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PubMed1986

The neuroanatomical basis for the protopathic sensibility of the human glans penis.

The human glans penis is covered by stratified squamous epithelium and a dense layer of connective tissue equivalent to the dermis of typical skin. Rete ridges of the epidermis are irregular and vary in height depending on location, age, and presence or absence of a foreskin. The papillary layer of the dermis blends into and is continuous with the dense connective tissue forming the tunica albuginea of the corpus spongiosum of the glans penis. The most numerous nerve terminals are free nerve endings (FNEs) present in almost every dermal papilla, as well as scattered throughout the deeper dermis. FNEs are characterized by an incomplete Schwann cell investment, and contain irregularly scattered neurofilaments and neurotubules, clusters of mitochondria, vesicles of variable size and various inclusions. The ratio of FNEs to corpuscular receptors is approximately 10:1 and a similar ratio of small to large axons is seen in dermal nerves. Genital end bulbs are present throughout the glans, but are most numerous in the corona and near the frenulum. The unique corpuscular receptor of the glans penis consists of axon terminals that at an ultrastructural level resemble a tangled skein of FNEs. Simple, Pacinian and Ruffini corpuscles were occasionally identified predominantly in the corona glandis. Epidermal Merkel nerve endings and other types of mechanoreceptors typically found in primate glabrous skin (lip or digit) are not present. Rarely, dermal Merkel cells have been identified associated with genital end bulbs. The abundance of FNEs in isolated as well as corpuscular form can be correlated with the embryogenesis and known neurophysiologic and psychophysical parameters of sensory function of the glans penis. Finally, the divergence in reported values for the threshold of tactile and painful stimuli when applied to glabrous skin of fingertip and glans penis can be considered as an example of dissociated sensibility. The anatomical basis for this dissociation is the abundance of FNEs and absence of Merkel terminals and typical Meissner corpuscles in the covering of the glans, and the converse in glabrous skin of the digit.

Adolescent↗
PubMed1994

Immunohistochemical studies of neurochemical markers in normal human buccal mucosa.

The content of various substances, such as regulatory peptides, hormones and structural proteins, was investigated in normal buccal mucosa using indirect immunofluorescence. Thin nerve fibres, which from a morphological point of view were most probably sensory, showed immunoreactivity for substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide K (NPK) and neurokinin A (NKA). Also galanin (GAL), gamma-melanocyte stimulating hormone (gamma-MSH) and somatostatin (SOM) stained thin fibres were found in the propria, which were, however, few in number and the gamma-MSH staining was weak. CGRP, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI) and neuropeptide Y (NPY) immunoreactive nerve fibres were observed in close connection to blood vessels. SOM positive cells with processes were found, mostly scattered, in the connective tissue. A population of cells within the epithelium also showed somatostatin immunoreactivity. Protein S-100 (S-100) stained distinct populations of cells at two separate locations. In the propria, cells with one or two slender processes were seen, being mostly single but sometimes forming groups. In the epithelium, dendritic cells with many processes with or without 'spines' were observed, mainly located to the basal layer of the lamina epithelialis. Single nerve fibres and nerve bundles were also stained. Neurofilament (NF) positive fibres, singly and in bundles, as well as endorgan-like structures were seen. Neuron-specific enolase (NSE) and protein gene product 9.5 (PGP 9.5) both stained the same structures, namely single fibres, nerve bundles, nerves surrounding vessels and innervating muscles and glands (if present in the section), as well as Merkel cells. Also with these two markers endorgan-like structures were seen. No clear innervation of the epithelium could be observed with the markers used. No methionine-enkephalin (ENK) or synaptophysin (SYN) immunoreactive material was found.

Adolescent↗
PubMed2026

HMGB1 as a convergent host factor in virus-induced carcinogenesis.

