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PubMed1986

Responsiveness and ultrastructure of slowly adapting type I cutaneous mechanoreceptors in vitamin A deficient rats.

Single-unit recordings were made from afferent nerve fibres supplying slowly adapting type I (s.a. I) cutaneous mechanoreceptors in anaesthetized vitamin A deficient and control rats. Trains of thirty repetitive mechanical stimuli with 0.1 s rise time, 1.9 s plateau phase, and 0.7 s interstimulus interval were applied. A feed-back mechanism maintained the force of stimulation at 20 mN during the plateau phases and the contact force between stimuli at 0.5 mN. All displacement values in the group of vitamin A deficient rats were significantly larger than the corresponding control values. Residual indentations were increased by 70-100% while maximal indentations were only about 40% higher. These results indicate a non-linear increase in compliance of the skin and underlying tissues. S.a. I receptors were found to be significantly less responsive in vitamin A deficient animals. Mean numbers of impulses were about 25% lower in the vitamin A deficient group than in controls throughout the entire train of thirty stimuli. In vitamin A deficient rats, Merkel cells and adjoining nerve terminals showed signs of degeneration of a variety of cell organelles, particularly the mitochondria. Degenerative changes induced by vitamin A deficiency especially in the Merkel cells appeared to be a major cause of the reduction of responsiveness in s.a. I receptors.

Animals↗
PubMed1987

Synaptophysin and neurofilament proteins as markers for neuroendocrine tumors.

Synaptophysin, a membrane glycoprotein of presynaptic vesicles, and neurofilament (NF) proteins were tested as immunohistochemical markers for neuroendocrine tumors. Synaptophysin was consistently present in the tumor cells of pheochromocytomas (10/10), thyroid medullary carcinomas (8/8), and pancreatic islet cell tumors (6/6). Most gastrointestinal and thoracic carcinoid tumors (12/13) were positive, as were neuroendocrine carcinomas (7/9), of which two Merkel cell carcinomas were negative. The NF proteins were present in all pheochromocytomas, in three thoracic and one gastric carcinoid tumors, in four of eight thyroid medullary carcinomas, and in five of six pancreatic islet cell tumors. All intestinal carcinoids were negative for NF proteins, as were neuroendocrine carcinomas, except for two Merkel cell carcinomas that were positive. The 68-kilodalton (kd) NF subunit protein was the most prevalent in all NF-positive neuroendocrine tumors, and the 160-kd subunit was relatively often present, although in a smaller number of cells. The 200-kd NF subunit protein was regularly found in pheochromocytomas and only occasionally found in other neuroendocrine tumors. A series of nonneuroendocrine tumors, such as adenocarcinomas, sarcomas, lymphomas, and melanomas, were negative for both synaptophysin and NF proteins. Thus, synaptophysin is a specific and fairly sensitive marker for neuroendocrine tumors of both low and high grades of malignancy. The NF proteins are good markers for pheochromocytoma, and their presence is of basic tumor biologic interest and of potential diagnostic value in other neuroendocrine neoplasms.

Adenoma, Islet Cell↗
PubMed1977

[Woringer-Kolopp syndrome. Histological and ultrastructural study of a case].

The authors report a case of Woringer-Kolopp syndrome. This was a rare form with multiple cutaneous features with a typical clinical and histological appearance. Ultrastructural study revealed the presence of granules with an opaque centre in the cytoplasm of the abnormal cells, and the close relationship of the latter with neurites. On the basis of these characteristics, they may be likened to the Merkel cells of the epidermis. Thus Woringer-Kolopp disease could be related to the proliferation of Merkel cells.

