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Biomedical subjects

S Werner

Publications and source records attributed to S Werner.

At least 109 records · Page 6Linked to original sources
PubMed1998

Q-switched ruby laser treatment of tattoos and benign pigmented skin lesions: a critical review.

The Q-switched ruby laser (694 nm, 25-40 nsec) is an effective and safe therapeutic device for the treatment of tattoos and well-defined, benign, pigmented epidermal and dermal lesions. Because of its selective mode of action, dermal pigments of natural and artificial origin are destroyed photothermically and removed without scar. This method is exceptionally suited for the elimination of lay and professional tattoos, traumatic tattoos, and permanent makeup. Other frequent indications include benign pigmented lesions such as lentigines, freckles, café-au-lait spots, seborrheic keratosis, and Becker nevi. As a dermal pigmented lesion, the nevus of Ota is perfectly treatable. However, chloasma can no longer be considered an indication for ruby laser treatment due to unsatisfactory results. Melanocytic nevi and congenital nevi should be treated only in clinical studies. The effectiveness of the long-term epilation of dark hair with this laser device has to be verified in future investigations. Particularly attractive is the nonproblematic and straightforward removal of pigmented lesions in precarious anatomic regions like the lips, eyelids, and genitals (e.g., benign melanosis of the lips or of the penis, seborrheic keratosis of the lid angle).

Dermatologic Surgical Procedures↗
PubMed1998

[Illness and social status--the special case of neurodermatitis].

Neither the prevalence of atopic dermatitis (AD) in children nor the magnitude of risk factors such as socioeconomic status or environmental pollution are well known in Germany. In cooperation with the public health service, we therefore carried out a cross-sectional study during a 1992 preschool examination in Hannover covering 4,219 children. Lifetime prevalence of atopic dermatitis was 10.5%; the range for prevalence in 49 districts of Hannover was 2.8-25.0%. The AD prevalence differed significantly between German and non-German children (12.4 vs. 2.1%) and among children from families of different socio-economic status (6.5% low; 18.1% high). Statistically significant associations between AD risk and social variables (family structure, nationality, socio-economic status, occupation) and the lack of definite associations with environmental factors support the hypothesis that life style may be an important risk factor for atopic dermatitis.

Adolescent↗
PubMed1998

[Pore-forming leukotoxins from Staphylococcus aureus: variability of the target cells and 2 pharmacological processes].

The staphylococcal bi-component leukotoxins constitute a family included in the super-family of the beta-sheet-structured pore-forming toxins. They may be produced by Staphylococcus aureus and by Staphylococcus intermedius and their target cells vary according to the molecules. The mode of action proceeds by the sequential binding of the class S proteins, then by that of the class F proteins at the surface of the membranes. Then, the activation of cellular calcium-channels precedes the pore formation which seems to be sensitive to several monovalent cations. The cell response is inflammatory and includes the neosynthesis as well as the secretion of leukotriene B4, interleukin -8, histamine. The injection of leukotoxins to rabbits generates cell chemotaxis , vasodilatation, and tissue necrosis. The association of the production of leukotoxins with clinical syndromes concerns several aspects of the pathology of S. aureus, and confers to these leukotoxins an important role of virulence factors.

Animals↗
PubMed1998

[Molecular biology contributions to wound healing and practical applications].

Keratinocyte growth factor (KGF) is a potent mitogen for keratinocytes which is strongly expressed at the wound edge after skin injury. Inhibition of KGF receptor signalling in the epidermis of transgenic mice caused a delay in wound reepithelialization. To determine the mechanisms of KGF action in keratinocytes, we searched for genes which are regulated by KGF. One of these genes codes for activin which we identified as a novel important player in the repair process. Furthermore, expression of a novel peroxidase was induced by KGF. The expression pattern of this enzyme during wound repair suggests that it could protect keratinocytes from reactive oxygen species during the early inflammatory phase. Taken together, our studies provide new insights into the mechanisms of action of growth factors during the healing process.

Animals↗
PubMed1997

Formation of DNA adducts by cyproterone acetate and some structural analogues in primary cultures of human hepatocytes.

