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PubMed1999

Immunocytochemical evidence of plasticity in the nervous structures of the rat lower lip.

In this immunocytochemical study we investigated the distribution of nervous structures in the lower lip of adult rats. The region is characterized by a rich cutaneous and mucosal sensory innervation originating from terminal branches of the trigeminal system. Lower lip innervation was investigated by detection of the general neuronal marker protein gene product 9.5 (PGP 9.5) and the growth-associated protein 43 (GAP-43), a neurochemical marker of neuronal plasticity. The entire neural network of both cutaneous and mucosal aspects was stained by the antibody to PGP 9.5. In particular, nerve fibers were observed in the submucosal and the subepithelial plexuses. Thin immunoreactive fibers were observed within the epithelial layers ending as free fibers or as fibers associated with immunopositive Merkel cells. Well-identified anatomical structures receiving sensory or autonomic innervation were also surrounded by PGP 9.5-ir nerve fibers, in particular, hair follicles, vibrissae, glands, and blood vessels. GAP-43-immunostained nerve fibers were observed in all these structures; however, they were generally less numerous than the PGP 9.5-immunoreactive elements. An equal amount of PGP 9.5 and GAP-43 immunoreactivity occurred, in contrast, in the subepidermal and the submucosal plexuses, or in the epidermis and the mucosal epithelium. The present results show that GAP-43 is normally expressed in the mature trigeminal sensory system of the rat. Skin and oral mucosa are characterized by continuous remodeling that may also involve the sensory nervous apparatus. Continuous neural remodeling, regeneration and sprouting may be the reason for the observed expression of GAP-43.

Animals↗
PubMed2003

Feasibility of preoperative lymphoscintigraphy for identification of sentinel lymph nodes in patients with conjunctival and periocular skin malignancies.

PURPOSE: To determine the feasibility of preoperative lymphoscintigraphy for identification of sentinel lymph nodes (SLNs) in patients with conjunctival and periocular skin tumors and to determine the patterns of lymphatic drainage from such tumors. METHODS: We retrospectively reviewed the records of all patients with biopsy-confirmed conjunctival and periocular skin malignancies who underwent lymphoscintigraphy with or without SLN biopsy between January 1999 and June 2000. Patients underwent lymphoscintigraphy with 0.3 to 1 mCi of technetium Tc-99m sulfur colloid in a volume of either 0.2 mL or 1 mL. Images were taken as soon as the first SLNs were detected through the camera and every 15 minutes thereafter. Intraoperative mapping and SLN biopsy was performed 1 to 2 days after lymphoscintigraphy unless the patient refused or there were medical contraindications to the procedure. RESULTS: The study included 7 patients with malignant melanoma of the conjunctiva or periocular skin and 1 patient with Merkel cell carcinoma of the eyelid. On lymphoscintigraphy, at least 1 SLN was identified in 7 of the 8 patients. Although all lesions located in the lateral half of the ocular adnexa drained to at least one SLN in the parotid (preauricular) area, there was some variability in the drainage patterns of lesions located in the medial half of the ocular adnexa. A smaller injection volume (0.2 mL) was adequate for detecting the nodes draining the area of injection and led to less spread of technetium to the surrounding areas. Six patients underwent SLN biopsy. In all but one, the nodes identified during surgery corresponded with those visualized on lymphoscintigraphy. CONCLUSIONS: Preoperative lymphoscintigraphy successfully identifies SLNs in most patients with conjunctival and periocular skin malignancies. Smaller injection volumes (0.2 mL) appear to be adequate for identification of the sentinel nodes and lead to less spread to surrounding tissues.

Adolescent↗
PubMed2002

Potential of tomotherapy for total scalp treatment.

