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Biomedical subjects

I Moll

Publications and source records attributed to I Moll.

At least 19 recordsLinked to original sources
PubMed2006

Tight junction proteins in the skin.

It has long been accepted that tight junctions (TJ) are crucial for the formation and maintenance of the paracellular barrier and for cell polarity in simple epithelia and endothelia. Moreover, it is long known that they play a role in barrier function of amphibian skin. However, only in recent years were TJ and TJ proteins identified in the epidermis of men and mice. Their involvement in the barrier function of mammalian skin has been shown. This review summarizes our current knowledge about TJ and TJ proteins in mammalian skin.

Animals↗
PubMed2006

Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus.

BACKGROUND: Lichen sclerosus is a chronic inflammatory autoimmune disease causing significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory, with potent corticosteroids being the most effective therapy. OBJECTIVES: To conduct a multicentre, phase II trial to assess the safety and efficacy of tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up period of 18 months at 10 university and teaching hospitals in Germany and Austria. METHODS: Eighty-four patients (49 women, 32 men and three girls) aged between 5 and 85 years with long-standing, active lichen sclerosus (79 with anogenital and five with extragenital localization) were treated with topical tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the lesional area was performed. The primary endpoint was clearance of active lichen sclerosus. Secondary endpoints were time to optimal response, reduction of sclerosis and duration of remission. RESULTS: The primary endpoint (clearance of active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment. Partial resolution was reached in 34% of patients. Maximal effects occurred between week 10 and 24 of therapy. Treatment led to a significant reduction of the total lesional area (P < 0.01) and to a significant decline in the total symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema, erosions and induration) showed significant improvement. No serious adverse events were observed. There were three (9%) recurrences during the follow-up period. CONCLUSIONS: Topical tacrolimus ointment 0.1% was safe and effective for the treatment of long-standing active lichen sclerosus.

Adolescent↗
PubMed2005

[Allergic and irritant skin and airway diseases in masseurs and medical bath attendants].

The profession of masseur or bath attendant involves intense contact with multiple potential allergens and irritants. There is a complete lack of epidemiological studies for this professional group in spite of the general agreement that sensitization to ingredients of beauty and healthcare products such as fragrances is common. In this review, we critically review the relevant literature, and present own results from recently performed analyses of the German Information Network of Departments of Dermatology (IVDK). Fragrances, preservatives, emulsifiers, and antioxidants are relevant from the allergological perspective. In order to evaluate the particular importance of these and other potentially important allergens for occupational dermatology, further systematic research in allergology as well as epidemiological studies are needed.

Balneology↗
PubMed2005

Use of a hydrocapillary dressing in the management of highly exuding ulcers: a comparative study.

OBJECTIVE: To evaluate the safety and performance of Alione Hydrocapillary dressing (Coloplast A/S) in the management of highly exuding chronic venous leg ulcers and compare it with two hydropolymer dressings,Tielle and Tielle Plus (Johnson & Johnson). METHOD: A comparative clinical trial was conducted on 97 patients with an ankle brachial pressure index > or = 0.8 and a highly exuding leg ulcer. Ulcer duration was at least four weeks. Treatment continued until healing or for a maximum of 12 months. RESULTS: There was no statistically significant difference in healing time or wound area reduction between the two treatment protocols. The test dressing (Alione Hydrocapillary) had better absorption capacity and was more comfortable for the patients than the comparator dressings (Tielle/Tielle Plus) and adhered less to the wound bed.Also, more patients preferred the test dressing to their previous treatment. Although severe leakage and maceration were observed more frequently in the comparator group compared with the test group, this was not statistically significant. CONCLUSION: Both treatment protocols were safe and effective in treating highly exuding chronic venous leg ulcers. The test dressing performed as well as or better than the comparator dressings for all study parameters and more patients preferred the test dressing to their previous dressing compared with the comparator dressings.

Adult↗
PubMed2004

Polymorphous light eruption (PLE) and a new potent antioxidant and UVA-protective formulation as prophylaxis.