Recently, we have shown that the therapeutically-used progestin and antiandrogen cyproterone acetate (CPA) causes the formation of high levels of DNA adducts in rat hepatocytes and rat liver [J. Topinka, U. Andrae, L.R. Schwarz, T. Wolff, Cyproterone acetate generates DNA adducts in rat liver and in primary rat hepatocyte cultures, Carcinogenesis 14 (1993) 423-427: J. Topinka, B. Binkova, L.R. Schwarz, T. Wolff, Cyproterone acetate is an integral part of hepatic DNA adducts induced by this steroidal drug, Carcinogenesis 17 (1996) 167-169; S. Werner, J. Topinka, T. Wolff, L.R. Schwarz, Accumulation and persistence of DNA adducts of the synthetic steroid cyproterone acetate in rat liver, Carcinogenesis 16 (1995) 2369-2372; J. Topinka, B. Binkova, H.K. Zhu, U. Andrae, I. Neumann, L.R. Schwarz, S. Werner, T. Wolff, DNA damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver, Carcinogenesis 16 (1995) 1483-1487]. Its structural analogues, chlormadinone acetate (CMA) and megestrol acetate (MGA) were much less active in this respect [J. Topinka, B. Binkova, H.K. Zhu, U. Andrae, I. Neumann, L.R. Schwarz, S. Werner, T. Wolff, DNA damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver, Carcinogenesis 16 (1995) 1483-1487]. In the present study we addressed the question whether these compounds and two further analogues, medroxyprogesterone acetate (MPA) and progesterone, induce the formation of DNA adducts in primary cultures of human hepatocytes. Incubation of CPA with human hepatocytes from two male and four female donors induced the formation of significant levels of CPA-DNA adducts detectable by 32P-postlabeling. The by far most prevalent DNA adduct is most likely identical with adduct A formed in CPA-treated rats. DNA binding was found even at 0.03 microM CPA, the lowest concentration used. The maximum effect occurred at about 10 microM in 5 of the 6 cell preparations. At this concentration 480 and 2690 adducts x 10(-9) nucleotides were detected in hepatocytes of the two male donors and 1072, 816, 613 and 659 adducts x 10(-9) nucleotides in the hepatocytes of the four female donors after an exposure of 6 h with CPA. Extending the incubation time to 20 h resulted in a roughly three-fold higher binding. CMA and MGA were assayed in two of the liver cell preparations from the female donors. At a concentration of 20 microM and an incubation time of 6 h, DNA adduct levels for CMA were 21 and 43% and for MGA 31 and 65% of the levels observed with 20 microM CPA. In contrast, DNA binding of MPA amounted to less than 1% of that observed with CPA and DNA binding of the natural occurring progestin progesterone was below the level of detection. The results point to a genotoxic risk associated with the therapeutic use of CPA and possibly of CMA and MGA. Furthermore, the findings suggest that the significant genotoxicity observed with CPA, MGA and CMA is associated with the presence of the double bond in position 6-7 of the steroid, which is absent in MPA and progesterone.

Adult↗
PubMed1997

cDNA cloning and expression of the gene encoding murine stromelysin-2 (MMP-10).

Recently, we demonstrated a biphasic induction of the epithelial broad-spectrum matrix metalloproteinase (MMP) stromelysin-2 during cutaneous wound healing. Now we have generated a murine wound cDNA libary and have used it to isolate the putative cDNA of this murine matrix metalloproteinase. The predicted sequence of the protein shows 76 and 89% identity with its human and rat analogues, respectively. Stromelysin-2 and stromelysin-1 transcripts were both detected at very low levels in the lung and the heart of adult Balb/c mice, whereas stromelysin-2 mRNA expression alone was found at comparatively high levels in the small intestine, a tissue characterized by continuous epithelial renewal. Recombinant forms of murine stromelysin-1 and -2 produced in transfected COS cells were secreted and could be induced to undergo autocatalytic processing by addition of the organomercurial salt 4-aminophenylmercuric acetate (APMA).

Amino Acid Sequence↗
PubMed1997

A novel type of glutathione peroxidase: expression and regulation during wound repair.

We have previously identified and cloned a novel keratinocyte growth factor (KGF)-regulated gene in human keratinocytes that encodes the human homologue of a bovine non-selenium glutathione peroxidase (GPx). To gain insight into the regulation of this gene in vivo, we isolated the murine homologue from a mouse skin cDNA library. In vitro transcription/translation demonstrated that the cDNA encodes a 27 kDa protein. Furthermore, we amplified by PCR a partial cDNA that most likely corresponds to a related gene. RNase protection analysis revealed tissue-specific expression of both genes and the occurrence of alternative splicing or RNA editing of at least one of the primary transcripts. Similar to that of KGF, expression of GPx was strongly induced after cutaneous injury, and each isoform displayed unique kinetics of expression during the repair process. In situ hybridization studies demonstrated high levels of GPx mRNA in keratinocytes of the hyperproliferative epithelium at the wound edge. Since these cells express functional KGF receptors, induction of GPx expression by KGF might also occur in vivo. These data suggest a role for GPx in the protection of epithelial cells against oxidative stress, particularly during the inflammatory phase of wound repair.

