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PubMed1996

The distribution and origin of keratin 20-containing taste buds in rat and human.

Sections of tissues containing lingual and extra-lingual taste buds were evaluated with monoclonal antibodies against cytokeratins. In the caudal third of the rat's tongue, keratin 20 immunoreactivity was restricted to taste buds, whereas keratins 7, 8, 18, and 19 were expressed in vallate and foliate taste buds and in cells of salivary ducts that merge with these taste epithelia. Hence, antibodies against keratin 20 most clearly distinguished differentiated taste cells from all other cells. In rat epiglottis, taste buds and isolated bipolar cells were keratin-20-positive. In rat nasopalatine papilla and palate, antibodies against keratin 20 identified Merkel cells, none of which was near to the keratin-20-negative taste buds. Nor were Merkel cells present at epiglottal taste buds or the keratin-20-negative fungiform taste buds or elsewhere in rat tongue. Hence, Merkel cells make no contribution to rat fungiform, epiglottal, nasopalatine, or palatal taste buds. Human and rat keratin-20-positive tissues are reported to be endodermal derivatives with the exception of Merkel cells and luminal urothelial cells. In rats the distribution of keratin-20-positive taste buds was in full agreement with the classical view that the posterior third of the tongue is derived from endoderm (keratin-20-positive taste buds), whereas the anterior two-thirds of the tongue is derived from stomadeal ectoderm (keratin-20-negative taste buds). The equally intense keratin 20 immunoreactivity of human fungiform and vallate taste buds violates this traditional rostro-caudal segregation and suggests that endodermally derived tissues may be present in the tip of the human tongue.

Adult↗
PubMed1983

The value of S-100 immunostaining as a diagnostic tool in human malignant melanomas. A comparative study using S-100 and neuron-specific enolase antibodies.

The brain proteins S-100 and neuron-specific enolase have been reported by separate groups to be present in human malignant melanomas. There is no systematic study comparing the occurrence of these proteins in the same tumour specimens. We have examined 33 primary malignant melanomas, including 5 which were amelanotic, and 25 metastatic melanomas using immunohistochemical methods with specific, non-cross-reacting antibodies to S-100 and NSE. We found S-100 immunoreactivity to be present in all cases but one, whereas NSE immunoreaction was very weak and patchy, and present in only 6 cases. S-100 immunoreactivity was not demonstrated in 40 control tumours, either primary or metastatic in skin, including basal- and squamous-cell carcinomas, spindle-cell sarcomas, lymphomas and Merkel cell tumours. All intradermal (n = 4) and compound (n = 1) naevi were positive for S-100, 2 blue naevi showing much less reaction. NSE immunoreactivity was detected in Merkel cell tumours (n = 8), undifferentiated (n = 2) and small cell (n = 1) carcinomas, and all melanocytic naevi. It is suggested therefore that antibody to S-100 is the reagent of choice for demonstration of melanocytic tumours, and may be especially valuable in the diagnosis of amelanotic melanoma or metastatic tumours of doubtful origin where melanoma is suspected.

Fluorescent Antibody Technique↗
PubMed1998

Expression of cytokeratin-20 in endometrial carcinoma.

OBJECTIVE: Cytokeratins are constituents of the intermediate filaments of epithelial cells which are expressed in various combinations depending on the epithelial type and the degree of differentiation. The recently identified cytokeratin-20 (CK-20) was found with immunohistochemical methods to be expressed in gastrointestinal epithelium, uroepithelial cells, and Merkel cells. Clues were also found for low expression of CK-20 in endometrial carcinoma cells. The aim of this study was to examine whether CK-20 expression can be measured in endometrial carcinoma with the more sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) methods and therefore used as a potential diagnostic tumor biomarker for endometrial carcinoma. METHODS: In the present study we have used RT-PCR methods to determine expression of CK-20 in endometrial epithelial cells. Endometrial specimens were collected from 18 patients with endometrial carcinoma and 22 patients that underwent hysterectomy due to benign diseases. The specimens were prepared for both RT-PCR and immunohistochemical analysis. RNA, of the various cell pellets, was extracted and RT-PCR was performed with CK-20 and CK-19 primers (CK-19 was used as a marker for normal epithelial cells). Immunohistochemistry was carried out with the avidin-biotin-peroxidase complex method on formalin-fixed paraffin sections using CK-20 antibody. RESULTS: CK-20 amplification band (370 bp) was obtained with mRNA extracted from endometrial carcinoma cells of 17 of the patients with endometrial carcinoma (sensitivity, 94.4%). CK-20 was negative in 21 patients with benign endometrial disease (specificity, 91.3%). No positive results were obtained with the immunohistochemical methods. CONCLUSION: These results indicate that RT-PCR of CK-20, because of its high sensitivity, is a potential biomarker for detecting endometrial carcinoma.

