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Biomedical subjects

J Ring

Publications and source records attributed to J Ring.

At least 181 records · Page 10Linked to original sources

Identification of immunological relevant phenotypes in ENU mutagenized mice.

The immunology screen focuses on the identification of novel gene products involved in the mammalian immune response and on the establishment of mouse models for immunological disorders. For this purpose, high throughput and semi-automated techniques were developed and optimized for low cost per sample and reproducibility. All assays are designed to be nonconsumptive and are based on peripheral blood or direct PCR amplification.

Animals↗

Long-term efficacy of medium-dose UVA1 phototherapy in atopic dermatitis.

BACKGROUND: UVA1 (340-400 nm) therapy proved to be highly effective in patients with severe atopic dermatitis. The optimal dose regarding therapeutic efficacy and possible side effects is still to be evaluated. In vitro cell culture as well as in vivo animal studies recently indicated that a correlation between UVA irradiation and photoaging, skin carcinogenesis, or melanoma induction may exist. Therefore it seems appropriate to focus research activities on reducing the UVA1 dose applied during phototherapeutic regimens minimizing nonbeneficial side effects. OBJECTIVE: The present study was performed to evaluate the therapeutic effectiveness and long-term efficacy of medium-dose UVA1 irradiation in patients treated for acute exacerbated atopic dermatitis. METHODS: Thirty-two patients underwent a medium-dose UVA1 therapy consisting of 15 treatments applied from Monday to Friday for a period of 3 weeks. The applied dose per treatment was 50 J/cm(2) resulting in a cumulative dose of 750 J/cm(2). Clinical severity was assessed according to the SCORAD index before and after irradiation as well as in monthly intervals up to 3 months after cessation of phototherapy. RESULTS: Medium-dose UVA1 phototherapy is effective for alleviating acute exacerbated atopic dermatitis as shown by a significant reduction of SCORAD ratings (P <.001) at the end of the active UV treatment period. A significant skin improvement was still present 1 month later (P <.001). However, at the end of the 3-month posttreatment observation period the skin condition had reached the pretreatment level. CONCLUSION: According to our data, medium-dose UVA1 phototherapy is a highly effective, nonsteroidal, therapeutic alternative for treatment of acute exacerbated atopic dermatitis. However, effectiveness is merely short term, limited, and is followed by recurrence of symptoms within a 3-month observation interval.

Adolescent↗

Subcutaneous oleomas induced by self-injection of sesame seed oil for muscle augmentation.

This case presentation describes a 48-year-old man who experienced subcutaneous nodules 9 months after self-injection of sesame seed oil into the pectoral area for muscle augmentation. This procedure was reported by our patient to be frequently performed in the body-building and fitness scene. Ultrasound imaging showed multiple, low reflecting round nodular areas of up to 1 cm diameter in both breasts. Excision of a representative nodule revealed a cyst filled with oily material, surrounded by granulomatous tissue. This case report demonstrates an unusual side effect of augmentation measures in body-builders.

Calcinosis↗

Systemic vitamin C and vitamin E do not prevent photoprovocation test reactions in polymorphous light eruption.

The possible influence of oxidative stress is discussed in the pathogenesis of polymorphous light eruption (PLE). A double-blind, placebo-controlled study of prophylactic treatment with systemic administration of vitamin C (3 g/d) and E (1500 IU/d) for 8 days was undertaken in 9 patients with PLE (verum, n=4; placebo, n=5). Evaluation of the maximal effects after photoprovocation before and after intake of the antioxidants revealed a reduction of most skin reactions (overall skin reaction, papules/vesicles) in both groups with marked differences in the placebo group. The antioxidants in the doses given and over the time period used did not influence the development of PLE, but might interfere with immunosuppressive effects of repeated photoprovocation tests.

Administration, Oral↗

Parental sun protection management in preschool children.

A total of 287 children (5 to 8 years old) were investigated for parental sun protection management techniques in a questionnaire-based survey. We evaluated the parents' knowledge about the risk of melanoma, their level of education, their nationality and the child's skin type with the children's use of sunscreen, clothes and shade. In general, the parents' knowledge about the correlation of skin cancer with extensive sun exposure in childhood was good. There was no correlation between the level of parental education and the frequency of sun protection measures. Children of non-German parents had significantly less sun protection. Our results indicate the need for special teaching programs for children in Germany to achieve a more responsible sun protection management.

Child↗

Genome-wide, large-scale production of mutant mice by ENU mutagenesis.

In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper, leads to a significant increase in the number of mouse models available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html).

Animals↗

Changes in collagen I and collagen III metabolism in patients with generalized atopic eczema undergoing medium-dose ultraviolet A1 phototherapy.