Amino Acid Sequence↗
PubMed1997

The human homologue of a bovine non-selenium glutathione peroxidase is a novel keratinocyte growth factor-regulated gene.

Keratinocyte growth factor is a potent and specific mitogen for different types of epithelial cells, including keratinocytes of the skin. Furthermore, it has been implicated in morphogenetic processes of several organs. To further define the mechanisms of KGF action in the skin, we attempted to identify genes which are regulated by KGF in keratinocytes. Using the differential display RT-PCR technology, a gene was identified which was strongly induced in these cells by treatment with KGF but not with serum growth factors or pro-inflammatory cytokines. Molecular cloning of the full-length cDNA revealed a strong homology of the corresponding gene product with a bovine non-selenium glutathione peroxidase. Upon transfection of COS cells with the full-length cDNA, a 27 kD cytoplasmic protein was obtained which had the expected size of glutathione peroxidase. Expression of the novel gene was detected in normal human skin and at particularly high levels in psoriatic skin, indicating a possible in vivo function of the protein in this tissue. Identification of a peroxidase as a KGF-regulated gene suggests that prevention from oxygen toxicity is a novel and specific mechanism of KGF action.

Amino Acid Sequence↗
PubMed1997

[Granuloma pyogenicum--removal with the CO2 laser].

13 patients with pyogenic granuloma were treated with a CO2 laser using the continuous wave laser in all cases and using additionally the ultrapulsed laser in 7 patients. The pyogenic granuloma was removed in all patients in one session. Side effects included transient erythema in 8 patients and scars in 2 cases. There was no hypo- or hyperpigmentation. The use of the CO2 laser is a fast and bloodless way to treat pyogenic granuloma with slight side effects and is an elegant alternative to standard approaches.

Adolescent↗
PubMed1997

Mouse fibroblast growth factor 10: cDNA cloning, protein characterization, and regulation of mRNA expression.

Fibroblast growth factor 7 (FGF-7) or keratinocyte growth factor (KGF), is a potent and specific mitogen for epithelial cells. We have recently identified a novel human FGF-7 homologue, named FGF-10. To study the expression of this new FGF family member and its regulation in wound repair, we cloned the mouse FGF-10 (mFGF-10) cDNA. The encoded protein is 92% identical to human FGF-10 and 91% identical to rat FGF-10. When expressed in mammalian 293 cells, the mFGF-10 protein was glycosylated but remained cell- or extracellular matrix-associated. Upon addition of heparin, mFGF-10 protein was released into the media. mRNA encoding mFGF-10 was relatively abundant in lung, skin, brain and heart. In the skin, both FGF-7 and mFGF-10 were expressed in the dermal, but not the epidermal compartment. In contrast to FGF-7, mFGF-10 expression was not induced during cutaneous wound repair. In cultured fibroblasts, expression of mFGF-10 was strongly repressed by transforming growth factor beta and tumor necrosis factor alpha, whereas epidermal growth factor and interleukin-1beta had no effect. These results demonstrate a differential regulation of mFGF-10 and FGF-7 expression in vitro and during the wound healing process.

3T3 Cells↗
PubMed1997

[Facial wrinkles--ultrapulsed CO2 laser: alternative or supplement to surgical face lift?].