Adult↗
PubMed2005

[Dermato-oncological rehabilitation].

National insurance companies in Germany support health cures for patients with malignant tumors (malignant melanoma, squamous cell carcinoma, Merkel cell tumor, malignant cutaneous lymphoma). The clinical requirements are an invasively growing tumor, problems of self-assurance, and dis-integration of the patient regarding his social and/or professional environment. The decision for a health cure is made by the treating dermatologist in the hospital. In this context, the following sociomedical criteria should be applied: impairment, disability, and handicap. Usually, rehabilitation starts after the patient is discharged from the hospital. The inpatient rehabilitation program should be performed at an institution capable of providing dermatological and psychological treatment. The dermatologist acts as a manager for the members of the rehabilitation team (psychologists, physiotherapists, social workers, and ergo-therapists). In conclusion, dermato-oncologic rehabilitation plays an important role in re-integrating the patient into his professional life to avoid retirement.

Combined Modality Therapy↗
PubMed1993

Opioid peptide release evoked by noxious stimulation of the hind instep of rats.

Previous studies showed that opioids and opioid peptides modulate vascular reactions such as plasma extravasation and vasodilatation through inhibition of substance P release from peripheral nerve endings of primary afferent fibers, and suggested the existence of endogenous opioid peptide activity related to regulation of inflammatory responses. Here we examined the effect of heat stimulation and antidromic stimulation of primary afferent fibers on the release of immunoreactive opioid peptides into the perfusate of the subcutaneous space in the rat instep. Antidromic stimulation of sectioned sciatic and saphenous nerves did not have any significant effect on the release of Met-enkephalin (Met-EK), while immersion of the hind paw in hot water (47 degrees C) for 30 min caused an increase in Met-EK release into the perfusate. High-pressure liquid chromatography of the perfusate revealed that noxious heat stimulation induced increase in release of Leu-enkephalin (Leu-EK) as well as Met-EK, although the maximal concentration of Leu-EK was less than 16% of that of Met-EK. No beta-endorphin was detected in the perfusate before, during or after heating. We conclude that noxious heat stimulation mainly leads to increase in Met-EK, and that this peptide originates mainly, from peripheral cells containing opioid peptides such as immune cells and/or Merkel cells, not from primary afferent fibers.

Animals↗
PubMed2005

Morphology of Bufo ictericus integument (Amphibia, Bufonidae).

Bufo ictericus integument was investigated by stereoscopic, low vacuum scanning electron microscopy, transmission electron microscopy and light microscopy. The studies revealed, that the dorsal integument surface is rougher than ventral. Three types of projections are visualized: larger rounded verrucae, smaller conical cornified tubercles, and conical short spines. Prominent verrucae are observed on the dorsal surface, being flatter on the ventral surface. The tubercles are visualized only on the dorsal surface. The verrucae are separated by grooves that may contribute spreading and retention of the glandular secretion upon the integument. The pattern of the epidermal grooves is also important for water distribution, protecting the animal against desiccation. The epidermis is composed of a stratified epithelium with intraepithelial blood vessels, where keratinocytes predominate, but flask cells, and Merkel cells also occur. In the spongious dermis, cutaneous glands are visualized. The compact dermis is a series of alternating layers of bundles of collagenous fibers, and between spongious and compact dermis there are basophilic areas that correspond to Eberth-Katschenko layer. The dorsal and the ventral surfaces of B. ictericus are morphologically distinct. The integument structure is related to the physiology of each surface and represents an adaptation to habitat, reflecting a lifestyle of the animal.

