Demonstration of S-100 protein in sustentacular cells of phaeochromocytomas and paragangliomas

Eighteen phaeochromocytomas, including both sporadic and familial cases, four cervical paragangliomas, two jugular paragangliomas, and one abdominal paraganglioma were examined immunohistochemically for the presence of S-100 protein. Positive staining in cells morphologically similar to the sustentacular cells of normal paraganglia and adrenal medulla were found in all paragangliomas and in the benign and aggressively growing phaeochromocytomas. In the two malignant tumours no positive reaction was demonstrated. In one tumour the sustentacular cells were shown to contain glial fibrillary acidic protein further supporting their Schwann cell relationship. The number of S-100 positive cells varied considerably. They demonstrated a spindle celled or elongated configuration with long slender processes. The nature of the sustentacular cell proliferation, neoplastic versus reactive, is discussed.     

Bronchial carcinoids with S-100 positive sustentacular cells. A comparative study with gastrointestinal carcinoids, pheochromocytomas and paragangliomas

Fourty-six bronchial carcinoids, twelve tumourlets and twenty areas of neuroendocrine cell dysplasia (NED) were immunohistochemically evaluated for various neuroendocrine markers, S-100 protein (S-100), myelin basic protein, intermediate filaments, actin, Leu-7 and several neurohormonal polypeptides. Eighteen of the bronchial carcinoids (39.1%) showed a biphasic cell pattern, with abundant stellate-shaped S-100 positive cells (SC). SC were not reactive for chromogranin A, myelin basic protein, cytokeratins, neurofilaments, glial fibrillary acidic protein or actin, and were only occasionally weakly positive for vimentin. SC were not detected in the tumourlets nor in the NED observed. For comparison a group of other neuroendocrine tumours (11 gastrointestinal carcinoids, 4 pheochromocytomas and 4 paragangliomas) were immunostained for S-100, chromogranin A and actin. SC similar to the ones detected in the bronchial carcinoids could be detected in appendiceal carcinoids, paragangliomas and in two out of four pheochromocytomas. Our present data are in keeping with a Schwannian/sustentacular nature of SC rather than that of a histiocytic or myoepithelial nature. We suggest that SC-rich bronchial carcinoids are biphasic tumours, which could be designed "paraganglioid" bronchial carcinoids. The relationship between SC-rich bronchial carcinoids and tumourlets/NED is a matter of further investigation: SC-rich bronchial carcinoids may either differentiate in a biphasic pattern during tumoural growth or may not be histogenetically related to tumourlets.     

Mast cells as sources of cytokines,chemokines, and growth factors

Mast cells are hematopoietic cells that reside in virtually all vascularized tissues and that represent potential sources of a wide variety of biologically active secreted products, including diverse cytokines and growth factors. There is strong evidence for important non-redundant roles of mast cells in many types of innate or adaptive immune responses, including making important contributions to immediate and chronic IgE-associated allergic disorders and enhancing host resistance to certain venoms and parasites. However, mast cells have been proposed to influence many other biological processes, including responses to bacteria and virus, angiogenesis, wound healing, fibrosis, autoimmune and metabolic disorders, and cancer. The potential functions of mast cells in many of these settings is thought to reflect their ability to secrete, upon appropriate activation by a range of immune or non-immune stimuli, a broad spectrum of cytokines (including many chemokines) and growth factors, with potential autocrine, paracrine, local, and systemic effects. In this review, we summarize the evidence indicating which cytokines and growth factors can be produced by various populations of rodent and human mast cells in response to particular immune or non-immune stimuli, and comment on the proven or potential roles of such mast cell products in health and disease.     

