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I Moll

Publications and source records attributed to I Moll.

At least 73 records · Page 4Linked to original sources

Merkel cell distribution in human hair follicles of the fetal and adult scalp.

The distribution of Merkel cells in fetal and adult terminal hair follicles of human scalp was studied immunohistochemically using cytokeratin (CK) 20 as a specific Merkel cell marker. In hair follicles of adult scalp, abundant Merkel cells were found enriched in two belt-like clusters, one in the deep infundibulum and one in the isthmus region. No Merkel cells were found in the deep follicular portions including the bulb, or in the dermis. In early fetal hair follicles (bulbous peg stage), Merkel cells were only detected in the basal layer of the developing infundibulum but not in deeper follicular areas. In later stages, Merkel cells were also present in the isthmus and bulge. No Merkel cells were seen in the dermis around developing hair follicles. Nerve growth factor receptor was not only present in nerves but was found to be widely distributed within fetal skin. In adult skin, this receptor was localized to the basal cell layers of the outer root sheath of the bulb and the suprabulbar area, but was not detectable in the areas containing Merkel cells. The present study localizing Merkel cells within the permanent hair follicle structures close to their possible stem cells suggests that they have paracrine functions.

Adult↗

[The Merkel cell].

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Biomarkers, Tumor↗

Establishment and characterization of two Merkel cell tumor cultures.

Two Merkel cell tumor cultures (MC-MA1, MC-MA2) have been established from metastases of typical Merkel cell tumors. The mestastases in vivo were characterized by co-expression of cytokeratins 8, 18, 19, 20 and neurofilaments, presence of intermediate filament whirls, expression of synaptophysin, neuron-specific enolase, and chromogranin A, rare and weak immunostaining for plakoglobin but absence of cadherins and desmoplakins. Both cultures grow, using supplemented RPMI medium on human irradiated fibroblast feeder layers, as loosely arranged floating small aggregates. Their karyotypes are mostly hyperdiploid. The mean doubling times were about 84 h in the first 8 months and later increased. Ultrastructural and immunoelectron microscopic studies of the Merkel cell tumor cells in vitro (MC-MA1, MC-MA2) revealed sparse membrane-bound neuroendocrine granules and typical IFs that were partly arranged in paranuclear whirls and were labeled by antibodies against cytokeratins and neurofilaments. In immunocytochemical studies using antibodies to cytokeratins 8, 18, 19, and 20 and neurofilament protein NF-L, Merkel cell tumor cells in vitro showed a uniform staining appearing as paranuclear whirls and cytoplasmic fibrils as well. Double-labeling experiments showed a co-localization of both intermediate filament types in most cells. Biochemically we found cytokeratins 8, 18, 19, and 20, and NF-L in tumor cells in vitro. Immunocytochemical staining was negative for desmoplakins, various cadherins, and cell adhesion molecules, whereas plakoglobin was only rarely detectable in some Merkel cell tumor cells in vitro. By immunoluminometric assay chromogranin A was detected in cell homogenates and culture supernatants as well. Immunocytochemically, synaptophysin and neuron-specific enolase were detectable additionally in some of the cells. These established cell cultures will allow further studies devoted to the biology, differentiation, and hormone secretion of Merkel cell tumors that may also increase our knowledge about normal Merkel cells.

Aged↗

Semiquantitative aspects of mast cells in normal skin and in neurofibromas of neurofibromatosis types 1 and 5.

Mast cells are supported to influence the growth of neurofibromas, because some of their mediators may also act as growth factors. Accordingly, mast cell stabilizers are claimed to reduce proliferation and itching of neurofibromas. Therefore, we quantified the mast cells of 19 neurofibromas and compared them with normal skin. We saw a statistically significant increase in mast cells in neurofibromas versus normal skin. However, there is no correlation between the age of neurofibromatosis (NF) patients and mast cell density. In our study the density of mast cells in neurofibromas is also independent of NF type; age of neurofibroma and chronic ultraviolet exposure in contrast to normal skin. Different tumors of the same patient had similar mast cell counts.

Adolescent↗

Effects of ultraviolet B radiation on cytoskeletal and adhesion molecules in human epidermis.

The expression of cytokeratins (CK), various adhesion molecules and growth factor receptors were investigated in ultraviolet (UV) erythemas 24 h and 48 h after exposure to 4 times the minimal erythema dose. Skin biopsies were analysed immunohistochemically using a battery of antibodies and biochemically by gel-electrophoresis. The CK pattern was shown to change within 24 h. CK typical of basal keratinocytes were detectable heterogeneously within the suprabasal compartment, and the staining for suprabasal CK was heterogeneous in prickle cells. Interestingly, CK 17, not detectable in normal epidermis, was induced within a few hours in suprabasal cells but not in basal ones. In addition, CK 6 and 16, typical for hyperproliferation, were intensively synthesized in all epidermal layers already 24 h after UV exposure. Moreover, integrin expression was studied and surprisingly integrins were heterogeneously detectable, the staining being patchy in suprabasal keratinocytes and reduced within the basal layer. Receptors of epidermal growth factor and nerve growth factor were distributed in UV erythema very irregularly and weakly. Our findings argue for profound changes in composition of cytoskeleton and of cell adhesion molecules in the epidermis shortly after UV exposure.

