altered penetration of polyethylene glycols into uninvolved skin of atopic dermatitis patients.

Involved regions of the skin in atopic dermatitis (AD) patients have an altered barrier function. Whether uninvolved skin also has a diminished barrier is controversial. To assess the barrier function of uninvolved skin in AD patients, the percutaneous penetration of polyethylene glycols (PEGs) of various molecular sizes was determined in vivo in AD patients and control subjects using tape stripping of the stratum corneum (SC). The diffusion and partition coefficients were determined using Fick's second law of diffusion. The SC thickness was similar in both groups; however, the trans-epidermal water loss was higher in atopic skin. The apparent diffusion coefficient of PEGs through atopic skin was twice as high as through normal skin, and decreased with increasing molecular weight (MW) in both groups. The partition coefficient in the skin of AD patients was half of that for normal skin but as for normal skin, there was no MW dependency. Although atopic skin exhibited altered barrier with respect to diffusion and partitioning, the permeability coefficients were nearly the same for atopic and normal skin. The results support the assumption of altered skin barrier of AD patients even in the skin that is visibly unaffected by disease.

Adolescent↗
PubMed2006

In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin.

Keratinocytes contribute to cutaneous immune responses through the expression of cytokines. We investigated whether human keratinocytes can express IL-23, a newly defined IFN-gamma-inducing cytokine composed of a unique p19 subunit and a p40 subunit shared with IL-12. Cultured keratinocytes from normal and lesional psoriatic skin were found to express constitutively mRNA for both subunits of IL-23. Low but significant levels of the heterodimeric IL-23 protein could be detected in cell lysates and supernatants from stimulated keratinocytes by immunoblotting and ELISA. Functional analysis showed that these low levels of keratinocyte-derived IL-23 were sufficient to enhance the IFN-gamma production by memory T cells. Immunostaining of skin sections confirmed expression of both subunits of IL-23 by keratinocytes in situ and also revealed expression of this cytokine in the dermal compartment. IL-23 expression was significantly higher in psoriatic lesional skin, compared with normal and psoriatic nonlesional skin. The immunostained preparations of cultured cells and IL-23 levels in culture supernatants did not show any difference between normal and psoriatic keratinocytes indicating no intrinsic aberration of IL-23 expression in keratinocytes from psoriatic skin. Double staining of cytospin preparations demonstrated that IL-23 p19 is also expressed by epidermal Langerhans cells, dermal dendritic cells, and macrophages. Psoriasis is a chronic inflammatory skin disease mediated by IFN-gamma-expressing type 1 memory T cells. As IL-23 is important to activate memory T cells to produce IFN-gamma, its augmented expression of IL-23 by keratinocytes and cutaneous APC may contribute to the perpetuation of the inflammation process in this disease.

Adjuvants, Immunologic↗
PubMed2006

Benzoyl peroxide/clindamycin/UVA is more effective than fluticasone/UVA in progressive macular hypomelanosis: a randomized study.

BACKGROUND: There is no effective treatment for progressive macular hypomelanosis. Recent findings indicate that Propionibacterium acnes may play a role in the pathogenesis. OBJECTIVES: We sought to compare the effectiveness of antimicrobial therapy with anti-inflammatory therapy in patients with progressive macular hypomelanosis. METHODS: A total of 45 patients were randomized to a within-patient left-right comparison study of benzoyl peroxide 5% hydrogel/clindamycin 1% lotion in combination with UVA irradiation versus fluticasone 0.05% cream in combination with UVA irradiation. Repigmentation was determined by photometric measurements of changes in skin color and by patient and dermatologist assessment using before and after photographs. RESULTS: Benzoyl peroxide 5% hydrogel, clindamycin 1% lotion, and UVA led to better repigmentation than fluticasone 0.05% cream in combination with UVA irradiation in all measurements. (Photometric measurements P = .007, patient assessment P < .0001, and dermatologist assessment P < .0001.) LIMITATIONS: There was difficult objective color measurement. Therefore, subjective assessment has important additional value. Right-left comparisons have certain inherent limitations. CONCLUSION: Antimicrobial therapy in conjunction with light was more effective in repigmentation in patients with progressive macular hypomelanosis than a combination of anti-inflammatory therapy and light.

Administration, Topical↗
PubMed2006

Proceedings of the 4th Georg Rajka International Symposium on Atopic Dermatitis, Arcachon, France, September 15-17, 2005.

