Gerhard W. Hacker

Co-expression of tenascin-C and vimentin in human breast cancer cells indicates phenotypic transdifferentiation during tumour progression: correlation with histopathological parameters, hormone receptors, and oncoproteins.

Loss of epithelial morphology and the acquisition of mesenchymal characteristics are typical for carcinoma cells in tumour progression. In human breast carcinomas, up‐regulation of tenascin‐C (TN‐C) and vimentin (Vim) is frequently observed in cancer cells and correlates with increased malignancy. Thus, it is possible that TN‐C is co‐expressed with Vim, representing cancer cells that have undergone epithelial–mesenchymal transition (EMT). This study examined 128 breast carcinomas using immunohistochemical techniques to demonstrate that mammary cancer cells are a prominent source of both TN‐C and Vim. Statistical analysis revealed a significant association between TN‐C and Vim expression in cancer cells. TN‐C expression also correlated positively with overexpression of c‐erbB‐2 oncoprotein and down‐regulation of oestrogen receptors (ERs). Eleven human mammary cancer cell lines and two ‘normal’ cell lines were examined by western blotting and immunohistochemistry. Co‐expression of TN‐C and Vim was detected in the carcinosarcoma cell line HS 578T, SK‐BR‐3 (B), fibroblast‐like MDA‐MB‐231 cells, and the myoepithelial cell line HBL 100. These findings suggest that TN‐C and Vim, when co‐expressed in mammary carcinoma cells, represent regulator genes likely to be involved in EMT during mammary carcinogenesis. Copyright

Associations between problematic mobile phone use and psychological parameters in young adults

ObjectivesThis study aims to address possible associations between excessive or dysfunctional use of mobile phones and certain psychological variables.MethodsOur study focuses on Problematic Mobile Phone Use (PU) in 196 young adults. A survey was arranged to measure PU, daily mobile phone use in minutes, use of short message service (SMS) and also included psychological and health variables (e.g., chronic stress, depression).ResultsStatistic analysis indicates that chronic stress, low emotional stability, female gender, young age, depression, and extraversion are associated with PU.ConclusionsFuture research needs to clarify the causality of these findings and should also intend to develop concepts for a more meaningful use of mobile phone and related technologies.

Autonomic and Peptidergic Innervation of Human Nasal Mucosa

The localization and distribution of vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), the novel peptide helospectin, neuropeptide tyrosine (NPY) and its C-flanking peptide (C-PON), substance P and calcitonin gene-related peptide (CGRP) were studied in the middle and inferior turbinate of the human nose using sensitive immunocytochemical and radioimmunological methods. For light microscopy, double immunofluorescence and immunogold-silver staining methods were applied. Ultrastructural immunoelectronmicroscopy was performed using a pre-embedding method. In addition, semithin Epon resin sections were immunostained. The concentrations of VIP, NPY, CGRP, substance P and neurokinin A were measured using radioimmunological methods. A dense network of autonomic and peptidergic nerve fibers in the normal human nasal mucosa was demonstrated. Colocalization studies showed the coexistence of peptides with components of the autonomic nervous system. Scattered chromogranin A-, CGRP and bombesin-flanking peptide (BFP)-immunoreactive endocrine-like cells were detected within the lamina propria and in groups within exocrine ducts. Highest radioimmunoassay (RIA) tissue concentrations were detected for VIP, followed by NPY, substance P, CGRP and neurokinin A.

Neuroendocrine cell markers for pancreatic islets and tumors.