PURPOSE: Total scalp radiotherapy is required in a variety of clinical situations. We compared conventional lateral photon-electron (LPE) technique with tomotherapy (intensity-modulated radiotherapy [IMRT]). METHODS AND MATERIALS: A patient with Merkel cell carcinoma was treated at our institution using conventional treatment techniques. Treatment plans were conducted using conventional three-dimensional treatment planning and IMRT. The clinical target volume included the entire scalp tissue volumes to the surface of underlying cranial bone, as well as superficial and deep neck nodes in the bilateral neck. To provide a consistent comparison between the IMRT and three-dimensional conventional treatment plans, the dose distributions were normalized such that 90% of the target volumes received the prescription dose. RESULTS: Examination of our results revealed an acceptable dose-volume histogram and adequate coverage of the clinical target volume using the conventional LPE technique. The IMRT plan provided a more homogeneous dose to the target volume; however, critical structure doses were uniformly higher than for the conventional treatment plan. CONCLUSIONS: The IMRT plan resulted in a substantial dose to the lens, brain, and orbit, making it clinically unacceptable compared with the LPE technique. Overall, the LPE technique was superior.

Carcinoma, Merkel Cell↗
PubMed2001

Pharmacokinetics and pharmacodynamics of melphalan in isolated limb infusion for recurrent localized limb malignancy.

Isolated limb infusion (ILI) is an attractive, less complex alternative to isolated limb perfusion (ILP). It has a lower morbidity in treating localized recurrences and in transit metastases of the limb for tumours such as melanoma, Merkel cell tumour and Kaposi's sarcoma, allowing administration of high concentrations of cytotoxic agent to the affected limb under hypoxic conditions. Melphalan is the preferred cytotoxic agent for the treatment of melanoma by ILP or ILI. We report pharmacokinetic data from 12 patients treated by ILI for tumours of the limb in Brisbane. The kinetics of drug distribution in the limb was calculated using a two-compartment vascular model, where both tissue and infusate act as well-stirred compartments. Analysis of melphalan concentrations in the perfusate during ILI showed good agreement between the values measured and the concentrations predicted by the model. Recirculation and wash-out flow rates, tissue concentrations and the permeability surface area product (PS) were calculated. Correlations between the PS value and the drug concentrations in the perfusate and tissue were supported by the results. These data contribute to a better understanding of the distribution of melphalan during ILI in the limb, and offer the opportunity to optimize the drug regimen for patients undergoing ILI.

Aged↗
PubMed1996

Response of monkey glabrous skin mechanoreceptors to random noise sequences: II. Dynamic stimulus state analysis.

The responses of monkey glabrous skin slowly adapting (SAI, Merkel cell), rapidly adapting (RA, Meissner) and Pacinian corpuscle (PC) mechanoreceptors were analyzed as a function of the instantaneous position, velocity, and acceleration of a dynamic stimulus. For these experiments, a vibrotactile punctate stimulator was driven by a non-repeating-noise sequence. The resulting data (sampled stimulus waveform, windowed impulse) were processed in several ways. Initially, input-output correlation analysis was implemented to generate spike-aligned averages of the stimulus waveform preceding and following impulse initiation. From this analysis, it was determined that dual-responding RA and PC afferents--that is, those afferents that responded to both indenting and extracting stimulus movements--universally responded in a nearly perfectly symmetrical manner to the stimulus. Subsequently, two-dimensional (position, velocity) state histograms were generated and used to assess mechanoreceptor dynamic stimulus sensitivities. From these state histograms, it was determined that the threshold for impulse initiation by SAI afferents was preferentially sensitive to the indentation position of the stimulus, with only a minor sensitivity to stimulus velocity. RA afferent thresholds were sensitive to a continuum of dynamic stimulus velocities and positions. At the extremes, RA afferent impulses could be initiated by either a highly indented, low-velocity stimulus or high-velocity stimulus with a limited indentation position. PC afferents appeared to be preferentially sensitive to a combination of stimulus velocity and acceleration, but the data-sampling interval was too coarse to adequately resolve the full range of dynamic stimulus sensitivities.

Afferent Pathways↗
PubMed2001

Microdialysis and response during regional chemotherapy by isolated limb infusion of melphalan for limb malignancies.