Multiparameter DNA flow-sorting demonstrates diploidy and SDHD wild-type gene retention in the sustentacular cell compartment of head and neck paragangliomas: chief cells are the only neoplastic component

Head and neck paragangliomas are considered to be biphasic tumours, composed of two distinct cell types: chief cells and sustentacular cells. A substantial number of these tumours show mutations in the SDHD gene located at chromosome 11q23. Although there is general agreement that paragangliomas are a neoplastic proliferation of chief cells, the nature of sustentacular cells is still a matter of debate. To clarify the nature of sustentacular cells further, multiparameter DNA flow cytometry was performed utilizing S-100 labelling as a selective marker of the sustentacular fraction simultaneously with DNA content measurement in six head and neck paragangliomas. S-100-positive fractions and other tumour-cell populations were flow-sorted and restriction digestion analysis of SDHD mutations was performed on each fraction. Flow cytometry demonstrated that the S-100 labelled cells were diploid. Restriction digestion analysis in informative cases revealed retention of the wild-type SDHD allele in S-100-positive fractions and loss of the wild-type allele in S-100-negative fractions. These data strongly suggest that sustentacular cells should be regarded as a non-neoplastic cell population that may be induced as a tumour-specific stromal component by chief cells.     

Topographical distribution of cells in the rat submandibular gland duct system with special reference to dark cells and tuft cells

The duct system of the rat submandibular gland consists of the intercalated duct, the granular convoluted tubule, the striated duct, the excretory duct, the main excretory duct, and the salivary bladder. The duct system contains special cell types, such as dark cells and tuft cells, in addition to principal cells. However, little is known about cell distribution in the duct system. The purpose of the present study was to examine cell distribution and to perform a morphometric analysis of the duct system. Transmission and scanning electron microscopy were used to examine the duct system of the rat submandibular gland. Six regions in the duct system, the striated duct, the interlobular excretory duct, the 5-mm proximal excretory duct from the hilus, the main excretory duct at the hilus, the 10-mm distal main excretory duct from the hilus, and the salivary bladder, were investigated. Morphometric and statistical analyses of the data were then performed. The epithelium of the duct system consisted of a heterogeneous cell population. Dark cells and tuft cells were present throughout the duct system. The principal, dark, and tuft cells were distinguished by their different microvilli by using a scanning electron microscope. The frequency of these cells in the total epithelial cell population was as follows: The percentage of principal cells in the six regions of the duct system varied from 87.5% to 94.4%, that of dark cells varied from 4.1% to 7.2%, and that of tuft cells varied from 1.8% to 7.2%. The number of principal and tuft cells was significantly different between the striated duct and the main excretory duct at the hilus (P < 0.01). However, no significant difference in number of dark cells throughout the duct system was observed (P > 0.05). The abundance of the principal, dark, and tuft cells in the duct system of the rat submandibular gland was determined. Few tuft cells were distributed in the striated duct, and most were found at the hilus. Dark cells were distributed equally throughout the duct system. Anat. Rec. 252:159–164, 1998. © 1998 Wiley-Liss, Inc.     

Juxtanodin in the rat olfactory epithelium: Specific expression in sustentacular cells and preferential subcellular positioning at the apical junctional belt

In the CNS, juxtanodin (JN) is an actin-binding oligodendroglial protein that functions to promote differentiation of the host cells during postnatal development. In other tissues, JN expression and function remain unknown. We surveyed rat peripheral nerve, skeletal muscle and various epithelial tissues using immunoblotting and light-microscopic immunohistochemistry, and found prominent JN expression only in the olfactory epithelium (OE). Confocal and immunoelectron microscopy further revealed specific JN expression in the glia-like sustentacular cells and in the ductal cells of Bowman's glands. JN immunoreactivity was especially prominent in sustentacular cell apices extending superficially from the zone of terminal webs and associated adherens junctions, through the zone of tight junctions, to the roots of sustentacular microvilli. Moderate JN was also found in the supranuclear regions of sustentacular cells, whereas distal parts of sustentacular microvilli were devoid of JN. Distribution of JN in the OE differed from that of class III β-tubulin or nestin, but partially overlapped with a zone of intense F-actin staining near the OE mucous surface. Together these results identify JN as a marker protein for OE sustentacular cells, and support the glia-like nature of OE sustentacular cells. Functionally, JN in the OE might help in the molecular specialization of distinct compartments of olfactory receptor neurons (ORNs), in the interaction of sustentacular cells with ORNs, and/or in maturation/maintenance of sustentacular cells.     

Expression of Growth Factors in Normal and Neoplastic Pituitary Tissues

Many growth factors are expressed in normal pituitary cells and pituitary tumors. They are involved in gene expression for pituitary hormones and in cell proliferation. Some appear to be important for prognosis or treatment. Strong overexpression of some growth factors may indicate a more rapid growth. The significance of the different growth factors for pituitary function and pathology is discussed.     