The authors review the application of a variety of neuroendocrine cell markers to identify pancreatic islet cells and tumors. In the past, several empiric histochemical techniques had been used to demonstrate neuroendocrine cells, particularly the Grimelius argyrophilic stain. The development of immunohistochemistry made it possible to demonstrate specific cell products such as regulatory peptides, thus allowing the classification of pancreatic neuroendocrine tumors with a view to clinical symptoms. However, it is not always possible to visualize regulatory peptides in these tumors. It is therefore important to use broad-spectrum neuroendocrine cell markers to identify the neuroendocrine nature. These markers are proteins localized in the secretory granules (core- or membrane-related), in the cytosol, or in the cellular membrane. The markers most commonly used in routine histopathology are the secretory granule proteins chromogranin A and synaptophysin and the cytosolic enzyme neuron-specific enolase. Other new markers (eg, synaptic vesicle protein 2) are of general diagnostic value. Region-specific antibodies to chromogranin A can be valuable in differentiating between benign and malignant neuroendocrine tumors. Some markers may be related to the functioning characteristics of pancreatic neuroendocrine tumors, such as prohormone convertases. In addition, markers giving further complementary information have been identified, such as five somatostatin receptor subtypes, the expression of which varies markedly in pancreatic neuroendocrine tumors. Antibodies against all somatostatin receptor subtypes are now commercially available, and immunohistochemical investigation of its expression should be routinely applied when considering treatment with somatostatin analogs.

Neuropeptides in Human Salivary (Submandibular and Parotid) Glands

The existence, distribution and density of various neuropeptides in human submandibular and parotid glands were investigated using immunocytochemistry and radioimmunoassay. Numerous nerve fibers containing vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), or neuropeptide Y (NPY) and C-flanking peptide of NPY (CPON) immunoreactivities (ir) were found in close association to acini, ducts and blood vessels. Only few calcitonin gene-related peptide (CGRP)- and substance P (SP)-ir nerve fibers could be demonstrated, mainly localized around blood vessels and ducts. Galanin and the newly discovered peptides helospectin and pituitary adenylate cyclase activating peptide (PACAP) could not be detected in human salivary glands.

PEPTIDERGIC INNERVATION OF THE HUMAN CLITORIS

In the present study, the distributions of neuropeptides in the normal human clitoris and in a clitoris from an adrenogenital syndrome (AGS) was demonstrated by immunohistochemistry (IHC). Immunohistochemical screening detected a complex network of nerve fibers containing vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), neuropeptide tyrosine (neuropeptide Y), C-flanking peptide of neuropeptide Y (CPON), calcitonin gene-related peptide (CGRP) and substance P immunoreactivities. Special attention was given to the VIP-related peptide helospectin, that has been detected in neuronal elements in the clitoris. No visible differences between the localization and distribution of peptidergic nerve fibers of normal and hypertrophic clitoris from AGS have been observed. Co-localization studies showed the co-existence of VIP, PHM and partly helospectin and neuropeptide Y with CPON within nerve fibers in the cavernous tissue and substance P and CGRP co-expression in nerve fibers especially underneath and within the glans clitoris.

Regulatory Peptides and General Neuroendocrine Markers in Human Nasal Mucosa, Soft Palate and Larynx

Various peptide immunoreactivities in the respiratory system have been reported, indicating complex physiological mechanisms. There is only little information on the upper respiratory system of man. The present study was carried out to demonstrate regulatory peptides in the nasal mucosa, larynx (vocal cords and ventricular folds) and soft palate of man using highly efficient immunocytochemical methods. In addition, some peptide immunoreactivities were measured by use of radioimmunoassay (RIA). Using indirect immunofluorescence and immunogold-silver staining (IGSS) with silver acetate autometallography, a series of peptides could be detected, including vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), galanin, calcitonin gene-related peptide (CGRP), substance P, neuropeptide tyrosine (NPY), C-flanking peptide of NPY (CPON) and somatostatin. In addition, antibodies to protein gene-product (PGP) 9.5, neuron-specific enolase (NSE), S-100, PHE-5 and neurofilament proteins gave positive reactions in tissue sections. Using RIA, CGRP, substance P, and neurokinin A were measured. Our results demonstrate a complex network of regulatory peptide-containing nerve fibers and the possible existence of endocrine cells regulating various functions of the upper respiratory system, which need to be further investigated.