This study sought to use a microdialysis technique to relate clinical and biochemical responses to the time course of melphalan concentrations in the subcutaneous interstitial space and in tumour tissue (melanoma, malignant fibrous histiocytoma, Merkel cell tumour and osteosarcoma) in patients undergoing regional chemotherapy by Isolated Limb Infusion (ILI). 19 patients undergoing ILI for treatment of various limb malignancies were monitored for intra-operative melphalan concentrations in plasma and, using microdialysis, in subcutaneous and tumour tissues. Peak and mean concentrations of melphalan were significantly higher in plasma than in subcutaneous or tumour microdialysate. There was no significant difference between drug peak and mean concentrations in interstitial and tumour tissue, indicating that there was no preferential uptake of melphalan into the tumours. The time course of melphalan in the microdialysate could be described by a pharmacokinetic model which assumed melphalan distributed from the plasma into the interstitial space. The model also accounted for the vascular dispersion of melphalan in the limb. Tumour response in the whole group to treatment was partial response: 53.8% (n = 7); complete response: 33.3% (n = 5); no response: 6.7% (n = 1). There was a significant association between tumour response and melphalan concentrations measured over time in subcutaneous microdialysate (P< 0.01). No significant relationship existed between the severity of toxic reactions in the limb or peak plasma creatine phosphokinase levels and peak melphalan microdialysate or plasma concentrations. It is concluded that microdialysis is a technique well suited for measuring concentrations of cytotoxic drug during ILI. The possibility of predicting actual concentrations of cytotoxic drug in the limb during ILI using our model opens an opportunity for improved drug dose calculation. The combination of predicting tissue concentrations and monitoring in microdialysate of subcutaneous tissue could help optimise ILI with regard to post-operative limb morbidity and tumour response.

Adult↗
PubMed1987

Lamellar cells of sensory receptors and perineural cells of nerve endings of pig skin contain cytokeratins.

The lamellar cells of the sensory corpuscles of the pig dermis must be considered to be epithelial cells as they contain cytokeratins. The cytokeratins detected are similar to those found in simple epithelia. Moreover, lamellar cells are embedded in an extracellular matrix reminiscent of the basement membrane of epithelium since it contains laminin and collagen IV. The perineural cells surrounding the nerves of pig dermis present the same features. These results suggest that lamellar cells and perineural cells have the same origin. The nature of the lamellar and perineural cells of the rabbit or human dermis is not as clear since cytokeratins were not detected in those cells. These results, together with recent observations on Merkel cells, may indicate that epithelio-neuronal junctions are a general feature of cutaneous sensory receptors.

Animals↗
PubMed1987

Differentiation-related changes of cytokeratin expression in cultured keratinocytes and in fetal, newborn, and adult epidermis.