Localization of Epidermal Growth Factor (EGF) and Epidermal Growth Factor Receptor (EGFr) in Human Pituitary Adenomas and Nontumorous Pituitaries: An Immunocytochemical Study

Epidermal growth factor (EGF) and epidermal growth factor receptor (EGFr) were investigated by immunocytochemistry (ICH) in 57 human pituitary adenomas and 10 nontumorous autopsy pituitaries. EGF immunoreactivity was demonstrated in 24 adenomas (42%), representing 23 functioning tumors and 1 nonfunctioning tumor of oncocytic type, and in all nontumorous pituitaries. Among 40 tumors, EGFr was found positive in 15 functioning adenomas (37.5%), representing 50% of them. The presence of both EGF and EGFr was found mainly in corticotroph adenomas (60%) and less frequently in somatotroph and lactotroph adenomas (20%). ICH on serial sections with EGF or EGFr and adrenocorticotrophic hormone (ACTH) or S-100 protein revealed that EGF and EGFr are localized specifically in corticotrophs and EGFr in stellate cells of nontumorous adenohypophysis. These results confirm the presence of EGF and EGFr in human pituitary adenomas and nontumorous pituitaries and highlight their frequent occurrence in hormone-producing adenomas. Further work is required to explore the possibility that EGF and EGFr play a role in hormone production, release, and tumor progression.     

Immunomodulatory properties of mesenchymal stem cells: cytokines and factors

Mesenchymal stem cells (MSCs) are defined as undifferentiated cells that are capable of self renewal and differentiation into several cell types such as chondrocyte, adipocyte, osteocyte, myocyte, hepatocyte, and neuron-like cells. MSC can be isolated from bone marrow, umbilical cord blood, adipose tissue, placenta, periosteum, trabecular bone, synovium, skeletal muscle, and deciduous teeth. Immunomodulatory of MSCs is one of the important issues nowadays, because this aspect can be clinically applied for graft-versus-host and autoimmune diseases. In this review, we tried to discuss in detail about cytokines and factors such as members of the transforming growth factor superfamily (transforming growth factor-β), hepatic growth factors (HGF), prostaglandin E2 (PGE2), IL-10, indolamine 2,3-dioxygenase (IDO), nitric oxide (NO), heme oxygenase-1 (HO-1), and human leukocyte antigen-G (HLA-G) that are involved in immunomodulatory of MSCs.     

Role of cytokines and growth factors in radioprotection

Cytokines and growth factors are growing groups of proteins that are responsible for the communication between cells of the immune system, hematopoietic cells, and other cell types. The cloning and large-scale production in a recombinant form of these agents in pharmacological quantities permitted investigations aimed at assessing the benefit they may provide in preserving and restoring functions of tissues compromised by irradiation. We have extensively examined past investigations which suggest that some cytokines and growth factors protect animals from radiation lethality when given prior to or after irradiation, and even in untreated animals, these cytokines serve in innate defenses against external stimuli. In contrast, some cytokines given before irradiation sensitize the animals to radiation lethality. Unfortunately, due to their adverse side effects, these cytokines were not found suitable as radioprotectors. Recent studies suggest that new approaches may bring cytokines and growth factors in clinic for radiation injury. The information and insight gained about therapeutic potential of cytokine manipulation will allow for more rational design of treatment protocols.     

大鼠垂体前叶腺细胞增龄变化及其与滤泡星形细胞的关系

目的:研究不同月龄大鼠垂体前叶腺细胞的形态学变化及其与滤泡星形细胞(folliculo-stellate cells,FSCs)之间的形态学关系。方法:透射电镜观察2～3月(青年组)、10～12月(中年组)、18～20月(老年组)3组大鼠垂体前叶的超微结构。结果:3组大鼠的FSCs和腺细胞之间均存在连接复合体样结构;在增龄过程中,FSCs的形态变化不明显,而腺细胞及其细胞间质变化明显:细胞排列散乱、细胞间隙增宽、纤维结缔组织增生,以中年组较为显著;脂褐素、髓样体、凋亡细胞增多,老年组比较明显。结论:FSCs可能通过与腺细胞的直接接触对腺细胞发挥作用;垂体前叶腺细胞及其细胞间隙的变化直接反映其增龄变化。     

Neutrophil-potentiating factors released from stimulated lymphocytes; special reference to the increase in neutrophil-potentiating factors from streptococcus-stimulated lymphocytes of patients with Behçet''s disease.

