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Biomedical subjects

I Moll

Publications and source records attributed to I Moll.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evaluating a superabsorbent hydropolymer dressing for exuding venous leg ulcers.

A new hydropolymer dressing was compared with an alginate dressing in a multicentre, prospective, controlled, randomised, stratified, open label trial of 113 patients with exuding venous leg ulcers. The study aimed to evaluate the performance of the dressings in terms of their ability to handle exudate, patient and user acceptability and cost-effectiveness. Patients were stratified according to volume of wound exudate (moderate/heavy) and randomised to the hydropolymer dressing or the alginate plus a secondary dressing. A statistically significant difference between treatment groups was observed in mean wear time, with a longer wear time observed in the hydropolymer group (3.91 days) compared with the alginate group (3.09 days, p = 0.001). In terms of patient and user acceptability, all 10 overall evaluations made by both patient and investigator were markedly in favour of the hydropolymer dressing (p < 0.001 to p = 0.020). The use of the hydropolymer dressing for patients with moderate to heavily exuding venous leg ulcers has statistically significant advantages over the alginate dressing in terms of wear time and investigator and patient acceptability. It is anticipated that this reduction in dressing frequency will translate into a cost-effective wound treatment.

Adult↗
PubMed2000

Hfq (HF1) stimulates ompA mRNA decay by interfering with ribosome binding.

The adaptation of mRNA stability to environmental changes is a means of cells to adjust the level of gene expression. The Escherichia coli ompA mRNA has served as one of the paradigms for regulated mRNA decay in prokaryotes. The stability of the transcript is known to be correlated inversely with the bacterial growth rate. Thus, the regulation of ompA mRNA stability meets the physiological needs to adjust the level of ompA expression to the rate of cell division. Recently, host factor I (Hfq/HF1) was shown to be involved in the regulation of ompA mRNA stability under slow growth conditions. Here, we present the first direct demonstration that 30S ribosomes bound to the ompA 5'-UTR protect the transcript from RNase E cleavage in vitro. However, the 30S protection was found to be abrogated in the presence of Hfq. Toeprinting and in vitro translation assays revealed that translation of ompA is repressed in the presence of Hfq. These in vitro studies are corroborated by in vivo expression studies demonstrating that the reduced synthesis rate of OmpA effected by Hfq results in functional inactivation of the ompA mRNA. The data are discussed in terms of a model wherein Hfq regulates the stability of ompA mRNA by competing with 30S ribosomes for binding to the ompA 5'-UTR.

5' Untranslated Regions↗
PubMed2000

[Unilateral laterothoracic exanthema. Case report and review of the literature].

Unilateral laterothoracic exanthem (ULE) developed in a 4-year-old-boy on maintenance therapy for acute lymphatic leukemia (ALL). This is the second reported case of an association between ULE and leukemia. The etiology of ULE is unknown. Endemic cases, frequently associated signs of upper respiratory infections, and the occurrence of ULE in immunocompromised hosts are suggestive of an infectious process.

Child, Preschool↗
PubMed2000

Effect of pentoxifylline on sunburn cell formation in a novel supravital human skin model.

BACKGROUND/AIM: The aim of this study was to determine whether pentoxifylline (Pf) has an effect on sunburn cell (SBC) formation in humans. METHODS: A novel supravital human skin model was used. Normal skin samples were placed on gauze in completed RPMI 1640 Medium and remained vital for 48 h. Three concentrations of Pf (7.5, 15.0 and 30.0 microg/ml) were tested. After 2 h, each skin sample was irradiated with 120 mJ/cm2 of UVB. After 24-h incubation, the samples were formalin fixed, paraffin embedded and sections were stained with haematoxylin-eosin. RESULTS: The mean count of SBC (10.43 +/- 1.35 (SEM)) was significantly higher in the control group (without Pf) compared with its mean count in 7.5 microg/ml Pf (5.18 +/- 0.62, P < 0.001), or 15.0 microg/ml Pf (5.79 +/- 1.70, P < 0.001), or 30.0 microg/ml Pf (4.37 +/- 1.47, P < 0.001). CONCLUSION: Pentoxifylline reduced SBC formation in our supravital human skin model. It presumably acts as an antioxidant agent.

Antioxidants↗
PubMed2000

Bcl-2 antisense oligonucleotides (G3139) inhibit Merkel cell carcinoma growth in SCID mice.