Cytokeratin expression in differentiating cultured foreskin keratinocytes was studied using chain-specific anti-cytokeratin monoclonal antibodies directed against cytokeratins 4, 8, 10, 13, 18, and 19, respectively. Keratinocytes were cultured at low Ca2+ concentration (0.06 mM) to repress differentiation. At confluency, the cells were switched to high Ca2+ concentration (1.6 mM) to induce differentiation. Cells were harvested 0, 3, 8, 16, 24, 48, and 72 h after the switch. Keratinocytes cultured throughout at high Ca2+ concentration were also harvested. Immunoblots of cytokeratin preparations isolated from these cultures showed that cytokeratins 4, 13, and 19 were not present in nondifferentiating keratinocytes but could be detected from about 16 h after the Ca2+ switch. Immunohistochemical studies were performed on frozen sections of cell sheets incubated with anti-cytokeratin and anti-vimentin. Expression of cytokeratins 4, 13, and 19 was seen in superficial cells. Cytokeratin 10 was locally present in suprabasal and superficial cells. Vimentin was present in 40-70% of the basal cells and in only a few differentiating keratinocytes. Expression of cytokeratins 8 and 18 could not be detected. The same antibodies were also used to stain sections from fetal (15, 20, and 29 weeks), newborn (40 weeks), and mature (5 and 75 years) epidermis. In the 15-week-old epidermis, basal cells were positive for cytokeratins 8 and 19 and locally for cytokeratin 4; intermediate cells expressed cytokeratins 4, 10, 13, and 19; and the periderm contained cytokeratins 4, 8, 13, 18, and 19. In the 20-week-old epidermis, cytokeratin 4 had disappeared from the basal cell layer and cytokeratin 19 was present only locally; in the intermediate cell layer, cytokeratins 4 and 19 had disappeared; and in the periderm, the expression of the cytokeratins studied was the same as that in the 15-week-old epidermis. The basal cells of the 29-week-old fetal epidermis, the newborn epidermis, and the mature epidermis are negative with all antibodies tested, except for some scattered cells in the fetal and newborn skin, presumably Merkel cells, that were positive for cytokeratins 8, 18, and 19. Suprabasal cells in all specimens were positive only for cytokeratin 10. With respect to the cytokeratins studied, our results show that cultured differentiating keratinocytes resemble the suprabasal cells of early fetal epidermis. Basal cells of cultured keratinocytes resemble the basal cells of late fetal, newborn, and adult epidermis and therefore support previous observations.

Adult↗
PubMed2002

Actin-binding protein fascin expression in skin neoplasia.

BACKGROUND: Fascin containing actin bundles provide mechanical support to cellular protrusions and stress fibers. In cancers, some malignant cells (e.g. subsets of breast and ovarian carcinomas) express fascin. In skin cancer, the role of fascin is unknown. METHODS: Cases of 61 keratocytic neoplasms, 35 melanocytic neoplasms, nine extramammary Paget's disease (four with adenocarcinoma) and five sarcomas (angiosarcoma and atypical fibroxanthoma) were examined by immunohistochemistry, using monoclonal antihuman fascin antibody, clone 55 k-2 (Dako Corporation, Carpinteria, CA, USA). RESULTS: Fascin labeled all sarcomas and all keratinocytic neoplasms except for pagetoid pattern Bowen's disease. The regions of most intense fascin labeling were seen in the basal cells of infiltrative tumor margins. A minority of Merkel cell carcinomas exhibited weak or absent immunoreactivity. All melanocytic nevi except for some junctional nests of dysplastic melanocytic nevi expressed fascin. However, pagetoid cells of melanoma in situ and epithelioid cells of invasive melanoma weakly expressed or did not express fascin, whereas melanoma cells exhibiting spindle cell morphologies labeled intensely with fascin. Lastly, all cells of extramammary Paget's disease and most associated adenocarcinomas cells did not or were faintly labeled by fascin antibodies. Decreased or absent fascin expression was significantly associated with skin cancers with a high risk for metastasis (e.g. melanoma) vs. those with a low risk (e.g. basal cell carcinoma) (24% vs. 100% with > 50% immunoreactivity; p = 0.0001, chi-squared test). CONCLUSION: Fascin is expressed by skin tumors that locally infiltrate and replace surrounding tissues indicating a role for fascin in cell adhesion, cell motility and invasiveness. No or weak fascin expression is exhibited by cancers with pagetoid intraepidermal spread and by invasive tumors with a high risk of metastasis. Downregulation or loss of fascin's actin-bundling properties, probably associated with disorganization of cell-cell and cell-matrix contacts, may be a crucial step in the progression from locally invasive to widely disseminating cancers.

Actins↗
PubMed2003

Diagnostic value of microtubule-associated protein-2 (MAP-2) for neuroendocrine neoplasms.

