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Biomedical subjects

A Kapp

Publications and source records attributed to A Kapp.

At least 19 recordsLinked to original sources
PubMed2002

[Hexadactyly of hand and feet in a patient with basal cell nevus syndrome].

A 35-year-old male patient with hexadactyly on the right hand and both feet presented with multiple basal cell carcinomas of the skin. The results of further investigations led to the diagnosis of basal cell nevus syndrome (BCNS). The basal cell nevus syndrome (Gorlin-Goltz syndrome) characterized by multiple basal cell carcinomas, odontogenic cysts, skeletal abnormalities and associated neoplasms belongs to the group of genodermatoses. Reviewing the current literature we discuss aspects of the pathogenesis of the basal cell nevus syndrome as well as diagnosis criteria and treatment options.

Acitretin↗
PubMed2002

Differentiation between malignant and benign follicular adnexal tumours of the skin by DNA image cytometry.

BACKGROUND: We have demonstrated in previous studies that DNA image cytometry (DNA ICM) can be helpful in detecting malignancy in sebaceous tumours of the Muir-Torre syndrome and sweat gland tumours. However, little is known about DNA ICM in cutaneous adnexal tumours with follicular differentiation. OBJECTIVES: To study a larger series of benign and malignant follicular adnexal tumours with DNA ICM. METHODS: We studied 13 malignant follicular tumours (seven trichilemmal carcinomas, five malignant proliferating pilar tumours, one pilomatrix carcinoma) and 55 benign follicular tumours (four tumours of the follicular infundibulum, seven Winer's pores, eight trichilemmomas, two trichofolliculomas, 16 trichoepitheliomas, 13 pilomatrixomas, five trichoblastomas) by DNA ICM. All cases were clear-cut as malignant or benign, respectively, on histopathological criteria. The stemline interpretation according to Böcking et al. (DNA distribution in gastric cancer and dysplasia. In: Precancerous Conditions and Lesions of the Stomach, Zhang YC, Kawai K, eds. Berlin: Springer-Verlag, 1993: 103-20) was performed in all cases. In addition, 5[c]-exceeding events (5cEE) and the 2[c] deviation index (2cDI) were calculated, except in one histopathologically benign tumour, which revealed euploid polyploidization, as the analysis of 5cEE and 2cDI is not valid in that case. RESULTS: A 2cDI threshold of 0.24 proved to be the most reliable marker for the distinction between malignant and benign follicular tumours. On the basis of this feature, all malignant and benign tumours were correctly classified. A specificity of 100% was achieved by all three interpretation methods, but the sensitivity of 2cDI for the detection of malignant tumours was superior to the analysis of 5cEE (sensitivity 77%) and to the stemline interpretation (sensitivity 23%). CONCLUSIONS: DNA ICM may be helpful in distinguishing between malignant and benign follicular tumours.

Aneuploidy↗
PubMed2002

Successful treatment of anogenital Bowen's disease with the immunomodulator imiquimod, and monitoring of therapy by DNA image cytometry.

Imiquimod (Aldara, 3M) is an immune response modifier used for the treatment of anogenital warts. We report a 55-year-old non-immunocompromised woman with extensive, human papillomavirus (HPV) 16-positive anogenital Bowen's disease. After 5 months of local treatment with imiquimod, the lesions completely regressed clinically and histologically, and HPV 16 DNA was no longer detectable. Moreover, DNA image cytometry revealed DNA aneuploidy (an indicator of prospective malignancy) in pretreatment samples but not in post-treatment samples. Therefore, imiquimod might be a treatment option for Bowen's disease, particularly in patients where other treatment modalities such as surgery are contraindicated.

Aminoquinolines↗
PubMed2002

The incidence of atopic dermatitis in school entrants is associated with individual life-style factors but not with local environmental factors in Hannover, Germany.