BACKGROUND: Polymorphous light eruption (PLE) is the most common photodermatosis. While its etiology still remains elusive, pathogenesis seems to involve UVA-induced oxidative stress and subsequent deregulation of antioxidative immune responses. Only few and often ineffective prophylactic and therapeutic measures exist to date. METHODS: In our randomized, double-blind, placebo-controlled clinical study, we compared the efficacy of a new topical formulation, consisting of 0.25%alpha-glucosylrutin (AGR) (a natural, modified flavonoid), 1% tocopheryl acetate (vitamin E) and a broad-spectrum, highly UVA-protective sunscreen (SPF 15) in a hydrodispersion gel vehicle, to a sunscreen-only gel and vehicle. Thirty patients with a history of PLE were pretreated with either the above formulation, a similar preparation (with the same concentration for vitamin E and AGR, but a different UV filter system), placebo or a SPF 15 sunscreen-only gel, 30 min prior to daily photoprovocation with UVA irradiations of 60-100 J/cm(2) to 5 x 5 cm(2) areas on the upper arms. RESULTS: After 4 days, results revealed a statistically highly significant difference (P<0.001) between the antioxidant containing formulations and placebo, and sunscreen-only formulation, respectively, in experimentally eliciting PLE. While only one patient developed clinical signs of PLE with accompanying itch in the area treated with the new antioxidant UV-protective gel formulation, 62.1% of the placebo-treated areas and 41.3% of the sunscreen-only treated areas showed mild to moderate signs of PLE. CONCLUSION: Combining a potent antioxidant with a broad-spectrum, highly UVA-protective sunscreen is far more effective in preventing PLE than sunscreen alone or placebo and should thus be employed as the prophylaxis of choice for PLE.

Administration, Topical↗
PubMed2003

The effect of homeopathic plant extract solutions on the cell proliferation of human cutaneous fibroblasts in vitro.

BACKGROUND: According to homotoxicology illness is defined as an overload of the connective tissue matrix with toxic substances, the homotoxins. In order to support elimination of these homotoxins, complex homeopathic medicines were developed. Fibroblasts are the local cells of this matrix and produce and modulate the composition of the extracellular matrix (ECM) in every organ. OBJECTIVE: In this study, the effect of 17 potentiated plant extracts, which are components of some antihomotoxic remedies, on the cell proliferation of human cutaneous fibroblasts (F54) was analyzed as an indication of their influence on the ECM. MATERIAL AND METHODS: Cell proliferation of the F54 cells was measured by a colorimetric XTT-based assay kit. RESULTS: Six of the tested agents had no effect on the cell proliferation of fibroblasts; 11 plant extracts had a dose-dependent inhibitory effect on cell proliferation. CONCLUSIONS: As the modulation of the ECM is dependent on the activity of the fibroblasts, these results indicate that the plant extracts may modulate the composition of the ECM via the inhibitory effect on fibroblasts cell growth.

Cell Division↗
PubMed2002

[Photoprotective mechanisms of human skin. Modulation by oligonucleotides].

There are at least two classic photoprotective DNA damage responses that can be elicited by UV exposure: induction of melanogenesis (tanning) and enhancement of DNA repair. Both mechanisms are mediated, at least in part, by the tumor-suppressor protein and transcription factor p53. Both of these responses can be induced in vitro as well as in vivo by small DNA fragments of specific sequences, without prior induction of actual DNA damage. The topical application of such fragments onto human skin might enhance photoprotection in human skin, as typically elicited by gradual sun exposure. The induction of photoprotection by this means, however, would not bear the mutagenic and carcinogenic risk of exposure to natural sunlight.

Animals↗
PubMed2002

Cloning, purification, and crystallization of a bacterial gene expression regulator--Hfq protein from Escherichia coli.

Thermostable RNA-binding protein Hfq (also denoted HF1) is a multifunctional expression regulator of many bacterial genes. The regulation takes place both at a translation level (directly) and transcription level (indirectly through the stimulation of bacterial RNA polymerase sigmaS-subunit translation). We have cloned and overexpressed the hfq gene from E. coli and developed a purification procedure for the protein. Using gel filtration and ultracentrifugation techniques it was shown that the obtained Hfq protein is highly homogeneous and well dissolved. It has been crystallized and can be used for structural investigations.

Amino Acid Sequence↗
PubMed2001

Modulation of ribosomal recruitment to 5'-terminal start codons by translation initiation factors IF2 and IF3.