The 4th Georg Rajka International Symposium on Atopic Dermatitis presented a comprehensive view of our current understanding and management of atopic dermatitis (AD). These proceedings highlight contributions related to the history of AD doctrines; genetic and epigenetic background; epidemiology; maturation of the immune system; infection and innate-adaptive immunity; epidermal inflammation, including neurogenic inflammation and pruritus; animal models; skin barrier; evidence-based therapy and education programs; prognostic and severity markers; and allergy testing. Several studies in animal models and human subjects point to impaired skin barrier function as a primary defect that facilitates the effect of environmental factors and immune dysregulation found in AD. The new frontier in AD therapy should, in the near future, reflect our better understanding of the skin barrier. The influence of environmental factors on the skin and other epithelial barriers in the perinatal period needs to be better understood to implement appropriate prevention programs.

Animals↗
PubMed2005

Digital image analysis for the evaluation of the inflammatory infiltrate in psoriasis.

Traditionally the evaluation of the cellular infiltrate and protein expression in skin tissue sections is done by manual quantification. However, for reliable evaluation of histology in the development of new anti-psoriatic treatments there is a need for a more time-efficient and reproducible method. To test the use of digital image analysis (DIA) in this situation we compared the assessment of immunohistochemically stained skin sections with the more traditional manual quantification (MQ) and semi-quantitative analysis (SQA). The number of CD3+ T cells and the expression of E-selectin were evaluated in stained paired skin biopsies from 11 patients with chronic plaque psoriasis before and after initiation of anti-psoriasis therapy. We observed significant correlations between MQ and DIA for the number of T cells (epidermis: r=0.88, P< or =0.01, dermis r=0.87, P< or =0.01). Both DIA and MQ were equally effective in detecting reductions of T-cell numbers in active-treated patients. MQ took 20 h, compared to 6 h for DIA. We also observed significant correlations between SQA and DIA for the expression of E-selectin (r=0.88, P< or =0.01), although DIA was more sensitive than SQA to detect (early) changes. SQA took 10 h, compared to 4 h for DIA. In conclusion, the quantification of the inflammatory infiltrate in psoriatic lesional skin by DIA generated similar results as MQ and SQA in a reliable, reproducible and higher time efficient fashion.

CD3 Complex↗
PubMed2005

Human keratinocytes produce the complement inhibitor factor H: synthesis is regulated by interferon-gamma.

Locally synthesized complement is believed to play an important role in host defense and inflammation at organ level. In the epidermis, keratinocytes have so far been shown to synthesize two complement components, C3 and factor B. Here, we studied the synthesis of factor H by human keratinocytes. We also studied the regulation of factor H synthesis in keratinocytes by several cytokines, namely IL-1alpha, IL-2, IL-6, TGF-beta1, TNF-alpha and IFN-gamma. Human keratinocytes expressed factor H mRNA and constitutively released small amounts of factor H protein into the culture medium. This release was strongly upregulated by IFN-gamma but not by other cytokines tested. Western blot analysis revealed that IFN-gamma augments the synthesis of both molecular species, factor H (FH; 155kDa) and factor H-like protein-1 (FHL-1; 45kDa), of factor H. Factor H released in response to IFN-gamma was functionally active. In conclusion, we demonstrate that keratinocytes are capable of synthesizing factor H and that this synthesis is regulated by IFN-gamma.

Blotting, Western↗
PubMed2005

UVB 311 nm tolerance of vitiligo skin increases with skin photo type.

It is assumed that skin is protected against sunburn by melanin. In patients with vitiligo, there are white patches in the normal pigmented skin. We noticed that there is a difference in burning capacity of these white patches between people with different skin types. With UVB 311 nm lamps, we irradiated both lesional and non-lesional skin with increasing doses in 33 patients with vitiligo, divided into 5 groups according to skin type (II-VI). Twenty-four hours later we assessed the minimal erythema dose and found a correlation between skin type and UV sensitivity in both lesional skin and normal skin. We suggest that there must be a protection mechanism, other than that offered by melanin pigmentation. The antioxidant status may play a role in this phenomenon.

Adolescent↗
PubMed2004

Neutrophils infiltrating ultraviolet B-irradiated normal human skin display high IL-10 expression.