Antibodies, Monoclonal↗

The desmosome and the syndesmos: cell junctions in normal development and in malignancy.

The cells of various normal and malignantly transformed tissues are connected by "adhering junctions"-plasma membrane domains characterized by close membrane-membrane contact, a dense cytoplasmic plaque and, in most cases, the attachment of cytoskeletal filaments. On the basis of their specific ultrastructural organization and molecular composition, three major types of intercellular adhering junctions can be distinguished: 1. Adherens junctions appear in different shapes and sizes (zonula adhaerens, fascia adh., punctum adh.) and contain the transmembrane glycoprotein E-cadherin. The cytoplasmic portion of E-cadherin forms complexes with alpha-, beta-, and gamma-catenin and plakoglobin which, together with other proteins such as vinculin and radicin, constitute a plaque at which actin microfilaments insert. 2. Desmosomes (maculae adhaerentes) are mostly isodiametric (diameters up to approximately 0.5 micron) membrane domains traversed by representatives of two types of desmosomal cadherins, the desmogleins (Dsg) and desmocollins (Dsc), whose cytoplasmic tails contribute to a dense plaque containing plakoglobin and desmoplakin I (with or without an alternative splice form, desmoplakin II) which anchor IFs. The specific Dsc and Dsg subtypes can differ in different cell types and up to three different human genes have so far been identified for each desmosomal cadherin. 3. Complexus adhaerentes are junctions of variable size and shape that occur in lymphatic endothelia. They have a desmoplakin- and plakoglobin-rich plaque, whose specific transmembrane proteins have not yet been fully elucidated but can include endothelial cadherin-5. In their most elaborate subform- the "syndesmos" connecting the retothelial cells of lymph node sinus-these junctions can occupy extended portions of the cell surface. The molecular arrangements in desmosomes and complexus adhaerentes have been studied to understand the assembly and disappearance of these structures. The diagnostic potential of their constituent proteins for cell typing in tumor diagnosis is emphasized, as is the role of transient junction dissociation during invasion and metastasis of carcinomas and the general importance of tumor cell interactions with the retothelial cell system in the formation of lymph node metastases.

Animals↗

Merkel cells in ontogenesis of human nails.

Digital skin of human fetuses is known to contain a particularly high concentration of Merkel cells. Using antibodies against the simple epithelial cytokeratins (CK) 18 and 20, which are sensitive and specific Merkel cell markers, we studied immunohistochemically the main adnexal structure of digital skin, the nail anlage, in human fetuses (9-22 weeks of gestation) for the presence of Merkel cells. As early as week 9 some clustered Merkel cells were detected in the early matrix primordium. In specimens of week 12-15, abundant Merkel cells were found in the nail anlagen, particularly in the epithelium of the proximal nail-fold and the dorsal and ventral side of the apex region. In contrast, Merkel cells were essentially absent from the epithelium of the ventral matrix (surface-near portion), lunula and nail bed. Correspondingly, in these region, the adjacent dermis contained hardly any nerve fibres, whereas such fibres, as detected by neurofilament antibodies, were quite numerous adjacent to the proximal nail-fold epithelium. At week 22, the Merkel cell number in the nail anlage had decreased, and in adult nail matrix such cells were very rare. No Merkel cells were found in the dermal tissue surrounding the nail anlage while finger-tip skin of week 15, and particularly of week 22, exhibited single Merkel cells in the upper dermis next to clusters of such cells in the glandular ridges. We also found that Merkel cells were negative for CK 17.(ABSTRACT TRUNCATED AT 250 WORDS)

Gestational Age↗

Special program of differentiation expressed in keratinocytes of human haarscheiben: an analysis of individual cytokeratin polypeptides.

Human haarscheiben, epidermal Merkel cell-rich sensory organs of hairy skin, were studied for the expression of various cytokeratin (CK) polypeptides and other epithelial and neuronal differentiation markers by applying immunoperoxidase and immunofluorescence microscopy to frozen sections and by two-dimensional gel electrophoresis. The basal clusters of Merkel cells were specifically detected by antibodies against CK 20. Haarscheiben keratinocytes were unique mainly by the prominent expression of CK 17 in the lower and middle layers. Further differences as compared to keratinocytes of usual epidermis included the enlargement of the basal compartment, characterized by the expression of CK 5 and the absence of the maturation-associated CKs 1/10/11, and the reduction of CK 15, which is a constituent of normal basal cells. Using CK 17 as a highly sensitive Haarscheibe marker in skin tissue sections, variabilities in the spatial relationship of the haarscheibe and the corresponding hair follicle were recorded. The results show that haarscheibe keratinocytes express a special program of differentiation that may be important for optimal stimulus perception. Immunohistochemical stainings for CK 17 will facilitate further studies on the distribution and biology of haarscheibe.