Humans↗
PubMed2004

Expression of insulin-like growth factor-I receptor in primary cutaneous carcinomas.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is the principal mediator of growth hormone, exerting its effects through binding of the insulin-like growth factor-I receptor (IGF-IR). Post-receptor activation leads to the production of transcription factors involved in cell proliferation, differentiation, transformation, and survival. Data indicate that IGF-IR is involved in tumorigenesis. To our knowledge, this receptor has not been previously studied in primary cutaneous carcinomas. METHODS: Twenty-five cases of primary cutaneous carcinomas consisting of three keratoacanthoma-type squamous cell carcinomas (KAs), two squamous cell carcinomas in situ (SCCs in situ), eight squamous cell carcinomas (SCCs), three conventional basal cell carcinomas (BCCs), two morpheaform basal cell carcinomas (M-BCCs), and seven Merkel cell carcinomas (MCCs) were analyzed for IGF-IR immunohistochemical expression using IGF-IR mouse monoclonal antibody (dilution 1 : 50) using the avidin-biotin-peroxidase complex method. RESULTS: Normal epidermis was negative for IGF-IR expression. Normal eccrine glands and outer root sheath strongly expressed IGF-IR. All KAs, SCCs in situ, SCCs, and BCCs were negative for IGF-IR expression. Six of seven (86%) of the MCCs stained with IGF-IR strongly, showing cell membrane accentuation and a perinuclear dot-like pattern. CONCLUSION: The data suggest that IGF-IR immunopositivity in MCCs might constitute a diagnostic tool in discriminating between SCCs and BCCs. Although the possible pathogenic significance of the perinuclear dot-like staining pattern observed in these neoplasms is unknown, its pattern is similar to what has been previously described with cytokeratin-20 immunostaining.

Antibodies, Monoclonal↗
PubMed1989

Distribution and fine structure of calcitonin gene-related peptide-like immunoreactive nerve fibers in the rat skin.

Distribution of calcitonin gene-related peptide-like immunoreactive (CGRPI) nerve fibers and their fine structure were examined in the skin of rat foot pads using immunocytochemistry. The CGRPI fibers formed bundles in the dermis and subcutaneous tissue. Two types of single-stranded CGRPI fibers were seen to leave the fiber bundles: one was located along the blood vessels or around the eccrine sweat glands, while the other entered the epidermis directly or through the Meissner's corpuscles in the dermal papillae. CGRPI fibers in the epidermis were distributed widely and were occasionally associated with Merkel cells. Immunoelectron microscopic study revealed that CGRPI fibers located around blood vessels, sweat glands, epidermal keratinocytes and Merkel cells, or in the Meissner's corpuscles did not form typical synaptic contacts with underlying cells, despite being varicose and filled with vesicles resembling synaptic ones. These findings suggested that the CGRP is released non-synaptically from these terminals to influence diffusely the organs surrounding the terminals. These cutaneous fibers seemed to originate from CGRPI neurons (both small type B cells and large type A cells) in the dorsal root ganglia (DRG), because injection of fast blue dye into the cutaneous nerve resulted in labeling of these CGRPI cells in the DRG and excision of the L3-L6 DRG resulted in the non-detection of cutaneous CGRPI fibers in the foot pads. Analysis of the composition of CGRPI fibers found in the rat skin has revealed that these are mostly unmyelinated. C-type fibers with some of them being thin myelinated fibers. This was true even of CGRPI fibers at the proximal end of peripheral neurites of the DRG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Trichogerminoma: a rare cutaneous adnexal tumor with differentiation toward the hair germ epithelium.

In 1992, Sau and colleagues described 14 cases of a rare cutaneous adnexal tumor with differentiation toward the hair germ epithelium. All cases in their study displayed a unique constellation of histological features which allowed the authors to consider the neoplasm to be a distinct entity and to designate it as 'trichogerminoma' (TG). We present a case of an adnexal tumor identical to that described as TG and report the immunophenotypical features of this neoplasm for the first time. A biopsy from a 41-year-old man revealed a well-demarcated epithelial tumor composed of multiple lobules located in the deep dermis without connection to the overlying epidermis and surrounded by a fibrous pseudocapsule. The tumorous lobules were composed of uniform basophilic cells with vesicular nuclei, dispersed chromatin and prominent nucleoli showing no prominent peripheral palisading. Some of the lobules had the appearance of densely packed 'cell balls' with peripheral condensation of the tumor cells. The stroma showed a moderate number of fibroblasts and mast cells. Reticulum staining revealed fine reticulum fibers surrounding the tumor aggregates with accentuation of the 'cell balls'. Immunohistochemically, the tumor cells expressed AE1/AE3, CK5/8, CK5/6, CAM5.2 and stained negatively for CK20, CK7, calretinin, Lu-5 and Thomsen- Friedensreich antigen. There was no increase in the numbers of CK20-positive Merkel cells in the epidermis overlying the tumor; however, a few Merkel cells were scattered in some tumor lobules. In addition, we stained 6 trichoblastomas (TBs) and found a particular pattern of calretinin expression in this tumor which was not observed in our case of TG. We conclude that pathological features allow the delineation of TG as a distinct adnexal neoplasm. Histological differential diagnosis includes basal-cell carcinoma (pilar type), large nodular TB, trichoblastic fibroma, trichoepithelioma, tricholemmoma, pilomatricoma and matrical carcinoma.