Helospectin and pituitary adenylate cyclase activating polypeptide in the human vagina

Helospectin and pituitary adenylate cyclase activating polypeptide (PACAP), both recently isolated from the poisonous saliva of the American lizard or from ovine hypothalamus respectively, belong to the same peptide family as vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM) and glucagon. In the present study, occurrence and distribution patterns of nerve fibers containing helospectin- and PACAP-like immunoreactivity in the human vagina were investigated by immunohistochemistry. Double immunofluorescent labeling showed that helospectin or PACAP are co-expressed with VIP and PHM within subpopulations of VIP-immunoreactive nerve fibers. Nervous structures containing helospectin and VIP were particularly numerous in the internal mucous lining of the vagina and in free epithelial nerve endings, and an abundant network of nerve fibers surrounding blood vessels was detected. Nerve fibers co-expressing PACAP and VIP were more numerous than those expressing helospectin and VIP and were mainly found in close association with blood vessels as well as beneath and within the epithelium. Due to the lack of non-rabbit helospectin or PACAP antibodies, possible co-localizations between these two peptides could not be investigated at this time. The localizations demonstrated suggest possible roles of the two peptides in the regulation of local blood flow and lubrication of the vagina.

Distribution of two VIP-related peptides, helospectin and pituitary adenylate cyclase activating peptide (PACAP), in the human upper respiratory system

Helospectin (HS) and pituitary adenylate cyclase activating peptide (PACAP) are newly discovered peptides isolated from the salivary gland venom of the lizard Heloderma horridum and the ovine hypothalamus, respectively. They show chemical similarities to vasoactive intestinal polypeptide (VIP), appear to have similar functions and are present in gut, brain, lung, male and female genitourinary tract. In the present study, the distribution of the helospectin and PACAP-27 in the human upper respiratory system was investigated using indirect immunofluorescence and electron-microscopical ABC-pre-embedding methods. Immunohistochemistry revealed helospectin-like (HS-LI) and PACAP-like (PACAP-LI) immunoreactivity in nerve fibers in human nasal, the larynx (vocal cord, ventricular fold, epiglottis), the tongue and the soft palate mucosa. Helospectin-LI and PACAP-LI containing nerve fibers were mainly found in close association to blood vessels and glandular structures. Colocalization studies carried out by application of double immunofluorescence showed that HS and/(or) PACAP-LI coexist with VIP in apparently the same nerve fibers in the upper respiratory system, although single nerve fibers seem to exclusively express helospectin. The localization patterns of helospectin and PACAP-LI in the human upper respiratory system suggests their possible involvement in the regulation of secretory activities and local blood flow.

CGRP and substance P in intraepithelial neuronal structures of the human upper respiratory system

The distribution of intraepithelial nerve fibres and neuroendocrine cells within the surface and glandular epithelium of human nasal mucosa and larynx was examined using immunohistochemical techniques. Neuronal structures were immunostained for the general neuroendocrine marker protein gene-product (PGP) 9.5, and the two neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) using immunofluorescence and streptavidin-biotin-peroxidase complex (S-ABC) methods. Intraepithelial nerve fibres with free nerve endings contained PGP 9.5 and were found within the respiratory surface epithelium of the nasal mucosa and the squamous epithelium of the larynx. A subpopulation of these nerve fibres showed positive immunoreactivties with antibodies against SP and CGRP. Nerve fibres within the ductal epithelium of subepithelial excretory ducts passing the basal membrane and reaching the luminal part were detected. These nerve fibres showed CGRP-like immunoreactivity but not for SP. A dense network of nerve fibres within the squamous surface epithelium was detected in the subglottic and epiglottic region containing CGRP and SP in a small subpopulation of nerve fibres. Single intraepithelial taste buds in the epiglottic region and neuroendocrine cells within the subglottic epithelium expressed PGP 9.5.