High-mobility group box 1 (HMGB1) is a chromatin-associated protein and a prototypical damage-associated molecular pattern whose dual intracellular and extracellular functions are increasingly implicated in cancer progression. Because viral proteins can harness HMGB1 to facilitate their own replication and remodel the microenvironment of transformed cells, human oncogenic viruses provide an instructive model for examining this duality. In this conceptual review, we organized the available evidence around two functional nodes. At the first node, intracellular HMGB1 supports viral replication, acting on viral chromatin in Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus, and on structured viral RNA in hepatitis C virus. At the second node, viral infection or specific viral oncoproteins induce HMGB1 secretion, which promotes infected-cell survival and remodels the tumor microenvironment, as reported for KSHV, hepatitis B virus, and human T-cell leukemia virus type 1. Human papillomavirus engage a receptor-level variant of this node through the HMGB1-TLR4 axis. Only KSHV currently supports both nodes in matched experimental systems. Therefore, we present a sequential two-node arrangement as a hypothesis, instead of an established property of oncogenic viruses. We further considered how viruses reverse the tumor-suppressive, genome-stabilizing functions of nuclear HMGB1, with conserved and divergent strategies apparent across viral families; why the absence of HMGB1 data for Merkel cell polyomavirus is a tractable and informative gap; and which HMGB1- and RAGE-directed agents are realistically positioned for evaluation in virus-associated cancers.

Damage-associated molecular pattern↗
PubMedDate not supplied

Mechanisms of metastasis.

Metastasis is the process by which a primary malignancy establishes distant and discontiguous disease. It is a dreaded and ominous event that usually portends a worse prognosis, with greater tissue destruction, organ dysfunction, and potential mortality. Fortunately, metastasis is a rare event for nonmelanoma skin cancers (NMSC). Basal cell carcinomas (BCC) comprise the vast majority of NMSC (60-80%) and have a metastasis rate of only 0.0028%. For squamous cell carcinomas (SCC), the rate of metastasis is 2-6% and rises with certain high-risk features. Malignant melanoma (MM) is perhaps the most feared among common skin malignancies. It has a marked propensity for metastasis, and deaths from MM far outnumber the combined mortalities of both BCC and SCC. The 5-year survival of localized stage IA melanoma is 95%. This decreases to 67% for nodal disease and less than 20% for distant metastasis. Even more aggressive than MM are rare cutaneous tumors, such as Merkel cell carcinoma and malignant fibrous histiocytoma. This chapter will discuss the mechanisms of metastasis as they apply to cutaneous malignancies, particularly melanoma.

Cell Adhesion Molecules↗
PubMed1985

Malignant lymphomas of the skin: their differentiation from lymphoid and nonlymphoid cutaneous infiltrates that simulate lymphoma.

Malignant lymphomas of the skin, excluding mycosis fungoides, are pathologically, immunologically, and clinically heterogeneous. Varying patterns and degrees of cutaneous infiltration are encountered in all histologic subtypes of non-Hodgkin's lymphomas. Immunologic studies have shown relatively equal numbers of cases with B and T cell phenotypes, but true histiocytic lymphomas of the skin also occur. Patients may be of any age, and they may have lymphoma in any clinical stage. A low clinical stage and a low-grade histologic subtype are significant factors for long survival. The differential diagnosis includes a variety of lymphoid infiltrates that are referred to as a group as cutaneous lymphoid hyperplasia; it also includes lymphomatoid papulosis as well as nonlymphoid cutaneous infiltrates such as myeloid leukemias, histiocytosis X, malignant histiocytosis, regressing atypical histiocytosis, and neuroendocrine (Merkel) cell carcinoma. Distinction of cutaneous lymphomas from these entities requires comprehension of multiple variables, including immunologic as well as morphologic and clinical factors.

B-Lymphocytes↗
PubMed1997

Extrapulmonary small cell carcinoma.