Animals↗
PubMed1990

Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns.

A major cytoskeletal polypeptide (Mr approximately 46,000; protein IT) of human intestinal epithelium was characterized by biochemical and immunological methods. The polypeptide, which was identified as a specific and genuine mRNA product by translation in vitro, reacted, in immunoblotting after SDS-PAGE, only with one of numerous cytokeratin (CK) antisera tested but with none of many monoclonal CK antibodies. In vitro, it formed heterotypic complexes with the type II CK 8, as shown by blot binding assays and gel electrophoresis in 4 M urea, and these complexes assembled into intermediate filaments (IFs) under appropriate conditions. A chymotrypsin-resistant Mr approximately 38,000 core fragment of protein IT could be obtained from cytoskeletal IFs, indicating its inclusion in a coiled coil. Antibodies raised against protein IT decorated typical CK fibril arrays in normal and transformed intestinal cells. Four proteolytic peptide fragments obtained from purified polypeptide IT exhibited significant amino acid sequence homology with corresponding regions of coils I and II of the rod domain of several other type I CKs. Immunocytochemically, the protein was specifically detected as a prominent component of intestinal and gastric foveolar epithelium, urothelial umbrella cells, and Merkel cells of epidermis. Sparse positive epithelial cells were noted in the thymus, bronchus, gall bladder, and prostate gland. The expression of protein IT was generally maintained in primary and metastatic colorectal carcinomas as well as in cell cultures derived therefrom. A corresponding protein was also found in several other mammalian species. We conclude that polypeptide IT is an integral IF component which is related, though somewhat distantly, to type I CKs, and, therefore, we propose to add it to the human CK catalogue as CK 20.

Amino Acid Sequence↗
PubMed1978

Development and differentiation of dermal cells in man.

Development and differentiation of the single free cells of mesenchyme and dermis of human embryos and fetuses from week 6 to term is described. From week 6 to week 14, three cell types are present: stellate general mesenchymal cells with long processes, phagocytic macrophages of probable yolk-sac origin, and a granule-secretory type of cell, which could be either a melanoblast or a mast stem cell. From week 14 to week 21, fibroblasts are numerous and active, and perineurial cells, pericytes, melanoblasts, mast cells, and Merkel cells can be individually identified. There is also present another cell type, possible of bone marrow origin, that may be ancestral to the Langerhans cell and that may be carried over into postanal dermis as the "histiocyte" or fixed dermal macrophage. From week 24 to term there is little change apart from the development of fat cells in the deeper dermis. Neither lymphocyte nor plasma cell was observed at any stage of development. These observations were used in the specification and identification of cells of fully developed postnatal dermis.

Cell Differentiation↗
PubMed2007

Role of radiotherapy in the management of organ transplant recipients diagnosed with non-melanoma skin cancers.

Organ transplantation has had a major effect on the lives of thousands of patients worldwide. In Australia and New Zealand, over 13 000 patients have become organ transplant recipients (OTR). Following transplantation, patients require lifelong immunosuppression to prevent organ rejection. The loss of immune surveillance results in OTR experiencing a higher incidence of infection and malignancy in comparison with the general (immunocompetent) population. Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most often on the sun-exposed head and neck. Organ transplant recipients experience a higher incidence of NMSC when compared with the general population and a higher incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ transplant recipients also develop NMSC at a younger age and experience multiple new NMSC. Australians experience the highest incidence of NMSC in the world with a consequence that NMSC arising in OTR can lead to significant morbidity and even mortality. Radiation oncologists treating patients with skin cancer will almost certainly make recommendations in the setting of NMSC arising in OTR. The aim of this article is to discuss the role of radiotherapy in the management of OTR diagnosed with NMSC. The emphasis will be on the treatment of patients with a high-risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable basal cell carcinoma) because this reflects the most common clinical scenario in which a recommendation of radiotherapy, usually adjuvant, may be considered.