Exposure to an erythemal dose of ultraviolet B (UVB) is known to induce interleukin (IL-10) expression in human skin. It is generally believed that this IL-10 is predominantly expressed by CD11b+ HLA-DR+ macrophages that infiltrate the UVB-exposed skin. This cytokine is presumed to contribute to the immunosuppressive effects of UVB by inhibiting cell-mediated immune responses. We recently demonstrated that neutrophils, which also invade UVB-irradiated skin, express CD11b and HLA-DR as well. In addition, we showed that the presence of these neutrophils affects T-cell responses in primary T-cell cultures derived from UVB-exposed skin. Since neutrophils invade UVB-exposed skin and, like macrophages, express CD11b and HLA-DR, we sought to determine whether neutrophils represent another source of IL-10. Skin biopsies were obtained from four healthy volunteers before and 2 days after exposure to four minimal erythema doses of UVB. A series of immunohistochemical double-staining procedures using the following markers was performed: IL-10, CD11b, HLA-DR, CD36, neutrophil elastase, and CD66b. As expected IL-10 could be detected in CD11b+ HLA-DR+ CD36+ macrophages in the epidermis and dermis of UVB-exposed skin. Surprisingly, the majority of the abundant IL-10 expression was found in CD11b+ HLA-DR+ elastase+ CD66b+ neutrophils. Cytospin preparations from dermal cell suspensions confirmed the IL-10 expression by neutrophils displaying characteristic multilobular nuclei. Thus, neutrophils in UVB-exposed skin express IL-10 and should be recognized as active coplayers in the creation of the UVB-induced immunosuppressive microenvironment.

Dermis↗
PubMed2004

Deactivation of endothelium and reduction in angiogenesis in psoriatic skin and synovium by low dose infliximab therapy in combination with stable methotrexate therapy: a prospective single-centre study.

Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-alpha therapy. To evaluate the effects of anti-tumour necrosis factor-alpha treatment on expression of adhesion molecules and angiogenesis in psoriatic lesional skin and synovial tissue, we performed a prospective single-centre study with infliximab therapy combined with stable methotrexate therapy. Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab (3 mg/kg) at baseline, and at weeks 2, 6, 14 and 22 in an open-label study. In addition, patients continued to receive stable methotrexate therapy in dosages ranging from 5 to 20 mg/week. Clinical assessments, including Psoriasis Area and Severity Index (PASI) and Disease Activity Score (DAS), were performed at baseline and every 2 weeks afterward. In addition, skin biopsies from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4. Immunohistochemical analysis was performed to detect the number of blood vessels, the expression of adhesion molecules and the presence of vascular growth factors. Stained sections were evaluated by digital image analysis. At week 16, the mean PASI was reduced from 12.3 +/- 2.4 at baseline to 1.8 +/- 0.4 (P <or= 0.02). The mean DAS was reduced from 6.0 +/- 0.5 to 3.6 +/- 0.6 (P <or= 0.02). We found some fluctuations in DAS response as compared with the change in PASI, with the latter exhibiting a steady decrease over time. After 4 weeks the cell infiltrate was reduced in both skin and synovium. There was a significant reduction in the number of blood vessels in dermis and synovium at week 4. A significant reduction in the expression of alphavbeta3 integrin, a marker of neovascularization, was also found in both skin and synovium at week 4. In addition, a significant reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4. We also observed a trend toward reduced expression of vascular endothelial growth factor in both skin and synovium. In conclusion, low-dose infliximab treatment leads to decreased neoangiogenesis and deactivation of the endothelium, resulting in decreased cell infiltration and clinical improvement in psoriasis and psoriatic arthritis.

Adult↗
PubMed2004

T cells in psoriatic lesional skin that survive conventional therapy with NB-UVB radiation display reduced IFN-gamma expression.