BACKGROUND: Extrapulmonary small cell carcinoma (EPSCCA) is often an underrecognized clinicopathologic entity, distinct from small cell lung carcinoma. The purpose of this study was to review the study institution's experience with EPSCCA with specific emphasis on the epidemiology and response to treatment of these uncommon neoplasms. METHODS: Using the tumor registry database of the study institution, the authors retrieved and reviewed the records of all patients with EPSCCA treated between 1974 and 1994. Study eligibility required that the patients had a normal chest radiograph, computed tomography scan of the chest, sputum cytology, and/or negative bronchoscopy. Patients with well differentiated neuroendocrine carcinomas and Merkel cell carcinomas of the skin were excluded. RESULTS: Primary sites of EPSCCA in the current series were: gastrointestinal system in 29 patients, ear, nose, and throat in 14, genitourinary system in 12, internal genitalia in 10, upper respiratory system in 5, unknown primary-lymph nodes in 5, unknown primary-other in 2, the thymus in 3, and the peritoneum in 1. After the initial evaluation and confirmation of histologic diagnosis, 10 of 81 patients had been lost to follow-up. Of the remaining 71 patients, 54 had limited disease. Forty of the 54 patients underwent surgical treatment of their malignancy; 10 patients (25%) remained alive and disease free at least 3 years after surgery, whereas 30 patients (75%) relapsed with a median disease free survival of 6 months. Six patients of 54 with limited disease were treated with chemotherapy and radiation. Five of these 6 (83%) relapsed at a median time of 11.5 months. Another 8 of the total of 54 patients received only radiation therapy and all had disease recurrence at a median time of 5 months. In the group of patients with extensive or recurrent disease, platinum-based chemotherapy was employed in 22 patients. There was a 72% response rate with a median duration of 8.5 months. Seven patients had doxorubicin-based chemotherapy. There was a 57% response rate with a median duration of 4.5 months. In the current study group of patients, the 3-year disease free and overall survival rates were 26% and 38%, respectively, whereas the 5-year disease free and overall survival rates were each 13%. CONCLUSIONS: EPSCCA is usually a fatal disease, with a 13% 5-year survival rate. In a small percentage of patients, surgery can be curative if the tumor is small and confined to the organ of origin. Because of the poor overall outcome, one needs to consider the possible use of adjuvant chemotherapy in appropriate circumstances if surgery is to be employed. In most patients with limited disease, the combination of chemotherapy and radiation as the primary treatment can be as effective as surgery. EPSCCA is responsive to commonly employed regimens for small cell lung carcinoma; however, the responses are short-lived. The extent of disease at diagnosis represents the most sensitive predictor of survival.

Adult↗
PubMed1985

Cytoskeletal differences between human neuroendocrine tumors: a cytoskeletal protein of molecular weight 46,000 distinguishes cutaneous from pulmonary neuroendocrine neoplasms.

The cytoskeletons of various human neuroendocrine (NE) tumors were analyzed immunohistochemically using antibodies against intermediate-filament (IF) proteins as well as by two-dimensional gel electrophoresis of proteins from microdissected tissue samples. All of the tumors studied were found to contain cytokeratin filaments and are therefore referred to as 'NE tumors of the epithelial type'. In addition, neurofilaments were found in most cutaneous and some pulmonary NE tumors, as well as in medullary carcinomas of the thyroid and in pancreatic islet cell tumors. The neurofilament staining was frequently concentrated in cytoplasmic IF aggregates. Gel-electrophoretic analyses showed that all NE tumors examined synthesize 'simple epithelium-type' cytokeratin polypeptides, cytokeratins nos. 8 and 18 being the most prominent ones, whereas cytokeratin no. 19 was found in variable and usually minor amounts. A new cytoskeletal protein, designated IT protein, with a relative molecular weight of 46,000 and an isoelectric pH value of approximately 6.1 (in 9.5 M urea) was detected in all 9 cases of cutaneous NE tumors ('Merkel-cell carcinomas'), including 2 lymph-node metastases, but was not found in any of the 17 cases of pulmonary NE tumors. In addition, 2 medullary carcinomas of the thyroid, 2 islet cell tumors of the pancreas, and 1 intestinal carcinoid tumor also seemed to lack this protein. A protein indistinguishable from IT protein by electrophoresis and tryptic peptide mapping was found in cytoskeletal preparations of mucosal cells of human intestine and in cultured human colon carcinoma cells of line HT-29. A possible relationship between IT protein and the type-I subfamily of cytokeratin polypeptides is discussed. Our study shows that the co-expression of cytokeratin filaments and neurofilaments may provide a criterion which is useful for the recognition of some NE tumors but which does not distinguish between NE tumors of different types and origins. In contrast, IT protein seems to be present specifically in cutaneous NE tumors, but absent in pulmonary NE tumors. The implications of these findings for the elucidation of the histogenesis of cutaneous NE tumors and for the histopathological differential diagnosis of NE tumors of cutaneous and pulmonary origin are discussed.