BACKGROUND: For many years, the treatment of facial wrinkles has been performed exclusively by dermabrasion, chemical peeling, or surgical face lifting. However, the recently introduced carbon dioxide lasers which emit ultrashort coherent light beams enable the cosmetic surgeon to ablate superficial epidemic layers with absent or very limited side effects. The purpose of this paper is to compare laser skin resurfacing with classical face lifting and discuss the potentials and limitations of each method. METHODS AND PATIENTS: Three patients suffering from facial wrinkles on photoaged skin were treated with the ultrapulsed CO2 laser (UltraPulse 5000 C; wavelength 10,600 nm, pulse duration 0.6 to 0.9 ms, maximum pulse energy 500 mJ). This laser guarantees vaporization of very thin superficial skin layers without scarring and with minimizing lateral thermal injury due to extreme short pulse duration. A special handpiece (CPG) permits an exact approach and a bloodless ablation of relatively large areas of facial skin. The fourth patient underwent a surgical face lift due to the depth of wrinkles. RESULTS: Excellent cosmetic results were achieved in all three patients with superficial wrinkles who were treated by laser skin resurfacing. When treating deeper wrinkles, e.g., glabella or nasolabial fold, the surgical face lift is the preferred method. CONCLUSION: Ultrapulsed CO2 laser treatment expands the therapeutic options for superficial facial wrinkles, especially for perioral, periorbital, forehead, and cheeks wrinkles. It proves to be a safe and effective method with very limited if any side effects. Nevertheless, deeper wrinkles are still a domain of the classical face lift. The combination of both methods may improve the overall outcome in the future.

Aged↗
PubMed1997

Effective treatment of hypertrichosis with pulsed light: a report of two cases.

Hypertrichosis is an often stigmatizing cosmetic problem not only for women but also for male-to-female transsexual patients. The hitherto described therapeutic measures include chemical epilation, razoring, camouflage, electrolysis and thermolysis, and waxing. All of these measures are transient, more or less painful, and may lead to severe side effects (e.g., inflammatory responses and scarring). We report the successful treatment of the perioral and mandibular area of two transsexual patients (male to female), who we treated with a recently introduced intense, pulsed light source--the PhotoDerm VL. Two days after the nearly painless treatment, hair could be epilated easily with forceps. Biopsies of the treated area show an atrophy of the follicles, which can be contributed either to direct thermal injury or to an indirect photothermolytical effect. Six months after the last treatment, there is no local recurrence and no side effects.

Adult↗
PubMed1997

Differential expression of the calpactin I subunits annexin II and p11 in cultured keratinocytes and during wound repair.

Transforming growth factor beta1 (TGF-beta1) is an important modulator of skin morphogenesis and cutaneous wound repair. To gain insight into the mechanisms of TGF-beta1 action in the skin, we used the differential display RT-PCR technique to identify genes that are regulated by this factor in cultured human keratinocytes. We obtained several partial cDNA clones. One of them was identical to the 3'-end of p11, the small and regulatory subunit of the calpactin I complex [(annexin II)2(p11)2]. RNase protection and northern blot analysis revealed specific regulation of expression of both subunits of this heterotetrameric protein (p11 and annexin II) by TGF-beta1 as well as by other growth factors, although the time course and degree of induction or suppression were different for each gene. Furthermore, we analyzed p11 and annexin II expression in normal and wounded skin. Both p11 and annexin II mRNAs were found in the dermal and epidermal compartments of normal human skin. Immunohistochemical studies demonstrated the presence of p11 at equally high levels in all layers of normal epidermis and in the hyper-proliferative epithelium at the wound edge. By contrast, annexin II expression was high in the basal layer of normal epidermis but low in the suprabasal layers and in the hyper-proliferative epithelium at the wound edge, suggesting a differentiation-specific regulation of this calpactin I subunit. The differential expression and regulation of p11 and annexin II subunits in keratinocytes suggest the existence of different ratios of monomeric versus p11-complexed annexin II that might be associated with different cellular functions.

Animals↗
PubMed1997

Reduced expression of PDGF and PDGF receptors during impaired wound healing.

A series of studies has shown that application of platelet-derived growth factor (PDGF) to a wound enhances the process of wound repair, especially in animals with wound-healing defects. In the current study, we investigated the regulation of PDGF A and PDGF B and their receptors during wound repair in mice. Both ligands and both types of receptor were expressed in normal and wounded skin, whereby PDGF A and PDGF B proteins were found at different sites in the healing wound. Surprisingly, no significant induction of these genes was observed after skin injury in normal mice, and expression levels were similar at all stages of the repair process. To determine a possible role of endogenous PDGF in normal wound healing, we subsequently analyzed the regulation of PDGF and PDGF receptors during wound healing in healing-impaired animals. Genetically diabetic db/db mice showed a significant reduction in PDGF A and A-type receptor expression in nonwounded and wounded back skin. Furthermore, expression of the B-type receptor was also reduced during the repair process. Systemic glucocorticoid treatment caused a severe defect in wound repair that was accompanied by reduced expression of PDGF A and B and of the B-type receptor in the early phase of wound healing. These results provide an explanation for the beneficial effect of exogenous PDGF in the treatment of wound-healing disorders. Furthermore, our data suggest that a certain expression level of PDGF and its receptors is essential for normal repair.