Fourteen patients suffering from acute, exacerbated atopic eczema were screened for changes in collagen I and collagen III metabolism in serum (n = 11), urine (n = 11) and skin biopsies (n = 9) before and after medium-dose ultraviolet (UV) A1 phototherapy (15 exposures of 50 J/cm2 over a 3-week period, total dose 750 J/cm2). Mature collagen I and, to a lesser extent, mature collagen III were found to be decreased after the therapy in skin samples from the irradiated patients. As markers of collagen I degradation, the cross-links pyridoline and deoxypyridoline were analysed in urine using high-performance liquid chromatography. Both cross-links were found to be mildly increased after UVA1 phototherapy, without reaching statistical significance. As markers of de novo collagen synthesis we screened for the procollagen I-carboxyterminal peptide (PICP) and procollagen III-aminoterminal peptide (PIIINP) levels in serum and skin. The ratio of PICP to PIIINP in serum dropped significantly after the UVA1 phototherapy, suggesting a different impact of UVA1 on the two collagens. These findings were paralleled by a diminished ratio of PICP to PIIINP in tissue samples. Staining for matrix metalloproteinase 1 (MMP-1) and its specific counterpart, tissue inhibitor of MMP-1 (TIMP-1), showed slight increases for both proteins by therapeutic UVA1; this was also seen in serum for TIMP-1 but not MMP-1. In our study, high-energy UVA1 doses induced changes of the skin collagens in patients with atopic eczema which are measurable by their metabolites in serum and urine.

Chromatography, High Pressure Liquid↗

The excess of atopic eczema in East Germany is related to the intrinsic type.

BACKGROUND: Prevalence data for atopic eczema based on a dermatological examination have not so far been available for East and West Germany. Possible differences in the proportions of extrinsic and intrinsic types of eczema, and how far these could explain differences in the prevalence of eczema, need to be clarified. OBJECTIVES: To compare the prevalence of atopic eczema in pre-school children between different locations in East and West Germany, and over a period of 7 years, at three time points. Additionally, to determine the proportions of intrinsic and extrinsic types of eczema by taking skin prick test reactivity into account. METHODS: Repeated cross-sectional studies in 1991, 1994 and 1997 in 5-6-year-old pre-school children at five different locations in West Germany (n = 2075) and six in East Germany (n = 1926) were carried out. Individuals with eczema were identified by an examination performed by physicians of the Department of Dermatology. In addition, a skin prick test and a standardized questionnaire were used. RESULTS: The overall prevalence of atopic eczema in these children was 10.4%. At all three times of investigation (1991, 17.5% vs. 11.2%; 1994, 12.6% vs. 8.7%; 1997, 11.2% vs. 4.5%) and in the total group (12.9% vs. 8.2%), the prevalence was significantly higher in East than in West Germany. After controlling for influences of sex, parental history of atopic diseases, observer and socio-economic status in multiple logistic regression analyses, these differences remained significant for 1991, 1994 and for the overall group (odds ratio, OR 1.78, 95% confidence interval, CI 1. 43-2.21). Girls (OR 1.56, 95% CI 1.27-1.92) and children whose parents had a higher level of school education (OR 1.17, 95% CI 1. 00-1.37) were affected more frequently. Of all children, 26.6%, and of those with eczema, 41.9% exhibited at least one reaction in the prick test (OR 2.21, 95% CI 1.75-2.80; sensitization in eczema vs. no eczema). Whereas 50.4% of the children with eczema in West Germany were sensitized, only 36.5% of the diseased children in East Germany reacted positively in the prick test (OR 1.77, 95% CI 1.12-2. 79). CONCLUSIONS: These results are in accordance with findings regarding allergic sensitization and hay fever and might indicate that factors other than allergy are responsible for the higher prevalence of atopic eczema in East Germany.

Allergens↗

Optimizing the therapeutic approach in tinea capitis of childhood with itraconazole.