Adult↗
PubMed1983

[Cutaneous neuroendocrine carcinoma : apropos of a case].

A case of neuroendocrine carcinoma (Merkel cell tumor) of the skin in a 76 years old woman is reported. The lesion, an erythematous nodule, 2 to 3 cm in diameter occurred on the face. Light microscopic examination showed sheets of indifferentiated cells that had a uniform round nucleus and scanty cytoplasm containing argyrophil granules. An ultrastructural study demonstrated neurosecretory type granules in the cytoplasm of the tumor cells. Immunocytochemical analysis was strongly positive for neuron specific enolase, but negative for Met-Enkephalin. This case is discussed in the light of a review of 73 cases already published in the literature. The origin of the cells involved in this tumor is still discussed. Several authors have suggested that this tumor is an Apudoma possibly arising from Merkel cells. In most cases, the lesion is an erythematous nodule. The most common localization is the face (45 p. 100). The tumor can be diagnosed by routine histology, but silver staining and electron microscopic study are often helpful. Removal of the tumor should be performed. This tumor appears to be of a low grade malignancy. Local recurrences or metastases have been reported in a few cases.

Adenocarcinoma↗
PubMed1994

Focal gaps in the basement membrane of involved and uninvolved skin of vitiligo: are they normal?

It has been suggested that, in vitiligo, the structural abnormalities may not be restricted to melanocytes alone, but also to keratinocytes of involved and uninvolved skin. Focal gaps in the vitiligo epidermal basement membrane have been furthermore interpreted as evidence of extramelanocyte alterations. To understand the occurrence of the gaps we undertook a study to establish which cells are related to them. Immunofluorescence and immunoperoxidase techniques were used to visualize, in involved, uninvolved, and control skin, the basement membrane, melanocytes, and Merkel cells. Double staining was performed with fluorescein-coupled anti-collagen IV antibodies and rhodamin-coupled antibodies against Nicein (GB3), a hemidesmosome component. Propidium iodide staining was used to detect infiltrating lymphocytes. The basement membrane structure was always found to be intact and unaltered. Absence of staining in areas of uninvolved skin was related to the presence of Merkel cells, melanocytes, and infiltrating lymphocytes. Gaps in the epidermal basement membrane are thus due to lack of staining caused by the presence of immigrant cells.

Adolescent↗
PubMed1986

The early embryogenesis of papillary (sweat duct) ridges in primate glabrous skin: the dermatotopic map of cutaneous mechanoreceptors and dermatoglyphics.

The present study documents the early innervation of the epidermis prior to the onset of differentiation of the papillary (sweat duct) ridge in glabrous digital skin of rhesus monkey embryos measuring 45, 50 and 55 mm (crown-rump) length. We observed small papillary ridges, spaced at a distance of approximately 40 microns, projecting into the dermis in the center of the distal glabrous digital pad of digits 2-5 in the 55-mm embryo. The other digital pads lacked any sign of ridge formation. A two-dimensional, approximately hexagonal grid of afferent nerves was present in the superficial dermis of all digital and palmar pads. At regular intervals of approximately 40 microns, afferent nerves ascended from the superficial dermal nerve plexus and innervated the overlying epidermis. By electron microscopy, axonal growth cones were identified contacting Merkel cells that projected several microns down into the superficial dermis in the digital pad of digit 3. Thus, the earliest wave of differentiated dorsal root ganglion neuroblasts innervates Merkel cells. Schwann cells partially encircled these growing axon tips and could be identified by the presence of rough endoplasmic reticulum and free ribosomes. The youngest embryo studied had no sign of ridge formation; however, axons ascended from the superficial dermal nerve net at 30-40-microns intervals to innervate the epidermis. We conclude that afferent nerve fibers provide a two-dimensional grid that could modulate the spacing and arrangement of the papillary or sweat duct ridges of successive digits. Such an interaction is possible between digits based on the overlapping dermatotopic maps of each rete ridge. An abnormal fingerprint could thus reflect abnormal dorsal root ganglion neuroblasts expressed through mesenchyme and epidermis.

Afferent Pathways↗
PubMed1988

Merkel tumor of the lower lip: a case report and updated review of the literature work performed at the University of Illinois.