Sequence determinants and structural features of the RNA govern mRNA-ribosome interaction in bacteria. However, ribosomal recruitment to leaderless mRNAs, which start directly with the AUG start codon and do not bear a Shine-Dalgarno sequence like canonical mRNAs, does not appear to rely on 16S rRNA-mRNA interactions. Here, we have studied the effects of translation initiation factors IF2 and IF3 on 30S initiation at a 5'-terminal AUG and at a competing downstream canonical ribosome binding site. We show that IF2 affects the forward kinetics of 30S initiation complex formation at the 5'-terminal AUG as well as the stability of these complexes. Moreover, the IF2:IF3 molar ratio was found to play a decisive role in translation initiation of a leaderless mRNA both in vitro and in vivo indicating that the translational efficiency of an mRNA is not only intrinsically determined but can be altered depending on the availability of components of the translational machinery.

Codon, Initiator↗
PubMed2001

Lectin binding to cutaneous malignant melanoma: HPA is associated with metastasis formation.

Changes in protein glycosylation of tumour cells, as detected by lectin histochemistry, have been associated with metastasis formation in several human malignancies. This study analysed the association between lectin binding and metastasis in cutaneous malignant melanoma. In a 10-year retrospective study, sections of 100 primary cutaneous malignant melanomas were histochemically stained for the following 5 lectins: HPA, SNA-I, MAA, WGA and PHA-L, differing in their carbohydrate specificity. Since differences in the results of HPA binding depending on methodology have been reported, an indirect and a biotinylated method were employed for HPA. Kaplan-Meier analysis of time to first metastasis revealed a positive correlation between HPA binding and metastasis for both methods, with the biotinylated HPA method (P< 0.0001) being superior to the 'indirect' method (P = 0.0006). Cox regression analysis demonstrated that even after adjustment for stage, HPA positivity is an independent predictor for metastasis. The results of the present study indicate that N -acetyl-galactosamine/-glucosamine residues, recognized by HPA, are linked to metastasis in malignant melanoma. In contrast, beta1-6 branched oligosaccharides or sialic acid residues, both of which were correlated with metastasis in other malignancies, are of no functional importance for metastasis formation in malignant melanoma. Thus, HPA proved to be a useful and independent prognostic marker for the metastatic phenotype of melanoma.

Adult↗
PubMed2001

PAS-positive loops and networks as a prognostic indicator in cutaneous malignant melanoma.

Recently, microvascular channels, as detected by PAS histochemistry, were positively correlated with poor prognosis in uveal malignant melanoma. Since uveal melanomas are not penetrated by lymphatic vessels, while cutaneous melanomas are, the question arises as to whether these loops and networks are also of prognostic relevance in cutaneous melanoma. Histochemically and immunohistochemically detected loops and networks in 100 cases of cutaneous malignant melanoma were correlated with the occurrence of metastasis in a 10-year follow-up study. To detect these patterns, the significance of various methods (PAS reaction with/without nuclear counterstain, anti-laminin immunohistochemistry) was investigated. The presence of loops and networks was a highly significant prognostic marker (p<0.0001) for metastasis in cutaneous malignant melanoma. The presence of these patterns proved to have higher prognostic relevance for metastasis than Breslow's tumour thickness, especially for stage IB and stage IIA tumours (intermediate thickness/risk). PAS reaction without nuclear counterstain proved to be the best method to detect these patterns. Compared with the conventional staging of Breslow's tumour thickness, and especially so for stage IB and IIA melanomas, the determination of PAS-positive loops and networks in cutaneous malignant melanoma provides additional prognostic information.

Adult↗
PubMed2001

Telomerase activity of Merkel cell carcinomas and Merkel cell carcinoma-derived cell cultures.

Merkel cell carcinomas are rare malignant tumors of the skin, which are predominantly observed in elderly patients (mean age 65-70 years). It is believed but not yet proven that these tumors are derived from the Merkel cells of the epidermis and hair follicles. The Merkel cells themselves probably originate from an asymmetric cell division of basal keratinocytes and the resulting differentiated Merkel cells have presumably, at least in humans, lost their growth potential. The capability of indefinite cell division in germ line cells and in the great majority of malignant tumors as well as an increased growth potential in certain somatic cells (such as basal cells of renewable tissues) is correlated with cellular telomerase activity, which is absent in differentiated somatic cells. In this study the telomerase activity in cryostat sections of frozen Merkel cell tumor biopsies and in in vitro cultivated Merkel cell carcinoma cells was analyzed. We detected telomerase activity in four tumors and three of four cell cultures. These results show that despite their pronounced neuroendocrine differentiation and their occurrence in patients of advanced age, Merkel cell carcinomas possess telomerase activity similar to that of common carcinoma types.