The type 1 T cell-derived cytokine interferon gamma (IFN-gamma) is overexpressed in psoriatic lesional skin. Recently, we have shown that a single high erythemal dose of broad-band ultraviolet B (UVB) irradiation reduces type 1 and favors type 2, i.e. interleukin-4 (IL-4), cytokine expression in normal and psoriatic skin. In this study, we wanted to see whether conventional narrow-band UVB (NB-UVB) therapy (i.e. repeated exposure to nonerythemal doses) also affects type 1/type 2 cytokine expression of T cells present in chronic plaque type psoriatic lesions. Staining of cryostat sections showed decreased expression of both IFN-gamma and IL-4 in situ after NB-UVB therapy. CD4(+) dermal T cell lines, derived from psoriatic lesional skin, displayed significantly decreased intracellular IFN-gamma expression during and after NB-UVB therapy as compared to pretreatment values. Intracellular IL-4 expression was increased in most patients after therapy. Analysis of the supernatants of these stimulated dermal T cells revealed that IFN-gamma production decreased significantly following NB-UVB therapy, whereas IL-4 expression increased in the T cell supernatants from most patients, confirming the intracellular determinations. In addition, IL-10 and transforming growth factor-beta levels in the supernatants appeared to be increased in the majority of patients following UVB therapy. Apart from the well-known killing effect of UVB on T cells, our results show that the improvement in psoriatic skin following NB-UVB therapy is also due to a reduced capacity of the surviving dermal T cells to express the proinflammatory cytokine IFN-gamma.

Humans↗
PubMed2004

Alefacept therapy reduces the effector T-cell population in lesional psoriatic epidermis.

Alefacept, a LFA-3/IgG1 fusion protein, interferes with the activation and proliferation of T cells by binding to the CD2 receptor on their surfaces. The clinical efficacy of this drug has been demonstrated in chronic plaque psoriasis. We performed a single-center, open-label study to investigate the immunohistochemical effects in psoriatic lesional skin. A group of 11 patients with plaque psoriasis all received 12 weekly doses of 7.5 mg alefacept intravenously. Skin biopsies were obtained at baseline and on days 8, 43 and 92, and were evaluated by digital image analysis after immunohistochemical staining. After completion of treatment, 8 out of the 11 patients experienced a reduction in PASI of 50% or more compared to baseline. Immunohistochemical analysis displayed a gradual decrease in the number of cutaneous T cells during therapy, with a significant reduction in epidermal CD8+ cells and dermal CD4+ cells on day 92. Patients with a reduction in PASI of 50% or more after therapy had a clearance of effector/memory T cells from the epidermis, in contrast to patients with a reduction in PASI of less than 50%. These findings support the hypothesis that effector/memory T cells play a prominent role in the pathogenesis of psoriasis, and that alefacept is capable of reducing these cells in lesional psoriatic skin.

Adult↗
PubMed2004

The course of chronic plaque-type psoriasis in placebo groups of randomized controlled studies.

OBJECTIVE: To determine the outcome in placebo-treated patients with plaque-type psoriasis. DATA SOURCES: Online search of MEDLINE and EMBASE until January 2001 and the Cochrane Library (2001, issue 1), supplemented by references, reviews, guidelines, and textbooks. STUDY SELECTION: Randomized controlled induction of remission trials of patients with chronic plaque-type psoriasis with systemic treatments with a placebo group not treated with antipsoriatic medication. Identified studies were examined by 2 independent reviewers. Through MEDLINE, 290 studies could be identified. Twenty-seven placebo-controlled studies were included (488 patients). DATA EXTRACTION: Two independent reviewers extracted data on first author, year of publication, design, comparison, placebo treatment, number of patients, treatment duration, type of psoriasis and baseline severity in the placebo group, mean relative change in outcome measures, and/or percentage of patients with worsening of psoriasis; no change; minimal, moderate, or good improvement; or complete clearance. DATA SYNTHESIS: Owing to substantial heterogeneity and differences in the way outcomes were reported, no summary estimates could be obtained. The outcome of placebo treatment was poor in most studies. Some reported a mean relative change of 11% to 47%. The highest percentages of patients ended up in the worsening, no change, or minimal improvement categories. Also, complete clearance was possible. No explanation for the differences in outcome between placebo groups could be found. Description of placebo groups was often insufficient. CONCLUSIONS: The effect of treatment in placebo groups varied across studies in an unpredictable way. To evaluate the variability, improvement of the standardization of study designs, entry criteria, and outcome measures is necessary in psoriasis trials.

Chronic Disease↗
PubMed2004

Costs of treatment in patients with moderate to severe plaque psoriasis: economic analysis in a randomized controlled comparison of methotrexate and cyclosporine.