An unusual case of Merkel cell carcinoma of the lower lip with metastasis to the submental nodes is presented. Clinical similarities and the histopathologic and prognostic differences between this tumor and basal or squamous cell carcinomas of the head and neck area are discussed and the current thoughts for treatment are presented. The capricious clinical course and the aggressive nature of the Merkel cell tumor is emphasized. A review of the existing literature is also included in an effort to familiarize the head and neck surgeon with this relatively new but potentially lethal pathological cutaneous entity.

Carcinoma↗
PubMed1993

Sensory nerve endings in the beak skin of Japanese quail.

This study is concerned with the distribution and ultrastructure of sensory nerve endings in the beak skin of adult Japanese quail (Coturnix coturnix japonica). The following nerve endings were found: free nerve endings, clusters of dermal Merkel nerve endings, Herbst corpuscles and Ruffini corpuscles. The latter were found only in the dermis of the tip of the upper beak. The remaining endings were present in the skin of all areas of upper and lower beak. Free nerve endings were supplied by either thin myelinated axons or unmyelinated C-fibers and were localized in the dermis close to the basal layer of the epidermis. Merkel cells formed clusters (up to 50) localized below and between the epidermal cones of the beak skin. Disc-shaped thickenings of nerve endings were squeezed between individual Merkel cells. Small Herbst corpuscles were found in the dermis close to the epidermal cones of the beak skin. Large Herbst corpuscles occurred in deep layers of the dermis. The Ruffini corpuscles were cylindrical in shape (80 microns x 400 microns) and arranged in groups of up to ten corpuscles. Each corpuscle was surrounded by an incomplete fibrous capsule.

Animals↗
PubMed1983

Effects of chronic denervation in type I cutaneous mechanoreceptors (Haarscheiben).

Cutaneous type I receptor sites (Haarscheiben or tactile domes) were examined at intervals of 4 to 275 days after chronic denervation of the skin. The number of domes decreased with denervation time, and only about one-third of the domes originally present were still visible at 275 days. Most but not all of the Merkel cells from these domes were absent by 48 days, and the epithelium was significantly thinner than in nondenervated domes. Only a few of the examined domes appeared to be completely devoid of Merkel cells. It is concluded that after nerve transection, domes degenerate but do not always disappear entirely. The remnants may thus act as target sites which either attract regenerating type I nerve fibers or facilitate the formation of new dome structures after nerve regeneration.

Animals↗
PubMed2000

Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases.

Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight cytokeratins. Their anatomic distribution is generally restricted to epithelia and their neoplasms. We surveyed 435 epithelial neoplasms from various organ systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies. Expression of CK 7 was seen in the majority of cases of carcinoma, with the exception of those carcinomas arising from the colon, prostate, kidney, and thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma of various origins were negative for CK 7, except cervical squamous cell carcinoma, in which 87% of cases were positive. Approximately two thirds of cases of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20-positive staining was also observed in cases of pancreatic carcinomas (62%), gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor, prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.

Biomarkers, Tumor↗
PubMed1996

[Structure and functions of the cutaneous nervous system].

Cutaneous nerves are either somatic sensory afferents to ganglion neurons or terminal efferents from the autonomous nervous system. Myelinated somatic nerves form subcutaneous and intradermal plexus from which arise various types of endings: free, dilated and included in corpuscles. Free terminals are ramified in the dermis, epidermis and the epithelial sheet of hairs. Dilated terminals are lanceolate fibres around hairs and those in close contact with Merkel cells. Well identified corpuscles are those of Meissner, Ruffini and Pacini. Physiologically, nerves are involved as mechano-, thermo- and pain receptors. Five mechanoreceptors are recognized according to their rate (slow/fast) of adaptation and their receptive field (type I, small; type II, large): Merkel cells (SA I), Ruffini corpuscles (SA II), Meissner corpuscles (FA I), Pacini corpuscles (FA II) and palisades of lanceolate nerve endings (FA with various field units). Thermo- and nociceptors are mainly thin unmyelinated free nerve endings with various rates of conduction velocity. The autonomic nervous system supplies sympathetic innervation appearing as unmyelinated small nerve endings in close contact with skin appendages, except sebaceous glands. Only sweat glands are innervated by cholinergic terminals.

Autonomic Nervous System↗
PubMed2003

Math1-driven GFP expression in the developing nervous system of transgenic mice.