Australia↗
PubMed1992

Simple epithelial cytokeratin-expression in seborrheic keratosis.

The cytokeratin expression of seborrheic keratosis was studied by means of immunohistochemistry and compared with that of normal human skin. The following findings were obtained in seborrheic keratosis: (1) a partial lack of high molecular weight cytokeratin (#1/68 kD, #10/56.6 kD) in all ten cases examined; (2) the detection of cytokeratin typical for simple epithelia (#8/52.5 kD, #18/45 kD, #19/40 kD) in eight of ten cases; and (3) the detection of cytokeratin #5/58 kD in suprabasal cells in 5 of 10 cases. An immunoelectron-microscopic investigation, using an anti-keratin antibody against cytokeratin #19/40 kD, revealed a whirl-like arrangement of keratin filaments within immunoreactive cells, in contrast to a linear, parallel arrangement in non-immunoreactive cells. Cells known to express cytokeratin typical for simple epithelia, such as sweat gland cells or Merkel cells, were not observed. The altered cytokeratin gene-expression in seborrheic keratosis may be attributable to de-differentiation of tumor cells or potential re-differentiation towards embryonic keratinocytes.

Adult↗
PubMed1991

Distinctive unclassified mesenchymal tumor of the digit of dogs.

Four examples of a mesenchymal tumor of undetermined histogenesis occurred in three mixed-breed dogs and one Yorkshire terrier. All tumors occurred as solitary, soft to firm, solid, tan, and ulcerated masses in the digits of dogs aged 11 to 15 years. The compact cellular tumor had cells with anisokaryotic round, oval, or irregular nuclei, some of which were multinucleated. The neoplastic cells appeared to arise in the tissue near the third phalanx in the area of dense collagenous trabeculae located proximal to the fat pad and sweat glands. The unclassifiable cells had some features of histiocytes by transmission electron microscopy, but failed to stain for lysozyme and alpha-1-antichymotrypsin, markers for monocyte-macrophage derived cells. Immunohistochemically, the cells stained for vimentin but not for cytokeratins, desmin, S-100 protein, epithelial membrane antigen, alpha-lactalbumin, lysozyme, alpha-1-antichymotrypsin, alpha-lactalbumin, casein, and heavy and light chain immunoglobulins. The combined findings of light and transmission electron microscopy and immunohistochemistry exclude tumor histogenesis from an epithelial cell, melanocyte, mast cell, plasma cell, Schwann cells, and Merkel cell.

Animals↗
PubMed2000

Functional conservation of atonal and Math1 in the CNS and PNS.

To determine the extent to which atonal and its mouse homolog Math1 exhibit functional conservation, we inserted (beta)-galactosidase (lacZ) into the Math1 locus and analyzed its expression, evaluated consequences of loss of Math1 function, and expressed Math1 in atonal mutant flies. lacZ under the control of Math1 regulatory elements duplicated the previously known expression pattern of Math1 in the CNS (i.e., the neural tube, dorsal spinal cord, brainstem, and cerebellar external granule neurons) but also revealed new sites of expression: PNS mechanoreceptors (inner ear hair cells and Merkel cells) and articular chondrocytes. Expressing Math1 induced ectopic chordotonal organs (CHOs) in wild-type flies and partially rescued CHO loss in atonal mutant embryos. These data demonstrate that both the mouse and fly homologs encode lineage identity information and, more interestingly, that some of the cells dependent on this information serve similar mechanoreceptor functions.

Animals↗
PubMed2004

Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells.