OBJECTIVES: To document and compare the costs of treatment of psoriasis with 2 established systemic agents that differ substantially in their unit costs: methotrexate vs cyclosporine. DESIGN: Cost-minimization analysis within a randomized controlled trial. SETTING: Outpatient dermatology department at an academic hospital. PATIENTS: Adults with moderate to severe plaque psoriasis, with no previous methotrexate or cyclosporine treatment. INTERVENTION: Sixteen weeks of treatment with methotrexate or cyclosporine and an additional 36 weeks of follow-up. MAIN OUTCOME MEASURES: Direct and indirect medical and nonmedical costs associated with resource utilization during treatment and follow-up. RESULTS: Average cumulative total costs associated with 16 weeks of treatment were 1593 US dollars for methotrexate and 2114 US dollars for cyclosporine (521 US dollars less for methotrexate); during 36 weeks of follow-up, these costs were 2418 US dollars and 2306 US dollars, respectively. The overall difference in cumulative 1-year costs was 409 US dollars, or approximately 10% of the total costs. CONCLUSIONS: After 1 year, the overall difference in total costs between methotrexate and cyclosporine for 16 weeks of treatment and follow-up is relatively small. Systemic medication costs are only a fraction of the costs directly and indirectly generated by utilization of health care resources and associated with individual patients rather than with methotrexate or cyclosporine. Economic arguments can be supportive of but not decisive for individual patient decisions and guidelines for systemic therapy. Rational decision making for the treatment of psoriasis may include costs only within a long-term horizon and may consider the societal and patient benefits of different alternatives.

Administration, Oral↗
PubMed2004

In situ demonstration of CD40- and CD154-positive cells in psoriatic lesions and keratinocyte production of chemokines by CD40 ligation in vitro.

In psoriatic lesions, T cells and keratinocytes are in an activated state. Ligation of CD40 expressed on activated keratinocytes with CD154 expressed on activated T cells is thought to be involved in the pathogenesis of psoriasis. However, the presence of CD40(+) and CD154(+) cells in psoriatic skin has not been thoroughly studied. The present study has therefore examined their presence by immunohistochemistry in the lesional and non-lesional skin of ten patients. The influence of CD154-CD40 ligation on the release of chemokines (IL-8, RANTES, and MCP-1) and complement components (C3 and factor B) from keratinocytes was also investigated in vitro. Studies using single and double staining showed that clusters of CD40(+) keratinocytes were present in both lesional and non-lesional skin; CD40(+)CD1a(+) Langerhans cells in lesional, non-lesional, and normal skin; and numerous CD40(+)CD83(+) cells in lesional skin. CD1a(+) and CD83(+) cells always expressed CD40 strongly. Numerous T cells were seen in lesional skin. A small number of T cells expressed CD154. CD154(+) T cells were seen in the lesional epidermis of seven of ten patients-in six, in juxtaposition to CD40(+) cells including keratinocytes. In non-lesional epidermis, CD154(+) T cells were seen in two patients-in one, in juxtaposition to CD40(+) keratinocytes. In vitro studies showed that IFN-gamma-treated keratinocytes released small amounts of IL-8, RANTES, and MCP-1; ligation of these cells with CD154-transfected J558 cells or soluble CD154 greatly enhanced the release. This ligation did not enhance the release of C3 and factor B. These results warrant further studies on the role of CD40 ligation in the pathogenesis of psoriasis.

Adult↗
PubMed2004

Increased incidence of hypercoagulability in patients with leg ulcers caused by leukocytoclastic vasculitis.

Vasculitis is a rare cause of leg ulceration. It is unclear why severe skin infarction develops in some patients with vasculitis, whereas others have only mild symptoms such as purpura, erythema, or urticaria. A coincidence of vasculitis and hypercoagulability may lead to more extensive thrombotic occlusion and hence explain the occurrence of large ulcers in a subset of patients. Our aim was to investigate whether patients with vasculitis ulcers have an increased incidence of hypercoagulability. Thirteen consecutive patients admitted to the hospital with necrotic ulcers caused by histologically confirmed vasculitis were screened for clotting disorders. In 7 of 13 patients (53%), hypercoagulable conditions were found. Five patients had factor V Leiden (38%), and 2 had lupus anticoagulant (15%). The normal frequency of these conditions is 5% to 6% and 3.6%, respectively. These data indicate that there is an increased incidence of hypercoagulable disorders in patients with vasculitis ulcers. We recommend screening these patients routinely for hypercoagulability.

Female↗