BACKGROUND: Atopic dermatitis (AD) is a common skin disease in childhood. Micro- and macro-environmental factors have not yet been studied simultaneously in a large cohort of the same area in detail. OBJECTIVES: The incidence of AD was investigated in 97% of all school entrants (n = 4219) in the city of Hannover, Germany, with regard to the influence of individual and environmental factors. METHODS: A standardized questionnaire based on the criteria of Hanifin and Rajka that has the sensitivity and specificity of 97% compared with the clinical diagnosis of a dermatologist and a logistic regression model were used. Multiple local-based environmental factors were analysed for all 49 city quarters. RESULTS: Of all children studied, 10.5% suffered from AD at some time in their lives. The frequency of AD was significantly increasing with more privileged socio-economic status (P < 0.01). Independent factors that were associated with a higher frequency of AD were German nationality (12.4% AD compared with 2.1% in non-German), higher paternal socio-economic status (i.e. father's profession), higher daily duration of the fathers' professional work and the lack of paternal shift work. In contrast, there was no significant association between the frequency of AD and local environmental factors such as the biological effective level of air pollution and urbanization. CONCLUSIONS: In conclusion, we confirm an association between a privileged life-style and a higher incidence of AD in a large number of investigated children between 5 and 9 years of age (97.6% of children were 6 or 7 years old) for the German city of Hannover. We propose the socio-economic status as a marker for different life-styles and social micro-environments in further studies as there were multiple significant correlations between individual social and environmental factors. The macro-environment seems to be less important for the disease outcome in this context.

Child↗
PubMed2002

Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis.

BACKGROUND: The skin of up to 100% of patients with atopic dermatitis (AD) is colonized with Staphylococcus aureus. Of all S. aureus strains isolated from lesional skin, up to 65% have been shown to produce exotoxins with superantigenic properties. Patients colonized with S. aureus have been treated with antibiotics in several open and double-blind placebo-controlled studies, with conflicting results. These studies did not consider the anterior nares as a reservoir of S. aureus, or the possibility of transmission between patients and their contacts. Moreover, adult patients have not so far been investigated. OBJECTIVES: To investigate the colonizing features of S. aureus in adults with AD and in their contacts, and the effect of an antimicrobial treatment of the patients and their partners. METHODS: Swabs were taken from the skin and anterior nares of 66 adults with AD. S. aureus strains were screened for the production of exotoxins in 32 patients. Ten patients (two with toxigenic strains, eight with non-toxigenic strains) were treated orally with cefalexin, chlorhexidine ointment was applied to the skin, and the anterior nares were treated with mupirocin ointment. A bath containing potassium permanganate was taken daily. In addition, their partners were treated topically. RESULTS: Sixty-two of 66 patients (94%) were carriers of S. aureus, and mostly harboured the bacteria on both skin and anterior nares. Ten of 32 (31%) patients were colonized with toxigenic strains. The Severity Scoring in AD (SCORAD) score decreased in nine of 10 patients who received antimicrobial treatment (P < 0.001), and this effect was more pronounced in patients with a baseline SCORAD > 50. CONCLUSIONS: S. aureus may play an important role as an aggravating factor in adults with AD, as antimicrobial treatment leads to a significant improvement of AD in patients who are colonized with the bacterium.

Adult↗
PubMed2002

Application of imiquimod by suppositories (anal tampons) efficiently prevents recurrences after ablation of anal canal condyloma.

BACKGROUND: After surgical removal, anal canal condyloma (ACC) has a higher risk of recurrence compared with extragenital warts. OBJECTIVES: To reduce local recurrences of ACC using follow-up treatment with imiquimod-containing suppositories (anal tampons). METHODS: After ablation of ACC, 10 male patients received treatment with imiquimod suppositories three times weekly for 3-4 months. RESULTS: Treatment with imiquimod anal tampons was well tolerated. Early initial recurrences in some patients cleared after treatment with the imiquimod suppositories. Within a mean follow-up of 9 months no patient demonstrated recurrence of ACC. CONCLUSIONS: These data suggest that imiquimod anal tampons may represent a new therapeutic option to prevent recurrences of ACC following ablative surgery.

Adult↗
PubMed2001

IL-3 induces down-regulation of CCR3 protein and mRNA in human eosinophils.