Merkel cell carcinoma was first described in 1972 by Toker and is an aggressive neuroendocrine skin tumor with a high metastatic potential. Merkel cell carcinoma is thought to derive from the neuroendocrine (Merkel) cells of the skin, although in contrast to fetal and especially adult Merkel cells, Merkel cell carcinomas express high levels of the Bcl-2 oncoprotein. Bcl-2 is capable of blocking programmed cell death and has been shown to play an important role in normal cell turnover, tumor biology, and chemoresistance. High Bcl-2 expression leading to prolonged survival of cells may therefore be of importance in the biological and clinical characteristics of Merkel cell carcinoma. In a SCID mouse xenotransplantation model for human Merkel cell carcinoma, we investigated the influence of the bcl-2 antisense oligonucleotide G3139 (Genta) on tumor growth in comparison with control oligonucleotides or cisplatin. Bcl-2 antisense treatment, targeting the first six codons of the bcl-2 mRNA, resulted in either a dramatic reduction of tumor growth or complete remission, whereas reverse sequence and two-base mismatch control oligonucleotides or cisplatin had no significant antitumor effects compared with saline-treated controls. Apoptosis was enhanced 2.4-fold in the bcl-2 antisense treated tumors compared with the saline-treated group, and no other treatment showed a comparable increase in apoptosis. Our findings suggest that bcl-2 antisense treatment may be a novel approach to improve treatment outcome of human Merkel cell carcinoma.

Animals↗
PubMed2000

Active hair growth (anagen) is associated with angiogenesis.

After the completion of skin development, angiogenesis, i.e., the growth of new capillaries from pre-existing blood vessels, is held to occur in the skin only under pathologic conditions. It has long been noted, however, that hair follicle cycling is associated with prominent changes in skin perfusion, that the epithelial hair bulbs of anagen follicles display angiogenic properties, and that the follicular dermal papilla can produce angiogenic factors. Despite these suggestive observations, no formal proof is as yet available for the concept that angiogenesis is a physiologic event that occurs all over the mature mammalian integument whenever hair follicles switch from resting (telogen) to active growth (anagen). This study uses quantitative histomorphometry and double-immunohistologic detection techniques for the demarcation of proliferating endothelial cells, to show that synchronized hair follicle cycling in adolescent C57BL/6 mice is associated with substantial angiogenesis, and that inhibiting angiogenesis in vivo by the intraperitoneal application of a fumagillin derivative retards experimentally induced anagen development in these mice. Thus, angiogenesis is a physiologic event in normal postnatal murine skin, apparently is dictated by the hair follicle, and appears to be required for normal anagen development. Anagen-associated angiogenesis offers an attractive model for identifying the physiologic controls of cutaneous angiogenesis, and an interesting system for screening the effects of potential antiangiogenic drugs in vivo.

Animals↗
PubMed1999

Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice.

Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32+/-0.15 g and 1.08+/-0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.

Aged↗
PubMed1999

Lectin binding pattern and proteoglycan distribution in human eccrine sweat glands.

The distribution pattern of glycoconjugates in human eccrine sweat glands has been studied by the binding of newly discovered lectins and by antibodies against a chondroitin sulphate proteoglycan and chondroitin sulphate glycosaminoglycans. Mannose-specific lectins labelled large intracellular granules, part of which could be extended cisternae of the endoplasmic reticulum or Golgi apparatus. In contrast, lectins specific for terminal mannose/glucose residues predominantly labelled basement membranes and the glycocalyx. Lectins recognizing terminal N-acetylgalactosamine groups left most parts of the glands unstained, but stained some dark cells intensely. These last cells were also intensively labelled by N-acetylglucosamine-specific and by fucose-specific lectins. Sialic acid residues were preferentially located in luminal borders of secretory coils. No terminal galactose residues were detected. All antibodies against chondroitin glycoconjugates stained large granules similar to those revealed by the mannose-specific lectins in the secretory cells. The basement membrane is only stained by the proteoglycan antibody and the chondroitin-6-sulphate antibody. Thus, a complex composition of glycoconjugates exists not only in matrix elements but also in the cells of eccrine glands of the human skin. A possible secretion of glycoconjugates is discussed.

Chondroitin Sulfate Proteoglycans↗
PubMed1999

Alterations in cell death and cell cycle progression in the UV-irradiated epidermis of bcl-2-deficient mice.