Adult↗

Molecular characterization of the body site-specific human epidermal cytokeratin 9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression.

Differentiation of human plantar and palmar epidermis is characterized by the suprabasal synthesis of a major special intermediate-sized filament (IF) protein, the type I (acidic) cytokeratin 9 (CK 9). Using partial amino acid (aa) sequence information obtained by direct Edman sequencing of peptides resulting from proteolytic digestion of purified CK 9, we synthesized several redundant primers by 'back-translation'. Amplification by polymerase chain reaction (PCR) of cDNAs obtained by reverse transcription of mRNAs from human foot sole epidermis, including 5'-primer extension, resulted in multiple overlapping cDNA clones, from which the complete cDNA (2353 bp) could be constructed. This cDNA encoded the CK 9 polypeptide with a calculated molecular weight of 61,987 and an isoelectric point at about pH 5.0. The aa sequence deduced from cDNA was verified in several parts by comparison with the peptide sequences and showed the typical structure of type I CKs, with a head (153 aa), and alpha-helical coiled-coil-forming rod (306 aa), and a tail (163 aa) domain. The protein displayed the highest homology to human CK 10, not only in the highly conserved rod domain but also in large parts of the head and the tail domains. On the other hand, the aa sequence revealed some remarkable differences from CK 10 and other CKs, even in the most conserved segments of the rod domain. The nuclease digestion pattern seen on Southern blot analysis of human genomic DNA indicated the existence of a unique CK 9 gene. Using CK 9-specific riboprobes for hybridization on Northern blots of RNAs from various epithelia, a mRNA of about 2.4 kb in length could be identified only in foot sole epidermis, and a weaker cross-hybridization signal was seen in RNA from bovine heel pad epidermis at about 2.0 kb. A large number of tissues and cell cultures were examined by PCR of mRNA-derived cDNAs, using CK 9-specific primers. But even with this very sensitive signal amplification, only palmar/plantar epidermis was found positive. By in situ hybridization and immunolocalization we further showed that CK 9 is only expressed in the suprabasal cell layers of this special epidermal tissue. We discuss the molecular properties of CK 9 and its cell type- and body site-specific expression in relation to the special differentiation of palmar/plantar epidermis and to diseases specific for this body site.

Amino Acid Sequence↗

[Keratinocytes from cell culture for therapy of skin defects. Review and personal results].

The development of a method to cultivate and expand human keratinocytes in vitro by Rheinwald and Green in the mid-1970s can be considered a milestone in the search for the ideal biological skin substitute. For more than 10 years, cultured keratinocytes have now been used for the treatment of various wounds. In this paper the present status knowledge and the authors own experience after treating 29 patients are discussed.

Adult↗

[Striped nail pigmentation with Hutchinson signs in a boxer].

We present a 68-year-old male patient, who had had longitudinal melanonychia with Hutchinson sign for 4 years. Melanocytic proliferation was ruled out by biopsy. Friction and pressure had been acting on this patient's nails during boxing for the past 40 years. These mechanical factors are discussed under the entity of "frictional longitudinal melanonychia". In addition, cellular and non-cellular mechanisms for longitudinal melanonychia are reviewed.

Aged↗

[Hair casts in lichen ruber].

We present a 59-year old male patient, who had small plant cylinders 1-2 mm in length adhering to the hair shafts and easily moved up and down along them. We found hair casts together with lichen ruber follicularis and pseudopelade of the Brocq type. The presence of hair casts is often misdiagnosed as pediculosis capitis, piedra alba or trichorrhexis nodosa. The case report and the literature are discussed.

Antifungal Agents↗

Distribution of Merkel cells in acute UVB erythema.

Merkel cells (MC) were identified immunohistochemically using antibodies specific for cytokeratin (CK) 20 within human epidermis 12 to 72 h after exposure to UVB (4 MED). 12 h after exposure all MC were normally localized within the epidermal basal layer. However, 24 h after exposure 4% of the MC were detected suprabasally, the remaining 96% still being situated in the basal layer. Surprisingly, at 48 h and 72 h more than 50% had lost contact with the basal membrane. The MC of hair follicles did not show any obvious changes. These results argue, in the context of acute epidermal UV damage, for an abnormal turnover in dermatitis.

Acute Disease↗