Math1 is a bHLH transcription factor expressed in neural progenitor cells in multiple regions of the nervous system. Previously we identified a Math1 enhancer that directs expression of reporter genes in a Math1 specific pattern [Development 127 (2000) 1185]. We have used a portion of this enhancer to drive expression of a nuclear GFP reporter in the Math1 lineage in transgenic mice. In this transgenic mouse strain, GFP is expressed in Math1 domains in the (1). developing spinal cord in progenitors to dI1 dorsal interneurons, (2). granule-cell progenitors in the developing cerebellum, (3). Merkel cells in the skin, and (4). hair cells in the developing vestibular and auditory systems. Furthermore, non-Math1 related expression is detected that is likely due to the absence of inhibitory regulatory sequences from the transgene. These expression domains include (1). the apical ectodermal ridge in developing limbs, (2). post-mitotic cells in the developing cortex and spinal cord, (3). the dentate gyrus, (4). retina, and (5). olfactory epithelium. Because GFP marks specific neuronal cell types in living tissue, this transgenic strain is a powerful tool for future studies on the development and electrophysiological properties of distinct cell types in the central nervous system and in sensory systems.

Animals↗
PubMedDate not supplied

Sentinel lymphonodectomy in non-melanoma skin cancers.

There are various types of non-melanoma skin cancers with an increased risk of local recurrence and metastasis. Metastases from non-melanoma skin cancer most frequently spread to the regional nodal basins, and the presence of nodal involvement carries a poor prognosis. Determination of nodal status is essential for the prognosis and management of these patients. Whereas extensive literature has shown the major role of sentinel lymphonodectomy in the management of malignant melanoma, experience with this procedure in non-melanoma skin cancers is fairly limited. We report on 10 selected patients with high-risk non-melanoma skin cancer, managed with sentinel lymphonodectomy. A metastatic sentinel lymph-node was found in 1 patient with recurrent cutaneous squamous cell carcinoma and in 1 patient with Merkel cell carcinoma. No false-negative results were observed. Previous reported data and our experience provide evidence that sentinel lymphonodectomy is a feasible and minimally invasive staging procedure also in patients with high-risk non-melanoma skin cancer. In particular, the technique is capable of selecting patients with nodal micrometastases, who can be submitted to completion lymphadenectomy, avoiding the morbidity of elective lymphadenectomy in patients with negative sentinel lymph-nodes.

Aged↗
PubMed1992

The differentiation of the skin and its appendages. II. Altered development of papillary ridges following neuralectomy.

In order to test the hypothesis that the nervous system is an important determinant of skin differentiation, deletions of the left lumbosacral dorsal root ganglia (DRGs), the sources of cutaneous afferents to the left hindpaw, were performed on opossum pups at day 1 when hindpaws have just begun to be innervated. At birth, each lumbosacral DRG measures about 200 microns rostrocaudally and a deletion measuring 1 mm would span 4-5 DRGs. Following survival periods of 5-24 days, serial sections through the trunk documented partial left lumbosacral DRG deletion and a variable degree of spinal cord destruction. The blood supply to the trunk and hindpaws was preserved. Bilateral enlargement of residual DRGs was observed and regenerating skin at the site of the deletion was hyperplastic and hyperinnervated. The skin of the plantar pads of the hindpaws was studied following the neuralectomies. Statistically significant differences were observed between the left (experimental) and right (control) hindpaws. The density of innervation of the left hindpaw was reduced compared to the right hindpaw, development of papillary ridges was retarded by 3-4 days, and non-innervated Merkel cells were hypogranulated. This period of delay in ridge development is probably a reflection of the expansion of residual DRGs into the peripheral domains of deleted DRGs. The present study confirms a role for afferent nerves in the timing of cutaneous differentiation and a mutual trophic dependence between cutaneous nerves and Merkel cells in the epidermis.

Animals↗
PubMed1993

Merkel-like basal cells in Necturus taste buds contain serotonin.

Several types of cells have been identified in vertebrate taste buds, including dark cells, light cells, intermediate cells, type III cells, and basal cells. The physiological roles of these cell types are not well understood, especially those of basal cells. In this paper we show that there are two types of basal cells in taste buds from Necturus maculosus. One type of basal cell is an undifferentiated cell, presumably a stem cell. By combining light microscopic immunocytochemistry with electron microscopy, we show that the other type of basal cell is positive for serotonin-like immunoreactivity and that these cells have ultrastructural features similar to those found in cutaneous Merkel cells. Based on these findings, and the fact that the Merkel-like taste cells have been shown to make synaptic contacts with adjacent taste cells and with innervating nerve fibers, we conclude that these Merkel-like basal taste cells are serotonergic interneurons.

Animals↗