The effect of bcl-2 gene ablation on epidermal cell death induced by UV-B irradiation was investigated in mice. Exposure of depilated back skin of bcl-2-/- mice to 0.5 J/cm2 UV-B caused a prolonged increase in the number of epidermal cells showing nuclear DNA fragmentation compared to wild-type littermates. Consistently, skin explants from bcl-2-deficient mice exhibited a higher number of sunburn cells per cm epidermis (16.6+/-2.1 vs 7.0+/-1.5) following exposure to 0.1 J/cm2 UV-B in vitro. Furthermore, UV irradiation failed to increase pre-melanosomes in skin explants from mutant animals, and primary menalocyte cultures derived from bcl-2 null mutants were highly susceptible to UV-induced cell death compared to cultures from wild-type littermates. An accelerated reappearance of proliferating cells, showing nuclear immunoreactivity for Ki-67 and c-Fos, was observed in the UV-irradiated epidermis of bcl-2-deficient mice. Taken together, these findings suggest that effects of UV radiation on epidermal cell death and cell cycle progression are influenced by survival-promoting Bcl-2.

Animals↗
PubMed1999

Forms of epithelial differentiation of draining sinus in acne inversa (hidradenitis suppurativa).

The draining sinus is a late complication of several forms of severe acne, leading to extensive, periodically inflamed lesions that are undermined by a system of fistulas, supposed to be of follicular origin. We investigated the expression of various cytokeratins (CKs) and desmosomal proteins in the draining sinus of acne inversa (hidradenitis suppurativa) using monoclonal antibodies in immunohistochemistry on paraffin-embedded sections. We were able to define three different phenotypes of stratified squamous epithelia covering the sinus tracts. Type I epithelium was cornifying and characterized by the presence of CK 10, desmogleins 1-3 and desmocollins 1-3 in an epidermis-like pattern. Type II epithelium was non-cornifying, negative for CK 10 and positive for CK 13. It was negative for desmocollin 1 but strongly immunopositive for desmoglein 1 suprabasally and for desmoglein 2 in the basal cells. Type III epithelium was non-cornifying and strongly inflamed. It was marked by the presence of CK 7, CK 19 and desmoglein 2 and the absence of CK 10, desmoglein 1 and desmocollin 1. In both type II and III epithelium, desmoglein 3, desmocollin 2 and desmocollin 3 showed an inverted staining pattern as compared with normal epidermis and type I epithelium. Desmoglein 2 and CK 5/14 always remained restricted to the basal cell layer. Antibodies against CK 6 and CK 13/15/16 were immunopositive in all three phenotypes and CK 17 was predominantly immunolocalized to suprabasal layers of type II and III epithelium. The three phenotypes are characterized as pathological stratified squamous epithelia reflecting the dynamic process of inflammation, proliferation and stratification taking place in acne inversa.

Antibodies, Monoclonal↗
PubMed1999

Translation initiation factor 3 antagonizes authentic start codon selection on leaderless mRNAs.

In this study, we have examined the influence of initiation factors on translation initiation of leaderless mRNAs whose 5'-terminal residues are the A of the AUG initiating codon. A 1:1 ratio of initiation factors to ribosomes abolished ternary complex formation at the authentic start codon of different leaderless mRNAs. Supporting this observation, in vitro translation assays using limiting ribosome concentrations with competing leaderless lambda cl and Escherichia coli ompA mRNAs, the latter containing a canonical ribosome binding site, revealed reduced cl synthesis relative to OmpA in the presence of added initiation factors. Using in vitro toeprinting and in vitro translation assays, we show that this effect can be attributed to IF3. Moreover, in vivo studies revealed that the translational efficiency of a leaderless reporter gene is decreased with increased IF3 levels. These studies are corroborated by the observed increased translational efficiency of a leaderless reporter construct in an infC mutant strain unable to discriminate against non-standard start codons. These results suggest that, in the absence of a leader or a Shine-Dalgarno sequence, the function(s) of IF3 limits stable 30S ternary complex formation.

5' Untranslated Regions↗
PubMed1998

Discrimination of 5'-terminal start codons by translation initiation factor 3 is mediated by ribosomal protein S1.