Cytokines and chemokines are responsible for the attraction and activation of eosinophils in allergic and inflammatory diseases. Whereas cytokines such as IL-3, IL-5, and GM-CSF activate eosinophils via heterodimeric receptors containing a distinct alpha-chain (binding domain) and a common beta-chain (signaling domain), chemokines such as eotaxin activate eosinophils via seven-transmembrane G(i) protein-coupled CCRs. Recent studies have demonstrated the importance of CCR3 on human eosinophils that undergo receptor recycling after chemokine activation, but the modulation of this receptor by cytokines has not yet been addressed. In this study, we demonstrate that IL-3 induces a dose- and time-dependent down-regulation of CCR3 from the surface of human eosinophils comparable to the CCR3-specific ligand eotaxin, whereas IL-5, GM-CSF, IL-4, IL-10, IL-13, IFN-gamma, and TNF-alpha had no effect. Maximal down-regulation of CCR3 in response to IL-3 was reached at 24 h. Reduction of CCR3 surface protein in response to IL-3 could be prevented by an anti-IL-3 mAb and was neither due to the release of CC chemokines nor to nonspecific binding of IL-3 to CCR3. Moreover, down-regulation was prevented by phenylarsine oxide, a nonspecific inhibitor of receptor internalization. After 24 h, IL-3-induced decrease of CCR3 surface expression correlated with diminished mRNA expression, suggesting a transcriptional regulation mechanism. Since wortmannin partially inhibited IL-3- but not eotaxin-induced CCR3 down-regulation, receptor down-modulation seems to underlie different signaling events. Therefore, these data suggest a novel role for the cytokine IL-3 in the activation process of eosinophils and its predominant chemokine receptor CCR3.

Androstadienes↗
PubMed2001

[Pyoderma gangrenosum: successful topical therapy with tacrolimus (FK506)].

Pyoderma gangrenosum is a distinct clinical entity characterized by chronic, recurring, destructive ulcerations. Although the pathogenesis of pyoderma gangrenosum is unknown, immunologic aberrations of neutrophil granulocytes seem to be important. Systemic steroids and macrolide lactones such as cyclosporin A and tacrolimus have been reported to be useful in the clinical management of disease. Pyoderma gangrenosum has been found to be associated with several systemic diseases. The association with chronic ulcerative colitis is well known, but the diagnosis may be complicated by early administration of systemic steroids. Therefore, local immunosuppression with topically applied agents could be an efficient therapeutic alternative especially for mild or early cutaneous lesions.We describe the successful topical treatment of a patient with multiple lesions of pyoderma gangrenosum with 0,1% tacrolimus (FK506) ointment which is known to have better dermal penetration and higher immunosuppressive potency than topical cyclosporin A. In addition, other indications for topical tacrolimus are discussed.

Abdomen↗
PubMed2001

[Hereditary C1 esterase inhibitor deficiency type I. Divergence of clinical symptoms and laboratory chemical findings].

A 35- and a 29-year-old woman presented with longstanding recurrent angioedema refractory to therapy with steroids and antihistaminic drugs. Laboratory data revealed in both cases a functional and immunohistochemical deficiency of C1-esterase-inhibitor protein (C1-INH). Further investigations of their families showed some individuals with the same pathological findings without any clinical symptoms. Thus we identified striking differences in degree of severity of clinical features in hereditary C1-INH-deficiency type I. These case-reports emphasize the importance of knowing further diagnostic steps in angioedema refractory to therapy with steroids and antihistamines drugs. Furthermore we give a picture of the different clinical courses of C1-INH-deficiency type I and underline that there is no correlation between clinical symptoms and laboratory findings.

Adult↗
PubMed2001

[Chemotherapy-induced erythema nodosum leprosum: successful treatment with thalidomide].

The severity and outcome of a chronic granulomatous infection caused by M. leprae depend on the cell-mediated immunity towards the pathogen. The disease classification is based on the host's response to M. leprae ranging from high to low resistance (polar tuberculoid leprosy to polar lepromatous leprosy). The host's position in the spectrum is not stable; leprosy reactions reflecting changed immune status may occur spontaneously or during chemotherapy. The type II reaction or erythema nodosum leprosum can most often be seen in patients with lepromatous leprosy, a multiorgan disease characterized by an unrestricted bacillary replication. Clinically, this reaction is characterized by crops of painful bright pink, dermal and subcutaneous nodules arising in clinically normal skin, in association with fever, malaise, glomerulonephritis and arthralgias. Therefore, prompt institution of immunosuppressive therapy with corticosteroids or thalidomide is recommended. This case report describes the development of erythema nodosum leprosum during chemotherapy treated successfully with thalidomide. Furthermore, immunologic effects and potential side effects of this drug are discussed.

Adult↗
PubMed2001

Urine eosinophil protein X (EPX) is an in vitro parameter of inflammation in atopic dermatitis of the adult age.