Carcinoid Tumor↗
PubMed1982

Potentiation of histamine-induced itch and flare responses in human skin by the enkephalin analogue FK-33-824, beta-endorphin and morphine.

The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.

Adolescent↗
PubMed1983

Neuromesenchyme. The concept of a neurocristic effector cell for dermal mesenchyme.

The elusive dermal neurocristic effector cell is identified by its expression of fibrogenic functions in a variety of cutaneous neurocristic dysplasias and neoplasms. It is a normal resident of the dermis that disguises its embryonic heritage by the acquisition of fibrocytic (or fibrohistiocytic) functions. It shares with other cutaneous neurocristic derivatives the capacity to express variably three basic functions: 1) fibrogenesis, 2) melanogenesis, or 3) neurosustentation in the manner of the supportive cells of peripheral nerves. Its role in developing skin is prominently displayed in congenital nevi. The fibrogenic potentials of its embryonic relatives, the neurosustentacular cells and melanocytes, are expressed in perineurial fibromas and desmoplastic malignant melanomas. In the latter neoplasms, neurosustentacular functions are also often displayed. In the normal skin, the potentials of the cutaneous neurocristic migrants are usually restricted to one of three options. In dysplasias, the controls are derepressed and migrations may offer new, environmental influences that favor expression of latent properties. A dysplastic melanocyte loses the primary epigenic influence of epithelium by migration into the dermis. In the dermis, it encounters peripheral nerves and mesenchyme. In response, it may express its latent fibrogenic or neurosustentacular possibilities. The dermis is neuromesenchyme. The adventitial dermis is a special adaptation of mesenchyme to the metabolic needs of epithelium. Melanocytes and Merkel cells are situated ideally to function as mediators between epithelium and dermis. Pigmented melanocytes that concentrate in the bulbs of growing hairs probably are more important as mediators of epithelial-mesenchymal reactions than as sources of pigment. The reticular dermis and retinacula represent transformation from fetal type III collagen to adult type I collagen. In Mongolian spots, melanocytes are confined to the reticular dermis. They identify neurocristic effector cells that have been diverted from fibrogenic to melanogenic functions. In all likelihood, the transformation in the dermis from type III to type I collagen is induced by neurocristic migrants that have lost their identity in the population of fibrocytic cells.

Histiocytes↗
PubMed1995

Neuroendocrine tumours in various organ systems in a ten-year period.

Neuroendocrine cells are present in various organ systems. These widely distributed cells as well as their histogenetically related tumours can produce various peptides and peptide hormones. From 1984 to 1993, 349 neuroendocrine tumours were found among 511,382 histological diagnoses at the Institute of Pathology of the Medical School of the Karl Franzens University in Graz. In 30% carcinoid of the appendix was diagnosed, in 16% carcinoid of the colorectum, in 9% carcinoid of the small intestine and in 2% duodenal carcinoid. Carcinoid of the stomach was detected in 14%. Seven of these cases showed microcarcinoidosis and five of them were combined with an adenocarcinoma. Carcinoid of the oesophagus was present in 1%, neuroendocrine pancreatic tumours in 6%. Neuroendocrine tumours of the bronchial system were found in 12%, medullary thyroid cancer in 5%. In 1% a Merkel-cell tumour was diagnosed. Other more rare localizations of neuroendocrine tumours were the uterus, ovary, breast, testes, epididymis, anal region and the upper respiratory tract.