Aged↗
PubMed2001

Lectin and proteoglycan histochemistry of Merkel cell carcinomas.

Changes in carbohydrate residue expression and in proteoglycan distribution occur during different stages of tumor development and progression. However, few data concerning carbohydrate residue analysis as performed by lectin histochemistry and proteoglycan distribution of Merkel cell carcinoma, a rare malignant tumor of the skin, have been reported. Hence, lectin- and proteoglycan immunohistochemistry was performed on paraffin wax material of 9 cases of Merkel cell carcinomas characterized by cytokeratin and neurofilament immunohistochemistry. The lectin binding pattern of tumor cells varied between lectins with different sugar binding specificities, while within a given nominal sugar specificity intensities were remarkably similar between tumors from different patients. The most intensive reaction was observed using Con A (mannose/glucose-specific) followed by LCA with the same specificity and the N-Acetyl glucosamine-specific lectins (WGA, UDA, CMA), while no fucose binding sites were detected (UEA-I). In addition, N-Acetyl galactosamine residues were only occasionally detected. The lectin binding pattern of Merkel cell carcinoma cells indicated that predominantly N-linked glycans and not O-linked glycans, typical for mucins of most epithelia, were present. Hence these tumor cells were relatively undifferentiated and resembled stem cells more closely than differentiated epithelia. The tumor stroma was especially evaluated in this study and showed a lectin reaction, which was intermediate between the tumor cells and extra-tumoral stroma. For example, the reactions of N-Acetyl galactosamine-specific lectins were intensive in the extra-tumoral stroma but nearly negative in tumor cells, while the lectin reaction of the intra-tumoral stroma was similar to the cellular reaction. These results indicated an influence of tumor cells on the stromal constituents. Antibodies against chondroitin type glycosaminoglycans reacted with the tumor stroma and the pericellular substance around the tumor cells most intensely in - and around the major tumor septae which, in general, were well vascularized. The most intensive immunoreactivity was detected using the chondroitin-6-sulfate antibody. The cellular and membrane-associated reaction for heparan sulfate was less intensive in comparison to epidermal cells. In conclusion the pattern of lectin-binding sites, the high chondroitin(sulfate) specific reactivity and the relatively low intensity of heparan sulfate immunohistochemistry indicate a low degree of differentiation and high malignity of the tumors, which is consistent with the clinical behavior of Merkel cell carcinomas.

Biomarkers, Tumor↗
PubMed2001

Drebrin particles: components in the ensemble of proteins regulating actin dynamics of lamellipodia and filopodia.

Drebrin, an actin-binding 70-kDa protein with an unusually slow SDS-PAGE mobility corresponding to approximately 120 kDa, containing a proline-rich, profilin-binding motif, had originally been reported from neuronal cells, but recently has also been found in diverse other kinds of tissues and cell lines. In biochemical analyses of various cells and tissues, employing gel filtration, sucrose gradient centrifugation, immunoprecipitation and -blotting, we have identified distinct states of soluble drebrin: a approximately 4S monomer, an 8S, ca. 217-kDa putative trimer, a 13S and a > 20S oligomer. In the 8S particles only [35S]methionine-labelled drebrin but no other actin-binding protein has been detected in stoichiometric amounts. By immunofluorescence and immunoelectron microscopy, drebrin-positive material often appeared as "granules" up to 400 nm in diameter, in some cell types clustered near the Golgi apparatus or in lamellipodia, particularly at leading edges, or in dense-packed submembranous masses at tips (acropodia) or ruffles of leading edges, in filopodia and at plaques of adhering junctions. We conclude that these drebrin complexes and drebrin-rich structures allow the build-up and maintenance of high local drebrin concentrations in strategic positions for the regulation of actin filament assembly, thereby contributing to cell motility and morphology, in particular local changes of plasticity and the formation of protrusions.