The interrelation between ribosomal protein S1 and IF3 in recognition/discrimination of 5'-terminal start codons by 30S ribosomes has been studied using in vitro toeprinting. The study has been performed with two naturally occurring leaderless mRNAs, lambda cI and phage r1t rro mRNA, as well as with an artificial leaderless mRNA derived from the E. coli ompA gene. We show that in the absence of S1, IF3 does not discriminate against the authentic 5'-terminal start codon of both cI and rro mRNA. Since IF3 was able to exert its proofreading function for initiator tRNA(fMet) on 30S ribosomes lacking S1, this observation cannot be attributed to a lack of binding to or action of IF3 on 30S(-S1) ribosomes. In contrast to leaderless mRNAs, ternary complex formation occurs in the presence of IF3 with 30S ribosomes when the start codon is preceded by a short 20-nucleotide 5'-untranslated region containing a canonical Shine and Dalgarno sequence. This suggests that 5'-terminal start codons are recognised by IF3 as non-standard because of the lack of 16S rRNA-mRNA contacts.

Bacteriophage lambda↗
PubMed1998

Epidermal adhesion molecules and basement membrane components as target structures of autoimmunity.

Intraepidermal and dermal-epidermal cohesion are of paramount importance for the integrity of the skin. Some constituent molecules of keratinocyte adhesion complexes and basement membrane-associated structures are the targets of antibody-mediated autoimmune reactions that give rise to various (muco-)cutaneous blistering diseases. The current state of our knowledge about these molecules--along with the main clinical, histological, and immunohistochemical features of the corresponding autoimmune diseases and their pathogenetic mechanisms--comprise the subjects surveyed in this review. Among the desmosomal cadherins (desmogleins and desmocollins) that mediate epidermal cell-cell adhesion, it has been demonstrated that desmoglein 1 and desmoglein 3 are the autoantigens of pemphigus foliaceus and pemphigus vulgaris, respectively, both diseases that result in intraepidermal blistering. Further, desmocollin autoantibodies may be involved in IgA pemphigus. Paraneoplastic pemphigus is associated with autoantibodies directed against the desmosomal plaque protein, desmoplakin. Of the constituents of hemidesmosomes, the plaque protein, BP230 (BPAG1), and the collagen-like transmembrane protein, BP180 (BPAG2), are the autoantigens of bullous pemphigoid and pemphigoid gestationis, the manifestations of both of which include subepidermal blistering. Several diseases arise from autoimmune reactions against certain proteins associated with the basement membrane located beneath hemidesmosomes, for example laminin 5 (cicatricial pemphigoid), ladinin (LAD-1; linear IgA disease), uncein, and collagen VII (epidermolysis bullosa acquisita), the last of which is the constituent protein of the anchoring fibrils. Such recent advances in the elucidation of the molecular nature of autoantigens may serve as the basis for the development of novel molecule-based therapeutic strategies.

Basement Membrane↗
PubMed1998

Compositionally different desmosomes in the various compartments of the human hair follicle.

Hair follicles are complex organs of the skin, in morphological and ontogenic continuity with the epidermis. We have examined the location of desmosomal cadherins and desmosomal plaque proteins in the hair follicle of adult and fetal human scalp skin by immunohistochemistry and have established a localization "map" of the hair follicle. Using antibodies against the plaque proteins desmoplakin I and II, plakoglobin, and plakophilin 1, we have found that these occur in most, if not all hair follicle desmosomes, whereas plakophilin 2 was absent, except in the basal cells of the outer root sheath, where a weak reactivity was found. By contrast, the desmosomal cadherins were mostly differentially synthesized, displaying a complicated map. While desmocollin Dsc3 was detected in all cell types examined, Dsc1 was detected only in the outer root sheath companion cell layer and the inner root sheath, and Dsc2 showed practically a mutually exclusive presence. Desmoglein Dsg2 was observed in basal cells of the outer root sheath as well as in the central cell layers of the subinfundibular outer rood sheath, matrix cells and trichocytes, in partial overlap with the otherwise different immunopositive reactions of Dsg1 and Dsg3. We have also determined when these proteins are synthesized during fetal hair follicle development. The differential molecular composition of desmosomes is discussed in relation to possible functional differences between the individual cell types.

Antibody Specificity↗
PubMed1998

Characterization of epidermal wound healing in a human skin organ culture model: acceleration by transplanted keratinocytes.