Adult↗
PubMed1988

Lymphoepithelioma-like carcinoma of the skin.

Carcinomas histologically resembling nasopharyngeal lymphoepithelioma have been identified in the salivary gland, thymus, tonsil, and uterine cervix. Five patients with similar tumors primary in the skin are described. The patients ranged in age from 50 to 81 yr. Four neoplasms were situated on the head, and one was located on the shoulder. Microscopically, they were concentrated in the mid- and deep dermis and lacked connections with epidermis. The pattern was of multiple nodules, smaller irregular islands, and cords. The uniform tumor cells had moderate amounts of lightly eosinophilic cytoplasm and vesicular nuclei with one or two prominent nucleoli. A lymphoid infiltrate was intimately associated with each neoplasm and obscured the malignant epithelium in one. Neither squamous nor glandular differentiation was present, but all tumors exhibited intracytoplasmic mucin. Immunohistochemistry was positive for cytokeratin (5 of 5; diffuse) and epithelial membrane antigen (4 of 5; 3 diffuse, 1 focal). Focal reactivity was also noted for carcinoembryonic antigen (1 of 5), neuron-specific enolase (1 of 5), and vimentin (1 of 5). S100 protein, leukocyte common antigen, Factor VIII-related antigen, prostate-specific antigen (males), Leu M1, and salivary amylase reactivity were absent. One patient developed local recurrence and metastases after 39 mo and was dead of disease at 57 mo. The remaining four were free of disease after 46, 27, 25, and 6 mo of follow-up. The diagnosis of lymphoepithelioma-like carcinoma of the skin is based on microscopic findings and exclusion of occult malignancy. The tumor can be confused with a lymphoid infiltrate and is differentiated from Merkel cell carcinoma primarily on cytologic grounds. The neoplasm may be of adnexal origin.

Aged↗
PubMed2005

Clinical applications of sentinel lymph-node biopsy for the staging and treatment of solid neoplasms.

A review of the clinical applications of sentinel lymph node (sN) biopsy has been performed with the aim of defining the rationale, the methods of detection, the accuracy, and the current indications to sN biopsy in different solid neoplasms. In melanoma patients, sN biopsy represents a standard procedure for staging purpose, although its therapeutic value is still under examination. The sN is an accurate method for the pathologic staging of the axilla in patients with early stage breast cancer, and it can be useful for the selection of patients with axillary metastasis who should undergo standard axillary dissection. In gynecologic malignancies, appreciable results are available in patients with vulvar and cervical cancer only. Patients with squamous cell vulvar cancer may benefit by sN biopsy because a complete bilateral inguino-femoral lymph-node dissection may be avoided whenever the sN is free of metastasis. As regards to cervical cancer, further studies are required with the combined technique (blue dye injection and gamma-probe guided surgery), which seems more promising, before abandoning pelvic lymphadenectomy in patients with histologically-negative sN. The experience in urologic cancer deals mainly with penile and prostate cancer; the modern procedures for the dynamic detection of sN are going to clarify its role in the surgical management of penile cancer; as regards to prostate cancer, very preliminary results suggest that the sN biopsy may enhance the pathologic staging of this neoplasm compared to modified pelvic lymphadenectomy, due to the individual variability of the lymphatic drainage of this cancer. In patients with clinically node-negative squamous head and neck cancer, the reliability of sN-guided neck lymph node dissection seems promising. The sN biopsy is also technically feasible in patients with differentiated thyroid cancer; however, the future role of this procedure in the clinical decision-making of these patients remains to be defined due to the questionable biological meaning of nodal metastases. Patients with non-small-cell lung cancer should be investigated by means of radiotracers injected at the time of thoracotomy or under CT-scan guidance in order to achieve a satisfactory identification rate (over 80%); the focused histopathologic staging of the sN improves current pathologic staging by conventional bi-valve assessment of all the lymph nodes of the surgical specimen; moreover, the prognostic role of isolated N2 metastasis can be better elucidated. In patients with gastrointestinal malignancies, the intraoperative lymphatic mapping with sN biopsy have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent. In patients with gastric cancer, current data show that it can be detected by means of peritumoral injection of indocyanine green; the detection of tumor positive lymph nodes beyond the perigastric area could select patients amenable to D2 lymphadenectomy. As regards to colorectal cancer patients, the focused analysis of the sN may reveal disease that might otherwise go undetected by conventional surgical and pathological methods, and those patients which are upstaged can benefit by adjuvant chemotherapy. Finally, in patients with Merkel cell carcinoma, notwithstanding the limited experiences with sN biopsy, sN histology seems to predict regional lymph node status and may aid in selecting which patients are amenable to therapeutic lymph node dissection.