BACKGROUND: Tinea capitis is the most common dermatophytosis of childhood with increasing incidence. Whereas griseofulvin is considered by many as the mainstay of treatment, newer oral antifungal agents, including fluconazole, itraconazole and terbinafine have demonstrated higher efficacy, resulting in shorter treatment durations. OBJECTIVES: We aimed to determine the optimum regimen for the treatment of childhood tinea capitis with itraconazole. METHODS: A mycological culture outcome-dependent combination of a 28-day continuous and facultative additional 14-day courses with itraconazole was used in 42 children (20 girls; 22 boys) aged 12-140 months (mean 66) with tinea capitis due to Microsporum canis (n = 26) and Trichophyton violaceum (n = 16). The drug was given orally according to the patients' body weight (50 mg daily for < 20 kg; 100 mg daily for > or = 20 kg) over 4 weeks. Direct microscopy and fungal culture as a parameter for efficacy were repeated 2 weeks after termination of treatment. Assessment of efficacy was based on the evaluation of results from light microscopy and culture at 8 weeks after initiation of treatment, and in the case of a further positive mycological culture at 14 and 20 weeks, respectively. A positive fungal culture at these times resulted in an additional course for 2 weeks with the initially chosen itraconazole dosage. RESULTS: In 34 of 42 patients a single 4-week course of itraconazole resulted in a complete mycological cure of lesions as demonstrated by light microscopy and mycological culture. Four of 42 patients had to be treated by a second itraconazole course for 2 weeks, and four children received a third course of itraconazole for 2 weeks until all lesions showed negative direct microscopy and mycological culture. No abnormal haematological or biochemical results occurred. Apart from transient, completely reversible indigestion in two children, no side-effects were observed. CONCLUSIONS: A culture-based 28-day continuous therapeutic regimen plus facultative cultural outcome-dependent additional 14-day courses of a body weight-adapted dosage of itraconazole in tinea capitis due to M. canis and T. violaceum is discussed; this offers the advantage of an effective therapy with complete negative direct microscopy as well as negative cultural results, within a shorter active treatment period (cf. previous studies with continuous administration of itraconazole).

Adolescent↗

Persistent annular erythema of infancy associated with intestinal Candida colonization.

We report a case of persistent annular erythema of infancy in a 4-month-old boy. Physical and laboratory parameters showed no sign of internal disease or specific infection except a massive Candida albicans colonization (> 103 organisms/mm3) of the lower gastrointestinal tract. Oral treatment with amphotericin B for 2 weeks resulted in a complete remission of the skin lesions indicating Candida colonization as a trigger.

Amphotericin B↗

Airborne and dietary allergens in atopic eczema: a comprehensive review of diagnostic tests.

Aeroallergens and food allergens are relevant eliciting factors of atopic eczema. This article focuses on the methods used for diagnosis in patients with suspected allergy to airborne or dietary allergens and who are suffering from atopic eczema. In addition to classical tests of IgE-mediated hypersensitivity (intracutaneous or in vitro testing), the role of provocation procedures is described. For aeroallergens, the atopy patch test yields the most specific results with regard to clinical history as compared with classical methods. For food allergens and pseudoallergic reactions to additives, this holds true for the double-blind, placebo-controlled food challenge. The methods and their limitations are discussed from a practical point of view.

Allergens↗

The urokinase plasminogen activator system in angiosarcoma, Kaposi's sarcoma, granuloma pyogenicum, and angioma: an immunohistochemical study.

UNLABELLED: Background Extracellular matrix proteolysis is one of the most important steps in angiogenesis. The urokinase-type plasminogen activator system (uPAS), consisting of the urokinase plasminogen activator (uPA), the uPA receptor (uPA-R), and their corresponding inhibitors, PAI-1 and PAI-2, is thought to play a role in this process. METHODS: We investigated the expression of the components of uPAS in angiosarcoma (AS, n = 4), Kaposi's sarcoma (KS, n = 31), granuloma pyogenicum (GP, n = 25), angioma (AN, n = 15), and healthy controls (CO, n = 15) with immunohistochemical methods. RESULTS: We found positive immunostaining for uPA-R and uPA in all cases of AS. Only two of four cases were positive for PAI-1, whereas all cases were negative for PAI-2. In KS, we observed positive immunostaining in 16 of 31 (51.6%) cases for uPA-R, in 11 of 31 (35.5%) cases for uPA, in 3 of 31 (9.6%) cases for PAI-1, and in 2 of 31 (6.4%) cases for PAI-2. The GP cases showed the following positive results: 4 of 25 (16%) for uPA-R, 6 of 25 (24%) for uPA, 10 of 25 (40%) for PAI-1, and 11 of 25 (44%) for PAI-2. Four cases (26.6%) of AN were positive for PAI-1 and five cases (25%) for PAI-2. In AN (n = 15), there was staining for neither uPA nor uPA-R. In none of the controls (n = 15) was immunostaining for the components of uPAS found in blood vessels. CONCLUSIONS: uPAS is involved in malignant, benign, and reactive proliferative angiomatous lesions, but is absent in normal blood vessels. The upregulation of uPA and its corresponding receptor, uPA-R, in AS and KS supports the hypothesis of the proliferative nature of these lesions; however, the upregulation of the inhibitors (PAI-1 and PAI-2) in benign and reactive proliferative angiomatous lesions (GP and AN) shows how this process may be limited.