Animals↗
PubMed1997

Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues.

Angiogenesis, the process of new vessels sprouting from the existing vasculature, is a critical process during early development. However, angiogenesis rarely occurs in the adult, except in response to cyclic hormonal stimulation in the ovary and uterus, in response to injury, and in response to pathological conditions such as tumorigenesis and diabetes mellitus. Tie2 (also known as Tek) is a novel endothelium-specific receptor tyrosine kinase, which has been demonstrated to be essential for the development of the embryonic vasculature; Tie2 knockout mice die by embryonic day 10.5 with specific defects in the formation of microvessels. Tie2 is downregulated later in embryogenesis, and its function in the adult has been relatively unexplored. To gain insight into the potential functions of Tie2 in the adult vasculature, Tie2 expression was examined in adult tissues undergoing angiogenesis and in quiescent tissues. Tie2 expression was localized by immunohistochemistry to the endothelium of neovessels in rat tissues undergoing angiogenesis during hormonally stimulated follicular maturation and uterine development and in healing skin wounds. Immunoprecipitation and RNase protection assay demonstrated upregulation of Tie2 protein and mRNA in rat and mouse skin wounds, respectively. Moreover, Tie2 immunoprecipitated from skin wounds was tyrosine-phosphorylated, indicating active downstream signaling. Surprisingly, Tie2 was also expressed in the entire spectrum of the quiescent vasculature (arteries, veins, and capillaries) in a wide range of adult tissues, and Tie2 immunoprecipitated from quiescent adult tissues was also tyrosine-phosphorylated. Together, these results suggest a dual function for Tie2 in adult tissues involving both angiogenesis and vascular maintenance.

Aging↗
PubMed1997

Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction.

Two studies are presented, with the aim of establishing the dose potency ratio for salbutamol given via Turbuhaler and via a pressurized metered-dose inhaler (pMDI). Both studies were of a double-blind, randomized design. Outpatients with mild-to-moderate chronic reversible airway obstruction were given single doses of salbutamol administered via Turbuhaler and via pMDI. Efficacy and safety variables were measured before and during 6 h after each dose. The first study was a four-way crossover study including 12 patients. The salbutamol doses given were: 50, 100 and 2x100 microg via Turbuhaler and 2x100 microg via pMDI (Ventolin). The study showed that 2x100 microg of salbutamol inhaled via Turbuhaler is more potent than 2x100 microg salbutamol inhaled via a pMDI, and that 100 microg salbutamol via Turbuhaler is at least as potent as 2x100 microg salbutamol inhaled via a pMDI. The second study including 50 patients was a placebo-controlled five-way crossover, study. Two doses of salbutamol via Turbuhaler, 50 and 2x100 microg, and via pMDI, 100 and 2x200 microg, were given. There was a dose-dependent response in forced expiratory volume in one second (FEV1) for both inhalers. Adjusted for differences in baseline FEV1 values, the estimated relative dose potency for Turbuhaler versus pMDI was 1.98:1 (95% confidence interval 12-3.2). These studies showed that the same bronchodilating effect can be achieved when half the dose of salbutamol given via a conventional pressurized metered-dose inhaler is given via Turbuhaler.

Administration, Inhalation↗
PubMed1997

Activin A: a novel player and inflammatory marker in inflammatory bowel disease?

Recently, we demonstrated a strong induction of activin expression after cutaneous injury. We speculated, therefore, that activin may be overexpressed during inflammatory processes in other tissues characterized by mesenchymal/epithelial structure. Herein, we show a strikingly increased expression of the activin beta A-subunit in surgical specimens from the gut of patients suffering from ulcerative colitis and Crohn's disease, whereas no activin beta A mRNA could be detected in the normal human digestive tract. The levels of activin beta A expression showed an outstanding correlation with the degree of inflammation as assessed by histologic analysis of adjacent tissue and expression analysis of the proinflammatory cytokine interleukin-1 beta. In situ hybridization studies revealed the highest levels of activin mRNA in the mucosa and submucosa of highly inflamed areas, particularly where the intestinal epithelium was damaged, but not in control tissue. In contrast, activin beta B mRNA levels in most specimens from inflamed areas were only slightly higher compared to control tissue. The strong overexpression of activin beta A in inflammatory bowel disease suggests a novel and important role of this growth and differentiation factor during inflammatory processes of the gut.

Activins↗