Microtubule associated proteins (MAPs) are major components of cytoskeleton proteins associated with microtubule assembly. Microtubule associated protein-2 (MAP-2), a component of the MAP family, has been shown to be specifically expressed in neuronally differentiated cells, and has been previously used as a sensitive and specific marker for neurons. Immunoreactivity of MAP-2 has been demonstrated in most neuroendocrine and neuroectodermal related neoplasms such as small cell carcinoma, large cell neuroendocrine carcinoma, carcinoid tumor of the lung, Merkel cell carcinoma of the skin, medulloblastoma, neurocytoma of the central nervous system, extrapulmonary small cell carcinoma and carcinoid tumor, and malignant melanomas. This report details the diagnostic value of MAP-2 on tumors with neuroendocrine differentiation and neoplasms derived from the neural crest.

Adult↗
PubMed1995

Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues: their use as markers of neuroendocrine differentiation.

By immunocytochemistry and immunoblotting, we examined normal and neoplastic human tissues with polyclonal antibodies raised against selected peptide regions of proprotein convertase-2 and -3 (PC2 and PC3), two proteases that have been shown to selectively cleave neuroendocrine precursor molecules at pairs of basic residues. Immunoreactivity for both enzymes was detected in neuroendocrine cells of pituitary, gut, pancreas, thyroid, and adrenals and in tumors thereof, but was absent in thyroid follicular cells, parathyroids, adrenal cortex, testes, and a number of nonneuroendocrine tissues, both normal and tumorous. Although both PCs were virtually universal concomitants of the neuroendocrine system, cells with a neural phenotype (e.g. pheochromocytes and Merkel cells) predominantly contained PC2, whereas classic endocrine cells contained mostly PC3. PC3 immunoreactive cells were abundant all along the gastrointestinal tract, whereas PC2 was highly expressed only in the pyloric antrum and proximal third of duodenum. Double immunostaining experiments revealed colocalization of PC3 with virtually all gastrointestinal peptides, whereas PC2 immunoreactivity was mostly expressed in gastrin, cholecystokinin, and somatostatin cells. Noticeably, the proportion of glucagon-producing cells immunoreactive for PC3 was high in the gut and low in pancreatic islets and glucagonomas, whereas the reverse occurred for PC2. At the ultrastructural level, immunostaining was confined to the mature dense core granules, the site of storage of granins and peptide hormones. With the exception of parathyroid cells, PC2 and/or PC3 expression correlated with the occurrence of granins, canonical markers of the secretory granules. Immunoblotting experiments confirmed the identity of the immunocytochemical reactivities. It is concluded that PC2 and PC3 are highly sensitive markers of neuroendocrine differentiation and have distinct distribution patterns, and that antibodies to these enzymes may play an important role in the analysis of tumors.

Aspartic Acid Endopeptidases↗
PubMed2003

The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival.

Gfi1 was first identified as causing interleukin 2-independent growth in T cells and lymphomagenesis in mice. Much work has shown that Gfi1 and Gfi1b, a second mouse homolog, play pivotal roles in blood cell lineage differentiation. However, neither Gfi1 nor Gfi1b has been implicated in nervous system development, even though their invertebrate homologues, senseless in Drosophila and pag-3 in C. elegans are expressed and required in the nervous system. We show that Gfi1 mRNA is expressed in many areas that give rise to neuronal cells during embryonic development in mouse, and that Gfi1 protein has a more restricted expression pattern. By E12.5 Gfi1 mRNA is expressed in both the CNS and PNS as well as in many sensory epithelia including the developing inner ear epithelia. At later developmental stages, Gfi1 expression in the ear is refined to the hair cells and neurons throughout the inner ear. Gfi1 protein is expressed in a more restricted pattern in specialized sensory cells of the PNS, including the eye, presumptive Merkel cells, the lung and hair cells of the inner ear. Gfi1 mutant mice display behavioral defects that are consistent with inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. They have a unique inner ear phenotype in that the vestibular and cochlear hair cells are differentially affected. Although Gfi1-deficient mice initially specify inner ear hair cells, these hair cells are disorganized in both the vestibule and cochlea. The outer hair cells of the cochlea are improperly innervated and express neuronal markers that are not normally expressed in these cells. Furthermore, Gfi1 mutant mice lose all cochlear hair cells just prior to and soon after birth through apoptosis. Finally, by five months of age there is also a dramatic reduction in the number of cochlear neurons. Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death.