Granuloma, Pyogenic↗

Digital gangrene: a rare skin symptom in systemic lupus erythematosus.

A case of digital gangrene in a patient with systemic lupus erythematosus without secondary anti-phospholipid syndrome is reported. The acute onset of the necrotizing acrovasculitis occurred without a history of Raynaud's phenomenon. Preceding symptoms of the systemic lupus erythematosus were arthritis, photosensitivity, alopecia and anorexia. Despite the seriousness of the acute episode the patient achieved an excellent outcome.

Female↗

Processing of histamine-induced itch in the human cerebral cortex: a correlation analysis with dermal reactions.

The subjective sensation of itch is a complex emotional experience depending on a variety of factors. In this study, the central nervous processing of pruritus was investigated in a human model. Activation of involved cerebral areas was correlated to scales of nociception and skin reactions. Six healthy male right-handed subjects participated in a standardized epidermal stimulus model with nine increasing doses of histamine dihydrochloride (0.03%-8%) on their right forearms. Controls consisted of three NaCl stimuli. Cerebral activation patterns were determined by H(2)(15)O positron emission tomography 120 s after stimulation. Dermal reactions to the stimulus (wheal, flare, temperature) were coregistered during the procedure. Itch sensation was determined by visual analog scale rating. Pain was not reported during the study; all volunteers had localized itch from 0.03% histamine on. Subtraction analysis versus control revealed significant activation of the left primary sensory cortex and motor-associated areas (mainly primary motor cortex, supplementary motor area, premotor cortex). Predominantly left-sided activations of frontal, orbitofrontal, and superior temporal cortex and anterior cingulate were also observed. Correlation analysis revealed coactivation of dermal reactions and cerebral response to itch in the following Brodmann areas with a Z score greater than 5: wheal, areas 5 (bilateral) and 19 (right); flare, areas 2-5 (left); temperature, area 10 (left) and left insula. Itch intensity ratings were mainly correlated with activation of the left sensory and motor areas. Functional covariates of the itch sensation in the central nervous system were identified. The intention to pruritofensive movements is probably mirrored by the activation of motor areas in the cortex. Other areas may be involved in emotional processing of sensations. Skin reactions wheal and flare also had significantly activated covariate areas in the central nervous system.J Invest Dermatol 115:1029-1033 2000

Adult↗

Autoallergy: a pathogenetic factor in atopic dermatitis?

Long before the discovery of IgE it was reported that human dander extract can elicit immediate-type skin reactions in patients with severe atopy and that this skin sensitivity can be passively transferred with serum. Several recent findings have rekindled the interest in this phenomenon and led to the concept that IgE autoreactivity may play a pathogenetic role in severe and chronic forms of atopy. The elucidation of the nature of several environmental allergens has revealed striking structural and immunologic similarities with human proteins. It was also reported that patients predominantly with severe and chronic manifestations of atopy (eg, atopic dermatitis) contain IgE autoantibodies against a wide variety of proteins expressed in histogenetically unrelated human cell types and tissue specimens. Last, complementary DNAs coding for autoallergens were isolated from human expression complementary DNA libraries and recombinant autoallergens were produced. The autoallergens characterized to date represent mainly intracellular proteins, but some of them could be detected as IgE immune complexes in sera of sensitized patients. We suggest that at least two pathomechanisms could play a role in autoallergy. First, autoallergens may cross-link effector cell-bound IgE autoantibodies and, by release of inflammatory mediators, lead to immediate-type symptoms. Second, IgE-mediated presentation of autoallergens may activate autoreactive T cells to release proinflammatory cytokines, contributing to the magnitude of the allergic tissue reaction.

Antibodies, Anti-Idiotypic↗

Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of primary school children.

Non-invasive investigations of skin morphology and function are standard tools to study the pathophysiology of several cutaneous disorders, yet they have not been used in population-based epidemiological studies. Here we examined skin surface pH, stratum corneum hydration, trans-epidermal water loss (TEWL) and skin roughness by profilometry in a study population comprising 377 primary school children (8-9 years old) as part of a multicentre survey on risk factors for allergic diseases in school children. Skin surface pH showed significant higher values (p=0.029) in the group with atopic eczema (n=45) compared with the group without atopic eczema; all other parameters did not differ significantly between children with and without atopic eczema. With increasing skin dryness there was a significant increase in pH values (p=0.004). Stratum corneum hydration showed a significant decrease with increasing dryness (p<0.001). Measurement of skin roughness also revealed a significant linear relationship with skin dryness (p=0.02). It is concluded that measurement of skin surface pH, corneometry and profilometry are useful non-invasive techniques to objectively assess skin dryness in epidemiological studies regarding atopic skin disease.

Body Water↗