Actins↗
PubMed2001

Results of photoprovocation and field studies on the efficacy of a novel topically applied antioxidant in polymorphous light eruption.

BACKGROUND: UVA-induced photooxidation is considered to play an essential role in the pathogenesis of polymorphous light eruption (PLE), and topical pretreatment of skin with alpha-glucosylrutin (AGR), a potent plant-derived antioxidant, has been shown to significantly suppress photoprovoked PLE eruption. AIM: In order to further elucidate the optimum pretreatment regimen and to investigate the efficacy and skin compatibility of topical preparations containing AGR under field conditions, two controlled clinical studies were conducted in PLE patients. METHODS: In the first study, photoprovocation of PLE was performed in 20 patients, using UVA irradiation (4 x 60-100 J/cm(2)), applied to four test sites at the individual areas of predilection. One site served as an untreated control. The remaining three sites received treatment with a SPF 15 sunscreen containing 0.25% AGR (Eucerin Gel Cream Phase 2) 30 minutes before irradiation. Two of these sites were additionally pretreated with the corresponding AGR-containing vehicle (Eucerin Gel Cream Phase 1) twice daily for 3 and 7 days, respectively. The second study was conducted as a controlled in-use-test in patients with PLE (n = 27) or acne aestivalis (n = 3), who had suffered from the disease during their last year's vacation. They were educated to apply the pre-sun preparation to the formerly affected skin areas twice daily for 1 week before their planned vacation and to use the SPF 15 sunscreen 30 minutes before each vacation sun exposure. Symptoms were recorded in patients' diaries throughout the vacation and documented by a physician after their return. RESULTS: In the first study, protection of skin with the SPF 15 sunscreen alone led to a significant prevention of PLE symptoms, especially itch, compared with the control area. Pretreatment further reduced the severity of PLE significantly and led to total prevention in 19 patients. In the second study, whereas 92.6% had reported severe and 7.4% mild PLE in the last year, there were currently only 7.4% severe cases, with 25.9% mild and 29.6% questionable cases; 37% had no symptoms at all. Also, two out of three acne aestivalis patients had diminished symptoms after treatment. CONCLUSION: The results confirm the prophylactic efficacy of the antioxidant AGR in PLE, applied as SPF 15 sunscreen alone or additionally to pretreatment with a corresponding pre-sun preparation, and also show an effect in acne aestivalis patients.

Administration, Topical↗
PubMed2001

Evidence against an Interaction between the mRNA downstream box and 16S rRNA in translation initiation.

Based on the complementarity of the initial coding region (downstream box [db]) of several bacterial and phage mRNAs to bases 1469 to 1483 in helix 44 of 16S rRNA (anti-downstream box [adb]), it has been proposed that db-adb base pairing enhances translation in a way that is similar to that of the Shine-Dalgarno (SD)/anti-Shine-Dalgarno (aSD) interaction. Computer modeling of helix 44 on the 30S subunit shows that the topography of the 30S ribosome does not allow a simultaneous db-adb interaction and placement of the initiation codon in the ribosomal P site. Thus, the db-adb interaction cannot substitute for the SD-aSD interaction in translation initiation. We have always argued that any contribution of the db-adb interaction should be most apparent on mRNAs devoid of an SD sequence. Here, we show that 30S ribosomes do not bind to leaderless mRNA in the absence of initiator tRNA, even when the initial coding region shows a 15-nucleotide complementarity (optimal fit) with the putative adb. In addition, an optimized db did not affect the translational efficiency of a leaderless lambda cI-lacZ reporter construct. Thus, the db-adb interaction can hardly serve as an initial recruitment signal for ribosomes. Moreover, we show that different leaderless mRNAs are translated in heterologous systems although the sequence of the putative adb's within helix 44 of the 30S subunits of the corresponding bacteria differ largely. Taken our data together with those of others (M. O'Connor, T. Asai, C. L. Squires, and A. E. Dahlberg, Proc. Natl. Acad. Sci. USA 96:8973-8978, 1999; A. La Teana, A. Brandi, M. O'Connor, S. Freddi, and C. L. Pon, RNA 6:1393-1402, 2000), we conclude that the db does not base pair with the adb.

Base Pairing↗