BACKGROUND: Eosinophils are important effector cells in several atopic diseases. The levels of eosinophil granule-derived mediators (ECP, EPX) in serum and body fluids have been proven to be correlated with disease activity in atopic respiratory diseases and atopic dermatitis. The study aimed to demonstrate an interrelationship between urine EPX and disease activity in adult patients with atopic dermatitis. METHODS: We determined urine EPX concentration, serum ECP concentration, and peripheral blood eosinophil count in 40 adult patients with mild to severe atopic dermatitis and compared it with the disease activity as assessed with the SCORAD index. RESULTS: Urine EPX and serum ECP concentrations were significantly higher in patients with severe atopic dermatitis than in patients with mild or moderate disease (median values 123.5 vs 78.3 microg/mmol creatinine, P<0.0001; 25.4 vs 14.9 microg/l, P<0.0001, respectively). We found a significant correlation between urine EPX levels, serum ECP levels, and the SCORAD (r=0.36, P<0.0001 and 0.34, P<0.0001, respectively). CONCLUSION: Urine EPX is a useful in vitro parameter of inflammation in atopic dermatitis of the adult age.

Adult↗
PubMed2001

Tissue eosinophilia in acute and chronic atopic dermatitis: a morphometric approach using quantitative image analysis of immunostaining.

BACKGROUND: The frequency and amount of tissue eosinophilia in spontaneous lesions of acute and chronic atopic dermatitis (AD) are still a matter of controversy, and little is known about the distribution of eosinophilia in skin. OBJECTIVES: To give a quantitative description of tissue eosinophilia in spontaneous lesions of acute and chronic AD based on morphometric data. METHODS: Thirty-one lesional skin biopsies of AD were evaluated using our recently described method for the quantitative assessment of eosinophilic granule protein (EGP) deposition by image analysis of immunostaining using the antibodies EG1, EG2, MBP, EPO and neutrophil elastase (NE). The frequency, amount and distribution of protein deposition including extracellular EGP deposition as an indicator of complete activation and degranulation of eosinophils were determined. Eosinophil count was performed in addition. Histopathological parameters of acute dermatitis (spongiosis) and chronic dermatitis (epidermal hyperplasia) were scored to look for a correlation with tissue eosinophilia. RESULTS: Tissue eosinophilia was found in nearly all biopsies (30 of 31). The most protein was detected by EG2, followed by EG1, MBP and EPO, with very small amounts of NE. A superficial tissue distribution of eosinophilia was found, with < 10% of total EGP deposition below a depth of 1.39 mm from the epidermis. Eosinophils were involved in acute, spongiotic dermatitis, but more tissue eosinophilia including EGP deposition was detected in lesions with pronounced epidermal hyperplasia than in biopsies without. CONCLUSIONS: These data provide further evidence for the involvement of activated eosinophils in acute and chronic AD by a new quantitative in situ approach. Pronounced tissue eosinophilia, especially EGP deposition as the result of complete activation of eosinophils, is found in chronic AD and may be involved in the development or maintenance of chronicity.

Acute Disease↗
PubMed2001

Detection of anaphylatoxin receptors on CD83+ dendritic cells derived from human skin.

Dendritic cells (DC) are recruited to sites of inflammation for the initiation of immune responses. As the anaphylatoxins C5a and C3a are important mediators of inflammation, we investigated the expression of their receptors (C3aR and C5aR) on human DC. DC were isolated from human skin or generated from purified blood monocytes and were identified by their expression of CD1a or CD83. Freshly isolated or cultured dermal CD1a+ and CD83+ DC bound anti-C5aR and anti-C3aR monoclonal antibodies (mAbs), as detected by flow cytometry. C5a induced calcium fluxes in dermal CD1a+ and CD83+ DC, which could be inhibited by C17/5, an anti-C5a mAb. C3a did not induce calcium fluxes in these cells. Anaphylatoxin receptor expression was down-regulated on dermal DC by adding tumour necrosis factor-alpha (TNF-alpha) to the culture medium. On CD1a+ CD83- cells generated from isolated blood monocytes by culture with 6.25 ng/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 125 U/ml of interleukin-4 (IL-4), expression of both C5aR and C3aR was observed. In these cells, both C5a and C3a induced calcium fluxes. After addition of TNF-alpha to the culture medium, the majority of the CD1a+ cells expressed CD83+. These cells - expressing a phenotype of 'mature DC' - down-regulated the expression of the anaphylatoxin receptors and lost their reactivity to the respective ligands. Our results demonstrate the expression of the anaphylatoxin receptors C5aR and C3aR on human skin-derived DC and blood-derived cells expressing the DC-associated membrane molecule, CD1a. Furthermore, the expression of anaphylatoxin receptors on CD83+ dermal DC is indicative of an intermediate stage of maturation of these cells, which was not observed on in vitro-differentiated CD83+ cells.