Few data are available on early regeneration of human epidermis in vivo. We have established a supravital skin organ culture model for epidermal wound healing by setting a central defect (3 mm diameter) in freshly excised skin specimens and culturing under air exposure. Re-epithelialization was followed for up to 7 d by histology and immunohistologic analysis of various markers for differentiation and proliferation. In 12 of 19 cases (63%; 5% fetal calf serum) or six of 21 cases (29%; 2% fetal calf serum), the wounds were re-epithelialized spontaneously after 7 d. After transplantation to the wounds of 1-2 x 10(6) dissociated allogenic cultured epidermal or about 1 x 10(6) autologous outer root sheath keratinocytes, 18 of 21 cases (86%; 5% fetal calf serum) or 17 of 21 cases (81%; 2% fetal calf serum) were healed within the same period. Histologically, early neoepithelium (3 d) was disordered after keratinocyte transplantation, whereas later (7 d) it had gained a more ordered stratification, exhibiting a thin discontinuous granular and a compact horny layer. At this stage, not only hyperproliferative (CK 6) but also, abundantly, maturation-associated cytokeratins (CK 1, CK 10) were detected immunohistochemically. Analyses of regenerated epidermis after transplantation of (i) keratinocytes labeled in vitro with BrdU and (ii) heterosexual keratinocytes by immunohistochemistry and fluorescence in situ hybridization for the Y chromosome, respectively, clearly showed that external keratinocytes are physically integrated into the regenerated epidermis and extendedly contribute to its formation. The data presented here demonstrate improvement and acceleration of epidermal re-epithelialization by transplantation of keratinocytes.

Adolescent↗
PubMed1998

Induction of bone morphogenetic protein-6 in skin wounds. Delayed reepitheliazation and scar formation in BMP-6 overexpressing transgenic mice.

Growth factors of the transforming growth factor-beta superfamily are involved in cutaneous wound healing. In this study we analyze the expression of the bone morphogenetic protein-6 (BMP-6) gene, a transforming growth factor-beta related gene, in skin wounds. In normal mouse skin high levels of BMP-6 mRNA and protein are expressed by postmitotic keratinocytes of stratified epidermis until day 6 after birth. BMP-6 expression is strongly reduced in adult epidermis with diminished mitotic activity. After skin injury we found large induction of BMP-6-specific RNA and protein in keratinocytes at the wound edge and keratinocytes of the newly formed epithelium as well as in fibroblast shaped cells in the wound bed. BMP-6-specific RNA was induced within 24 h after injury, whereas significant upregulation of BMP-6 on the protein level was detected only 2-3 d after injury. Protein was confined to outermost suprabasal epidermal layers, whereas BMP-6-specific RNA was distributed throughout all epidermal layers including basal keratinocytes and the leading edge of the migrating keratinocytes. We also detected high levels of BMP-6-specific RNA and protein in chronic human wounds of different etiology. In contrast to the overall distribution pattern of BMP-6-specific RNA, the protein was not detected in keratinocytes directly bordering the wound. In order to test the influence of BMP-6 abundance on the progress of wound healing, we analyzed the wound response of transgenic mice overexpressing BMP-6 in the epidermis. In these mice, reepitheliazation of skin wounds was significantly delayed, suggesting that strict spatial and temporal regulation of BMP-6 expression is necessary not only for formation but also for reestablishment of a fully differentiated epidermis.

Adult↗
PubMed1998

Expression of heat shock protein 27 in chromomycosis.

We report on a 58-year-old woman with long-lasting (36 years) chromomycosis on the foot and secondary self-inoculation from foot to hand 4 years ago. Mycological classification was performed after culture on Sabouraud glucose agar. We used haematoxylin and eosin and Giemsa staining and an antibody to heat shock protein (HSP) 27 (Stress Gen, Clone G3.1) on paraffin-embedded and cryostat specimens of chromomycosis. The mycological culture revealed the fungus Fonsecaea pedosoi. Histopathology revealed dermal fibrosis with persistent fungi (Medlar bodies), numerous mast cells and pseudoepitheliomatous hyperplasia. Immunohistochemically, HSP 27 was positively identified in F. pedrosoi. Moreover, in differentiating keratinocytes in the pseudoepitheliomatous lesions of chromomycosis, HSP 27 was increasingly expressed from basal layers to stratum spinosum in the epidermis but not in keratinocytes directly bordering Medlar bodies. In chromomycosis, HSP 27 is expressed, in accordance with its role as a marker of differentiation and proliferation, in keratinocytes and also in F. pedrosoi. It remains unknown if these results might explain the therapeutic efficacy of hyperthermic treatment.

Adult↗