Animals↗
PubMed1996

The gamma-probe-guided resection of radiolabeled primary lymph nodes.

The finding that the presence of micrometastases in the first draining primary (sentinel) lymph node potentially reflects the incidence of regional micrometastases has created a fundamental change in how a node-negative lymphatic basin can be evaluated and managed. In cutaneous melanoma and carcinoma of the breast, the data verify the significance of the primary lymph node and support the importance of primary lymph node biopsy. Gamma-probe localization and biopsy of the primary node is a safe, minimally invasive technique that is accurate and easy to perform. For many patients, this technique permits the surgical staging of the regional lymphatics to be performed under local anesthesia on an outpatient basis. Our experience with squamous cell carcinoma of the head and neck and Merkel cell carcinoma suggests that the assessment of the regional lymphatics using the gamma-probe technology for identification of the primary node may also be applicable to many other solid tumors.

Breast Neoplasms↗
PubMed1993

Medical treatment of neuroendocrine tumors.

BACKGROUND: Tumors of the neuroendocrine system are characterized by amine precursor uptake and decarboxylation, and they represent a heterogeneous group of carcinomas including carcinoids, islet cell carcinomas of the pancreas, medullary thyroid carcinomas and Merkel cell carcinomas. Their similar cytochemical and ultrastructural properties sustain the hypothesis of a common embryologic origin within the neural crest. Many of these tumors grow slowly, and reducing tumor burden represents the treatment of choice. However, when surgery is not feasible, medical treatment has to be considered. Therapeutic approaches in metastatic disease often do not consider the different biologic behaviors of these neoplasms. Moreover, efficacy of the treatment is associated with lack of a clear definition of the type of response: objective, symptomatic or biochemical. METHODS: In this review we have analyzed the different medical approaches used in the treatment of neuroendocrine tumors in an attempt to define their precise role in the different neoplasms. RESULTS: In carcinoid tumors, immunotherapy and the somatostatin analogue can be efficaciously used for the control of carcinoid syndrome. For inhibition of tumor growth, chemotherapy should be used only in patients with rapidly progressive disease, and the results are still unsatisfactory. CONCLUSIONS: Although all these tumors appear to have similar cytochemical properties, the responsiveness of the various neoplasms is very different. In the future, a specific treatment modality and a clear definition of the type of response (objective, symptomatic or biochemical) need to be defined for each type of neuroendocrine tumor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Immunologic characteristics of keratins in extramammary Paget's disease.

Six cases of extramammary Paget's disease were immunohistochemically investigated with several antikeratin monoclonal antibodies. Paget cells and surrounding epidermal keratinocytes were equally stained with an antikeratin monoclonal antibody, HKN-4, which recognizes a broad spectrum of keratins. However, Paget cells were clearly distinguished from the surrounding epidermal keratinocytes by HKN-2, which does not react with keratins of secretory cells but does react with keratins of ductal and myoepithelial cells of sweat glands and with epidermis and hair tissue of the normal skin. The HKN-2 did not bind to Paget cells, but the surrounding keratinocytes were positive. CK7, LE41, RGE53, and LP2K, which recognize simple epithelium-type keratins 7 (molecular weight [MW], 54,000; type II), 8 (MW, 52,500; type II), 18 (MW, 45,000; type I), and 19 (MW, 40,000; type I), respectively, stained Paget cells but not the surrounding keratinocytes. Two cases of Merkel cell carcinoma, examined as controls, showed positivity to LE41 and RGE53 but not to CK7 and LP2K. Since in the normal skin the secretory cells of sweat glands showed the same keratin expression as that of Paget cells, Paget cells of extramammary Paget's disease may be derived from or differentiate to the secretory cells of sweat glands.