Antigens, CD↗
PubMed2001

Distinct amplification of the C5a-receptor pathways in normodense and hypodense eosinophils of patients with atopic dermatitis.

In patients with atopic dermatitis two different types of blood eosinophils with distinct density can be isolated. The normodense cells represent the huge majority in count, whereas the hypodense eosinophils are characterized by higher effector activity. To understand the altered functional responsiveness of these two cell subtypes, the expression of C5a receptors as well as C5a-induced signal pathways and the production of reactive oxygen metabolites have been analyzed. Chemiluminescence measurements revealed significant higher production of reactive oxygen metabolites in hypodense eosinophils in comparison to normodense cells. However, no difference in the expression level of C5a receptors as well as in the C5a-induced Ca2+-transients between normodense and hypodense eosinophils were found. In contrast, hypodense eosinophils showed a significantly higher actin polymerization response and phosphatidylinositol 4,5 bisphosphate 3-kinase activation after stimulation with C5a than normodense eosinophils. Therefore, normodense and hypodense eosinophils from the blood of patients with atopic dermatitis are characterized by differential amplification of C5a-receptor signal pathways, which might explain the differences in their proinflammatory activity.

Actins↗
PubMed2001

Detection of mRNA for eotaxin-2 and eotaxin-3 in human dermal fibroblasts and their distinct activation profile on human eosinophils.

As many new biologically active chemokines have been cloned exploring the genomic DNA sequence database in the vicinity of already known chemokine sequences without demonstrating their natural origin, it is important to transfer findings from in vitro experiments with chemokines into the in vivo situation. With respect to eosinophils and fibroblasts that play an important part in the pathogenesis of allergic and autoimmune diseases, the role of the recently discovered members of the eotaxin family, eotaxin-2 and eotaxin-3, is not really understood. In order to elucidate the origin and biologic potency of the eotaxin family this study was performed. Conventional reverse transcription-polymerase chain reaction analysis was suitable to detect mRNA for eotaxin and eotaxin-3 but not for eotaxin-2 in dermal fibroblasts. In contrast to conventional reverse transcription-polymerase chain reaction, LightCycler analysis revealed that dermal fibroblasts constitutively expressed mRNA not only for eotaxin and eotaxin-3 but also for eotaxin-2. Moreover, with this technique we investigated mRNA expression levels after stimulation of fibroblasts with interleukin-4 and interleukin-4 plus tumor necrosis factor-alpha: the rank order of expression levels within the eotaxin family was eotaxin > eotaxin-3 > eotaxin-2. To address the question of the efficacy of eotaxin-3, we compared its activity with eotaxin, eotaxin-2, monocyte chemotactic protein-3, monocyte chemotactic protein-4, and RANTES in different test systems for eosinophils. The efficacy of the CC chemokines at equimolar concentrations with respect to the chemotactic response of human eosinophils was eotaxin-3 = eotaxin = eotaxin-2 > RANTES > monocyte chemotactic protein-4. The rank order of activity with respect to actin polymerization and release of toxic reactive oxygen species was eotaxin-3 = eotaxin = eotaxin-2 and eotaxin = eotaxin-2 > eotaxin-3 = monocyte chemotactic protein-3 = monocyte chemotactic protein-4 = RANTES, respectively. This study indicated a distinct profile in expression levels of the members of the eotaxin family in dermal fibroblasts. Indeed, all three eotaxin ligands demonstrated activation of human eosinophils with similar efficacies for chemotaxis, cytoskeletal rearrangements, activation of Gi proteins and transients of [Ca2+]i, but a distinct profile of activity with respect to the binding to CCR3 and the release of toxic reactive oxygen species. These findings may help to understand further the role of CC chemokines in fibroblast/eosinophil activation, which is of interest particularly in allergic and autoimmune diseases.

Actins↗