The potentiating effect of the soluble factors released from normal or diseased lymphocytes on neutrophil functions were investigated in the presence or absence of mitogens and wall preparations of Streptococcus pyogenes. When normal T lymphocyte populations were stimulated with T cell mitogens or with streptococcal preparations, the supernatants from these cultures potentiated neutrophil chemotaxis, phagocytosis and O2- generation. Upon gel-filtration of these stimulated lymphocyte supernatants, the neutrophil-potentiating activity was inactivated by trypsin or by a 30-min incubation at 130 degrees C, but was not affected by acid treatment at pH 2 or heat treatment at 56 degrees C for 60 min. Its activity was almost not affected by antisera against human interleukin-1, interleukin-2, interferon-gamma or tumour necrosis factor. With the stimulation of T cell mitogens, the supernatants released from the lymphocytes of not only the patients with Behçet''s disease but also healthy and diseased controls enhanced neutrophil functions. However, supernatants from streptococcal preparation-stimulated lymphocytes from patients with Behçet''s disease had a higher potentiating effect on neutrophil functions. Our study suggests that the enhanced neutrophil functions in patients with Behçet''s disease may be related to an abnormally high level of circulating activated T cells in these patients.     

Human Langerhans' cells and dermal-type dendritic cells generated from CD34 stem cells express different toll-like receptors and secrete different cytokines in response to toll-like receptor ligands

Langerhans' cells (LC) and dermal dendritic cells (dDC) are located in the superficial and deeper layers of the skin respectively and represent the main dendritic cell (DC) populations of the skin. LC-like and dDC-like DC can be generated from CD34 stem cells and this system is widely used as a model for investigating these cells and in therapeutic vaccination. Here we report toll-like receptor (TLR) expression in human LC and dDC derived from CD34 stem cells. In vitro-generated DC expressed TLR-1, 2, 4, 6, 8 and 10. LC, but not dDC, expressed TLR-5, whereas only dDC expressed TLR-3. Maturation of LC was mediated by TLR-2, 4 and 5 ligands, but not by a TLR-3 ligand. dDC maturation was induced by TLR-3 and -4, but not with TLR-5 ligand and only weakly by a TLR-2 ligand. Stimulated LC secreted interleukin (IL)-1beta, low levels of tumour necrosis factor-alpha (TNF-alpha) and IL-8, but not IL-6 or IL-10. dDC secreted TNF-alpha, IL-6, IL-8 and IL-10, but little IL-1beta. IL-12p70 was not produced by ligand-stimulated dDC or LC, but was secreted by monocyte-derived DC (mdDC) stimulated with lipopolysaccharide (LPS). Thus, in vitro-generated LC and dDC detect different pathogen-associated molecules and show different cytokine-secretion profiles in response to TLR ligands.     

创伤性脑外伤促进骨折愈合中的干细胞、细胞因子、激素、神经肽及基因

背景:骨折延迟愈合和不愈合是临床常见的并发症,脑外伤促进骨折愈合的机制是目前研究的热点.目的:总结创伤性脑外伤促进骨折愈合机制的最新研究进展,为临床应用提供理论依据.方法:文章第一作者通过检索中国知网、万方、维普、PubMed、Embase和Web of Science数据库2009年1月至2020年3月相关文献,检索...     