Breast Neoplasms↗
PubMed1980

Sensory nerve endings in rhesus monkey sinus hairs.

The sensory innervation of primate sinus hairs has been studied by light and electron microscopy. For light microscopy paraffin sections as well as thick frozen sections were impregnated with silver and compared with serial semi-thin sections of tissue prepared for electron microscopy. One type of sensory terminal is present in the epidermis surrounding the hair follicle, and four specific nerve terminals have been identified within the blood sinus. An epidermal rete ridge collar encircles the hair shaft and contains approximately 200 Merkel cell-neurite complexes. Numerous other Merkel cell-neurite complexes are present in the external root sheath of the hair follicle beneath a thick glassy membrane innervated by approximately 65 nerve fibers. At this level 10-15 lanceolate or palisade terminals are situated in the connective tissue. Up to 10 simple encapsulated corpuscles can be identified above the level of lanceolate endings and Merkel cell terminals. Ruffini corpuscles are closely applied to the glassy membrane below the lanceolate and Merkel terminals at the level where nerve fibers penetrate the capsule of the sinus. All of these terminals are supplied by 80-100 large diameter myelinated fibers distributed approximately as follows: 65 innervate Merkel cell-neurite complexes, 15 to lanceolate, 10 to simple corpuscles, and 10 to Ruffini corpuscles. The innervation of the rete ridge collar is independent of that of the sinus consisting of 10-12 fibers derived from the superficial dermal network. Each of these sensory terminals can be correlated with specific functional parameters as described in numerous neurophysiologic studies. Merkel cell-neurite complexes and Ruffini corpuscles ae slowly adapting receptors; lanceolate terminals and simple corpuscles are rapidly adapting receptors.

Animals↗
PubMed1978

Trabecular carcinoma of the skin: an ultrastructural study.

We report the electron microscopic studies of three trabecular carcinomas of the skin. The presence of neurosecretory granules in all three tumors suggests that trabecular carcinoma originates from one of the neurocrest derivatives, most probably, Merkel cells. The ultrastructural findings confirm Toker's original concept that trabecular carcinomas comprise a distinct group of skin tumor. The recognition of these tumors would enable one to make such a diagnosis on frozen section, which, in turn, might provide an opportunity for more specific cytochemical and immunofluorescent characterization.

Adenocarcinoma↗
PubMed1995

Therapy for paraneoplastic neurologic syndromes in six patients with protein A column immunoadsorption.

BACKGROUND: Paraneoplastic neurologic syndromes, although rare, cause significant morbidity and mortality. They are thought to be immunologically mediated, but to date those involving the central nervous system (CNS) have not been particularly responsive to immunologic therapy. The use of the novel immunomodulator, protein A immunoadsorption, was explored to address this question. METHODS: Six patients with neurologic paraneoplastic syndromes were treated with this technique, using the "off line" method. Two hundred fifty ml of plasma was perfused through a column containing protein A covalently attached to a silica matrix. The plasma was then returned to the patient. RESULTS: Five of the patients responded to the therapy, with complete and durable responses in three patients with opsoclonus-myoclonus, objective, though transient, improvement in one patient with paraneoplastic brainstem encephalitis associated with a Merkel cell tumor, and stabilization and partial improvement in one patient with paraneoplastic limbic encephalitis. The patient without response developed a cutaneous vasculitis after the second treatment, and therapy was discontinued. CONCLUSIONS: This therapy appears beneficial for a number of paraneoplastic syndromes, most dramatically in the opsoclonus/myoclonus syndrome.