Espins are associated with the parallel actin bundles of hair cell stereocilia and are the target of mutations that cause deafness and vestibular dysfunction in mice and humans. Here, we report that espins are also concentrated in the microvilli of a number of other sensory cells: vomeronasal organ sensory neurons, solitary chemoreceptor cells, taste cells, and Merkel cells. Moreover, we show that hair cells and these other sensory cells contain novel espin isoforms that arise from a different transcriptional start site and differ significantly from other espin isoforms in their complement of ligand-binding activities and their effects on actin polymerization. The novel espin isoforms of sensory cells bundled actin filaments with high affinity in a Ca(2+)-resistant manner, bound actin monomer via a WASP (Wiskott-Aldrich syndrome protein) homology 2 domain, bound profilin via a single proline-rich peptide, and caused a dramatic elongation of microvillus-type parallel actin bundles in transfected epithelial cells. In addition, the novel espin isoforms of sensory cells differed from other espin isoforms in that they potently inhibited actin polymerization in vitro, did not bind the Src homology 3 domain of the adapter protein insulin receptor substrate p53, and did not bind the acidic, signaling phospholipid phosphatidylinositol 4,5-bisphosphate. Thus, the espins constitute a family of multifunctional actin cytoskeletal regulatory proteins with the potential to differentially influence the organization, dimensions, dynamics, and signaling capabilities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells.

Actins↗
PubMed2002

Microscopic, immunocytochemical, and ultrastructural properties of peri-implant mucosa in humans.

BACKGROUND: Microscopic and immunocytochemical studies have demonstrated both similarities and differences between the gingival mucosa and the peri-implant mucosa restored around dental implants. METHODS: This study was performed on 10 samples of peri-implant mucosa from 10 patients who had undergone implant treatment 16 to 18 months before. Microscopic, ultrastructural, and immunocytochemical investigations were performed to characterize the epithelial and connective layers of the peri-implant mucosa. RESULTS: All specimens showed the morphologic characteristics of well restored tissues. The immunocytochemical reactions used to detect cytokeratins demonstrated that the restored peri-implant mucosa had a non-keratinized epithelium. The apical part of the inner epithelium was a few cell layers thick, like the corresponding junctional epithelium, but it stained positively with the markers for the cytokeratins expressed by the stratified epithelia. Ultrastructurally the keratinocytes adjacent to the implant displayed nuclei containing a rich cytoplasm with filaments and specialized intercellular junctions right up to the more superficial strata. Immunocytochemical reactions and ultrastructural observations demonstrated the presence of non-keratinocyte cells; i.e., Langerhans cells, melanocytes, and Merkel cells. Several cells were found to be proliferating by immunoreaction with mAb anti-PCNA, while immunoreactions with mAbs to detect von Willebrand factor, CD34, and vascular endothelial growth factor marked the well-developed networks of blood and lymphatic vessels in the connective tissue. S-100 and protein gene product 9.5 positive nerve fibers were marked. Immunocytochemical reactions with mAbs anti-vimentin, anti-laminin were also performed. CONCLUSIONS: Our results demonstrated that all the epithelial and connective components of the mucosa are involved in the substantial regrowth of the peri-implant tissue and subsequently in the success of the implant.

Actin Cytoskeleton↗
PubMedDate not supplied

Richner-Hanhart's syndrome: new ultrastructural observations on skin lesions of two cases.

New ultrastructural observations are described in skin lesions of two brothers with Richner-Hanhart's syndrome (RHS). Physical examination of the two patients showed painful skin lesions of palms and soles combined with denderitic corneal ulceration and mental retardation. The diagnosis of RHS was confirmed biochemically with high tyrosine levels in both blood and urine. Examination by transmission electron microscopy revealed several abnormal ultrastructural changes in the epidermal cells. The horny cells contained heterogeneously, electron-dense cytoplasm with many lipid droplets. The granular cell cytoplasm contained abundant tonofibrils and keratohyaline granules. The spinous cell cytoplasm was vacuolated due to the presence of minute tyrosine crystals, which are known to have a lytic effect. The surrounding keratinocytes contained multilobed nuclei. The basal epidermal cells appeared normal except for Merkel cells, which were severely damaged by vacuolatio, also due to the presence of tyrosine crystals. This study showed that high tyrosine levels can induce several ultrastructural pathological changes in the epidermal cells, including the skin chemoreceptor Merkel cells.

Adult↗
PubMed1984

[Differential diagnosis of pseudolymphomas].