Adult↗
PubMed2004

Ultrastructures of mechanoreceptors in the oral mucosa.

The present review describes the fine structures of lamellated mechanoreceptive corpuscles, Merkel cell-neurite complexes and free nerve endings in the oral mucosae of mammals, with special attention to axon terminals and lamellar cells. The mechanoreceptive nerve endings of the oral mucosa were studied using histochemistry, immunohistochemistry and transmission electron microscopy techniques. The organized mechanoreceptive corpuscles are present in the mucosae of gingiva, cheek, tongue and soft and hard palate. They are elongated or globular in shape, being located in the connective tissue papillae. The capsule is composed of several layers of cytoplasmic extensions of perineural cells. Numerous bundles of collagen fibers are noted at the periphery of the corpuscle. The lamellated corpuscles are surrounded by several layers of superimposed flattened capsular cell processes. The interlamellar spaces are 0.2-0.4 micron in width and filled with thin fibrillar collagen fibers embedded in the amorphous substance. The lamellar cells contain rich microtubules and are characterized by the presence of caveolae on the surface plasma membrane. The terminal axon contains an abundance of mitochondria and small clear vesicles (20-50 nm in diameter). There are neurofilaments in the center of the axon terminal. Intermediate-type junctions are seen between the adjacent lamellar cells and between the axon and adjacent lamellae. The free nerve endings are found in the subepithelial regions, very close to the basal laminae of mucosal epithelium. They are surrounded by a thin cytoplasm of Schwann cells. Sometimes Schwann cell basal larinae become multilayered. Merkel cells are present within the basal layer of mucosal epithelium and contain characteristic electron-dense granules that are located almost exclusively at the side of cytoplasm in contact with axon terminals. Intermediate-type junctions are noted between axon terminals and Merkel cells.

Animals↗
PubMed1983

Characterization of opioid peptides in guinea-pig heart and skin.

Using reverse phase HPLC separations, and assay of eluate fractions in the mouse vas deferens, extracts of heart and skin from guinea-pigs were shown to contain several species of opioid-active material in low amounts (3-20 pmol/g as [Met5]enkephalin). Immunohistochemical studies revealed in the heart a small number of enkephalin-immunoreactive nerve fibres, particularly in cardiac ganglia and some small cells (paraganglionic cells, APUD cells). In the skin, enkephalin-immunoreactivity was confined to Merkel cells. Cardiac and cutaneous opioid peptides may modulate peripheral cardiovascular and sensory functions.

Animals↗
PubMed1991

Dual presence of chromogranin A-like immunoreactivity in a population of endocrine-like cells and in nerve fibers in the human anal canal.

Light microscopic immunohistochemistry was used to investigate the presence and distribution of chromogranin A-like immunoreactivity in the human anal canal. In the anal transitional zone (ATZ), anal duct and anal gland epithelium, a varied number of mostly elongated cells strongly stained for CGA, using an antibody directed to a highly species-conserved region of the CGA molecule or the monoclonal antibody LK2H10. The density of CGA-immunoreactive (ir) cells strikingly increased from the ATZ epithelium towards the anal gland epithelium. CGA-ir cells possessed single processes running perpendicularly to reach the epithelial surface and exhibited basal ramifications that extended parallel to the basal lamina. The number of CGA-ir cells in anal glands exceeded CGA-ir cells in the crypt-bearing colorectal-type mucosa. The abundant population of CGA-ir cells in the anal canal most likely represents a population of specialized endocrine or paracrine cells. CGA-like immunoreactivity was also present in anocutaneous Merkel cells. A sparse number of vascular and non-vascular CGA-ir varicose nerve fibers was present throughout the layers and rostrocaudal divisions of the anal canal and in the perianal skin. Proposed functions of CGA in neuroendocrine cells and nerves of the anal canal include calcium binding and regulation, secretory granule matrix formation, and generation of bioactive peptides.

Amino Acid Sequence↗