Adult↗
PubMed1990

The innervation of human teeth and gingival epithelium as revealed by means of an antiserum for protein gene product 9.5 (PGP 9.5).

The innervation of human teeth and oral mucosa has been studied in the past by different methods, none of which offered a clear description of the precise morphology of nerve fibers and terminals and of nerve organization as a whole. Recently, interesting findings have been obtained by means of immunohistochemical investigations for neurofilaments and S-100 proteins. A new brain-specific molecule, protein gene product 9.5 (PGP 9.5), has been used for the first time in the present research to investigate the distribution of nerves in human oral mucosa and decalcified teeth, about which there is a paucity of information. The data provided in this study, confirming previous work in other species, may be of value for understanding the anatomy of human oral innervation. In the oral mucosa, the antiserum labels nerve fibers, corpuscles, and neuroendocrine (Merkel) cells. In sections of decalcified teeth, numerous PGP 9.5 positive fibers are demonstrated in the pulp and in the inner 100 microns of dentin. The novel nerve tissue protein used, PGP 9.5, thus appears to be a reliable marker for studies of nerve fibers in human tissues and not to be affected by decalcification procedures. It could then be used for investigations on the innervation of normal and pathological calcified human tissues.

Dentin↗
PubMed1989

Vestibular system of the newborn marsupial cat Dasyurus hallucatus.

The ultrastructure of the ear of the newborn native cat was examined to determine whether the vestibular system contained sensory receptors. A sensory region, presumably the utricle, was identified in each ear and consisted of a discrete population of otoliths overlying a sensory epithelium which possessed kinocilia and stereocilia. The remainder of the vestibular system did not appear to be developed anatomically. The newborn cat has rudimentary vestibular, olfactory, and mechanoreceptors (Merkel cells), and these structures may aid the newborn marsupial in the journey from the urogenital sinus to the pouch and in locating the teat.

Animals↗
PubMed2002

Similarities and differences in the innervation of mystacial vibrissal follicle-sinus complexes in the rat and cat: a confocal microscopic study.

Our confocal three-dimensional analyses revealed substantial differences in the innervation to vibrissal follicle-sinus complexes (FSCs) in the rat and cat. This is the first study using anti-protein gene product 9.5 (PGP9.5) immunolabeling and confocal microscopy on thick sections to examine systematically the terminal arborizations of the various FSC endings and to compare them between two species, the rat and the cat, that have similar-appearing FSCs but different exploratory behaviors, such as existence or absence of whisking. At least eight distinct endings were clearly discriminated three dimensionally in this study: 1) Merkel endings at the rete ridge collar, 2) circumferentially oriented lanceolate endings, 3) Merkel endings at the level of the ring sinus, 4) longitudinally oriented lanceolate endings, 5) club-like ringwulst endings, 6) reticular endings, 7) spiny endings, and 8) encapsulated endings. Of particular contrast, each nerve fiber that innervates Merkel cells at the level of the ring sinus in the rat usually terminates as a single, relatively small cluster of endings, whereas in the cat they terminate en passant as several large clusters of endings. Also, individual arbors of reticular endings in the rat ramify parallel to the vibrissae and distribute over wide, overlapping territories, whereas those in the cat ramify perpendicular and terminate in tightly circumscribed territories. Otherwise, the inner conical body of rat FSCs contains en passant, circumferentially oriented lanceolate endings that are lacking in the cat, whereas the cavernous sinus of the cat has en passant corpuscular endings that are lacking in the rat. Surprisingly, the one type of innervation that is the most similar in both species is a major set of simple, club-like endings, located at the attachment of the ringwulst, that had not previously been recognized as a morphologically unique type of innervation. Although the basic structure of the FSCs is similar in the rat and cat, the numerous differences in innervation suggest that these species would have different tactile capabilities and perceptions possibly related to their different vibrissa-related exploratory behaviors.

Animals↗