The term pseudolymphoma indicates the physician's opinion concerning the prognosis but is not a diagnosis. Several benign conditions mimic lymphomas, but neoplastic lymphocytes may also be overcome by the organism. In some "pseudolymphomas" the malignant lymphocytes are just kept in check for some time but finally the outcome is fatal. Modern techniques to classify cells by monoclonal antibodies and lectins indicate that proliferations of non-lymphocytes, like histiocytes, Langerhans cells, or Merkel cells, may simulate malignant lymphomas too, so a new type of pseudolymphomas has to be acknowledged. The most important question, however, whether the proliferation is malignant or benign, cannot be answered satisfactorily yet, at least with borderline cases or very early proliferation.

Adenocarcinoma↗
PubMed1995

Florid vascular proliferation associated with neural and neuroendocrine neoplasms. A diagnostic clue and potential pitfall.

We report the light microscopic and immunohistochemical features of vascular proliferations associated with 26 extracranial neural and neuroendocrine neoplasms including esthesioneuroblastoma, neuroblastoma/ganglioneuroblastoma, the primitive neural component of immature teratoma, mediastinal teratoma, primitive neuroectodermal tumor, intra-abdominal desmoplastic small cell tumor, Merkel cell carcinoma of the skin, and thyroid medullary carcinoma. These vascular proliferations were similar to those associated with high-grade glial neoplasms and were characterized by tufts of vessels with a glomeruloid configuration or by long cords of vessels. Immunohistochemical evaluation documented the presence of endothelial cells, perithelial cells, and basement membrane components within the foci of proliferating vessels. We propose that these vascular proliferations represent a characteristic feature of the neuroendocrine/neural neoplastic phenotype and that they possibly arise as the result of angiogenic factors produced by the neoplastic cells. The presence of these distinctive vascular lesions in the stroma of a poorly differentiated neoplasm should alert the pathologist to the possibility of the neoplasm being of a neural or neuroendocrine nature.

Esthesioneuroblastoma, Olfactory↗
PubMed2004

Lip cancer experience in Mexico. An 11-year retrospective study.

Lip cancer is the most frequent malignant neoplasm of the oral cavity; however, there is no information available on the incidence of this type of cancer in Mexico. This study provides information about the clinico-pathological features of lip cancer patients admitted at a cancer hospital in Mexico City during an 11-year period and describes the treatment modalities performed and their results. A total of 113 patients were studied. There were 74 men (65.5%) and 39 women (34.5%), ranging in age from 14 to 106 years (mean 70 years). In 53 cases (46.9%) an association was found between the disease and chronic sun exposure. Additionally, positive smoking antecedents were recorded in 58 cases (51.3%). As 15 patients were followed for less than 1 month, they were excluded for further analysis. There were 82 cases (83.7%) of squamous cell carcinoma, 10 (10.2%) basal cell carcinomas, and one case (1%) each of adenocarcinoma NOS, melanoma, adenoid cystic carcinoma, Merkel cell carcinoma, lymphoepithelioma and angiosarcoma. We observed an incidence of malignant neoplasms in the upper lip of 33.7%, which is higher than most of the published series and may be due to the fact that in this series we included all histological types of lip cancers. Fifty percent of the cases were found in stages III and IV. Cervical lymph node metastases were found in 21% of patients with no previous treatment, and they developed in 5.3% after treatment. Our data suggest that tumoral size is directly related to the possibility of developing node metastases, as none of them occurred in patients T1, whereas 10 (62.5%) of the patients in T4 presented them. Seven deaths were documented (7.1%), five of which corresponded to squamous cell carcinoma, one to Merkel cell carcinoma, and one to adenocarcinoma. Deaths were directly related to the disease in six cases, and one patient died due to surgical complications. Distant metastases were found in only two patients, one of which coursed with an adenocarcinoma and the other with a Merkel cell carcinoma. Based on the present results, we suggest that the differences encountered with respect to other series, particularly the higher incidence found in women, the frequent presentation of this type of neoplasms in the upper lip, the wide variety of histopathological diagnoses and the high frequency of cases with cervical lymph node affection, should lead us to search for multi-modal treatment alternatives in this population.

Adolescent↗