Genetic factors in human sleep disorders with special reference to Norrie disease, Prader–Willi syndrome and Moebius syndrome

Sleep–wake problems are common in specific inborn errors of metabolism and structure of the central nervous system. Psychological factors, behavioural difficulties, metabolic disturbances, and widespread rather than focal damage to the nervous system are present in many of these diseases and all influence the sleep–wake cycle. However, a number of conditions cause relatively focal damage to the neuroanatomical substrate of sleeping and waking. These include fatal familial insomnia, with involvement of the prion protein gene on chromosome 20, Norrie disease, the Prader–Willi syndrome and the Moebius syndrome. The last three important conditions, although rare, are considered in detail in this review. They result in sensory deprivation, hypothalamic and mid-brain damage, and involve the X-chromosome, chromosome 15, and chromosome 13, respectively. These conditions cause a wide variety of sleep disturbance, including parasomnias, daytime sleepiness, and a condition like cataplexy. The place of the relevant gene products in normal sleep regulation needs further exploration.     

Loss of responsiveness in senescent human TIG-1 cells to the DNA synthesis-inducing effect of various growth factors

Responses of human diploid cells, TIG-1, were examined with respect to their ability to initiate DNA synthesis under the influence of various growth factors and their combinations. The following agents stimulated DNA synthesis in quiescent TIG-1 cells at 37-49 PDL (population doubling level) (66-79% of lifespan completed): fetal bovine serum; tumor-derived DNA synthesis factors such as those from rat rhodamine fibrosarcoma, human adenoma and from the conditioned medium of cultured human pituitary cells; human and mouse epidermal growth factors; tumor promotors such as 12-O-tetradecanoylphorbol 13-acetate and teleocidin; microtubule-disrupting agents as colchicine, vinblastine, podophyllotoxin and TN-16; melittin; and dexamethasone. Cells at 58-60 PDL (94-97% of lifespan completed) were stimulated to synthesize DNA by fetal bovine serum, tumor-derived DNA synthesis factors and epidermal growth factors, but not by other agents. Finally, in senescent cells at 62 PDL (100% of lifespan completed), any of these growth factors and of their combinations failed to induce DNA synthesis at all. These senescent cells, however, still retained the ability to initiate DNA synthesis following infection with SV40 as reported previously [Exp. Cell Res., 143 (1983) 343-349].     

Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26

The family of IL-10-related cytokines includes several human members, IL-19, IL-20, IL-22, IL-24 and IL-26, and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival ad expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA(+) T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles. After three to four cycles of stimulation, IL-10 and CMV-IL-10 led to increased IFN-gamma and IL-10 but decreased IL-4 and IL-13. Interestingly, long-term exposure of T cells to IL-19, IL-20 and IL-22 down-regulated IFN-gamma but up-regulated IL-4 and IL-13 in T cells and supported the polarization of naive T cells to Th2-like cells. In contrast, neutralization of endogenous IL-22 activity by IL-22-binding protein decreased IL-4, IL-13 and IFN-gamma synthesis. The antigen-specific suppressor activity of IL-10 and CMV-IL-10 was not observed for any of the other IL-10-family cytokines. These data demonstrate that IL-19, IL-20 and IL-22 may participate in T cell-mediated diseases by distinct regulation of T cell cytokine profiles.     

In vitro culture of testicular germ cells: Regulatory factors and limitations

Spermatogenesis is regulated mainly by endocrine factors and also by testicular paracrine/autocrine growth factors. These factors are produced by Sertoli cells, germ cells, peritubular cells and interstitial cells, mainly Leydig cells and macrophages. The interactions and the ratio between Sertoli and germ cells in the seminiferous tubules ensure successful spermatogenesis. In order to culture spermatogonial stem cells (SSCs) in vitro, researchers tried to overcome some of the obstacles—such as the low number of stem cells in the testis, absence of specific markers to identify SSCs—in addition to difficulties in keeping the SSCs alive in culture. Recently, some growth factors important for the proliferation and differentiation of SSCs were identified, such as glial cell line derived neurotrophic factor (GDNF), stem cell factor (SCF) and leukemia inhibitory factor (LIF); also, markers for SSCs at different stages were reported. Therefore, some groups succeeded in culturing SSCs (under limitations), or more differentiated cells and even were able to produce in vitro germ cells from embryonic stem cells.

Thus, success in culturing SSCs is dependent on understanding the molecular mechanisms behind self-renewal and differentiation. Culture of SSCs should be a good tool for discovering new therapeutic avenue for some infertile men or for patients undergoing chemotherapy/radiotherapy (pre-puberty or post-puberty).